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{{Redirect|Alzheimer}}

{{DiseaseDisorder infobox
| Name = Alzheimer's disease
| Image = COMPARISONSLICE HIGH.JPG
| Caption = Comparison of a normal aged brain (left) and an Alzheimer's patient's brain (right). Differential characteristics are pointed out.
| DiseasesDB = 490
| ICD10 = {{ICD10|G|30||g|30}}, {{ICD10|F|00||f|00}}
| ICD9 = {{ICD9|331.0}}, {{ICD9|290.1}}
| ICDO =
| OMIM = 104300
| MedlinePlus = 000760
| eMedicineSubj = neuro
| eMedicineTopic = 13
| MeshID = D000544
| GeneReviewsID = alzheimer
|}}
'''Alzheimer's disease'''
('''AD'''), also called '''Alzheimer disease''', '''Senile Dementia of the Alzheimer Type''' ('''SDAT''') or simply '''Alzheimer's''', is the most common form of [[dementia]]. This incurable, [[degenerative disease|degenerative]], and [[Terminal illness|terminal disease]] was first described by German psychiatrist and neuropathologist [[Alois Alzheimer]] in 1906 and was named after him.<ref name="pmid9661992"/> Generally, it is diagnosed in people over 65&nbsp;years of age,<ref>{{cite journal
|author=Brookmeyer R, Gray S, Kawas C
|title=Projections of Alzheimer's disease in the United States and the public health impact of delaying disease onset
|journal=Am J Public Health
|volume=88
|issue=9
|pages=1337–42
|year=1998
|month=September
|pmid=9736873
|pmc=1509089
|doi=10.2105/AJPH.88.9.1337
}}</ref> although the less-prevalent [[early-onset Alzheimer's]] can occur much earlier. In 2006, there were {{Nowrap|26.6 million}} sufferers worldwide. Alzheimer's is predicted to affect 1 in 85 people globally by 2050.<ref name="Brookmeyer2007"/>

Although the course of Alzheimer's disease is unique for every individual, there are many common symptoms.<ref name="alzheimers.org">
{{cite web
| title=What is Alzheimer's disease?
| url=http://www.alzheimers.org.uk/site/scripts/documents_info.php?documentID=100
| publisher=Alzheimers.org.uk
| year=2007
| month=August
| accessdate=2008-02-21
}}</ref> The earliest observable symptoms are often mistakenly thought to be 'age-related' concerns, or manifestations of [[Stress (biological)|stress]].<ref name="pmid17222085">{{cite journal
|author=Waldemar G, Dubois B, Emre M, ''et al.''
|title=Recommendations for the diagnosis and management of Alzheimer's disease and other disorders associated with dementia: EFNS guideline
|journal=Eur J Neurol
|volume=14
|issue=1
|pages=e1–26
|year=2007
|month=January
|pmid=17222085
|doi=10.1111/j.1468-1331.2006.01605.x
}}</ref> In the early stages, the most commonly recognised symptom is inability to acquire new memories, such as difficulty in recalling recently observed facts. When AD is suspected, the diagnosis is usually confirmed with behavioural assessments and [[cognitive tests]], often followed by a [[neuroimaging|brain scan]] if available.<ref name="alzres">
{{cite web
| title=Alzheimer's diagnosis of AD
| url=http://www.alzheimers-research.org.uk/info/diagnosis/
| publisher=Alzheimer's Research Trust
| accessdate=2008-02-29
}}</ref>

As the disease advances, symptoms include [[Mental confusion|confusion]], irritability and aggression, [[mood swing]]s, language breakdown, [[long-term memory]] loss, and the general withdrawal of the sufferer as their senses decline.<ref name="pmid17222085"/><ref name="pmid17823840">
{{cite journal
|author=Tabert MH, Liu X, Doty RL, Serby M, Zamora D, Pelton GH, Marder K, Albers MW, Stern Y, Devanand DP
|title=A 10-item smell identification scale related to risk for Alzheimer's disease
|journal=Ann. Neurol.
|volume=58
|issue=1
|pages=155–160
|year=2005
|pmid=15984022
|doi=10.1002/ana.20533
}}</ref> Gradually, bodily functions are lost, ultimately leading to death.<ref name="nihstages">
{{cite web
| title=Understanding stages and symptoms of Alzheimer's disease
| url=http://www.nia.nih.gov/Alzheimers/Publications/stages.htm
| publisher=National Institute on Aging
| date=2007-10-26
| accessdate=2008-02-21
}}</ref> Individual [[prognosis]] is difficult to assess, as the duration of the disease varies. AD develops for an indeterminate period of time before becoming fully apparent, and it can progress undiagnosed for years. The mean life expectancy following diagnosis is approximately seven years.<ref name="pmid3776457">{{cite journal
|author=Mölsä PK, Marttila RJ, Rinne UK
|title=Survival and cause of death in Alzheimer's disease and multi-infarct dementia
|journal=Acta Neurol Scand
|volume=74
|issue=2
|pages=103–7
|year=1986
|month=August
|pmid=3776457
|accessdate=2008-08-04
|doi=10.1111/j.1600-0404.1986.tb04634.x
}}</ref> Fewer than three percent of individuals live more than fourteen years after diagnosis.<ref name="pmid7793228">{{cite journal
|author=Mölsä PK, Marttila RJ, Rinne UK
|title=Long-term survival and predictors of mortality in Alzheimer's disease and multi-infarct dementia
|journal=ActaNeurol Scand
|volume=91
|issue=3
|pages=159–64
|year=1995
|month=March
|pmid=7793228
}}</ref>

The cause and progression of Alzheimer's disease are not well understood. Research indicates that the disease is associated with [[Senile plaques|plaques]] and [[neurofibrillary tangles|tangles]] in the [[brain]].<ref name="pmid15184601"/> Currently used treatments offer a small symptomatic benefit; no treatments to delay or halt the progression of the disease are as yet available. {{as of
|2008}}, more than 500 [[clinical trials]] have been conducted for identification of a possible treatment for AD, but it is unknown if any of the tested intervention strategies will show promising results.<ref>{{cite web
|url=http://www.clinicaltrials.gov/ct2/results?term=alzheimer
|title= Alzheimer's Disease Clinical Trials
|accessdate= 2008-08-18
|publisher= US National Institutes of Health
}}</ref> A number of non-invasive, life-style habits have been suggested for the [[preventive medicine|prevention]] of Alzheimer's disease, but there is a lack of adequate evidence for a link between these recommendations and reduced degeneration. [[Mental exercise|Mental stimulation]], [[exercise]], and a [[balanced diet]] are suggested, as both a possible prevention and a sensible way of managing the disease.<ref name="prevention1">
{{cite web
| title=Can Alzheimer's disease be prevented
| url=http://www.nia.nih.gov/NR/rdonlyres/63B5A29C-F943-4DB7-91B4-0296772973F3/0/CanADbePrevented.pdf
| format=pdf
| publisher=National Institute on Aging
| accessdate=2008-02-29
| date =2006-08-29
}}</ref>

Because AD cannot be cured and is degenerative, management of patients is essential. The role of the main [[caregiver]] is often taken by the spouse or a close relative.<ref name="metlife.com">{{cite web
| title= The MetLife study of Alzheimer's disease: The caregiving experience
| month= August | year= 2006 |archivedate=2008-06-25
| archiveurl=http://web.archive.org/web/20080625071754/http://www.metlife.com/WPSAssets/14050063731156260663V1FAlzheimerCaregivingExperience.pdf
| publisher=MetLife Mature Market Institute
| format=PDF
| accessdate=2008-02-12
}}</ref> Alzheimer's disease is known for [[caregiving and dementia|placing a great burden on caregivers]]; the pressures can be wide-ranging, involving social, psychological, physical, and economic elements of the caregiver's life.<ref name="pmid17662119">{{cite journal
|author=Thompson CA, Spilsbury K, Hall J, Birks Y, Barnes C, Adamson J
|title=Systematic review of information and support interventions for caregivers of people with dementia
|journal=BMC Geriatr
|volume=7
|page=18
|year=2007
|pmid=17662119
|pmc=1951962
|doi=10.1186/1471-2318-7-18
}}</ref><ref name="pmid10489656">{{cite journal
|author=Schneider J, Murray J, Banerjee S, Mann A
|title=EUROCARE: a cross-national study of co-resident spouse carers for people with Alzheimer's disease: I—Factors associated with carer burden
|journal=International Journal of Geriatric Psychiatry
|volume=14
|issue=8
|pages=651–661
|year=1999
|month=August
|pmid=10489656
|doi=10.1002/(SICI)1099-1166(199908)14:8<651::AID-GPS992>3.0.CO;2-B
|accessdate=2008-07-04
}}</ref><ref name="pmid10489657">{{cite journal
|author=Murray J, Schneider J, Banerjee S, Mann A
|title=EUROCARE: a cross-national study of co-resident spouse carers for people with Alzheimer's disease: II—A qualitative analysis of the experience of caregiving
|journal=International Journal of Geriatric Psychiatry
|volume=14
|issue=8
|pages=662–667
|year=1999
|month=August
|pmid=10489657
|doi=10.1002/(SICI)1099-1166(199908)14:8<662::AID-GPS993>3.0.CO;2-4
}}</ref> In [[developed country|developed countries]], AD is one of the most costly diseases to society.<ref name="pmid15685097">{{cite journal
|author=Bonin-Guillaume S, Zekry D, Giacobini E, Gold G, Michel JP
|title=Impact économique de la démence (English: The economical impact of dementia)
|language=French
|journal=Presse Med
|issn=0755-4982
|volume=34
|issue=1
|pages=35–41
|year=2005
|month=January
|pmid=15685097
}}</ref><ref name="pmid9543467">{{cite journal
|author=Meek PD, McKeithan K, Schumock GT
|title=Economic considerations in Alzheimer's disease
|journal=Pharmacotherapy
|volume=18
|issue=2 Pt 2
|pages=68–73; discussion 79–82
|year=1998
|pmid=9543467
}}</ref>

==Characteristics==
The disease course is divided into four stages, with progressive patterns of [[cognitive]] and [[functional]] [[impairment]]s.

===Pre-dementia===
The first symptoms are often mistaken as related to [[aging]] or [[Stress (biological)|stress]].<ref name="pmid17222085"/> Detailed [[neuropsychology|neuropsychological]] testing can reveal mild cognitive difficulties up to eight years before a person fulfills the clinical criteria for [[diagnosis]] of AD.<ref name="pmid15324363">{{cite journal
|author=Bäckman L, Jones S, Berger AK, Laukka EJ, Small BJ
|title=Multiple cognitive deficits during the transition to Alzheimer's disease
|journal=J Intern Med
|volume=256
|issue=3
|pages=195–204
|year=2004
|month=Sep
|pmid=15324363
|doi=10.1111/j.1365-2796.2004.01386.x
}}</ref> These early symptoms can affect the most complex [[Activities of daily living|daily living activities]].<ref>{{cite journal
|author= Nygård L
|title=Instrumental activities of daily living: a stepping-stone towards Alzheimer's disease diagnosis in subjects with mild cognitive impairment?
|journal=Acta Neurol Scand
|volume=Suppl
|issue=179
|pages=42–6
|year=2003
|month=
|pmid=12603250
|doi= 10.1034/j.1600-0404.107.s179.8.x
}}</ref> The most noticeable deficit is memory loss, which shows up as difficulty in remembering recently learned facts and inability to acquire new information.<ref name="pmid15324363"/><ref name="pmid12603249">{{cite journal
|author=Arnáiz E, Almkvist O
|title=Neuropsychological features of mild cognitive impairment and preclinical Alzheimer's disease
|journal=Acta Neurol. Scand., Suppl.
|volume=179
|pages=34–41
|year=2003
|pmid=12603249
|doi=10.1034/j.1600-0404.107.s179.7.x
|accessdate=2008-06-12
}}</ref>

Subtle problems with the [[executive functions]] of [[attention|attentiveness]], [[planning]], flexibility, and [[abstraction|abstract thinking]], or impairments in [[semantic memory]] (memory of meanings, and concept relationships), can also be symptomatic of the early stages of AD.<ref name="pmid15324363"/> [[Apathy]] can be observed at this stage, and remains the most persistent [[neuropsychiatry|neuropsychiatric]] symptom throughout the course of the disease.<ref>{{cite journal
|author=Landes AM, Sperry SD, Strauss ME, Geldmacher DS
|title=Apathy in Alzheimer's disease
|journal=J Am Geriatr Soc
|volume=49
|issue=12
|pages=1700–7
|year=2001
|month=Dec
|pmid=11844006
|doi=10.1046/j.1532-5415.2001.49282.x
}}</ref> The preclinical stage of the disease has also been termed [[mild cognitive impairment]],<ref name="pmid12603249"/> but whether this term corresponds to a different diagnostic stage or identifies the first step of AD is a matter of dispute.<ref name="pmid17279076">
{{cite journal
|author=Petersen RC
|title=The current status of mild cognitive impairment—what do we tell our patients?
|journal=Nat Clin Pract Neurol
|volume=3
|issue=2
|pages=60–1
|year=2007
|month=February
|pmid=17279076
|doi=10.1038/ncpneuro0402
}}</ref>

===Early dementia===
In people with AD the increasing impairment of learning and memory eventually leads to a definitive diagnosis. In a small portion of them, difficulties with language, executive functions, [[perception]] ([[agnosia]]), or execution of movements ([[apraxia]]) are more prominent than memory problems.<ref name="pmid10653284">
{{cite journal
|author=Förstl H, Kurz A
|title=Clinical features of Alzheimer's disease
|journal=European Archives of Psychiatry and Clinical Neuroscience
|volume=249
|issue=6
|pages=288–290
|year=1999
|pmid=10653284
|doi=10.1007/s004060050101
}}</ref> AD does not affect all memory capacities equally. [[long-term memory|Older memories]] of the person's life ([[episodic memory]]), facts learned ([[semantic memory]]), and [[implicit memory]] (the memory of the body on how to do things, such as using a fork to eat) are affected to a lesser degree than new facts or memories.<ref name="pmid1300219">
{{cite journal
|author=Carlesimo GA, Oscar-Berman M
|title=Memory deficits in Alzheimer's patients: a comprehensive review
|journal=Neuropsychol Rev
|volume=3
|issue=2
|pages=119–69
|year=1992
|month=June
|pmid=1300219
|doi=10.1007/BF01108841
}}</ref><ref name="pmid8821346">
{{cite journal
|author=Jelicic M, Bonebakker AE, Bonke B
|title=Implicit memory performance of patients with Alzheimer's disease: a brief review
|journal=International Psychogeriatrics
|volume=7
|issue=3
|pages=385–392
|year=1995
|pmid=8821346
| doi = 10.1017/S1041610295002134
}}</ref>

[[semantic memory|Language problems]] are mainly characterised by a shrinking [[vocabulary]] and decreased word [[fluency]], which lead to a general impoverishment of oral and [[written language]].<ref name="pmid10653284"/><ref name="pmid1856925">{{cite journal
|author=Taler V, Phillips NA
|title=Language performance in Alzheimer's disease and mild cognitive impairment: a comparative review
|journal= J Clin Exp Neuropsychol
|volume=30
|issue=5
|pages=501–56
|year=2008
|month=Jul
|pmid=1856925
|doi=10.1080/13803390701550128
}}</ref> In this stage, the person with Alzheimer's is usually capable of adequately communicating basic ideas.<ref name="pmid10653284"/><ref name="pmid1856925"/><ref name="pmid7967534">{{cite journal
|author=Frank EM
|title=Effect of Alzheimer's disease on communication function
|journal=J S C Med Assoc
|volume=90
|issue=9
|pages=417–23
|year=1994
|month=September
|pmid=7967534
}}</ref> While performing [[fine motor skill|fine motor tasks]] such as writing, drawing or dressing, certain movement coordination and planning difficulties ([[apraxia]]) may be present but they are commonly unnoticed.<ref name="pmid10653284"/> As the disease progresses, people with AD can often continue to perform many tasks independently, but may need assistance or supervision with the most cognitively demanding activities.<ref name="pmid10653284"/>

===Moderate dementia===
Progressive deterioration eventually hinders independence; with subjects being unable to perform most common activities of daily living.<ref name="pmid10653284" /> Speech difficulties become evident due to an inability to recall vocabulary, which leads to frequent incorrect word substitutions ([[paraphasia]]s). Reading and writing skills are also progressively lost.<ref name="pmid10653284" /><ref name="pmid7967534"/> Complex motor sequences become less coordinated as time passes and AD progresses, so the risk of falling increases.<ref name="pmid10653284" /> During this phase, memory problems worsen, and the person may fail to recognise close relatives.<ref name="pmid10653284" /> [[Long-term memory]], which was previously intact, becomes impaired.<ref name="pmid10653284" />

Behavioural and [[neuropsychiatric]] changes become more prevalent. Common manifestations are [[Wandering (dementia)|wandering]], [[irritability]] and [[labile affect]], leading to crying, outbursts of unpremeditated [[aggression]], or resistance to caregiving.<ref name="pmid10653284" /> [[Sundowning (dementia)|Sundowning]] can also appear.<ref>{{cite journal
|author=Volicer L, Harper DG, Manning BC, Goldstein R, Satlin A
|title=Sundowning and circadian rhythms in Alzheimer's disease
|journal=Am J Psychiatry
|volume=158
|issue=5
|pages=704–11
|year=2001
|month=May
|pmid=11329390
|url=http://ajp.psychiatryonline.org/cgi/content/full/158/5/704
|accessdate=2008-08-27
|doi=10.1176/appi.ajp.158.5.704
}}</ref> Approximately 30% of patients develop [[Delusional misidentification syndrome|illusionary misidentifications]] and other [[delusion]]al symptoms.<ref name="pmid10653284" /> Subjects also lose insight of their disease process and limitations ([[anosognosia]]).<ref name="pmid10653284" /> [[Urinary incontinence]] can develop.<ref name="pmid10653284" /> These symptoms create [[Stress (biological)|stress]] for relatives and caretakers, which can be reduced by moving the person from [[home care]] to other [[Nursing home|long-term care facilities]].<ref name="pmid10653284" /><ref name="pmid7806732">{{cite journal
|author=Gold DP, Reis MF, Markiewicz D, Andres D
|title=When home caregiving ends: a longitudinal study of outcomes for caregivers of relatives with dementia
|journal=J Am Geriatr Soc
|volume=43
|issue=1
|pages=10–6
|year=1995
|month=January
|pmid=7806732
}}</ref>

===Advanced dementia===
During this last stage of AD, the patient is completely dependent upon caregivers.<ref name="pmid10653284" /> Language is reduced to simple phrases or even single words, eventually leading to complete loss of speech.<ref name="pmid10653284" /><ref name="pmid7967534"/> Despite the loss of verbal language abilities, patients can often understand and return emotional signals.<ref name="pmid10653284" /> Although aggressiveness can still be present, extreme apathy and [[exhaustion]] are much more common results.<ref name="pmid10653284" />
Patients will ultimately not be able to perform even the most simple tasks without assistance.<ref name="pmid10653284" /> [[musculature|Muscle mass]] and mobility deteriorate to the point where they are bedridden, and they lose the ability to feed themselves.<ref name="pmid10653284" /> AD is a terminal illness with the cause of death typically being an external factor such as infection of [[bedsore|pressure ulcers]] or [[pneumonia]], not the disease itself.<ref name="pmid10653284" />

==Causes==
[[File:TAU HIGH.JPG|thumb|right|Upright| Microscopy image of a neurofibrillary tangle, conformed by hyperphosphorylated [[tau protein]]]]
Several competing hypotheses exist trying to explain the cause of the disease. The oldest, on which most currently available drug therapies are based, is the ''[[cholinergic]] hypothesis'',<ref name="pmid10071091">{{cite journal |author=Francis PT, Palmer AM, Snape M, Wilcock GK |title=The cholinergic hypothesis of Alzheimer's disease: a review of progress |journal=J. Neurol. Neurosurg. Psychiatr. |volume=66 |issue=2 |pages=137–47 |year=1999 |month=February |pmid=10071091 |pmc=1736202 |doi= 10.1136/jnnp.66.2.137|url=}}</ref> which proposes that AD is caused by reduced synthesis of the [[neurotransmitter]] [[acetylcholine]]. The cholinergic hypothesis has not maintained widespread support, largely because medications intended to treat acetylcholine deficiency have not been very effective. Other cholinergic effects have also been proposed, for example, initiation of large-scale aggregation of amyloid,<ref name="pmid15236795">{{cite journal
|author=Shen ZX
|title=Brain cholinesterases: II. The molecular and cellular basis of Alzheimer's disease
|journal=Med Hypotheses
|volume=63
|issue=2
|pages=308–21
|year=2004
|pmid=15236795
|doi=10.1016/j.mehy.2004.02.031
}}</ref> leading to generalised neuroinflammation.<ref name="pmid12934968">{{cite journal
|author=Wenk GL
|title=Neuropathologic changes in Alzheimer's disease
|journal=J Clin Psychiatry
|volume=64 Suppl 9
|pages=7–10
|year=2003
|pmid=12934968
}}</ref>

