Alzheimer's disease

Alzheimer's disease
Specialty	Neurology
Frequency	5.05% (Europe)

Alzheimer's disease (AD), also called Alzheimer disease or simply Alzheimer's, is the most common cause of dementia, afflicting 24 million people worldwide. Alzheimer's is a degenerative and terminal disease for which there is currently no known cure. In its most common form, it occurs in people over 65 years old although a less-prevalent early-onset form also exists. The disease can begin many years before it is eventually diagnosed. In its early stages, short-term memory loss is the most common symptom, often initially thought to be caused by aging or stress by the sufferer. Later symptoms include confusion, anger, mood swings, language breakdown, long-term memory loss, and the general withdrawal of the sufferer as his or her senses decline. Gradually the sufferer loses minor, and then major bodily functions, until death occurs. Although the symptoms are common, each individual experiences the symptoms in unique ways. The duration of the disease is estimated as being between 5 and 20 years.

The symptoms of Alzheimer's disease are generally reported to a physician when memory-loss causes concern, and on suspecting Alzheimer’s disease, the physician or healthcare specialists will confirm the diagnosis with a behavioral assessment and cognitive tests, often followed by a brain scan.

The cause and progression of Alzheimer's disease is not well understood, but is associated with plaques and tangles in the brain. Possible causes and potential cures of the disease have been conjectured, with varying evidence supporting each claim. No treatment has been found to stop or reverse the disease, and it is not known whether current treatments slow the progression, or simply manage the symptoms. Many preventative measures have been suggested for Alzheimer's disease, but their value is often uncertain: mental stimulation, exercise and a balanced diet are usually recommended, both as a possible prevention and as a sensible way of managing the disease.

Due to the incurable and degenerative nature of the disease care-management of Alzheimer's is essential. The role of the main caregiver is often taken by the spouse or a close relative. Caregivers may themselves suffer from stress, over-work, depression, and being physically hit or struck.

Characteristics

The disease course is typically divided into four stages, with a different pattern of cognitive and functional impairment occurring at each stage.

Predementia

Detailed neuropsychological testing can reveal mild cognitive difficulties up to eight years before a person fullfils clinical criteria of diagnosis. It is not yet clear if these early symptoms affect daily living activities. Recent studies show impairments in the most complex activities. The most noticeable deficit is short-term memory loss and the resultant inability to acquire new information. In addition, subtle executive problems or semantic memory impairments can also occur. Apathy can be observed at this stage, and is the most common and persistent neuropsychiatric symptom throughout the course of the disease. This stage of the disease has also been termed mild cognitive impairment, but there is still a debate on whether this term corresponds to a different diagnostic entity by itself or just a first step of the disease.

Early dementia

File:Portion of Reagan's Alzheimer's letter.png

In 1994 United States ex-president R. Reagan informed via a hand-written letter of his diagnosis of AD. In this letter, partly shown in picture, clear signs of the disease can be recognised.

In most people with the disease the increasing impairments in learning and memory will lead to diagnosis, while in a small proportion of them language, executive or visuoconstructional difficulties will be more salient. Nevertheless memory problems do not affect all memory subcapacities equally. Older memories of the patient's life (episodic memory) and facts he learned (declarative memory); or implicit memory (the memory of the body on how to do things, such as using a knife to eat) are affected to a much lesser degree than the capacities needed to learn new facts or make new memories. On the other hand, language problems are mainly characterized by a shrinking vocabulary and a decreased word fluency which leads to a general impoverishment of oral and written language but the person with the disease is usually capable of communicating ideas adequately. While performing fine motor tasks such as writing, drawing or dressing, certain visoconstructional difficulties, or apraxia, may be present, which may appear as clumsiness. As the disease progresses to the middle stage, patients might still be able to live and perform tasks independently for most of the time, but may need assistance or supervision with the most complicated activities.

Moderate dementia

In the early stage, people with Alzheimer's can usually care for themselves. At the moderate stage, progressive deterioration seriously hinders the possibility of independence. Language difficulties become clearly noticeable: the person makes frequent paraphasias due to difficulties in finding words, and content is poor. Reading and writing are also progressively forgotten. As time passes, complex motor sequences become less coordinated, costing the patient most of their daily-living abilities. Memory problems worsen, and the person may not recognize close relatives. Long-term memory, which was previously left intact, is now also impaired. Patients are usually almost completely unaware of their own deficits, and behavior changes are the norm. Common neuropsychiatric manifestations in this stage are irritability and labile affect, leading to crying or outbursts of unpremeditated aggression and physical violence, even in patients whose life-long behavior has been peaceful. Approximately 30% of the patients also develop illusionary misidentifications and other delusional symptoms. Often urinary incontinence develops. Because of the communication deficit along with delusions, patients often resist when caregivers attempt to provide care. It is important to prevent escalation of resistiveness to care into combativeness when patient might strike out. All these symptoms create stress for relatives and caretakers, increasing the likelihood of moving the patient from home care to other long-term care facilities.

Advanced

Pressure ulcers are a common complication in advanced AD.

In the last stage of Alzheimer's disease all human behavior is likely to become entirely automatic. Language is reduced to simple phrases or even single words before being lost altogether. Nevertheless many patients can receive and return emotional signals long after the loss of verbal language. Although aggressiveness can still present, extreme apathy and exhaustion are much more common. Patients will ultimately not be able to perform even the most simple tasks independently. Finally, deterioration of muscle and mobility will develop, leading the patient to become bedridden and to lose the ability to feed oneself if death from some external cause, such as infection due to pressure ulcers or pneumonia, does not occur first.

Causes

Most cases of Alzheimer's disease do not exhibit familial inheritance. At least 80% of sporadic AD cases involve genetic risk factors. Inheritance of the ε4 allele of the apolipoprotein E (ApoE) gene is regarded as a risk factor for development of up to 50% of late-onset sporadic Alzheimer's. The presence of this gene allele along with infection by Herpes simplex virus type 1 (HSV-1) further increases the risk of Alzheimer's disease. Several viral-host interactions are postulated, most relating to HSV-1’s targeting of Alzheimer’s susceptibility genes. Genetic experts agree that there are other risk and protective factor genes that influence the development of late onset Alzheimer's disease. Over 400 genes have been tested for association with late-onset sporadic AD.

Five to ten percent of AD cases involve a clear familial pattern of inheritance in which the patient has at least two first-degree relatives with a history of AD. These cases often have an early age of onset (usually younger than sixty years). Nearly