In 1991, the ''[[amyloid beta|amyloid]] hypothesis'' postulated that amyloid beta (Aβ) deposits are the fundamental cause of the disease.<ref name="pmid1763432">{{cite journal
|author=Hardy J, Allsop D
|title=Amyloid deposition as the central event in the aetiology of Alzheimer's disease
|journal=Trends Pharmacol. Sci.
|volume=12
|issue=10
|pages=383–88
|year=1991
|month=October
|pmid=1763432
|doi=10.1016/0165-6147(91)90609-V
}}</ref><ref name="pmid11801334">{{cite journal
|author=Mudher A, Lovestone S
|title=Alzheimer's disease-do tauists and baptists finally shake hands?
|journal=Trends Neurosci.
|volume=25
|issue=1
|pages=22–26
|year=2002
|month=January
|pmid=11801334
|doi=10.1016/S0166-2236(00)02031-2
}}</ref> Support for this postulate comes from the location of the gene for the [[amyloid precursor protein|amyloid beta precursor protein]] (APP) on [[chromosome 21]], together with the fact that people with [[trisomy 21]] ([[Down Syndrome]]) who thus have an extra [[gene dosage|gene copy]] almost universally exhibit AD by 40&nbsp;years of age.<ref name="pmid16904243">{{cite journal
|author=Nistor M, Don M, Parekh M, ''et al.''
|title=Alpha- and beta-secretase activity as a function of age and beta-amyloid in Down syndrome and normal brain
|journal=Neurobiol Aging
|volume=28
|issue=10
|pages=1493–1506
|year=2007
|month=October
|pmid=16904243
|doi=10.1016/j.neurobiolaging.2006.06.023
|last12=Head
|first12=E
}}</ref><ref name="pmid15639317">{{cite journal
|author=Lott IT, Head E
|title=Alzheimer disease and Down syndrome: factors in pathogenesis
|journal=Neurobiol Aging
|volume=26
|issue=3
|pages=383–89
|year=2005
|month=March
|pmid=15639317
|doi=10.1016/j.neurobiolaging.2004.08.005
}}</ref> Also [[APOE4]], the major genetic risk factor for AD, leads to excess amyloid buildup in the brain before AD symptoms arise. Thus, Aβ deposition precedes clinical AD.<ref name="pmid7566000">{{cite journal
|author=Polvikoski T, Sulkava R, Haltia M, ''et al.''
|title=Apolipoprotein E, dementia, and cortical deposition of beta-amyloid protein
|journal=N Engl J Med
|volume=333
|issue=19
|pages=1242–47
|year=1995
|month=November
|pmid=7566000
|doi=10.1056/NEJM199511093331902
}}</ref> Further evidence comes from the finding that [[Genetically modified organism|transgenic]] mice that express a mutant form of the human APP gene develop fibrillar amyloid plaques and Alzheimer's-like brain pathology with spatial learning deficits.<ref>Transgenic mice:
*{{cite journal
|author=Games D, Adams D, Alessandrini R, ''et al.''
|title=Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein
|journal=Nature
|volume=373
|issue=6514
|pages=523–27
|year=1995
|month=February
|pmid=7845465
|doi=10.1038/373523a0
}}
*{{cite journal
|author=Masliah E, Sisk A, Mallory M, Mucke L, Schenk D, Games D
|title=Comparison of neurodegenerative pathology in transgenic mice overexpressing V717F beta-amyloid precursor protein and Alzheimer's disease
|journal=J Neurosci
|volume=16
|issue=18
|pages=5795–811
|year=1996
|month=September
|pmid=8795633
}}
*{{cite journal
|author=Hsiao K, Chapman P, Nilsen S, ''et al.''
|title=Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice
|journal=Science (journal)
|volume=274
|issue=5284
|pages=99–102
|year=1996
|month=October
|pmid=8810256
|doi=10.1126/science.274.5284.99
}}
*{{cite journal
|author=Lalonde R, Dumont M, Staufenbiel M, Sturchler-Pierrat C, Strazielle C.
|title=Spatial learning, exploration, anxiety, and motor coordination in female APP23 transgenic mice with the Swedish mutation.
|journal=Brain Research (journal)
|volume=956
|pages=36–44, year=2002
|pmid=12426044
|doi=10.1016/S0006-8993(02)03476-5
|year=2002
|issue=1
}}</ref>

An experimental vaccine was found to clear the amyloid plaques in early human trials, but it did not have any significant effect on dementia.<ref name="pmid18640458">{{cite journal
|author=Holmes C, Boche D, Wilkinson D, ''et al.''
|title=Long-term effects of Abeta42 immunisation in Alzheimer's disease: follow-up of a randomised, placebo-controlled phase I trial
|journal=Lancet
|volume=372
|issue=9634
|pages=216–23
|year=2008
|month=July
|pmid=18640458
|doi=10.1016/S0140-6736(08)61075-2
|last12=Nicoll
|first12=JA
}}</ref> Researchers have been led to suspect non-plaque Aβ oligomers (aggregates of many monomers) as the primary pathogenic form of Aβ. These toxic oligomers, also referred to as Amyloid-Derived Diffusible Ligands (ADDLs), bind to a surface receptor on neurons and change the structure of the synapse, thereby disrupting neuronal communication.<ref name="pmid17251419">
{{cite journal
|author=Lacor PN,''et al.''
|title=Aß Oligomer-Induced Aberrations in Synapse Composition, Shape, and Density Provide a Molecular Basis for Loss of Connectivity in Alzheimer's Disease
|journal=Journal of Neuroscience
|volume=27
|issue=4
|pages=796–807
|year=2007
|month=January
|pmid=17251419
|doi=10.1523/JNEUROSCI.3501-06.2007
|last2=Buniel
|first2=MC
|last3=Furlow
|first3=PW
|last4=Clemente
|first4=AS
|last5=Velasco
|first5=PT
|last6=Wood
|first6=M
|last7=Viola
|first7=KL
|last8=Klein
|first8=WL
}}</ref>
One receptor for Aβ Oligomers may be the [[PRNP|Prion Protein]], the same protein that has been linked to [[Bovine Spongiform Encephalopathy|mad cow disease]] and the related human condition, [[Creutzfeldt-Jakob disease]], thus potentially linking the underlying mechanism of these neurodegenerative disorders with that of Alzheimer's disease.<ref name="pmid19242475">
{{cite journal
|author=Lauren J, Gimbel D, ''et al.''
|title=Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers
|journal=Nature
|volume=457
|issue=7233
|pages=1128–32
|year=2009
|month=February
|pmid=19242475
|doi=10.1038/nature07761
|pmc=2748841
}}</ref>

In 2009, this theory was updated, suggesting that a close relative of the beta-amyloid protein, and not necessarily the beta-amyloid itself, may be a major culprit in the disease. The theory holds that an amyloid-related mechanism that prunes neuronal connections in the brain in the fast-growth phase of early life may be triggered by aging-related processes in later life to cause the neuronal withering of Alzheimer's disease.<ref name="Nikolaev">{{cite journal
| first= Anatoly | last= Nikolaev
| coauthors= Todd McLaughlin, Dennis O'Leary, Marc Tessier-Lavigne
| date= 19 February 2009
| title= N-APP binds DR6 to cause axon pruning and neuron death via distinct caspases
| journal= Nature
| volume= 457
| issue= 7232
| pages= 981–989
| issn= 0028-0836
| pmid= 19225519
| pmc= 2677572
| doi= 10.1038/nature07767
| accessdate= May 2009 }}
</ref> N-APP, a fragment of APP from the peptide's [[N-terminus]], is adjacent to beta-amyloid and is cleaved from APP by one of the same enzymes. N-APP triggers the self-destruct pathway by binding to a neuronal receptor called death receptor 6 (DR6, also known as [[TNFRSF21]]).<ref name="Nikolaev" /> DR6 is highly expressed in the human brain regions most affected by Alzheimer's, so it is possible that the N-APP/DR6 pathway might be hijacked in the aging brain to cause damage. In this model, Beta-amyloid plays a complementary role, by depressing synaptic function.

A 2004 study found that deposition of amyloid plaques does not correlate well with neuron loss.<ref name="pmid15039236">{{cite journal
|author=Schmitz C, Rutten BP, Pielen A, ''et al.''
|title=Hippocampal neuron loss exceeds amyloid plaque load in a transgenic mouse model of Alzheimer's disease
|journal=Am J Pathol
|volume=164
|issue=4
|pages=1495–1502
|year=2004
|month=April
|pmid=15039236
|pmc=1615337
|last12=Steinbusch
|first12=HW
|last13=Pradier
|first13=L
|last14=Bayer
|first14=TA
}}</ref> This observation supports the ''tau hypothesis'', the idea that [[tau protein]] abnormalities initiate the disease cascade.<ref name="pmid11801334"/> In this model, hyperphosphorylated tau begins to pair with other threads of tau. Eventually, they form [[neurofibrillary tangles]] inside nerve cell bodies.<ref name="pmid1669718">{{cite journal
|author=Goedert M, Spillantini MG, Crowther RA
|title=Tau proteins and neurofibrillary degeneration
|journal=Brain Pathol
|volume=1
|issue=4
|pages=279–86
|year=1991
|month=July
|pmid=1669718
|doi=10.1111/j.1750-3639.1991.tb00671.x
}}</ref> When this occurs, the [[microtubules]] disintegrate, collapsing the neuron's transport system.<ref name="pmid15615638">{{cite journal
|author=Iqbal K, Alonso Adel C, Chen S, ''et al.''
|title=Tau pathology in Alzheimer disease and other tauopathies
|journal=Biochim Biophys Acta
|volume=1739
|issue=2–3
|pages=198–210
|year=2005
|month=January
|pmid=15615638
|doi=10.1016/j.bbadis.2004.09.008
|url=
|last12=Grundke-Iqbal
|first12=I
}}</ref> This may result first in malfunctions in biochemical communication between neurons and later in the death of the cells.<ref name="pmid17127334">{{cite journal
|author=Chun W, Johnson GV
|title=The role of tau phosphorylation and cleavage in neuronal cell death
|journal=Front Biosci
|volume=12
|pages=733–56
|year=2007
|pmid=17127334
|doi=10.2741/2097
}}</ref>
[[Herpes_simplex#Alzheimer.27s_disease|Herpes simplex]] virus type 1 has also been proposed to play a causative role in people carrying the susceptible versions of the [[Apolipoprotein E|apoE]] gene.<ref name="pmid18487848">
{{cite journal
|author=Itzhaki RF, Wozniak MA |title=Herpes simplex virus type 1 in Alzheimer's disease: the enemy within
|journal=J Alzheimers Dis
|volume=13
|issue=4
|pages=393–405
|year=2008
|month=May
|pmid=18487848
|doi=
|issn=1387-2877
|url=http://iospress.metapress.com/openurl.asp?genre=article&issn=1387-2877&volume=13&issue=4&spage=393
}}</ref>

Another hypothesis asserts that the disease may be caused by age related [[myelin]] breakdown in the brain. Demyelination leads to axonal transport disruptions, leading to loss of neurons that become stale. Iron released during myelin breakdown is hypothesized to cause further damage. Homeostatic myelin repair processes contribute to the development of proteinaceous deposits such as Amyloid-beta and tau.<ref>{{Cite pmid| 19775776}}</ref><ref>{{Cite pmid| 15665415}}</ref><ref>{{Cite pmid|18596894}}</ref>

[[Oxidative stress]] is a significant cause in the formation of the pathology.<ref>{{cite pmid|19075578}}</ref>

AD individuals show 70% loss of [[locus ceruleus]] cells that provide [[norepinephrine]] (in addition to its neurotransmitter role) that locally diffuses from "varicosities" as an endogenous [[antiinflammatory]] agent in the microenvironment around the neurons, glial cells, and blood vessels in the neocortex and hippocampus.<ref name="Heneka">Heneka MT, Nadrigny F, Regen T, Martinez-Hernandez A, Dumitrescu-Ozimek L, Terwel D, Jardanhazi-Kurutz D, Walter J, Kirchhoff F, Hanisch UK, Kummer MP. (2010). [http://www.pnas.org.libproxy.ucl.ac.uk/content/107/13/6058.full.pdf Locus ceruleus controls Alzheimer's disease pathology by modulating microglial functions through norepinephrine.] Proc Natl Acad Sci U S A. 107:6058–6063 {{doi|10.1073/pnas.0909586107}} PMID 20231476</ref> It has been shown that norepinephrine stimulates mouse microglia to suppress Aβ-induced production of cytokines and their [[phagocytosis]] of Aβ.<ref name="Heneka"/> This suggests that degeneration of the locus ceruleus might be responsible for increased Aβ deposition in AD brains.<ref name="Heneka"/>

==Pathophysiology==
{{Main|Biochemistry of Alzheimer's disease}}
[[File:Alzheimer dementia (3) presenile onset.jpg|thumb|[[Histopathology|Histopathologic]] image of senile plaques seen in the cerebral cortex of a person with Alzheimer's disease of presenile onset. Silver impregnation.]]

===Neuropathology===
Alzheimer's disease is characterised by loss of [[neuron]]s and [[synapse]]s in the [[cerebral cortex]] and certain subcortical regions. This loss results in gross [[atrophy]] of the affected regions, including degeneration in the [[temporal lobe]] and [[parietal lobe]], and parts of the [[frontal cortex]] and [[cingulate gyrus]].<ref name="pmid12934968"/> Studies using [[magnetic resonance imaging|MRI]] and [[positron emission tomography|PET]] have documented reductions in the size of specific brain regions in patients as they progressed from mild cognitive impairment to Alzheimer's disease, and in comparison with similar images from healthy older adults.<ref>{{cite journal |author=Moan R|title=MRI software accurately IDs preclinical Alzheimer's disease |journal=Diagnostic Imaging |date=July 20, 2009 |url=http://www.diagnosticimaging.com/news/display/article/113619/1428344}}</ref>

Both [[amyloid plaques]] and [[neurofibrillary tangle]]s are clearly visible by [[microscopy]] in brains of those afflicted by AD.<ref name="pmid15184601">{{cite journal
|author=Tiraboschi P, Hansen LA, Thal LJ, Corey-Bloom J
|title=The importance of neuritic plaques and tangles to the development and evolution of AD
|journal=Neurology
|volume=62
|issue=11
|pages=1984–9
|year=2004
|month=June
|pmid=15184601
}}</ref> Plaques are dense, mostly [[insoluble]] deposits of [[Beta amyloid|amyloid-beta]] [[peptide]] and [[Cell (biology)|cellular]] material outside and around neurons. Tangles (neurofibrillary tangles) are aggregates of the microtubule-associated protein tau which has become hyperphosphorylated and accumulate inside the cells themselves. Although many older individuals develop some plaques and tangles as a consequence of aging, the brains of AD patients have a greater number of them in specific brain regions such as the temporal lobe.<ref name="pmid8038565">{{cite journal
|author=Bouras C, Hof PR, Giannakopoulos P, Michel JP, Morrison JH
|title=Regional distribution of neurofibrillary tangles and senile plaques in the cerebral cortex of elderly patients: a quantitative evaluation of a one-year autopsy population from a geriatric hospital
|journal=Cereb. Cortex
|volume=4
|issue=2
|pages=138–50
|year=1994
|pmid=8038565
|doi=10.1093/cercor/4.2.138
}}</ref> [[Lewy body|Lewy bodies]] are not rare in AD patient's brains.<ref name="pmid11816795">{{cite journal
|author=Kotzbauer PT, Trojanowsk JQ, Lee VM
|title=Lewy body pathology in Alzheimer's disease
|journal=J Mol Neurosci
|volume=17
|issue=2
|pages=225–32
|year=2001
|month=Oct
|pmid=11816795
|doi=10.1385/JMN:17:2:225
}}</ref>

===Biochemistry===
[[File:Amyloid-plaque formation-big.jpg|right|thumb|border|Enzymes act on the APP (amyloid precursor protein) and cut it into fragments. The beta-amyloid fragment is crucial in the formation of senile plaques in AD.]]
Alzheimer's disease has been identified as a [[protein folding|protein misfolding]] disease ([[proteopathy]]), caused by accumulation of abnormally folded A-beta and tau proteins in the brain.<ref name="pmid14528050">{{cite journal
|author=Hashimoto M, Rockenstein E, Crews L, Masliah E
|title=Role of protein aggregation in mitochondrial dysfunction and neurodegeneration in Alzheimer's and Parkinson's diseases
|journal=Neuromolecular Med.
|volume=4
|issue=1–2
|pages=21–36
|year=2003
|pmid=14528050
|doi=10.1385/NMM:4:1-2:21
}}</ref> Plaques are made up of small [[peptide]]s, 39–43&nbsp;[[amino acid]]s in length, called [[beta-amyloid]] (also written as A-beta or Aβ). Beta-amyloid is a fragment from a larger protein called [[amyloid precursor protein]] (APP), a [[transmembrane protein]] that penetrates through the neuron's membrane. APP is critical to neuron growth, survival and post-injury repair.<ref name="pmid16822978">{{cite journal
|author=Priller C, Bauer T, Mitteregger G, Krebs B, Kretzschmar HA, Herms J
|title=Synapse formation and function is modulated by the amyloid precursor protein
|journal=J. Neurosci.
|volume=26
|issue=27
|pages=7212–21
|year=2006
|month=July
|pmid=16822978
|doi=10.1523/JNEUROSCI.1450-06.2006
}}</ref><ref name="pmid12927332">{{cite journal
|author=Turner PR, O'Connor K, Tate WP, Abraham WC
|title=Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory
|journal=Prog. Neurobiol.
|volume=70
|issue=1
|pages=1–32
|year=2003
|month=May
|pmid=12927332
|doi=10.1016/S0301-0082(03)00089-3
}}</ref> In Alzheimer's disease, an unknown process causes APP to be divided into smaller fragments by [[enzymes]] through [[proteolysis]].<ref name="pmid15787600">{{cite journal
|author=Hooper NM
|title=Roles of proteolysis and lipid rafts in the processing of the amyloid precursor protein and prion protein
|journal=Biochem. Soc. Trans.
|volume=33
|issue=Pt 2
|pages=335–8
|year=2005
|month=April
|pmid=15787600
|doi=10.1042/BST0330335
}}</ref> One of these fragments gives rise to fibrils of beta-amyloid, which form clumps that deposit outside neurons in dense formations known as [[senile plaques]].<ref name="pmid15184601"/><ref name="pmid15004691">{{cite journal
|author=Ohnishi S, Takano K
|title=Amyloid fibrils from the viewpoint of protein folding
|journal=Cell. Mol. Life Sci.
|volume=61
|issue=5
|pages=511–24
|year=2004
|month=March
|pmid=15004691
|doi=10.1007/s00018-003-3264-8
}}</ref>
[[File:TANGLES HIGH.jpg|right|thumb|In Alzheimer's disease, changes in tau protein lead to the disintegration of microtubules in brain cells.]]

AD is also considered a [[tauopathy]] due to abnormal aggregation of the [[tau protein]]. Every neuron has a [[cytoskeleton]], an internal support structure partly made up of structures called [[microtubules]]. These microtubules act like tracks, guiding nutrients and molecules from the body of the cell to the ends of the [[axon]] and back. A protein called ''tau'' stabilizes the microtubules when [[phosphorylation|phosphorylated]], and is therefore called a [[microtubule-associated protein]]. In AD, tau undergoes chemical changes, becoming [[Hyperphosphorylation|hyperphosphorylated]]; it then begins to pair with other threads, creating neurofibrillary tangles and disintegrating the neuron's transport system.<ref name="pmid17604998">{{cite journal
|author=Hernández F, Avila J
|title=Tauopathies
|journal=Cell. Mol. Life Sci.
|volume=64
|issue=17
|pages=2219–33
|year=2007
|month=September
|pmid=17604998
|doi=10.1007/s00018-007-7220-x
}}</ref>

===Disease mechanism===
Exactly how disturbances of production and aggregation of the beta amyloid peptide gives rise to the pathology of AD is not known.<ref name="pmid17622778">{{cite journal
|author=Van Broeck B, Van Broeckhoven C, Kumar-Singh S
|title=Current insights into molecular mechanisms of Alzheimer disease and their implications for therapeutic approaches
|journal=Neurodegener Dis
|volume=4
|issue=5
|pages=349–65
|year=2007
|pmid=17622778
|doi=10.1159/000105156
}}</ref> The amyloid hypothesis traditionally points to the accumulation of beta amyloid [[peptide]]s as the central event triggering neuron degeneration. Accumulation of aggregated amyloid [[fibril]]s, which are believed to be the toxic form of the protein responsible for disrupting the cell's [[calcium]] [[ion]] [[homeostasis]], induces [[programmed cell death]] ([[apoptosis]]).<ref name="pmid2218531">{{cite journal
|author=Yankner BA, Duffy LK, Kirschner DA
|title=Neurotrophic and neurotoxic effects of amyloid beta protein: reversal by tachykinin neuropeptides
|journal=Science (journal)
|volume=250
|issue=4978
|pages=279–82
|year=1990
|month=October
|pmid=2218531
|doi=10.1126/science.2218531
}}</ref> It is also known that Aβ selectively builds up in the [[Mitochondrion|mitochondria]] in the cells of Alzheimer's-affected brains, and it also inhibits certain [[enzyme]] functions and the utilisation of [[glucose]] by neurons.<ref name="pmid17424907">{{cite journal
|author=Chen X, Yan SD
|title=Mitochondrial Abeta: a potential cause of metabolic dysfunction in Alzheimer's disease
|journal=IUBMB Life
|volume=58
|issue=12
|pages=686–94
|year=2006
|month=December
|pmid=17424907
|doi=10.1080/15216540601047767}}</ref>

Various inflammatory processes and [[cytokine]]s may also have a role in the pathology of Alzheimer's disease. [[Inflammation]] is a general marker of [[Tissue (biology)|tissue]] damage in any disease, and may be either secondary to tissue damage in AD or a marker of an immunological response.<ref name="pmid15681814">{{cite journal
|author=Greig NH, Mattson MP, Perry T, ''et al.''
|title=New therapeutic strategies and drug candidates for neurodegenerative diseases: p53 and TNF-alpha inhibitors, and GLP-1 receptor agonists
|journal=Ann. N. Y. Acad. Sci.
|volume=1035
|pages=290–315
|year=2004
|month=December
|pmid=15681814
|doi=10.1196/annals.1332.018
}}</ref>

Alterations in the distribution of different [[neurotrophic factor]]s and in the expression of their receptors such as the [[brain derived neurotrophic factor]] (BDNF) have been described in AD.<ref>{{cite journal
|author=Tapia-Arancibia L, Aliaga E, Silhol M, Arancibia S
|title=New insights into brain BDNF function in normal aging and Alzheimer disease
|journal=[[Brain Research Reviews]]
|volume=59
|issue=1
|pages=201–20
|year=2008
|month=Nov
|pmid=18708092
|doi=10.1016/j.brainresrev.2008.07.007
}}</ref><ref>{{cite journal
|doi=10.1111/j.1601-183X.2007.00378.x
|author=Schindowski K, Belarbi K, Buée L
|title=Neurotrophic factors in Alzheimer's disease: role of axonal transport
|journal= [[Genes, Brain and Behavior]]
|volume=7
|issue=Suppl 1
|pages=43–56
|year=2008
|month=Feb
|pmid=18184369
|pmc=2228393
}}</ref>

===Genetics===
The vast majority of cases of Alzheimer's disease are sporadic, meaning that they are not genetically inherited although some genes may act as risk factors. On the other hand, around 0.1% of the cases are familial forms of autosomal-dominant inheritance, which usually have an onset before age 65.<ref name="pmid16876668">{{cite journal
|author=Blennow K, de Leon MJ, Zetterberg H
|title=Alzheimer's disease
|journal=Lancet
|volume=368
|issue=9533
|pages=387–403
|year=2006
|month=July
|pmid=16876668
|doi=10.1016/S0140-6736(06)69113-7
|url=
}}</ref>

Most of autosomal dominant familial AD can be attributed to mutations in one of three genes: [[amyloid precursor protein]] (APP) and [[presenilin]]s 1 and 2.<ref name="pmid18332245">{{cite journal
|author=Waring SC, Rosenberg RN
|title=Genome-wide association studies in Alzheimer disease
|journal=Arch Neurol
|volume=65
|issue=3
|pages=329–34
|year=2008
|month=March
|pmid=18332245
|doi=10.1001/archneur.65.3.329
}}</ref> Most mutations in the APP and presenilin genes increase the production of a small protein called [[Aβ]]42, which is the main component of [[senile plaques]].<ref name="pmid8938131">{{cite journal
|author=Selkoe DJ
|title=Translating cell biology into therapeutic advances in Alzheimer's disease
|journal=Nature
|volume=399
|issue=6738 Suppl
|pages=A23–31
|year=1999
|month=June
|pmid=10392577
|doi=10.1038/19866
}}</ref> Some of the mutations merely alter the size ratio between Aβ42 and the other major forms—e.g., Aβ40—without increasing Aβ42 levels.<ref name="pmid8938131">{{cite journal
|author=Borchelt DR, Thinakaran G, Eckman CB, ''et al.''
|title=Familial Alzheimer's disease-linked presenilin 1 variants elevate Aβ1-42/1-40 ratio in vitro and in vivo.
|journal=Neuron
|volume=17
|issue=5
|pages=1005–13
|year=1996
|month=Nov
|pmid=8938131
|doi=10.1016/S0896-6273(00)80230-5
|last12=Wang
|first12=R
|last13=Seeger
|first13=M
|last14=Levey
|first14=AI
|last15=Gandy
|first15=SE
|last16=Copeland
|first16=NG
|last17=Jenkins
|first17=NA
|last18=Price
|first18=DL
|last19=Younkin
|first19=SG
|last20=Sisodia
|first20=SS
}}</ref><ref name="pmid17254019">{{cite journal
|author=Shioi J, Georgakopoulos A, Mehta P, ''et al.''
|title=FAD mutants unable to increase neurotoxic Aβ 42 suggest that mutation effects on neurodegeneration may be independent of effects on Abeta.
|journal=J Neurochem.
|volume=101
|issue=3
|pages=674–81
|year=2007
|month=May
|pmid=17254019
|doi=10.1111/j.1471-4159.2006.04391.x
}}</ref> This suggests that presenilin mutations can cause disease even if they lower the total amount of Aβ produced and may point to other roles of presenilin or a role for alterations in the function of APP and/or its fragments other than Aβ.

Most cases of Alzheimer's disease do not exhibit autosomal-dominant inheritance and are termed sporadic AD. Nevertheless genetic differences may act as [[risk factors]]. The best known genetic risk factor is the inheritance of the ε4 [[allele]] of the [[apolipoprotein E]] (APOE).<ref name="pmid8446617">{{cite journal
|author=Strittmatter WJ, Saunders AM, Schmechel D, ''et al.''
|title=Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease
|journal=Proc. Natl. Acad. Sci. USA
|volume=90
|issue=5
|pages=1977–81
|year=1993
|month=March
|pmid=8446617
|pmc=46003
|doi=10.1073/pnas.90.5.1977
}}</ref><ref name="pmid16567625">{{cite journal
|author=Mahley RW, Weisgraber KH, Huang Y
|title=Apolipoprotein E4: a causative factor and therapeutic target in neuropathology, including Alzheimer's disease
|journal=Proc. Natl. Acad. Sci. U.S.A.
|volume=103
|issue=15
|pages=5644–51
|year=2006
|month=April
|pmid=16567625
|pmc=1414631
|doi=10.1073/pnas.0600549103
|url=
}}</ref> Between 40 and 80% of patients with AD possess at least one apoE4 allele.<ref name="pmid16567625"/> The APOE4 allele increases the risk of the disease by three times in heterozygotes and by 15 times in homozygotes.<ref name="pmid16876668"/> Geneticists agree that numerous other genes also act as risk factors or have protective effects that influence the development of late onset Alzheimer's disease.<ref name="pmid18332245" /> Over 400 genes have been tested for association with late-onset sporadic AD,<ref name="pmid18332245"/> most with null results.<ref name="pmid16876668"/>

==Diagnosis==
[[File:PET Alzheimer.jpg|thumb|right||Upright|[[Positron emission tomography|PET scan]] of the brain of a person with AD showing a loss of function in the temporal lobe]]
Alzheimer's disease is usually diagnosed clinically from the patient history, collateral history from relatives, and clinical observations, based on the presence of characteristic [[Neurology|neurological]] and [[neuropsychology|neuropsychological]] features and the [[Diagnosis of exclusion|absence of alternative conditions]].<ref name="pmid17407994">{{cite journal
|author=Mendez MF
|title=The accurate diagnosis of early-onset dementia
|journal=International Journal of Psychiatry Medicine
|volume=36
|issue=4
|pages=401–412
|year=2006
|pmid=17407994
|doi=10.2190/Q6J4-R143-P630-KW41
}}</ref><ref name="pmid17018549">{{cite journal
|author=Klafki HW, Staufenbiel M, Kornhuber J, Wiltfang J
|title=Therapeutic approaches to Alzheimer's disease
|journal=Brain
|volume=129
|issue=Pt 11
|pages=2840–55
|year=2006
|month=November
|pmid=17018549
|doi=10.1093/brain/awl280
}}</ref> Advanced [[medical imaging]] with [[computed tomography]] (CT) or [[magnetic resonance imaging]] (MRI), and with [[single photon emission computed tomography]] (SPECT) or [[positron emission tomography]] (PET) can be used to help exclude other cerebral pathology or subtypes of dementia.<ref>
{{cite web
|url = http://www.nice.org.uk/nicemedia/pdf/CG042quickrefguide.pdf
|format = PDF
|title = Dementia: Quick reference guide
|publisher = (UK) [[National Institute for Health and Clinical Excellence]]
|location = London
|month = November
|year = 2006
|isbn = 1-84629-312-X
|accessdate = 2008-02-22
}}</ref> Moreover, it may predict conversion from prodromal stages (mild cognitive impairment) to Alzheimer's disease.<ref name="pmid16327345">{{cite journal
|author=Schroeter ML, Stein T, Maslowski N, Neumann J
|title=Neural correlates of Alzheimer's disease and mild cognitive impairment – A meta-analysis including 1351 patients.
|journal=NeuroImage
|volume=47
|issue=4
|pages=1196–1206
|year=2009
|pmid=19463961
|pmc=2730171
|doi=10.1016/j.neuroimage.2009.05.037
}}</ref>

[[Neuropsychological assessment|Assessment of intellectual functioning]] including memory testing can further characterise the state of the disease.<ref name="pmid17222085"/> Medical organisations have created diagnostic criteria to ease and standardise the diagnostic process for practicing physicians. The diagnosis can be confirmed with very high accuracy [[Autopsy|post-mortem]] when brain material is available and can be examined [[Histology|histologically]].<ref name="pmid6610841">{{cite journal
|author=McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM
|title=Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease
|journal=Neurology
|volume=34
|issue=7
|pages=939–44
|year=1984
|month=July
|pmid=6610841
}}</ref>

===Diagnostic criteria===
The [[National Institute of Neurological and Communicative Disorders and Stroke]] (NINCDS) and the [[Alzheimer's Disease and Related Disorders Association]] (ADRDA, now known as the [[Alzheimer's Association]]) established the most commonly used [[NINCDS-ADRDA Alzheimer's Criteria]] for diagnosis in 1984,<ref name="pmid6610841" /> extensively updated in 2007.<ref name="pmid17616482">{{cite journal
|author=Dubois B, Feldman HH, Jacova C, ''et al.''
|title=Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria
|journal=Lancet Neurol
|volume=6
|issue=8
|pages=734–46
|year=2007
|month=August
|pmid=17616482
|doi=10.1016/S1474-4422(07)70178-3
|last12=O'brien
|first12=J
|last13=Pasquier
|first13=F
|last14=Robert
|first14=P
|last15=Rossor
|first15=M
|last16=Salloway
|first16=S
|last17=Stern
|first17=Y
|last18=Visser
|first18=PJ
|last19=Scheltens
|first19=P
}}</ref> These criteria require that the presence of [[Developmental disability|cognitive impairment]], and a suspected dementia syndrome, be confirmed by [[Neuropsychological assessment|neuropsychological testing]] for a clinical diagnosis of possible or probable AD. A [[histopathologic]] confirmation including a [[microscopic]] examination of [[brain tissue]] is required for a definitive diagnosis. Good [[Reliability (statistics)|statistical reliability]] and [[Validity (statistics)|validity]] have been shown between the diagnostic criteria and definitive histopathological confirmation.<ref name="pmid7986174">{{cite journal
|author=Blacker D, Albert MS, Bassett SS, Go RC, Harrell LE, Folstein MF
|title=Reliability and validity of NINCDS-ADRDA criteria for Alzheimer's disease. The National Institute of Mental Health Genetics Initiative
|journal=Arch. Neurol.
|volume=51
|issue=12
|pages=1198–204
|year=1994
|month=December
|pmid=7986174
}}</ref> Eight cognitive domains are most commonly impaired in AD—[[memory]], [[language]], [[perception|perceptual skills]], [[attention]], constructive abilities, [[orientation (mental)|orientation]], [[problem solving]] and functional abilities. These domains are equivalent to the NINCDS-ADRDA Alzheimer's Criteria as listed in the ''[[Diagnostic and Statistical Manual of Mental Disorders]]'' (DSM-IV-TR) published by the [[American Psychiatric Association]].<ref>{{cite book
|last=American Psychiatric Association
|title=Diagnostic and statistical manual of mental disorders: DSM-IV-TR
|edition=4th Edition Text Revision
|publisher=American Psychiatric Association
|year=2000
|location=Washington, DC
|isbn=0890420254
}}</ref><ref name="pmid8752526">{{cite journal
|author=Ito N
|title=[Clinical aspects of dementia]
|language=Japanese
|journal=Hokkaido Igaku Zasshi
|volume=71
|issue=3
|pages=315–20
|year=1996
|month=May
|pmid=8752526
}}</ref>

===Diagnostic tools===
[[File:InterlockingPentagons.svg|right|thumb|Neuropsychological screening tests can help in the diagnosis of AD. In them patients have to copy drawings similar to the one shown in the picture, remember words, read, and subtract serial numbers.]]

[[Neuropsychological test]]s such as the [[mini-mental state examination]] (MMSE), are widely used to evaluate the cognitive impairments needed for diagnosis. More comprehensive test arrays are necessary for high reliability of results, particularly in the earliest stages of the disease.<ref name="pmid1512391">{{cite journal
|author=Tombaugh TN, McIntyre NJ
|title=The mini-mental state examination: a comprehensive review
|journal=J Am Geriatr Soc
|volume=40
|issue=9
|pages=922–35
|year=1992
|month=September
|pmid=1512391
}}</ref><ref name="pmid9987708">{{cite journal
|author=Pasquier F
|title=Early diagnosis of dementia: neuropsychology
|journal=J. Neurol.
|volume=246
|issue=1
|pages=6–15
|year=1999
|month=January
|pmid=9987708
|doi=10.1007/s004150050299
}}</ref> [[Neurological examination]] in early AD will usually provide normal results, except for obvious cognitive impairment, which may not differ from that resulting from other diseases processes, including other causes of dementia.

Further neurological examinations are crucial in the [[differential diagnosis]] of AD and other diseases.<ref name="pmid17222085"/> Interviews with family members are also utilised in the assessment of the disease. Caregivers can supply important information on the daily living abilities, as well as on the decrease, over time, of the person's [[mental function]].<ref name="pmid16327345">{{cite journal
|author=Harvey PD, Moriarty PJ, Kleinman L, ''et al.''
|title=The validation of a caregiver assessment of dementia: the Dementia Severity Scale
|journal=Alzheimer Dis Assoc Disord
|volume=19
|issue=4
|pages=186–94
|year=2005
|pmid=16327345
|doi=10.1097/01.wad.0000189034.43203.60
}}</ref> A caregiver's viewpoint is particularly important, since a person with AD is commonly unaware of his own [[anosognosia|deficits]].<ref name="pmid15738860">{{cite journal
|author=Antoine C, Antoine P, Guermonprez P, Frigard B
|title=[Awareness of deficits and anosognosia in Alzheimer's disease.]
|language=French
|journal=Encephale
|volume=30
|issue=6
|pages=570–7
|year=2004
|pmid=15738860
|doi=10.1016/S0013-7006(04)95472-3
}}</ref> Many times, families also have difficulties in the detection of initial dementia symptoms and may not communicate accurate information to a physician.<ref name="pmid16197855">{{cite journal
|author=Cruz VT, Pais J, Teixeira A, Nunes B
|title=[The initial symptoms of Alzheimer disease: caregiver perception]
|language=Portuguese
|journal=Acta Med Port
|volume=17
|issue=6
|pages=435–44
|year=2004
|pmid=16197855
}}</ref>

Another recent objective marker of the disease is the analysis of [[cerebrospinal fluid]] for amyloid beta or tau proteins,<ref name="pmid17612711">{{cite journal
|author=Marksteiner J, Hinterhuber H, Humpel C
|title=Cerebrospinal fluid biomarkers for diagnosis of Alzheimer's disease: beta-amyloid(1-42), tau, phospho-tau-181 and total protein
|journal=Drugs Today
|volume=43
|issue=6
|pages=423–31
|year=2007
|month=June
|pmid=17612711
|doi=10.1358/dot.2007.43.6.1067341
}}</ref> both total tau protein and phosphorylated tau<sub>181P</sub> protein concentrations.<ref name=demeyer/> Searching for these proteins using a [[Lumbar puncture|spinal tap]] can predict the onset of Alzheimer's with a [[sensitivity and specificity|sensitivity]] of between 94% and 100%.<ref name=demeyer/> When used in conjunction with existing [[Functional neuroimaging|neuroimaging]] techniques, doctors can identify patients with significant memory loss who are already developing the disease.<ref name=demeyer>{{cite journal
|author=De Meyer G, Shapiro F, Vanderstichele H, Vanmechelen E, Engelborghs S, De Deyn PP, Coart E, Hansson O, Minthon L, Zetterberg H, Blennow K, Shaw L, Trojanowski JQ
|title=Diagnosis-Independent Alzheimer Disease Biomarker Signature in Cognitively Normal Elderly People
|journal=Arch Neurol.
|volume=67
|issue=8
|pages=949–56
|year=2010
|month=August
|doi=10.1001/archneurol.2010.179
}}</ref> Spinal fluid tests are commercially available, unlike the latest neuroimaging technology.<ref>{{cite news
|author=Kolata G
|title=Spinal-Fluid Test Is Found to Predict Alzheimer's
|url=http://www.nytimes.com/2010/08/10/health/research/10spinal.html
|work=[[The New York Times]]
|date=August 9, 2010
|accessdate=August 10, 2010
}}</ref> Alzheimer's was diagnosed in one-third of the people who did not have any symptoms in a 2010 study, meaning that disease progression occurs well before symptoms occur.<ref>{{cite news
|author=Roan S
|title=Tapping into an accurate diagnosis of Alzheimer's disease
|url=http://www.latimes.com/health/boostershots/aging/la-heb-alzheimers-20100809,0,5683387.story
|work=[[Los Angeles Times]]
|date=August 9, 2010
|accessdate=August 10, 2010
}}</ref>

Supplemental testing provides extra information on some features of the disease or is used to rule out other diagnoses. [[Blood test]]s can identify other causes for dementia than AD<ref name="pmid17222085"/>—causes which may, in rare cases, be reversible.<ref>{{cite journal
|author=Clarfield AM
|title=The decreasing prevalence of reversible dementias: an updated meta-analysis
|journal=Arch. Intern. Med.
|volume=163
|issue=18
|pages=2219–29
|year=2003
|month=October
|pmid=14557220
|doi=10.1001/archinte.163.18.2219
}}</ref> It is common to perform [[thyroid function tests]], assess [[B12]], rule out [[syphillis]], rule out metabolic problems (including tests for kidney function, electrolyte levels and for diabetes), assess levels of heavy metals (e.g. lead, mercury) and anemia. (See differential diagnosis for Dementia). (It is also necessary to rule out [[delirium]]).

[[Psychological testing|Psychological tests]] for [[clinical depression|depression]] are employed, since depression can either be concurrent with AD (see [[Depression of Alzheimer disease]]), an early sign of cognitive impairment,<ref>{{cite journal |author=Sun x, Steffens DC, Au R, ''et al.'' |title=Amyloid-Associated Depression: A Prodromal Depression of Alzheimer Disease? |journal=Arch Gen Psychiatry |volume=65 |issue=5 |pages=542–550|year=2008 |url=http://archpsyc.ama-assn.org/cgi/content/short/65/5/542 |doi=10.1001/archpsyc.65.5.542 |pmid=18458206 |last1=Sun |first1=X |last2=Steffens |first2=DC |last3=Au |first3=R |last4=Folstein |first4=M |last5=Summergrad |first5=P |last6=Yee |first6=J |last7=Rosenberg |first7=I |last8=Mwamburi |first8=DM |last9=Qiu |first9=WQ}}</ref> or even the cause.<ref name="pmid9153154">{{cite journal
|author=Geldmacher DS, Whitehouse PJ
|title=Differential diagnosis of Alzheimer's disease
|journal=Neurology
|volume=48
|issue=5 Suppl 6
|pages=S2–9
|year=1997
|month=May
|pmid=9153154
}}</ref><ref name="pmid17495754">{{cite journal
|author=Potter GG, Steffens DC
|title=Contribution of depression to cognitive impairment and dementia in older adults
|journal=Neurologist
|volume=13
|issue=3
|pages=105–17
|year=2007
|month=May
|pmid=17495754
|doi=10.1097/01.nrl.0000252947.15389.a9
}}</ref>

====Diagnostic imaging====
When available as a diagnostic tool, [[single photon emission computed tomography]] (SPECT) and [[positron emission tomography]] (PET) neuroimaging are used to confirm a diagnosis of Alzheimer's in conjunction with evaluations involving [[mental status examination]].<ref name="pmid16785801">{{cite journal
|author=Bonte FJ, Harris TS, Hynan LS, Bigio EH, White CL
|title=Tc-99m HMPAO SPECT in the differential diagnosis of the dementias with histopathologic confirmation
|journal=Clin Nucl Med
|volume=31
|issue=7
|pages=376–8
|year=2006
|month=July
|pmid=16785801
|doi=10.1097/01.rlu.0000222736.81365.63
}}</ref> In a person already having dementia, SPECT appears to be superior in differentiating Alzheimer's disease from other possible causes, compared with the usual attempts employing mental testing and [[medical history]] analysis.<ref name="pmid15545324">{{cite journal
|author=Dougall NJ, Bruggink S, Ebmeier KP
|title=Systematic review of the diagnostic accuracy of 99mTc-HMPAO-SPECT in dementia
|journal=Am J Geriatr Psychiatry
|volume=12
|issue=6
|pages=554–70
|year=2004
|pmid=15545324
|doi=10.1176/appi.ajgp.12.6.554
}}</ref> Advances have led to the proposal of new diagnostic criteria.<ref name="pmid17222085"/><ref name="pmid17616482"/>

A new technique known as [[Pittsburgh compound B|PiB PET]] has been developed for directly and clearly imaging beta-amyloid deposits [[in vivo]] using a [[Radioactive tracer|tracer]] that [[Binding (molecular)|binds]] selectively to the A-beta deposits.<ref>PiB PET:
*{{cite journal
|author=Kemppainen NM, Aalto S, Karrasch M, ''et al.''
|title=Cognitive reserve hypothesis: Pittsburgh Compound B and fluorodeoxyglucose positron emission tomography in relation to education in mild Alzheimer's disease
|journal=Ann. Neurol.
|volume=63
|issue=1
|pages=112–8
|year=2008
|month=January
|pmid=18023012
|doi=10.1002/ana.21212
}}
*{{cite journal
|author=Ikonomovic MD, Klunk WE, Abrahamson EE, ''et al.''
|title=Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease
|journal=Brain
|volume=131
|issue=Pt 6
|pages=1630–45
|year=2008
|month=June
|pmid=18339640
|pmc=2408940
|doi=10.1093/brain/awn016
|last12=Hope
|first12=CE
|last13=Isanski
|first13=BA
|last14=Hamilton
|first14=RL
|last15=Dekosky
|first15=ST
}}
*{{cite journal
|author=Jack CR, Lowe VJ, Senjem ML, ''et al.''
|title=11C PiB and structural MRI provide complementary information in imaging of Alzheimer's disease and amnestic mild cognitive impairment
|journal=Brain
|volume=131
|issue=Pt 3
|pages=665–80
|year=2008
|month=March
|pmid=18263627
|doi=10.1093/brain/awm336
|pmc=2730157
}}</ref> The PiB-PET compound uses [[carbon-11]] PET scanning. Recent studies suggest that PiB-PET is 86% accurate in predicting which people with mild cognitive impairment will develop Alzheimer's disease within two years, and 92% accurate in ruling out the likelihood of developing Alzheimer's.<ref>{{cite journal
|author=Abella HA
|title=Report from SNM: PET imaging of brain chemistry bolsters characterization of dementias
|journal=Diagnostic Imaging |date=June 16, 2009
|url=http://www.diagnosticimaging.com/imaging-trends-advances/cardiovascular-imaging/article/113619/1423022
}}</ref>

A similar PET scanning [[radiopharmaceutical]] compound called (E)-4-(2-(6-(2-(2-(2-([<sup>18</sup>F]-fluoroethoxy)ethoxy)ethoxy)pyridin-3-yl)vinyl)-N-methyl benzenamine, or <sup>18</sup>F AV-45, or florbetapir-fluorine-18, or simply [[florbetapir]], contains the longer-lasting radionuclide [[fluorine-18]], has recently been created, and tested as a possible diagnostic tool in Alzheimer's patients.<ref>{{cite journal
|journal=Q J Nucl Med Mol Imaging
|date=2009 Aug
|volume=53
|issue=4
|pages=387–93
|title=The use of the exploratory IND in the evaluation and development of <sup>18</sup>F-PET radiopharmaceuticals for amyloid imaging in the brain: a review of one company's experience
|author=Carpenter AP Jr, Pontecorvo MJ, Hefti FF, Skovronsky DM
|pmid=19834448
}}</ref><ref>{{cite web |author=Leung K |url=http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=micad&part=AV-45-18F |title=(E)-4-(2-(6-(2-(2-(2-(<sup>18</sup>F-fluoroethoxy)ethoxy)ethoxy)pyridin-3-yl)vinyl)-N-methyl benzenamine <nowiki>[[</nowiki><sup>18</sup>F<nowiki>]AV-45]</nowiki> |work=Molecular Imaging and Contrast Agent Database |date=April 8, 2010 |accessdate=2010-06-24}}</ref><ref>{{cite news
|author=[[Gina Kolata|Kolata G]]
|url=http://www.nytimes.com/2010/06/24/health/research/24scans.html
|title=Promise Seen for Detection of Alzheimer's
|work=[[The New York Times]]
|date=June 23, 2010
|accessdate=June 23, 2010
}}</ref><ref name="pmid20501908">{{cite journal |doi=10.2967/jnumed.109.069088 |journal=J Nucl Med |date=2010 Jun |volume=51 |issue=6 |pages=913–20 |title=In vivo imaging of amyloid deposition in Alzheimer disease using the radioligand 18F-AV-45 (flobetapir F 18) |author=Wong DF, Rosenberg PB, Zhou Y, Kumar A, Raymont V, Ravert HT, Dannals RF, Nandi A, Brasić JR, Ye W, Hilton J, Lyketsos C, Kung HF, Joshi AD, Skovronsky DM, Pontecorvo MJ |pmid=20501908 |laysummary=http://www.diagnosticimaging.com/news/display/article/113619/1598949 }}</ref> Florbetapir, like PiB, binds to beta-amyloid, but due to its use of fluorine-18 has a half-life of 110 minutes, in contrast to PiB's radioactive half life of 20 minutes. Wong ''et al.'' found that the longer life allowed the tracer to accumulate significantly more in the brains of the AD patients, particularly in the regions known to be associated with beta-amyloid deposits.<ref name="pmid20501908" />

One review predicted that amyloid imaging is likely to be used in conjunction with other markers rather than as an alternative.<ref name="pmid19847050">{{cite journal
|author=Rabinovici GD, Jagust WJ
|journal=Behav Neurol
|year=2009
|volume=21
|issue=1
|pages=117–28
|title=Amyloid imaging in aging and dementia: testing the amyloid hypothesis in vivo
|pmid=19847050
|pmc=2804478
|doi=10.3233/BEN-2009-0232
}}</ref>

Volumetric [[magnetic resonance imaging|MRI]] can detect changes in the size of brain regions. Measuring those regions that atrophy during the progress of Alzheimer's disease is showing promise as a diagnostic indicator. It may prove less expensive than other imaging methods currently under study.<ref name="pmid18445747">{{cite journal
|author=O'Brien JT
|title=Role of imaging techniques in the diagnosis of dementia
|journal=Br J Radiol
|date=2007 Dec
|volume=80 |issue=Spec No 2 |pages=S71–7
|pmid=18445747
|doi=10.1259/bjr/33117326
}}</ref>

Recent studies suggest that brain metabolite levels may be utilized as biomarkers for Alzheimer's disease.<ref name="pmid 19501936">{{cite journal
|author=Rupsingh R, Borrie M, Smith M, Wells JL, Bartha R
|title=Reduced hippocampal glutamate in Alzheimer disease
|journal=[[Neurobiol Aging]]
|year=2009
|month=June
|pmid=19501936
|doi=10.1016/j.neurobiolaging.2009.05.002
}}</ref>

==Prevention==
[[File:Honoré Daumier 032.jpg|right|thumb|Intellectual activities such as playing [[chess]] or regular social interaction have been linked to a reduced risk of AD in epidemiological studies, although no causal relationship has been found.]]

At present, there is no definitive evidence to support that any particular measure is effective in preventing AD.<ref>Prevention recommendations not supported:
* {{cite journal |author=Kawas CH |title=Medications and diet: protective factors for AD? |journal=Alzheimer Dis Assoc Disord |volume=20 |issue=3 Suppl 2 |pages=S89–96 |year=2006 |pmid=16917203|doi=}}
* {{cite journal |author=Luchsinger JA, Mayeux R |title=Dietary factors and Alzheimer's disease |journal=Lancet Neurol |volume=3 |issue=10 |pages=579–87 |year=2004 |pmid=15380154 |doi=10.1016/S1474-4422(04)00878-6}}
* {{cite journal |author=Luchsinger JA, Noble JM, Scarmeas N |title=Diet and Alzheimer's disease |journal=Curr Neurol Neurosci Rep |volume=7 |issue=5 |pages=366–72 |year=2007 |pmid=17764625 |doi=10.1007/s11910-007-0057-8}}
* {{cite press release |url=http://www.nih.gov/news/health/apr2010/od-28.htm |title=Independent Panel Finds Insufficient Evidence to Support Preventive Measures for Alzheimer's Disease |date=April 28, 2010 |publisher=[[National Institutes of Health]] }}
* {{cite web |url=http://consensus.nih.gov/2010/alzstatement.htm |title=NIH State-of-the-Science Conference: Preventing Alzheimer's Disease and Cognitive Decline |date=April 26–28, 2010 |author=Daviglus ML ''et al.''}}</ref> Global studies of measures to prevent or delay the onset of AD have often produced inconsistent results.
However, epidemiological studies have proposed relationships between certain modifiable factors, such as diet, cardiovascular risk, pharmaceutical products, or intellectual activities among others, and a population's likelihood of developing AD. Only further research, including clinical trials, will reveal whether these factors can help to prevent AD.<ref>
{{cite journal
|author=Szekely CA, Breitner JC, Zandi PP
|title=Prevention of Alzheimer's disease
|journal=Int Rev Psychiatry
|volume=19
|issue=6
|pages=693–706
|year=2007
|pmid=18092245
|doi=10.1080/09540260701797944
}}</ref>

Although cardiovascular risk factors, such as [[hypercholesterolemia]], [[hypertension]], [[diabetes]], and smoking, are associated with a higher risk of onset and course of AD,<ref name="pmid18299540">{{cite journal
|author=Patterson C, Feightner JW, Garcia A, Hsiung GY, MacKnight C, Sadovnick AD
|title=Diagnosis and treatment of dementia: 1. Risk assessment and primary prevention of Alzheimer disease
|journal=CMAJ
|volume=178
|issue=5
|pages=548–56
|year=2008
|month=February
|pmid=18299540
|pmc=2244657
|doi=10.1503/cmaj.070796
}}</ref><ref name="pmid17483665">{{cite journal
|author=Rosendorff C, Beeri MS, Silverman JM
|title=Cardiovascular risk factors for Alzheimer's disease
|journal=Am J Geriatr Cardiol
|volume=16
|issue=3
|pages=143–9
|year=2007
|pmid=17483665
|doi=10.1111/j.1076-7460.2007.06696.x
}}</ref> [[statins]], which are [[cholesterol]] lowering drugs, have not been effective in preventing or improving the course of the disease.<ref name="pmid17927279">{{cite journal
|author=Reiss AB, Wirkowski E
|title=Role of HMG-CoA reductase inhibitors in neurological disorders: progress to date
|journal=Drugs
|volume=67
|issue=15
|pages=2111–20
|year=2007
|pmid=17927279|doi=10.2165/00003495-200767150-00001
}}</ref><ref name="pmid17877925">{{cite journal
|author=Kuller LH
|title=Statins and dementia
|journal=Curr Atheroscler Rep
|volume=9
|issue=2
|pages=154–61
|year=2007
|month=August
|pmid=17877925
|doi=10.1007/s11883-007-0012-9
}}</ref> The components of a [[Mediterranean diet]], which include fruit and vegetables, [[bread]], [[wheat]] and other [[cereal]]s, [[olive oil]], [[fish]], and [[red wine]], may all individually or together reduce the risk and course of Alzheimer's disease.<ref name="pmid18088206">{{cite journal
|author=Solfrizzi V, Capurso C, D'Introno A, ''et al.''
|title=Lifestyle-related factors in predementia and dementia syndromes
|journal=Expert Rev Neurother
|volume=8
|issue=1
|pages=133–58
|year=2008
|month=January
|pmid=18088206
|doi=10.1586/14737175.8.1.133
|url=
}}</ref> Its beneficial cardiovascular effect has been proposed as the mechanism of action.<ref name="pmid18088206"/> There is limited evidence that light to moderate use of alcohol, particularly red wine, is associated with lower risk of AD.<ref>{{cite journal
|author=Panza F, Capurso C, D'Introno A, Colacicco AM, Frisardi V, Lorusso M, Santamato A, Seripa D, Pilotto A, Scafato E, Vendemiale G, Capurso A, Solfrizzi V.
|title=Alcohol drinking, cognitive functions in older age, predementia, and dementia syndromes
|journal=J Alzheimers Dis
|volume=17
|issue=1
|pages=7–31
|date=May 2009
|pmid=19494429
|doi=10.3233/JAD-2009-1009
|last12=Capurso
|first12=A
|last13=Solfrizzi
|first13=V
}}</ref>

Reviews on the use of [[vitamin]]s have not found enough evidence of efficacy to recommend vitamin C,<ref name="pmid16227450">{{cite journal
|author=Boothby LA, Doering PL
|title=Vitamin C and vitamin E for Alzheimer's disease
|journal=Ann Pharmacother
|volume=39
|issue=12
|pages=2073–80
|year=2005
|month=December
|pmid=16227450
|doi=10.1345/aph.1E495
|url=
}}</ref> E,<ref name="pmid16227450"/><ref>{{cite journal
|author=Isaac MG, Quinn R, Tabet N
|title=Vitamin E for Alzheimer's disease and mild cognitive impairment
|journal=Cochrane Database Syst Rev
|volume=
|issue=3
|pages=CD002854
|year=2008
|pmid=18646084
|doi=10.1002/14651858.CD002854.pub2
|url=
}}</ref> or folic acid with or without vitamin B<sub>12</sub>,<ref>{{cite journal
|author=Malouf R, Grimley Evans J
|title=Folic acid with or without vitamin B<sub>12</sub> for the prevention and treatment of healthy elderly and demented people
|journal=Cochrane Database Syst Rev
|volume=
|issue=4
|pages=CD004514
|year=2008
|pmid=18843658
|doi=10.1002/14651858.CD004514.pub2
|url=
}}</ref> as preventive or treatment agents in AD. Additionally vitamin E is associated with important health risks.<ref name="pmid16227450"/>

Long-term usage of [[non-steroidal anti-inflammatory drug]] (NSAIDs) is associated with a reduced likelihood of developing AD.<ref name="pmid17612054">{{cite journal
|author=Szekely CA, Town T, Zandi PP
|title=NSAIDs for the chemoprevention of Alzheimer's disease
|journal=Subcell Biochem
|volume=42
|issue=
|pages=229–48
|year=2007
|month=
|pmid=17612054
|doi=10.1007/1-4020-5688-5_11
}}</ref> Human [[postmortem]] studies, in [[animal model]]s, or [[in vitro]] investigations also support the notion that NSAIDs can reduce inflammation related to amyloid plaques.<ref name="pmid17612054"/> However trials investigating their use as palliative treatment have failed to show positive results while no prevention trial has been completed.<ref name="pmid17612054"/> [[Curcumin]] from the [[curry]] spice [[turmeric]] has shown some effectiveness in preventing [[brain damage]] in [[mouse model]]s due to its anti-inflammatory properties.<ref>{{cite journal
|author=Ringman JM, Frautschy SA, Cole GM, Masterman DL, Cummings JL
|title=A potential role of the curry spice curcumin in Alzheimer's disease
|journal=Curr Alzheimer Res
|issn=1567-2050
|volume=2
|issue=2
|pages=131–6
|year=2005
|month=April
|pmid=15974909
|pmc=1702408
|doi=10.2174/1567205053585882
|url=
}}</ref><ref>{{cite journal
|author=Aggarwal BB, Harikumar KB
|title=Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases
|journal=Int J Biochem Cell Biol
|volume=41
|issue=1
|pages=40–59
|year=2009
|month=January
|pmid=18662800
|doi=10.1016/j.biocel.2008.06.010
|url=
|pmc=2637808
}}</ref> [[Hormone therapy|Hormone replacement therapy]], although previously used, is no longer thought to prevent dementia and in some cases may even be related to it.<ref name="pmid19370593">{{cite journal
|author=Farquhar C, Marjoribanks J, Lethaby A, Suckling JA, Lamberts Q
|title=Long term hormone therapy for perimenopausal and postmenopausal women
|journal=Cochrane Database Syst Rev
|volume=
|issue=2
|pages=CD004143
|date=15 April 2009
|pmid=19370593
|doi=10.1002/14651858.CD004143.pub3
|url=
}}</ref><ref name="pmid19401958">{{cite journal
|author=Barrett-Connor E, Laughlin GA
|title=Endogenous and exogenous estrogen, cognitive function, and dementia in postmenopausal women: evidence from epidemiologic studies and clinical trials
|journal=Semin Reprod Med
|volume=27
|issue=3
|date=May 2009
|pages=275–82
|pmc=2701737
|doi=10.1055/s-0029-1216280
|pmid=19401958
|last1=Barrett-Connor
|first1=E
|last2=Laughlin
|first2=GA
}}</ref> There is inconsistent and unconvincing evidence that [[Ginkgo Biloba|ginkgo]] has any positive effect on cognitive impairment and dementia,<ref>{{cite journal
|author=Birks J, Grimley Evans J
|title=Ginkgo biloba for cognitive impairment and dementia
|journal=Cochrane Database Syst Rev
|volume=
|issue=1
|pages=CD003120
|year=2009
|pmid=19160216
|doi=10.1002/14651858.CD003120.pub3
|url= http://mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD003120/frame.html
|accessdate=2009-08-13
}}</ref> and a recent study concludes that it has no effect in reducing the rate of AD incidence.<ref>{{cite journal
|author=DeKosky ST, Williamson JD, Fitzpatrick AL ''et al.''
|title=Ginkgo biloba for Prevention of Dementia
|journal=Journal of the American Medical Association
|year=2008
|volume=300
|issue=19
|pages=2253–2262
|pmid=19017911
|doi=10.1001/jama.2008.683
|url=http://jama.ama-assn.org/cgi/content/full/300/19/2253
|accessdate=2008-11-18
|last12=Robbins
|first12=JA
|last13=Tracy
|first13=RP
|last14=Woolard
|first14=NF
|last15=Dunn
|first15=L
|last16=Snitz
|first16=BE
|last17=Nahin
|first17=RL
|last18=Furberg
|first18=CD
|last19=Ginkgo Evaluation Of Memory (Gem) Study
|first19=Investigators
|pmc=2823569
}}</ref> A 21-year study found that coffee drinkers of 3–5 cups per day at midlife had a 65% reduction in risk of dementia in late-life.<ref>{{cite journal
|author=Eskelinen MH, Ngandu T, Tuomilehto J, Soininen H, Kivipelto M
|title=Midlife coffee and tea drinking and the risk of late-life dementia: a population-based CAIDE study
|journal=J Alzheimers Dis
|volume=16
|issue=1
|pages=85–91
|year=2009
|month=January
|pmid=19158424
|doi=10.3233/JAD-2009-0920
}}</ref>

People who engage in intellectual activities such as reading, playing board games, completing crossword puzzles, playing [[musical instrument]]s, or regular [[social interaction]] show a reduced risk for Alzheimer's disease.<ref name="pmid16917199">{{cite pmid|16917199}}</ref> This is compatible with the [[cognitive reserve]] theory, which states that some life experiences result in more efficient neural functioning providing the individual a cognitive reserve that delays the onset of dementia manifestations.<ref name="pmid16917199"/> Education delays the onset of AD syndrome, but is not related to earlier death after diagnosis.<ref name="pmid19026089">{{cite journal
|author=Paradise M, Cooper C, Livingston G
|title=Systematic review of the effect of education on survival in Alzheimer's disease
|journal=Int Psychogeriatr
|volume=21
|issue=1
|pages=25–32
|year=2009
|month=February
|pmid=19026089
|doi=10.1017/S1041610208008053
}}</ref> [[Physical activity]] is also associated with a reduced risk of AD.<ref name="pmid19026089"/>

Some studies have shown an increased risk of developing AD with [[environmental factor]]s such the intake of [[metal]]s, particularly [[aluminium]],<ref name="pmid17522444">{{cite journal
|author=Shcherbatykh I, Carpenter DO
|title=The role of metals in the etiology of Alzheimer's disease
|journal=J Alzheimers Dis
|volume=11
|issue=2
|pages=191–205
|year=2007
|month=May
|pmid=17522444
}}</ref><ref>{{cite journal
|author=Rondeau V, Commenges D, Jacqmin-Gadda H, Dartigues JF
|title=Relation between aluminum concentrations in drinking water and Alzheimer's disease: an 8-year follow-up study
|journal=Am J Epidemiol
|volume=152
|issue=1
|pages=59–66
|year=2000
|month=July
|pmid=10901330
|pmc=2215380
|doi=10.1093/aje/152.1.59
}}</ref> or exposure to [[solvent]]s.<ref name="pmid7771442">{{cite journal
|author=Kukull WA, Larson EB, Bowen JD, ''et al.''
|title=Solvent exposure as a risk factor for Alzheimer's disease: a case-control study
|journal=Am J Epidemiol
|volume=141
|issue=11
|pages=1059–71; discussion 1072–9
|year=1995
|month=June
|pmid=7771442
}}</ref> The quality of some of these studies has been criticised,<ref>{{cite journal
|author=Santibáñez M, Bolumar F, García AM
|title=Occupational risk factors in Alzheimer's disease: a review assessing the quality of published epidemiological studies
|journal=Occupational and Environmental Medicine
|volume=64
|issue=11
|pages=723–732
|year=2007
|pmid=17525096
|doi=10.1136/oem.2006.028209
}}</ref> and other studies have concluded that there is no relationship between these environmental factors and the development of AD.<ref>{{cite journal
|author=Seidler A, Geller P, Nienhaus A, ''et al.''
|title=Occupational exposure to low frequency magnetic fields and dementia: a case-control study
|journal=Occup Environ Med
|volume=64
|issue=2
|pages=108–14
|year=2007
|month=February
|pmid=17043077
|doi=10.1136/oem.2005.024190
|pmc=2078432
}}</ref><ref name="pmid12222737">{{cite journal
|author=Rondeau V
|title=A review of epidemiologic studies on aluminum and silica in relation to Alzheimer's disease and associated disorders
|journal=Rev Environ Health
|volume=17
|issue=2
|pages=107–21
|year=2002
|pmid=12222737
}}</ref><ref name="pmid9115023">{{cite journal
|author=Martyn CN, Coggon DN, Inskip H, Lacey RF, Young WF
|title=Aluminum concentrations in drinking water and risk of Alzheimer's disease
|journal=Epidemiology
|volume=8
|issue=3
|pages=281–6
|year=1997
|month=May
|pmid=9115023
|doi=10.1097/00001648-199705000-00009
}}</ref><ref name="pmid9861186">{{cite journal
|author=Graves AB, Rosner D, Echeverria D, Mortimer JA, Larson EB
|title=Occupational exposures to solvents and aluminium and estimated risk of Alzheimer's disease
|journal=Occup Environ Med
|volume=55
|issue=9
|pages=627–33
|year=1998
|month=September
|pmid=9861186
|pmc=1757634
|doi=10.1136/oem.55.9.627
}}</ref>

[[Extremely low frequency]] electromagnetic fields may increase the risk for Alzheimer's disease but further epidemiological and laboratory investigations of this observation are needed.<ref>{{Cite document |title=Health Effects of Exposure to EMF |author=Scientific Committee on Emerging and Newly Identified Health Risks-SCENIHR|date=January 2009|publisher=Directorate General for Health&Consumers; European Commission |location=Brussels |pages=4–5 |url=http://ec.europa.eu/health/ph_risk/committees/04_scenihr/docs/scenihr_o_022.pdf |accessdate=2010-04-27 |postscript=<!--None-->}}</ref> Smoking is a significant AD risk factor.<ref>{{cite journal
|author=Cataldo JK, Prochaska JJ, Glantz SA
|title=Cigarette smoking is a risk factor for Alzheimer's disease: an analysis controlling for tobacco industry affiliation
|journal=J Alzheimers Dis
|year=2010
|volume=19
|issue=2
|pages=465–80
|pmid= 20110594
|doi=10.3233/JAD-2010-1240
}}</ref>
[[Inflammation#Systemic effects|Systemic markers]] of the [[innate immune system]] are risk factors for late-onset AD.<ref>{{cite pmid|20160456}}</ref>

==Management==
There is no cure for Alzheimer's disease; available treatments offer relatively small symptomatic benefit but remain [[palliative care|palliative]] in nature. Current treatments can be divided into pharmaceutical, psychosocial and caregiving.

===Pharmaceutical===
[[File:Donepezil 1EVE.png‎|right|thumb|Three-dimensional [[molecular model]] of [[donepezil]], an [[acetylcholinesterase inhibitor]] used in the treatment of AD symptoms]]
[[File:Memantine.svg|right|thumb||Upright|Molecular structure of [[memantine]], a medication approved for advanced AD symptoms]]
Four medications are currently approved by regulatory agencies such as the U.S. [[Food and Drug Administration]] (FDA) and the [[European Medicines Agency]] (EMEA) to treat the cognitive manifestations of AD: three are [[acetylcholinesterase inhibitor]]s and the other is [[memantine]], an [[NMDA receptor antagonist]]. No drug has an indication for delaying or halting the progression of the disease.

Reduction in the activity of the [[cholinergic]] neurons is a well-known feature of Alzheimer's disease.<ref name="pmid8534419">{{cite journal
|author=Geula C, Mesulam MM
|title=Cholinesterases and the pathology of Alzheimer disease
|journal=Alzheimer Dis Assoc Disord
|volume=9 Suppl 2
|pages=23–28
|year=1995
|pmid=8534419
}}</ref> [[Acetylcholinesterase inhibitor]]s are employed to reduce the rate at which [[acetylcholine]] (ACh) is broken down, thereby increasing the concentration of ACh in the brain and combating the loss of ACh caused by the death of cholinergic neurons.<ref name="pmid11105732">{{cite journal
|author=Stahl SM
|title=The new cholinesterase inhibitors for Alzheimer's disease, Part 2: illustrating their mechanisms of action
|journal=J Clin Psychiatry
|volume=61
|issue=11
|pages=813–814
|year=2000
|pmid=11105732
}}</ref> {{as of
| 2008}}, the cholinesterase inhibitors approved for the management of AD symptoms are [[donepezil]] (brand name ''Aricept''),<ref>{{cite web
|url=http://www.nlm.nih.gov/medlineplus/druginfo/meds/a697032.html
|title=Donepezil
|accessdate=2010-02-03
|date=2007-01-08
|publisher= US National Library of Medicine (Medline Plus)
}}</ref> [[galantamine]] (''Razadyne''),<ref>{{cite web
|url=http://www.nlm.nih.gov/medlineplus/druginfo/meds/a699058.html
|title=Galantamine
|accessdate=2010-02-03
|date=2007-01-08
|publisher= US National Library of Medicine (Medline Plus)
}}</ref> and [[rivastigmine]] (branded as ''Exelon''<ref>{{cite web
|url=http://www.nlm.nih.gov/medlineplus/druginfo/meds/a602009.html
|title=Rivastigmine
|accessdate=2010-02-03
|date=2007-01-08
|publisher= US National Library of Medicine (Medline Plus)
}}</ref> and ''Exelon Patch''<ref>{{cite web
|url=http://www.nlm.nih.gov/medlineplus/druginfo/meds/a607078.html
|title=Rivastigmine Transdermal
|accessdate=2010-02-03
|date=2007-01-08
|publisher= US National Library of Medicine (Medline Plus)
}}</ref>). There is evidence for the efficacy of these medications in mild to moderate Alzheimer's disease,<ref name="pmid16437532">{{cite journal
|author=Birks J
|title=Cholinesterase inhibitors for Alzheimer's disease
|journal=Cochrane Database Syst Rev
|issue=1
|pages=CD005593
|year=2006
|pmid=16437532
|doi=10.1002/14651858.CD005593
|last2=Birks
|first2=Jacqueline
}}</ref> and some evidence for their use in the advanced stage. Only donepezil is approved for treatment of advanced AD dementia.<ref name="pmid16437430">{{cite journal
|author=Birks J, Harvey RJ
|title=Donepezil for dementia due to Alzheimer's disease
|journal=Cochrane Database Syst Rev
|issue=1
|pages=CD001190
|year=2006
|pmid=16437430
|doi=10.1002/14651858.CD001190.pub2
}}</ref> The use of these drugs in [[mild cognitive impairment]] has not shown any effect in a delay of the onset of AD.<ref name="pmid18044984">{{cite journal
|author=Raschetti R, Albanese E, Vanacore N, Maggini M
|title=Cholinesterase inhibitors in mild cognitive impairment: a systematic review of randomised trials
|journal=PLoS Med
|volume=4
|issue=11
|pages=e338
|year=2007
|pmid=18044984
|doi=10.1371/journal.pmed.0040338
|pmc=2082649
}}</ref> The most common [[adverse drug reaction|side effect]]s are [[nausea]] and [[vomiting]], both of which are linked to cholinergic excess. These side effects arise in approximately 10–20% of users and are mild to moderate in severity. Less common secondary effects include [[muscle cramp]]s, decreased [[heart rate]] ([[bradycardia]]), decreased [[appetite]] and weight, and increased [[gastric acid]] production.<ref>Acetylcholinesterase inhibitors prescribing information:
*{{cite web
|url=http://www.aricept.com/images/AriceptComboFullPINovember02006.pdf
|form=pdf
|title=Aricept Prescribing information
|accessdate=2008-08-18
|format= PDF
|publisher= Eisai and Pfizer
}}
*{{cite web
|url=http://web.archive.org/web/20080528195504/http://razadyneer.com/razadyneer/pages/pdf/razadyne_er.pdf
|title=Razadyne ER U.S. Full Prescribing Information
|accessdate=2008-02-19
|format=PDF
|publisher=Ortho-McNeil Neurologics
}}
*{{cite web
|url=http://www.pharma.us.novartis.com/product/pi/pdf/exelonpatch.pdf
|archiveurl=http://web.archive.org/web/20070728014715/http://www.pharma.us.novartis.com/product/pi/pdf/exelonpatch.pdf
|archivedate=2007-07-28
|title=Exelon ER U.S. Prescribing Information
|accessdate=2008-02-19
|format=PDF
|publisher=Novartis Pharmaceuticals
}}
*{{cite web
|url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/020823s016,021025s008lbl.pdf
|archiveurl=http://web.archive.org/web/20070710074347/http://www.fda.gov/cder/foi/label/2006/020823s016,021025s008lbl.pdf
|archivedate=2007-07-10
|title=Exelon U.S. Prescribing Information
|date=June 2006
|accessdate=2009-07-30
|format= PDF
|publisher=Novartis Pharmaceuticals
}}
*{{cite web
|url=http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/EnforcementActivitiesbyFDA/WarningLettersandNoticeofViolationLetterstoPharmaceuticalCompanies/ucm054180.pdf
|format=PDF |title=Exelon Warning Letter
|date=August 2007
|accessdate=2009-07-30
|publisher=FDA
}}</ref>

[[Glutamate]] is a useful excitatory [[neurotransmitter]] of the [[nervous system]], although excessive amounts in the [[brain]] can lead to [[Cell (biology)|cell]] death through a process called [[excitotoxicity]] which consists of the overstimulation of glutamate [[Receptor (biochemistry)|receptors]]. Excitotoxicity occurs not only in Alzheimer's disease, but also in other neurological diseases such as [[Parkinson's disease]] and [[multiple sclerosis]].<ref name="pmid16424917">{{cite journal
|author=Lipton SA
|title=Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond
|journal=Nat Rev Drug Discov
|volume=5
|issue=2
|pages=160–170
|year=2006
|pmid=16424917
|doi=10.1038/nrd1958
}}</ref> [[Memantine]] (brand names ''Akatinol'', ''Axura'', ''Ebixa''/''Abixa'', ''Memox'' and ''Namenda''),<ref>{{cite web
|url=http://www.nlm.nih.gov/medlineplus/druginfo/meds/a604006.html
|title=Memantine
|accessdate=2010-02-03
|date=2004-01-04
|publisher= US National Library of Medicine (Medline)
}}</ref> is a noncompetitive [[NMDA receptor antagonist]] first used as an anti-[[influenza]] agent. It acts on the [[glutamatergic system]] by blocking [[NMDA receptor]]s and inhibiting their overstimulation by glutamate.<ref name="pmid16424917" /> Memantine has been shown to be moderately efficacious in the treatment of moderate to severe Alzheimer's disease. Its effects in the initial stages of AD are unknown.<ref name="pmid15495043">{{cite journal
|author=Areosa Sastre A, McShane R, Sherriff F
|title=Memantine for dementia
|journal=Cochrane Database Syst Rev
|issue=4
|pages=CD003154
|year=2004
|pmid=15495043
|doi=10.1002/14651858.CD003154.pub2
}}</ref> Reported adverse events with memantine are infrequent and mild, including [[hallucination]]s, [[confusion]], [[dizziness]], [[headache]] and [[fatigue (medical)|fatigue]].<ref>{{cite web
|url=http://www.frx.com/pi/namenda_pi.pdf
|title=Namenda Prescribing Information
|accessdate=2008-02-19
|format=PDF
|publisher=Forest Pharmaceuticals
}}<!-- also available at http://web.archive.org/web/*/http://www.frx.com/pi/namenda_pi.pdf --></ref> The combination of memantine and donepezil has been shown to be "of [[Statistical significance|statistically significant]] but clinically marginal effectiveness".<ref name="pmid18316756">{{cite journal
|author=Raina P, Santaguida P, Ismaila A, ''et al.''
|title=Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline
|journal=Annals of Internal Medicine
|volume=148
|issue=5
|pages=379–397
|year=2008
|pmid=18316756
}}</ref>

[[Antipsychotic]] drugs are modestly useful in reducing [[aggression]] and [[psychosis]] in Alzheimer's patients with behavioural problems, but are associated with serious adverse effects, such as [[cerebrovascular]] events, [[extra-pyramidal|movement difficulties]] or cognitive decline, that do not permit their routine use.<ref>Antipsychotics use:
*{{cite journal
|author=Ballard C, Waite J
|title=The effectiveness of atypical antipsychotics for the treatment of aggression and psychosis in Alzheimer's disease
|journal=Cochrane Database Syst Rev
|issue=1
|pages=CD003476
|year=2006
|pmid=16437455
|doi=10.1002/14651858.CD003476.pub2}}
*{{cite journal
|author=Ballard C, Lana MM, Theodoulou M, ''et al.''
|title=A Randomised, Blinded, Placebo-Controlled Trial in Dementia Patients Continuing or Stopping Neuroleptics (The DART-AD Trial)
|journal=PLoS Med.
|volume=5
|issue=4
|pages=e76
|year=2008
|pmid=18384230
|doi=10.1371/journal.pmed.0050076
|pmc=2276521
}}
*{{cite journal
|author=Sink KM, Holden KF, Yaffe K
|title=Pharmacological treatment of neuropsychiatric symptoms of dementia: a review of the evidence
|journal=JAMA
|volume=293
|issue=5
|pages=596–608
|year=2005
|pmid=15687315
|doi=10.1001/jama.293.5.596
}}</ref><ref name="pmid19138567">
{{cite journal
|author=Ballard C, Hanney ML, Theodoulou M, Douglas S, McShane R, Kossakowski K, Gill R, Juszczak E, Yu L-M, Jacoby R
|title=The dementia antipsychotic withdrawal trial (DART-AD): long-term follow-up of a randomised placebo-controlled trial
|journal=Lancet Neurology
|date=9 January 2009
|pmid=19138567
|doi=10.1016/S1474-4422(08)70295-3
|laysummary=http://www.physorg.com/news150695213.html
|volume=8
|page=151
|issue=2
}}</ref> When used in the long-term, they have been shown to associate with increased mortality.<ref name="pmid19138567" />

===Psychosocial intervention===
[[File:Snoezelruimte.JPG|righ|thumb||Upright|A specifically designed room for sensory integration therapy, also called [[snoezelen]]; an emotion-oriented psychosocial intervention for people with dementia]]
[[Psychosocial]] interventions are used as an adjunct to pharmaceutical treatment and can be classified within behaviour-, emotion-, cognition- or stimulation-oriented approaches. Research on efficacy is unavailable and rarely specific to AD, focusing instead on dementia in general.<ref name="pracGuideAPA">{{cite web
| url=http://www.psychiatryonline.com/pracGuide/loadGuidelinePdf.aspx?file=AlzPG101007
| format=PDF
| title =Practice Guideline for the Treatment of Patients with Alzheimer's disease and Other Dementias
| publisher =[[American Psychiatric Association]]
| month=October | year=2007
| accessdate=2007-12-28
| doi=10.1176/appi.books.9780890423967.152139
}}</ref>

[[Behavior modification|Behavioural interventions]] attempt to identify and reduce the antecedents and consequences of problem behaviours. This approach has not shown success in improving overall functioning,<ref name="pmid16323385">{{cite journal
|author=Bottino CM, Carvalho IA, Alvarez AM, ''et al.''
|title=Cognitive rehabilitation combined with drug treatment in Alzheimer's disease patients: a pilot study
|journal=Clin Rehabil
|volume=19
|issue=8
|pages=861–869
|year=2005
|pmid=16323385
|doi=10.1191/0269215505cr911oa
}}</ref>
but can help to reduce some specific problem behaviours, such as [[Urinary incontinence|incontinence]].<ref name="pmid11342679">{{cite journal
|author=Doody RS, Stevens JC, Beck C, ''et al.''
|title=Practice parameter: management of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology
|journal=Neurology
|volume=56
|issue=9
|pages=1154–1166
|year=2001
|pmid=11342679
}}</ref> There is a lack of high quality data on the effectiveness of these techniques in other behaviour problems such as wandering.<ref name="pmid17253573">{{cite journal
|author=Hermans DG, Htay UH, McShane R
|title=Non-pharmacological interventions for wandering of people with dementia in the domestic setting
|journal=Cochrane Database Syst Rev
|issue=1
|pages=CD005994
|year=2007
|pmid=17253573
|doi=10.1002/14651858.CD005994.pub2
}}</ref><ref name="pmid17096455">{{cite journal
|author=Robinson L, Hutchings D, Dickinson HO, ''et al.''
|title=Effectiveness and acceptability of non-pharmacological interventions to reduce wandering in dementia: a systematic review
|journal=Int J Geriatr Psychiatry
|volume=22
|issue=1
|pages=9–22
|year=2007
|pmid=17096455
|doi=10.1002/gps.1643
}}</ref>

Emotion-oriented interventions include [[reminiscence therapy]], [[validation therapy]], supportive [[psychotherapy]], [[sensory integration]], also called [[snoezelen]], and [[simulated presence therapy]]. Supportive psychotherapy has received little or no formal scientific study, but some clinicians find it useful in helping mildly impaired patients adjust to their illness.<ref name="pracGuideAPA"/> Reminiscence therapy (RT) involves the discussion of past experiences individually or in group, many times with the aid of photographs, household items, music and sound recordings, or other familiar items from the past. Although there are few quality studies on the effectiveness of RT, it may be beneficial for [[cognition]] and [[Mood (psychology)|mood]].<ref name="pmid15846613">{{cite journal
|author=Woods B, Spector A, Jones C, Orrell M, Davies S
|title=Reminiscence therapy for dementia
|journal=Cochrane Database Syst Rev
|issue=2
|pages=CD001120
|year=2005
|pmid=15846613
|doi=10.1002/14651858.CD001120.pub2
}}</ref>
Simulated presence therapy (SPT) is based on [[Attachment theory|attachment theories]] and involves playing a recording with voices of the closest relatives of the person with Alzheimer's disease. There is partial evidence indicating that SPT may reduce [[challenging behaviour]]s.<ref name="pmid19023729">{{cite journal
|author=Zetteler J
|title=Effectiveness of simulated presence therapy for individuals with dementia: a systematic review and meta-analysis
|journal=Aging Ment Health
|volume=12
|issue=6
|pages=779–85
|year=2008
|month=November
|pmid=19023729
|doi=10.1080/13607860802380631
}}</ref>
Finally, validation therapy is based on acceptance of the reality and personal truth of another's experience, while sensory integration is based on exercises aimed to stimulate [[sense]]s. There is little evidence to support the usefulness of these therapies.<ref name="pmid12917907">{{cite journal
|author=Neal M, Briggs M
|title=Validation therapy for dementia
|journal=Cochrane Database Syst Rev
|issue=3
|pages=CD001394
|year=2003
|pmid=12917907
|doi=10.1002/14651858.CD001394
}}</ref><ref name="pmid12519587">{{cite journal
|author=Chung JC, Lai CK, Chung PM, French HP
|title=Snoezelen for dementia
|journal=Cochrane Database Syst Rev
|issue=4
|pages=CD003152
|year=2002
|pmid=12519587
|doi=10.1002/14651858.CD003152
}}</ref>

The aim of cognition-oriented treatments, which include reality orientation and [[Rehabilitation (neuropsychology)|cognitive retraining]], is the reduction of [[cognitive deficit]]s. Reality orientation consists in the presentation of information about time, place or person in order to ease the understanding of the person about its surroundings and his or her place in them. On the other hand cognitive retraining tries to improve impaired capacities by exercitation of mental abilities. Both have shown some efficacy improving cognitive capacities,<ref name="pmid17636652">{{cite journal
|author=Spector A, Orrell M, Davies S, Woods B
|title=Withdrawn: Reality orientation for dementia
|journal=Cochrane Database Syst Rev
|issue=3
|pages=CD001119
|year=2000
|pmid=17636652
|doi=10.1002/14651858.CD001119.pub2
}}</ref><ref name="pmid12948999">{{cite journal
|author=Spector A, Thorgrimsen L, Woods B, ''et al.''
|title=Efficacy of an evidence-based cognitive stimulation therapy programme for people with dementia: randomised controlled trial
|journal=Br J Psychiatry
|volume=183
|pages=248–254
|year=2003
|pmid=12948999
|doi=10.1192/bjp.183.3.248
}}</ref> although in some studies these effects were transient and negative effects, such as frustration, have also been reported.<ref name="pracGuideAPA"/>

Stimulation-oriented treatments include [[Art therapy|art]], [[Music therapy|music]] and [[Animal-assisted therapy|pet]] therapies, [[Physical therapy|exercise]], and any other kind of [[Recreational therapy|recreational activities]]. Stimulation has modest support for improving behaviour, mood, and, to a lesser extent, function. Nevertheless, as important as these effects are, the main support for the use of stimulation therapies is the change in the person's routine.<ref name="pracGuideAPA"/>

===Caregiving===
{{Further|[[Caregiving and dementia]]}}

Since Alzheimer's has no cure and it gradually renders people incapable of tending for their own needs, caregiving essentially is the treatment and must be carefully managed over the course of the disease.

During the early and moderate stages, modifications to the living environment and lifestyle can increase [[patient safety]] and reduce caretaker burden.<ref name="pmid11220813">{{cite journal
|author = Gitlin LN, Corcoran M, Winter L, Boyce A, Hauck WW
|title = A randomized, controlled trial of a home environmental intervention: effect on efficacy and upset in caregivers and on daily function of persons with dementia
|journal = Gerontologist
|volume = 41
|issue = 1
|pages = 4–14
|date = 1 February 2001
|pmid = 11220813
|url = http://gerontologist.gerontologyjournals.org/cgi/pmidlookup?view=long&pmid=11220813
|accessdate=2008-07-15
}}</ref><ref name="pmid15860476">{{cite journal
|author=Gitlin LN, Hauck WW, Dennis MP, Winter L
|title=Maintenance of effects of the home environmental skill-building program for family caregivers and individuals with Alzheimer's disease and related disorders
|journal=J. Gerontol. A Biol. Sci. Med. Sci.
|volume=60
|issue=3
|pages=368–74
|year=2005
|month=March
|pmid=15860476
}}</ref> Examples of such modifications are the adherence to simplified routines, the placing of safety locks, the labelling of household items to cue the person with the disease or the use of modified daily life objects.<ref name="pracGuideAPA"/><ref>
{{cite web
|url=http://web.archive.org/web/20060925112503/http://www.alz.org/Health/Treating/agitation.asp
|title= Treating behavioral and psychiatric symptoms
|year=2006
|accessdate=2006-09-25
|publisher = Alzheimer's Association
}}</ref><ref name="pmid15297089">
{{cite journal
| author = Dunne TE, Neargarder SA, Cipolloni PB, Cronin-Golomb A
| title = Visual contrast enhances food and liquid intake in advanced Alzheimer's disease
| journal = Clinical Nutrition
| volume = 23
| issue = 4
| pages = 533–538
| year = 2004
| pmid = 15297089
| doi = 10.1016/j.clnu.2003.09.015
}}</ref> The patient may also become incapable of feeding themselves, so they require food in smaller pieces or pureed.<ref>{{cite book
|author=Dudek, Susan G.
|title=Nutrition essentials for nursing practice
|publisher=Lippincott Williams & Wilkins
|location=Hagerstown, Maryland
|year=2007
|page=360
|isbn=0-7817-6651-6
|oclc=
|doi=
|url= http://books.google.com/?id=01zo6yf0IUEC&pg=PA360&dq=alzheimer%27s+chew
|accessdate=2008-08-19
}}</ref> When [[Dysphagia|swallowing difficulties]] arise, the use of [[feeding tube]]s may be required. In such cases, the medical efficacy and ethics of continuing feeding is an important consideration of the caregivers and family members.<ref name="pmid16415742">{{cite journal
|author=Dennehy C
|title=Analysis of patients' rights: dementia and PEG insertion
|journal=Br J Nurs
|volume=15
|issue=1
|pages=18–20
|year=2006
|pmid=16415742
}}</ref><ref name="pmid16556924">{{cite journal
|author=Chernoff R
|title=Tube feeding patients with dementia
|journal=Nutr Clin Pract
|volume=21
|issue=2
|pages=142–6
|year=2006
|month=April
|pmid=16556924
|doi=10.1177/0115426506021002142
}}</ref> The use of physical restraints is rarely indicated in any stage of the disease, although there are situations when they are necessary to prevent harm to the person with AD or their caregivers.<ref name="pracGuideAPA"/>

As the disease progresses, different medical issues can appear, such as [[dental disease|oral and dental disease]], [[Bedsore|pressure ulcers]], [[malnutrition]], [[hygiene]] problems, or [[Respiratory system|respiratory]], [[skin]], or [[eye]] [[infection]]s. Careful management can prevent them, while professional treatment is needed when they do arise.<ref name="pmid10369823">{{cite journal
|author=Gambassi G, Landi F, Lapane KL, Sgadari A, Mor V, Bernabei R
|title=Predictors of mortality in patients with Alzheimer's disease living in nursing homes
|journal=J. Neurol. Neurosurg. Psychiatr.
|volume=67
|issue=1
|pages=59–65
|year=1999
|month=July
|pmid=10369823
|pmc=1736445
|doi=10.1136/jnnp.67.1.59
}}</ref><ref>Medical issues:
*{{cite journal
|author=Head B
|title=Palliative care for persons with dementia
|journal=Home Healthc Nurse
|volume=21
|issue=1
|pages=53–60; quiz 61
|year=2003
|month=January
|pmid=12544465
|doi=10.1097/00004045-200301000-00012
}}
*{{cite journal
|author=Friedlander AH, Norman DC, Mahler ME, Norman KM, Yagiela JA
|title=Alzheimer's disease: psychopathology, medical management and dental implications
|journal=J Am Dent Assoc
|volume=137
|issue=9
|pages=1240–51
|year=2006
|month=September
|pmid=16946428
}}
*{{cite journal
|author=Belmin J
|title=Practical guidelines for the diagnosis and management of weight loss in Alzheimer's disease: a consensus from appropriateness ratings of a large expert panel
|journal=J Nutr Health Aging
|volume=11
|issue=1
|pages=33–7
|year=2007
|pmid=17315078
|author2=Expert Panel and Organisation Committee
}}
*{{cite journal
|author=McCurry SM, Gibbons LE, Logsdon RG, Vitiello M, Teri L
|title=Training caregivers to change the sleep hygiene practices of patients with dementia: the NITE-AD project
|journal=J Am Geriatr Soc
|volume=51
|issue=10
|pages=1455–60
|year=2003
|month=October
|pmid=14511168
|doi=10.1046/j.1532-5415.2003.51466.x
}}
*{{cite journal
|author=Perls TT, Herget M
|title=Higher respiratory infection rates on an Alzheimer's special care unit and successful intervention
|journal=J Am Geriatr Soc
|volume=43
|issue=12
|pages=1341–4
|year=1995
|month=December
|pmid=7490383
}}</ref> During the final stages of the disease, treatment is centred on relieving discomfort until death.<ref name="pmid12854952">{{cite journal
|author=Shega JW, Levin A, Hougham GW, ''et al.''
|title=Palliative Excellence in Alzheimer Care Efforts (PEACE): a program description
|journal=J Palliat Med
|volume=6
|issue=2
|pages=315–20
|year=2003
|month=April
|pmid=12854952
|doi=10.1089/109662103764978641
}}</ref>

A small recent study in the US concluded that patients whose caregivers had a realistic understanding of the prognosis and clinical complications of late dementia were less likely to receive aggressive treatment near the end of life.
<ref>{{cite journal
|author=Mitchell SL, Teno JM, Kiely DK, ''et al.''
|title=The clinical course of advanced dementia
|journal=N Engl J Med
|volume=361
|issue=16
|pages=1529–38
|year=2009
|month=Oct
|pmid=19828530
|doi=10.1056/NEJMoa0902234
|pmc=2778850}}</ref>

==Prognosis==
[[File:Alzheimer and other dementias world map - DALY - WHO2004.svg|thumb|[[Disability-adjusted life year]] for Alzheimer and other dementias per 100,000&nbsp;inhabitants in 2004.<div class="references-small" style="-moz-column-count:3; column-count:3;">
{{legend|#b3b3b3|no data}}
{{legend|#ffff65|≤&nbsp;50}}
{{legend|#fff200|50–70}}
{{legend|#ffdc00|70–90}}
{{legend|#ffc600|90–110}}
{{legend|#ffb000|110–130}}
{{legend|#ff9a00|130–150}}
{{legend|#ff8400|150–170}}
{{legend|#ff6e00|170–190}}
{{legend|#ff5800|190–210}}
{{legend|#ff4200|210–230}}
{{legend|#ff2c00|230–250}}
{{legend|#cb0000|≥&nbsp;250}}
</div>]]

The early stages of Alzheimer's disease are difficult to diagnose. A definitive diagnosis is usually made once cognitive impairment compromises daily living activities, although the person may still be living independently. The symptoms will progress from mild cognitive problems, such as memory loss through increasing stages of cognitive and non-cognitive disturbances, eliminating any possibility of independent living.<ref name="pmid10653284" />

[[Life expectancy]] of the population with the disease is reduced.<ref name="pmid3776457"/><ref name="pmid8757016">{{cite journal
|author=Bowen JD, Malter AD, Sheppard L, ''et al.''
|title=Predictors of mortality in patients diagnosed with probable Alzheimer's disease
|journal=Neurology
|volume=47
|issue=2
|pages=433–9
|year=1996
|month=August
|pmid=8757016
}}</ref><ref name="pmid12580712">{{cite journal
|author=Dodge HH, Shen C, Pandav R, DeKosky ST, Ganguli M
|title=Functional transitions and active life expectancy associated with Alzheimer disease
|journal=Arch. Neurol.
|volume=60
|issue=2
|pages=253–9
|year=2003
|month=February
|pmid=12580712
|doi=10.1001/archneur.60.2.253
}}</ref> The mean life expectancy following diagnosis is approximately seven years.<ref name="pmid3776457"/> Fewer than 3% of patients live more than fourteen years.<ref name="pmid7793228"/> Disease features significantly associated with reduced survival are an increased severity of cognitive impairment, decreased functional level, history of falls, and disturbances in the neurological examination. Other coincident diseases such as [[Heart disease|heart problems]], [[Diabetes mellitus|diabetes]] or history of [[alcohol abuse]] are also related with shortened survival.<ref name="pmid8757016"/><ref name="pmid15068977">{{cite journal
|author=Larson EB, Shadlen MF, Wang L, ''et al.''
|title=Survival after initial diagnosis of Alzheimer disease
|journal=Ann. Intern. Med.
|volume=140
|issue=7
|pages=501–9
|year=2004
|month=April
|pmid=15068977
}}</ref><ref name="pmid7792352">{{cite journal
|author=Jagger C, Clarke M, Stone A
|title=Predictors of survival with Alzheimer's disease: a community-based study
|journal=Psychol Med
|volume=25
|issue=1
|pages=171–7
|year=1995
|month=January
|pmid=7792352
|doi=10.1017/S0033291700028191
}}</ref> While the earlier the age at onset the higher the total survival years, life expectancy is particularly reduced when compared to the healthy population among those who are younger.<ref name="pmid12580712"/> Men have a less favourable survival prognosis than women.<ref name="pmid7793228"/><ref name="pmid15883266">{{cite journal
|author=Ganguli M, Dodge HH, Shen C, Pandav RS, DeKosky ST
|title=Alzheimer disease and mortality: a 15-year epidemiological study
|journal=Arch. Neurol.
|volume=62
|issue=5
|pages=779–84
|year=2005
|month=May
|pmid=15883266
|doi=10.1001/archneur.62.5.779
}}</ref>

The disease is the underlying [[Death|cause of death]] in 70% of all cases.<ref name="pmid3776457"/> [[Pneumonia]] and [[dehydration]] are the most frequent immediate causes of death, while [[cancer]] is a less frequent cause of death than in the general population.<ref name="pmid3776457"/><ref name="pmid15883266"/>

==Epidemiology==
{| align="left" border="2"| class="wikitable" style="text-align:center"
|+Incidence rates<br /> after age 65<ref name="pmid17727890"/>
|-
! Age !! New affected<br /> per thousand<br /> person–years
|-
!65–69
|&nbsp;3
|-
!70–74
|&nbsp;6
|-
!75–79
|&nbsp;9
|-
!80–84
|23
|-
!85–89
|40
|-
!90–&nbsp;&nbsp;&nbsp;&nbsp;<!-- The nonbreaking spaces to the left of this comment make the numbers line up properly. -->
|69
|}

Two main measures are used in [[epidemiology|epidemiological]] studies: incidence and prevalence. [[Incidence (epidemiology)|Incidence]] is the number of new cases per unit of person–time at risk (usually number of new cases per thousand person–years); while [[prevalence]] is the total number of cases of the disease in the population at any given time.

Regarding incidence, [[cohort study|cohort]] [[longitudinal studies]] (studies where a disease-free population is followed over the years) provide rates between 10 and 15 per thousand person–years for all dementias and 5–8 for AD,<ref name="pmid17727890">{{cite journal
|author=Bermejo-Pareja F, Benito-León J, Vega S, Medrano MJ, Román GC
|title=Incidence and subtypes of dementia in three elderly populations of central Spain
|journal=J. Neurol. Sci.
|volume=264
|issue=1–2
|pages=63–72
|year=2008
|month=January
|pmid=17727890
|doi=10.1016/j.jns.2007.07.021
}}</ref><ref name="pmid12028245">{{cite journal
|author=Di Carlo A, Baldereschi M, Amaducci L, ''et al.''
|title=Incidence of dementia, Alzheimer's disease, and vascular dementia in Italy. The ILSA Study
|journal=J Am Geriatr Soc
|volume=50
|issue=1
|pages=41–8
|year=2002
|month=January
|pmid=12028245
|doi=10.1046/j.1532-5415.2002.50006.x
|last12=Ilsa Working
|first12=Group
}}</ref> which means that half of new dementia cases each year are AD. Advancing age is a primary risk factor for the disease and incidence rates are not equal for all ages: every five years after the age of 65, the risk of acquiring the disease approximately doubles, increasing from 3 to as much as 69 per thousand person years.<ref name="pmid17727890"/><ref name="pmid12028245"/> There are also sex differences in the incidence rates, women having a higher risk of developing AD particularly in the population older than 85.<ref name="pmid12028245"/><ref>{{cite journal
|author=Andersen K, Launer LJ, Dewey ME, ''et al.''
|title=Gender differences in the incidence of AD and vascular dementia: The EURODEM Studies. EURODEM Incidence Research Group
|journal=Neurology
|volume=53
|issue=9
|pages=1992–7
|year=1999
|month=December
|pmid=10599770
|last12=Martinez-Lage
|first12=JM
|last13=Stijnen
|first13=T
|last14=Hofman
|first14=A
}}</ref>

Prevalence of AD in populations is dependent upon different factors including incidence and survival. Since the incidence of AD increases with age, it is particularly important to include the mean age of the population of interest. In the United States, Alzheimer prevalence was estimated to be 1.6% in 2000 both overall and in the 65–74 age group, with the rate increasing to 19% in the 75–84 group and to 42% in the greater than 84 group.<ref>2000 U.S. estimates:
*{{cite journal
|author=Hebert LE, Scherr PA, Bienias JL, Bennett DA, Evans DA
|title=Alzheimer disease in the US population: prevalence estimates using the 2000 census
|journal=Arch. Neurol.
|volume=60
|issue=8
|pages=1119–22
|year=2003
|month=August
|pmid=12925369
|doi=10.1001/archneur.60.8.1119
}}
*{{cite web
|title=Profiles of general demographic characteristics, 2000 census of population and housing, United States
|year=2001
|publisher=U.S. Census Bureau
|url=http://www.census.gov/prod/cen2000/dp1/2kh00.pdf
|format=PDF
|accessdate=2008-08-27
}}</ref> Prevalence rates in less developed regions are lower.{{Dead link|date=February 2010}}<ref name="pmid16360788"/> The [[World Health Organization]] estimated that in 2005, 0.379% of people worldwide had dementia, and that the prevalence would increase to 0.441% in 2015 and to 0.556% in 2030.<ref name="isbn9789241563369">{{cite book
| last = World Health Organization
| title = Neurological Disorders: Public Health Challenges
| publisher = World Health Organization
| year = 2006
| location = Switzerland
| pages = 204–207
| url = http://www.who.int/mental_health/neurology/neurodiso/en/index.html
| isbn = 978-92-4-156336-9 }}</ref> Other studies have reached similar conclusions.<ref name="pmid16360788">{{cite journal
|author=Ferri CP, Prince M, Brayne C, ''et al.''
|title=Global prevalence of dementia: a Delphi consensus study
|journal=Lancet
|volume=366
|issue=9503
|pages=2112–7
|year=2005
|month=December
|pmid=16360788
|pmc=2850264
|doi=10.1016/S0140-6736(05)67889-0
|url=http://web.archive.org/web/20080625071754/http://www.sbgg.org.br/profissional/artigos/pdf/demencia_mundo.pdf
|accessdate=2008-06-25
|format=PDF
|last12=Mathers
|first12=C
|last13=Menezes
|first13=PR
|last14=Rimmer
|first14=E
|last15=Scazufca
|first15=M
|last16=Alzheimer's Disease
|first16=International}}</ref> Another study estimated that in 2006, 0.40% of the world population (range 0.17–0.89%; absolute number {{Nowrap|26.6 million}}, range {{Nowrap|11.4–59.4 million}}) were afflicted by AD, and that the prevalence rate would triple and the absolute number would quadruple by 2050.<ref name="Brookmeyer2007">2006 prevalence estimate:
*{{cite journal
|author=Brookmeyer R, Johnson E, Ziegler-Graham K, MH Arrighi
|title=Forecasting the global burden of Alzheimer's disease
|journal=Alzheimer's and Dementia
|volume=3
|issue=3
|pages=186–91
|year=2007
|month=July
|doi=10.1016/j.jalz.2007.04.381
|url=http://works.bepress.com/cgi/viewcontent.cgi?article=1022&context=rbrookmeyer
|accessdate=2008-06-18
|pmid=19595937
|last1=Brookmeyer
|first1=R
|last2=Johnson
|first2=E
|last3=Ziegler-Graham
|first3=K
|last4=Arrighi
|first4=HM
}}
*{{cite paper
|url=http://un.org/esa/population/publications/wpp2006/WPP2006_Highlights_rev.pdf
|format=PDF
|accessdate=2008-08-27
|year=2007
|title=World population prospects: the 2006 revision, highlights
|publisher=Population Division, Department of Economic and Social Affairs, United Nations
|version=Working Paper No. ESA/P/WP.202
}}</ref>

==History==
[[File:Auguste D aus Marktbreit.jpg|thumb|Alois Alzheimer's patient [[Auguste Deter]] in 1902. Hers was the first described case of what became known as Alzheimer's disease.]]
The [[Classical antiquity|ancient Greek and Roman]] [[philosopher]]s and [[physician]]s associated old age with increasing [[dementia]].<ref name="pmid9661992">{{cite journal
|author=Berchtold NC, Cotman CW
|title=Evolution in the conceptualization of dementia and Alzheimer's disease: Greco-Roman period to the 1960s
|journal=Neurobiol. Aging
|volume=19
|issue=3
|pages=173–89
|year=1998
|pmid=9661992
|doi=10.1016/S0197-4580(98)00052-9
}}</ref> It was not until 1901 that German [[psychiatry|psychiatrist]] Alois Alzheimer identified the first case of what became known as Alzheimer's disease in a fifty-year-old woman he called [[Auguste D]]. Alzheimer followed her until she died in 1906, when he first reported the case publicly.<ref>Auguste D.:
* {{
cite journal
| author=Alzheimer Alois
| title=Über eine eigenartige Erkrankung der Hirnrinde [About a peculiar disease of the cerebral cortex]
| journal=Allgemeine Zeitschrift fur Psychiatrie und Psychisch-Gerichtlich Medizin
| volume=64
| issue=1–2
| pages=146–148
| year=1907
| language={{de icon}}
}}
*{{cite journal
|author=Alzheimer Alois
|title=About a peculiar disease of the cerebral cortex. By Alois Alzheimer, 1907 (Translated by L. Jarvik and H. Greenson)
|journal=Alzheimer Dis Assoc Disord
|volume=1
|issue=1
|pages=3–8
|year=1987
|pmid=3331112
}}
*{{cite book
|author=Maurer Ulrike, Maurer Konrad
|title=Alzheimer: the life of a physician and the career of a disease
|publisher=Columbia University Press
|location=New York
|year=2003
|page=270
|isbn=0-231-11896-1
|oclc=
}}</ref> During the next five years, eleven similar cases were reported in the [[medical literature]], some of them already using the term Alzheimer's disease.<ref name="pmid9661992">{{cite journal
|author=Berchtold NC, Cotman CW
|title=Evolution in the conceptualization of dementia and Alzheimer's disease: Greco-Roman period to the 1960s
|journal=Neurobiology of Aging
|volume=19
|issue=3
|pages=173–189
|year=1998
|pmid=9661992
|doi=10.1016/S0197-4580(98)00052-9
}}</ref> The disease was first described as a distinctive disease by [[Emil Kraepelin]] after suppressing some of the clinical (delusions and hallucinations) and pathological features (arteriosclerotic changes) contained in the original report of Auguste D.<ref>{{cite journal
|author=Berrios G E
|title=Alzheimer's disease: a conceptual history
|journal=Int. J. Ger. Psychiatry
|volume=5
|issue=
|pages=355–365
|year=1990
|month=
|pmid=
|doi=10.1002/gps.930050603
}}</ref> He included ''Alzheimer's disease'', also named ''presenile'' [[dementia]] by Kraepelin, as a subtype of ''senile dementia'' in the eighth edition of his ''Textbook of Psychiatry'', published in 1910.<ref name="isbn1-4325-0833-4">{{cite book
|author=Kraepelin Emil, Diefendorf A. Ross (translated by)
|title=Clinical Psychiatry: A Textbook For Students And Physicians (Reprint)
|publisher=Kessinger Publishing
|date=2007-01-17
|page=568
|isbn=1-4325-0833-4
|oclc=
}}</ref>

For most of the 20th century, the diagnosis of Alzheimer's disease was reserved for individuals between the ages of 45 and 65 who developed symptoms of dementia. The terminology changed after 1977 when a conference on AD concluded that the clinical and [[pathological]] manifestations of presenile and senile dementia were almost identical, although the authors also added that this did not rule out the possibility that they had different causes.<ref name="isbn0-89004-225-X">{{cite book
|author=Katzman Robert, Terry Robert D, Bick Katherine L (editors)
|title=Alzheimer's disease: senile dementia and related disorders
|publisher=Raven Press
|location=New York
|year=1978
|page=595
|isbn=0-89004-225-X
|oclc=
}}</ref> This eventually led to the diagnosis of ''Alzheimer's disease'' independently of age.<ref name="pmid9702682">{{cite journal
|author=Boller F, Forbes MM
|title=History of dementia and dementia in history: an overview
|journal=J. Neurol. Sci.
|volume=158
|issue=2
|pages=125–33
|year=1998
|month=June
|pmid=9702682
|doi=10.1016/S0022-510X(98)00128-2
}}</ref> The term ''senile dementia of the Alzheimer type'' (SDAT) was used for a time to describe the condition in those over 65, with classical Alzheimer's disease being used for those younger. Eventually, the term Alzheimer's disease was formally adopted in medical [[nomenclature]] to describe individuals of all ages with a characteristic common symptom pattern, disease course, and [[neuropathology]].<ref name="pmid3531918">{{cite journal
|author=Amaducci LA, Rocca WA, Schoenberg BS
|title=Origin of the distinction between Alzheimer's disease and senile dementia: how history can clarify nosology
|journal=Neurology
|volume=36
|issue=11
|pages=1497–9
|year=1986
|month=November
|pmid=3531918
}}</ref>

==Society and culture==
===Social costs===
Dementia, and specifically Alzheimer's disease, may be among the most costly diseases for society in Europe and the United States,<ref name="pmid15685097"/><ref name="pmid9543467"/> while their cost in other countries such as [[Argentina]],<ref name="pmid16870037">{{cite journal
|author=Allegri RF, Butman J, Arizaga RL, ''et al.''
|title=Economic impact of dementia in developing countries: an evaluation of costs of Alzheimer-type dementia in Argentina
|journal=Int Psychogeriatr
|volume=19
|issue=4
|pages=705–18
|year=2007
|month=August
|pmid=16870037
|doi=10.1017/S1041610206003784
}}</ref> or [[South Korea]],<ref name="pmid16858741">{{cite journal
|author=Suh GH, Knapp M, Kang CJ
|title=The economic costs of dementia in Korea, 2002
|journal=Int J Geriatr Psychiatry
|volume=21
|issue=8
|pages=722–8
|year=2006
|month=August
|pmid=16858741
|doi=10.1002/gps.1552
}}</ref> is also high and rising. These costs will probably increase with the [[ageing]] of society, becoming an important [[Social issues|social problem]]. AD-associated costs include direct medical costs such as [[nursing]] [[home care]], direct nonmedical costs such as in-home [[day care]], and indirect costs such as lost [[productivity]] of both patient and caregiver.<ref name="pmid9543467"/> Numbers vary between studies but dementia costs worldwide have been calculated around $160&nbsp;billion,<ref name="pmid16401889">{{cite journal
|author=Wimo A, Jonsson L, Winblad B
|title=An estimate of the worldwide prevalence and direct costs of dementia in 2003
|journal=Dement Geriatr Cogn Disord
|volume=21
|issue=3
|pages=175–81
|year=2006
|pmid=16401889
|doi=10.1159/000090733
}}</ref> while costs of Alzheimer in the United States may be $100&nbsp;billion each year.<ref name="pmid9543467"/>

The greatest origin of costs for society is the [[long-term care]] by [[Health care provider|health care professionals]] and particularly [[institutionalisation]], which corresponds to 2/3 of the total costs for society.<ref name="pmid15685097"/> [[Cost-of-living index|The cost of living]] at home is also very high,<ref name="pmid15685097"/> especially when informal costs for the family, such as caregiving time and caregiver's lost earnings, are taken into account.<ref name="pmid11445614">{{cite journal
|author=Moore MJ, Zhu CW, Clipp EC
|title=Informal costs of dementia care: estimates from the National Longitudinal Caregiver Study
|journal=J Gerontol B Psychol Sci Soc Sci
|volume=56
|issue=4
|pages=S219–28
|year=2001
|month=July
|pmid=11445614
}}</ref>

Costs increase with dementia severity and the presence of behavioural disturbances,<ref name="pmid16676288">{{cite journal
|author=Jönsson L, Eriksdotter Jönhagen M, Kilander L, ''et al.''
|title=Determinants of costs of care for patients with Alzheimer's disease
|journal=Int J Geriatr Psychiatry
|volume=21
|issue=5
|pages=449–59
|year=2006
|month=May
|pmid=16676288
|doi=10.1002/gps.1489
}}</ref> and are related to the increased caregiving time required for the provision of physical care.<ref name="pmid11445614"/> Therefore any treatment that slows cognitive decline, delays institutionalisation or reduces caregivers' hours will have economic benefits. Economic evaluations of current treatments have shown positive results.<ref name="pmid9543467"/>

===Caregiving burden===
{{Further|[[Caregiving and dementia]]}}
The role of the main [[Caregiving and dementia|caregiver]] is often taken by the spouse or a close relative.{{Dead link|date=February 2010}}<ref name="metlife.com"/> Alzheimer's disease is known for placing a great burden on [[carer|caregivers]] which includes social, psychological, physical or economic aspects.<ref name="pmid17662119"/><ref name="pmid10489656"/><ref name="pmid10489657">{{cite journal
|author=Murray J, Schneider J, Banerjee S, Mann A
|title=EUROCARE: a cross-national study of co-resident spouse carers for people with Alzheimer's disease: II—A qualitative analysis of the experience of caregiving
|journal=Int J Geriatr Psychiatry
|volume=14
|issue=8
|pages=662–7
|year=1999
|month=August
|pmid=10489657
|doi=10.1002/(SICI)1099-1166(199908)14:8<662::AID-GPS993>3.0.CO;2-4
}}</ref> Home care is usually preferred by patients and families.<ref name="pmid18044111">{{cite journal
|author=Zhu CW, Sano M
|title=Economic considerations in the management of Alzheimer's disease
|journal=Clin Interv Aging
|volume=1
|issue=2
|pages=143–54
|year=2006
|pmid=18044111
|doi=10.2147/ciia.2006.1.2.143
|pmc=2695165
}}</ref> This option also delays or eliminates the need for more professional and costly levels of care.<ref name="pmid18044111"/><ref>{{cite journal
|author=Gaugler JE, Kane RL, Kane RA, Newcomer R
|title=Early community-based service utilization and its effects on institutionalization in dementia caregiving
|journal=Gerontologist
|volume=45
|issue=2
|pages=177–85
|year=2005
|month=April
|pmid=15799982
}}</ref> Nevertheless two-thirds of nursing home residents have dementias.<ref name="pracGuideAPA"/>

[[Depression of Alzheimer disease|Dementia]] caregivers are subject to high rates of physical and [[mental disorder|mental]] disorders.<ref name="pmid12480441">{{cite journal
|author=Ritchie K, Lovestone S
|title=The dementias
|journal=Lancet
|volume=360
|issue=9347
|pages=1759–66
|year=2002
|month=November
|pmid=12480441
|doi=10.1016/S0140-6736(02)11667-9
}}</ref> Factors associated with greater psychosocial problems of the primary caregivers include having an affected person at home, the carer being a spouse, demanding behaviours of the cared person such as depression, behavioural disturbances, hallucinations, sleep problems or walking disruptions and [[social isolation]].<ref name="pmid2241719">{{cite journal
|author=Brodaty H, Hadzi-Pavlovic D
|title=Psychosocial effects on carers of living with persons with dementia
|journal=Aust N Z J Psychiatry
|volume=24
|issue=3
|pages=351–61
|year=1990
|month=September
|pmid=2241719
|doi=10.3109/00048679009077702
}}</ref><ref name="pmid9646153">{{cite journal
|author=Donaldson C, Tarrier N, Burns A
|title=Determinants of carer stress in Alzheimer's disease
|journal=Int J Geriatr Psychiatry
|volume=13
|issue=4
|pages=248–56
|year=1998
|month=April
|pmid=9646153
|doi=10.1002/(SICI)1099-1166(199804)13:4<248::AID-GPS770>3.0.CO;2-0
}}</ref> Regarding economic problems, family caregivers often give up time from work to spend 47&nbsp;hours per week on average with the person with AD, while the costs of caring for them are high. Direct and indirect costs of caring for an Alzheimer's patient average between $18,000 and $77,500 per year in the United States, depending on the study.<ref name="pmid11445614"/>{{Dead link|date=February 2010}}<ref>{{Dead link|date=February 2010}}
{{cite web
| title= The MetLife Study of Alzheimer's Disease: The Caregiving Experience
| month=August | year=2006
| url=http://www.metlife.com/WPSAssets/14050063731156260663V1FAlzheimerCaregivingExperience.pdf
| publisher=MetLife Mature Market Institute
| format=PDF
| accessdate=2008-02-12
}}</ref>

[[Cognitive behavioral therapy|Cognitive behavioural therapy]] and the teaching of [[Coping (psychology)|coping strategies]] either individually or in group have demonstrated their efficacy in improving caregivers' psychological health.<ref name="pmid17662119"/><ref name="pmid11511058">{{cite journal
|author=Pusey H, Richards D
|title=A systematic review of the effectiveness of psychosocial interventions for carers of people with dementia
|journal=Aging Ment Health
|volume=5
|issue=2
|pages=107–19
|year=2001
|month=May
|pmid=11511058
|doi=10.1080/13607860120038302
}}</ref>

===Notable cases===
{{Further|[[Alzheimer's in the media]]}}
[[File:Ronald Reagan Charlton Heston.jpg|thumb|Charlton Heston and Ronald Reagan at a meeting in the [[White House]]. Both of them would later develop Alzheimer's disease.]]

As Alzheimer's disease is highly prevalent, many notable people have developed it. Well-known examples are former [[United States President]] [[Ronald Reagan]] and Irish writer [[Iris Murdoch]], both of whom were the subjects of scientific articles examining how their cognitive capacities deteriorated with the disease.<ref name="pmid15574466">{{cite journal
|author=Garrard P, Maloney LM, Hodges JR, Patterson K
|title=[http://brain.oxfordjournals.org/cgi/content/full/128/2/250 The effects of very early Alzheimer's disease on the characteristics of writing by a renowned author]
|journal=Brain
|volume=128
|issue=Pt 2
|pages=250–60
|year=2005
|month=February
|pmid=15574466
|doi=10.1093/brain/awh341
}}</ref><ref name="pmid15461232">{{cite journal
|author=Sherman FT
|title=[http://www.modernmedicine.com/modernmedicine/article/articleDetail.jsp?id=121676 Did President Reagan have mild cognitive impairment while in office? Living longer with Alzheimer's Disease]
|journal=Geriatrics
|volume=59
|issue=9
|pages=11, 15
|year=2004
|month=September
|pmid=15461232
}}</ref><ref name="pmid15788549">{{cite journal
|author=Venneri A, Forbes-Mckay KE, Shanks MF
|title=Impoverishment of spontaneous language and the prediction of Alzheimer's disease
|journal=Brain
|volume=128
|issue=Pt 4
|pages=E27
|year=2005
|month=April
|pmid=15788549
|doi=10.1093/brain/awh419
|url=
}}</ref> Other cases include the retired [[Association football|footballer]] [[Ferenc Puskas]],<ref>{{cite news
| url=http://news.bbc.co.uk/sport1/hi/football/europe/6155766.stm
|title=Hungary legend Puskas dies at 79
|publisher=BBC News |date=2006-11-17
|accessdate=2008-01-25}}
</ref> the former [[Prime Minister]]s [[Harold Wilson]] (United Kingdom) and [[Adolfo Suárez]] ([[Spain]]),<ref>{{cite web
|url=http://www.number10.gov.uk/history-and-tour/prime-ministers-in-history/harold-wilson
|title=Prime Ministers in History: Harold Wilson
|publisher=10 Downing Street
|location=London
|accessdate=2008-08-18
}}</ref><ref>{{cite web
|url=http://www.elpais.com/articulo/espana/padre/reconocio/Rey/noto/carino/elpepiesp/20080718elpepinac_11/Tes
|title="Mi padre no reconoció al Rey pero notó el cariño"
|publisher=El País
|location=Madrid
|year=2008
|accessdate=2008-10-01
}}</ref> the actress [[Rita Hayworth]],<ref>{{cite web
|url=http://www.alz.org/galas/Rita/overview.asp
|title=Chicago Rita Hayworth Gala
|publisher=Alzheimer's Association
|year=2007
|accessdate=2010-02-03 }}
</ref> the actor [[Charlton Heston]],<ref>{{cite web
|url=http://archives.cnn.com/2002/US/08/09/heston.illness/
|title=Charlton Heston has Alzheimer's symptoms
|publisher=CNN
|date=2002-08-09
|accessdate=2008-01-25}}
</ref> the novelist [[Terry Pratchett]],<ref>{{cite news
|url=http://www.guardian.co.uk/books/2007/dec/12/news.michellepauli1
|author=Pauli Michelle
|title=Pratchett announces he has Alzheimer's
|publisher=Guardian News and Media
|date=2007-12-12
|accessdate=2008-08-18
| location=London}}</ref> and the 2009 [[Nobel Prize]] in Physics recipient [[Charles K. Kao]].<ref>{{cite web
|url=http://www.straitstimes.com/Breaking%2BNews/Asia/Story/STIStory_439665.html
|title=Nobel Prize Winner has Alzheimer's
|publisher=The Straits Times
|date=2009-10-08
|accessdate=2009-10-09
}}</ref>

AD has also been portrayed in films such as: ''[[Iris (film)|Iris]]'' (2001),<ref>{{cite web
|url=http://www.imdb.com/title/tt0280778/
|title=Iris
|date=2002-01-18 |publisher=IMDB
|accessdate=2008-01-24}}</ref> based on [[John Bayley (writer)|John Bayley]]'s memoir of his wife [[Iris Murdoch]];<ref>{{cite book
|title=Iris: a memoir of Iris Murdoch
|author=Bayley John
|publisher=Abacus
|location=London
|year=2000
|isbn=9780349112152
|oclc=41960006 }}</ref>
''[[The Notebook (film)|The Notebook]]'' (2004),<ref>{{cite web
|url=http://www.imdb.com/title/tt0332280/
|title=The notebook |publisher=IMDB
|accessdate=2008-02-22}}</ref> based on [[Nicholas Sparks (author)|Nicholas Sparks]]' 1996 [[The Notebook|novel of the same name]];<ref>{{cite book
|title=The notebook
|author=Sparks Nicholas
|year=1996
|publisher=Thorndike Press
|location=Thorndike, Maine
|page=268
|isbn=078620821X }}
</ref> ''[[A Moment to Remember]]'' (2004);''[[Thanmathra]]'' (2005);<ref>{{cite web
|url=http://www.webindia123.com/movie/regional/thanmatra/index.htm
|title=Thanmathra
|publisher=Webindia123.com
|accessdate=2008-01-24}}
</ref> ''[[Memories of Tomorrow (Ashita no Kioku)]]'' (2006),<ref>{{cite web
|url=http://www.imdb.com/title/tt0494640/
|title=Ashita no kioku
|originallanguage={{jp icon}}
|publisher=IMDB
|accessdate=2008-01-24}}</ref> based on Hiroshi Ogiwara's novel of the same name;<ref>{{cite book
|author=Ogiwara Hiroshi
|year=2004
|title=Ashita no Kioku
|location=Tōkyō
|publisher=Kōbunsha
|isbn=9784334924461
|oclc=57352130
|language={{jp icon}}
|isbn-status=May be invalid – please double check
}}</ref> ; ''[[Away from Her]]'' (2006), based on [[Alice Munro]]'s [[short story]] "[[Hateship, Friendship, Courtship, Loveship, Marriage|The Bear Came over the Mountain]]".<ref>{{cite book
|title=[[Hateship, Friendship, Courtship, Loveship, Marriage|Hateship, Friendship, Courtship, Loveship, Marriage: Stories]]
|author=Munro Alice
|location=New York
|publisher=A.A. Knopf
|year=2001
|isbn=9780375413001
|oclc=46929223
|chapter-url=The bear came over the mountain}}</ref> Documentaries on Alzheimer's disease include ''Malcolm and Barbara: A Love Story'' (1999) and ''Malcolm and Barbara: Love's Farewell'' (2007), both featuring [[Malcolm Pointon]].<ref>Malcolm and Barbara:
* {{cite web
|url=http://www.dfgdocs.com/Directory/Titles/700.aspx
|title=Malcolm and Barbara: A love story
|publisher=Dfgdocs
|accessdate=2008-01-24}}
* {{cite web
|url=http://www.bbc.co.uk/cambridgeshire/content/articles/2007/08/06/pointon_audio_feature.shtml
|title=Malcolm and Barbara: A love story
|publisher=BBC Cambridgeshire
|accessdate=2008-03-02}}
* {{cite news
|url=http://www.guardian.co.uk/media/2007/aug/07/broadcasting.itv
|title=Alzheimer's film-maker to face ITV lawyers
|publisher=Guardian Media
|date=2007-08-07
|accessdate=2008-01-24 | location=London | first=John | last=Plunkett}}</ref>

==Research directions==
{{Main|Alzheimer's disease clinical research}}

{{as of
| 2008}}, the safety and efficacy of more than 400 pharmaceutical treatments are being investigated in [[clinical trial]]s worldwide, and approximately a quarter of these compounds are in [[Phase&nbsp;III]] trials; the last step prior to review by regulatory agencies.<ref>{{cite web
|url=http://www.clinicaltrials.gov/ct2/results?term=alzheimer
|title= Clinical Trials. Found 459 studies with search of: alzheimer
|accessdate= 2008-03-23
|publisher= US National Institutes of Health
}}</ref>

One area of clinical research is focused on treating the underlying disease pathology. Reduction of [[amyloid beta]] levels is a common target of compounds<ref>
{{cite journal
|author=Lashuel HA, Hartley DM, Balakhaneh D, Aggarwal A, Teichberg S, [[David J E Callaway|Callaway DJE]]
|title=New class of inhibitors of [[Beta amyloid|amyloid-beta]] fibril formation. Implications for the mechanism of pathogenesis in Alzheimer's disease
|url=http://www.jbc.org/cgi/content/abstract/277/45/42881
|journal=[[Journal of Biological Chemistry|J Biol Chem]]
|year=2002
|volume=277
|pages=42881–42890
|pmid=12167652
|doi=10.1074/jbc.M206593200
|issue=45
}}</ref> (such as [[apomorphine]]) under investigation. [[Immunotherapy]] or [[vaccination]] for the amyloid protein is one treatment modality under study.<ref>
{{cite journal
|author=Dodel r, Neff F, Noelker C, Pul R, Du Y, Bacher M Oertel W.
|title=Intravenous Immunoglobulins as a Treatment for Alzheimer's Disease: Rationale and Current Evidence
|url=http://adisonline.com/drugs/Abstract/2010/70050/Intravenous_Immunoglobulins_as_a_Treatment_for.1.aspx
|journal=Drugs
|year=2010
|volume=70
|pages=513–528
|pmid=20329802
|doi=10.2165/11533070-000000000-00000
|issue=5
}}</ref> Unlike preventative vaccination, the putative therapy would be used to treat people already diagnosed. It is based upon the concept of training [[Immune system|the immune system]] to recognise, attack, and reverse deposition of amyloid, thereby altering the course of the disease.<ref>Vaccination:
* {{cite journal
|author=Hawkes CA, McLaurin J
|title=Immunotherapy as treatment for Alzheimer's disease
|journal=Expert Rev Neurother
|volume=7
|issue=11
|pages=1535–48
|year=2007
|month=November
|pmid=17997702
|doi=10.1586/14737175.7.11.1535
}}
*{{cite journal
|author=Solomon B
|title=Clinical immunologic approaches for the treatment of Alzheimer's disease
|journal=Expert Opin Investig Drugs
|volume=16
|issue=6
|pages=819–28
|year=2007
|month=June
|pmid=17501694
|doi=10.1517/13543784.16.6.819
}}
*{{cite journal
|author=Woodhouse A, Dickson TC, Vickers JC
|title=Vaccination strategies for Alzheimer's disease: A new hope?
|journal=Drugs Aging
|volume=24
|issue=2
|pages=107–19
|year=2007
|pmid=17313199
|doi=10.2165/00002512-200724020-00003
}}</ref> An example of such a vaccine under investigation was ACC-001,<ref>{{cite web |url=http://www.clinicaltrials.gov/ct/show/NCT00498602
|title = Study Evaluating ACC-001 in Mild to Moderate Alzheimers Disease Subjects
|work = Clinical Trial |publisher =US National Institutes of Health
|accessdate=2008-06-05
|date = 2008-03-11}}</ref><ref>{{cite web
|url=http://clinicaltrials.gov/ct2/show/NCT00479557 |title=Study Evaluating Safety, Tolerability, and Immunogenicity of ACC-001 in Subjects With Alzheimer's Disease
|publisher=US National Institutes of Health
|accessdate=2008-06-05
}}</ref> although the trials were suspended in 2008.<ref>{{cite web
|url=http://www.medpagetoday.com/MeetingCoverage/AAN/tb/9165
|title = Alzheimer's Disease Vaccine Trial Suspended on Safety Concern |publisher =Medpage Today
|accessdate=2008-06-14
|date = 2008-04-18}}</ref> Another similar agent is [[bapineuzumab]], an antibody designed as identical to the naturally induced anti-amyloid antibody.<ref>{{cite web
|url=http://clinicaltrials.gov/ct2/show/NCT00574132
|title= Bapineuzumab in Patients With Mild to Moderate Alzheimer's Disease/ Apo_e4 non-carriers
|work = Clinical Trial
|accessdate=2008-03-23
|publisher= US National Institutes of Health
|date= 2008-02-29
}}</ref> Other approaches are neuroprotective agents, such as AL-108,<ref>{{cite web
|url = http://clinicaltrials.gov/ct2/show/NCT00422981
|title = Safety, Tolerability and Efficacy Study to Evaluate Subjects With Mild Cognitive Impairment
|work = Clinical Trial
|accessdate=2008-03-23
|publisher= US National Institutes of Health
|date = 2008-03-11
}}</ref> and metal-protein interaction attenuation agents, such as PBT2.<ref>{{cite web
|url = http://clinicaltrials.gov/ct2/show/NCT00471211
|title = Study Evaluating the Safety, Tolerability and Efficacy of PBT2 in Patients With Early Alzheimer's Disease
|work = Clinical Trial
|accessdate=2008-03-23
|publisher= US National Institutes of Health
|date = 2008-01-13
}}</ref> A [[tumor necrosis factor-alpha|TNFα]] receptor [[fusion protein]], [[etanercept]] has showed encouraging results.<ref name="pmid16926764">Etanercept research:
* {{cite journal
|author=Tobinick E, Gross H, Weinberger A, Cohen H
|title=TNF-alpha modulation for treatment of Alzheimer's disease: a 6-month pilot study
|journal=MedGenMed
|volume=8
|issue=2
|page=25
|year=2006
|pmid=16926764
|pmc=1785182
}}
* {{cite journal
|author=Griffin WS
|title=Perispinal etanercept: potential as an Alzheimer therapeutic
|journal=J Neuroinflammation
|volume=5
|page=3
|year=2008
|pmid=18186919
|pmc=2241592
|doi=10.1186/1742-2094-5-3
}}
* {{cite journal
|author=Tobinick E
|title=Perispinal etanercept for treatment of Alzheimer's disease
|journal=Curr Alzheimer Res
|volume=4
|issue=5
|pages=550–2
|year=2007
|month=December
|pmid=18220520
|doi=10.2174/156720507783018217
}}
</ref>

In 2008, two separate clinical trials showed positive results in modifying the course of disease in mild to moderate AD with [[methylthioninium chloride]] (trade name ''[[rember]]''), a drug that inhibits tau aggregation,<ref>{{cite journal
|title=Tau aggregation inhibitor (TAI) therapy with remberTM arrests disease progression in mild and moderate Alzheimer's disease over 50 weeks
|author=Wischik Claude M, Bentham Peter, Wischik Damon J, Seng Kwang Meng
|journal=Alzheimer's & Dementia
|publisher=Alzheimer's Association
|year=2008
|month=July
|volume=4
|issue=4
|page=T167
|url=http://www.abstractsonline.com/viewer/viewAbstractPrintFriendly.asp?CKey={E7C717CF-8D73-41E0-8DB0-FA92205978CD}&SKey={68E04DB5-AB1C-4F7B-9511-DA3173F4F755}&MKey={CFC5F7C6-CB6A-40C4-BC87-B30C9E64B1CC}&AKey={50E1744A-0C52-45B2-BF85-2A798BF24E02}
|accessdate=2008-07-30
|doi=10.1016/j.jalz.2008.05.438
}}</ref><ref>
{{cite journal
|author=Harrington Charles, Rickard Janet E, Horsley David, ''et al.''
|title=Methylthioninium chloride (MTC) acts as a Tau aggregation inhibitor (TAI) in a cellular model and reverses Tau pathology in transgenic mouse models of Alzheimer's disease
|journal=Alzheimer's & Dementia
|publisher=Alzheimer's Association
|year=2008
|month=July
|pages=T120–T121
|doi=10.1016/j.jalz.2008.05.259
|volume=4
}}</ref> and [[dimebon]], an [[antihistamine]].<ref name="pmid18640457">{{cite journal
|author=Doody RS, Gavrilova SI, Sano M, ''et al.''
|title=Effect of dimebon on cognition, activities of daily living, behaviour, and global function in patients with mild-to-moderate Alzheimer's disease: a randomised, double-blind, placebo-controlled study
|journal=Lancet
|volume=372
|issue=9634
|pages=207–15
|year=2008
|month=July
|pmid=18640457
|doi=10.1016/S0140-6736(08)61074-0
}}</ref>
The consecutive Phase-III trial of Dimebon failed to show positive effects in the primary and secondary endpoints.<ref>[http://www.alzforum.org/new/detail.asp?id=2387 Dimebon Disappoints in Phase 3 Trial]</ref>

The possibility that AD could be treated with [[antiviral drug|antiviral]] medication is suggested by a study showing colocation of [[herpes simplex]] virus with amyloid plaques.<ref>{{cite journal |author=Wozniak M, Mee A, Itzhaki R |title=Herpes simplex virus type 1 DNA is located within Alzheimer's disease amyloid plaques |journal=J Pathol |volume=217 |issue=1 |pages=131–138 |year=2008 |pmid=18973185 |doi=10.1002/path.2449}}</ref>

Preliminary research on the effects of meditation on retrieving memory and cognitive functions have been encouraging. Limitations of this research can be addressed in future studies with more detailed analyses.<ref>{{cite journal |pages=517–26 |last1=Newberg |first1=AB |issue=2 |last2=Wintering |first2=N |last3=Khalsa |first3=DS |last4=Roggenkamp |first4=H |last5=Waldman |first5=MR |author8=Newberg AB, Wintering N, Khalsa DS, Roggenkamp H, Waldman MR |volume=20 |title=Meditation effects on cognitive function and cerebral blood flow in subjects with memory loss: a preliminary study |year=2010 |journal=[[Journal of Alzheimer's Disease]] |url=http://www.j-alz.com/issues/20/vol20-2.html |pmid=20164557 |doi=10.3233/JAD-2010-1391}} (primary source)</ref>

==See also==
*[[Art and dementia]]

==References==
{{Reflist|colwidth=30em}}

==Further reading==
{{Spoken Wikipedia|Alzheimer's Disease.ogg|2008-09-12}}
*{{cite book
| title=Alzheimer's Disease: Unraveling the Mystery
| url=http://www.nia.nih.gov/Alzheimers/Publications/UnravelingTheMystery
| publisher=US Department of Health and Human Services, National Institute on Aging, NIH
| year=2008
}}
*{{cite book
|url=http://www.nia.nih.gov/Alzheimers/Publications/ADPrevented/
|title=Can Alzheimer's Disease Be Prevented?
|publisher=US Department of Health and Human Services, National Institute on Aging, NIH
|year=2009
}}
*{{cite book
| title=Caring for a Person with Alzheimer's Disease: Your Easy-to-Use Guide from the National Institute on Aging
| url=http://www.nia.nih.gov/Alzheimers/Publications/CaringAD/
| publisher=US Department of Health and Human Services, National Institute on Aging, NIH
| year=2009
}}
*{{cite journal
|author=Cummings JL, Frank JC, Cherry D, Kohatsu ND, Kemp B, Hewett L, Mittman B
|title=Guidelines for managing Alzheimer's disease: Part&nbsp;I. Assessment
|journal=American Family Physician
|volume=65
|issue=11
|pages=2263–2272
|year=2002
|pmid=12074525
|url=http://www.aafp.org/afp/20020601/2263.html
}}
*{{cite journal
|author= Cummings JL, Frank JC, Cherry D, Kohatsu ND, Kemp B, Hewett L, Mittman B
|title=Guidelines for managing Alzheimer's disease: Part&nbsp;II. Treatment
|journal=American Family Physician
|volume=65
|issue=12
|pages=2525–2534
|year=2002
|pmid=12086242
|url=http://www.aafp.org/afp/20020615/2525.html
}}
*{{cite web
| title=Alzheimer's Behavior Management: Learn to manage common behavior problems
| url=http://www.helpguide.org/elder/alzheimers_behavior_problems.htm
| author=Russell D, Barston S, White M
| publisher=helpguide.org
| date=2007-12-19
| accessdate=2008-02-29
}}

==External links==
* [http://www.nia.nih.gov/Alzheimers/ResearchInformation/ResearchCenters/ Alzheimer's Disease Centers (ADCs)]
* [http://www.nia.nih.gov/alzheimers Alzheimer's Disease Education and Referral (ADEAR) Center]
* [http://www.alz.org/index.asp Alzheimer's Association]
* [http://memory.ucsf.edu/ UCSF Memory and Aging Center]

{{Commons category|Alzheimer's disease}}

{{-}}
{{Mental and behavioral disorders|selected = neurological}}
{{Diseases of the nervous system}}
{{Amyloidosis}}

{{featured article}}

{{DEFAULTSORT:Alzheimer's Disease}}
[[Category:Alzheimer's disease]]
[[Category:Aging-associated diseases]]
[[Category:Unsolved problems in neuroscience]]
[[Category:Ailments of unknown etiology]]
[[Category:Neurodegenerative disorders]]

{{Link GA|es}}
{{Link GA|ru}}

[[af:Alzheimer se siekte]]
[[ar:داء ألزيمر]]
[[an:Malautía d'Alzheimer]]
[[ast:Alzheimer]]
[[be:Хвароба Альцгеймера]]
[[bs:Alzheimerova bolest]]
[[bg:Болест на Алцхаймер]]
[[ca:Malaltia d'Alzheimer]]
[[cs:Alzheimerova choroba]]
[[cy:Clefyd Alzheimer]]
[[da:Alzheimers sygdom]]
[[de:Alzheimer-Krankheit]]
[[et:Alzheimeri tõbi]]
[[el:Αλτσχάιμερ]]
[[es:Enfermedad de Alzheimer]]
[[eo:Alzheimer-malsano]]
[[eu:Alzheimer]]
[[fa:آلزایمر]]
[[fr:Maladie d'Alzheimer]]
[[ga:Galar Alzheimer]]
[[gl:Alzhéimer]]
[[gan:老人痴呆症]]
[[ko:알츠하이머병]]
[[hy:Ալցհայմերի հիվանդություն]]
[[hi:अलजाइमर रोग]]
[[hr:Alzheimerova bolest]]
[[id:Alzheimer]]
[[is:Alzheimer]]
[[it:Morbo di Alzheimer]]
[[he:אלצהיימר]]
[[la:Morbus Alzheimerianus]]
[[lv:Alcheimera slimība]]
[[lb:Alzheimer]]
[[lt:Alzheimerio liga]]
[[hu:Alzheimer-kór]]
[[mk:Алцхајмерова болест]]
[[ml:ആൽറ്റ്സ്‌ഹൈമേഴ്സ് രോഗം]]
[[ms:Alzheimer]]
[[nl:Ziekte van Alzheimer]]
[[ja:アルツハイマー型認知症]]
[[no:Alzheimers sykdom]]
[[pl:Choroba Alzheimera]]
[[pt:Mal de Alzheimer]]
[[ro:Boala Alzheimer]]
[[ru:Болезнь Альцгеймера]]
[[sq:Sëmundja e Alzheimerit]]
[[si:ඇල්zසයිම' රෝගය]]
[[simple:Alzheimer's disease]]
[[sk:Alzheimerova choroba]]
[[sl:Alzheimerjeva bolezen]]
[[sr:Алцхајмерова болест]]
[[sh:Alzheimerova bolest]]
[[su:Panyakit Alzheimer]]
[[fi:Alzheimerin tauti]]
[[sv:Alzheimers sjukdom]]
[[ta:ஆல்சைமர் நோய்]]
[[th:โรคอัลไซเมอร์]]
[[tr:Alzheimer hastalığı]]
[[uk:Хвороба Альцгеймера]]
[[vi:Bệnh Alzheimer]]
[[war:Sakit nga Alzheimer]]
[[yi:אלצהיימערס קרענק]]
[[bat-smg:Alzhaimerė lėga]]
[[zh:阿兹海默病]]

Revision as of 11:00, 18 August 2010

Neil is a spaz

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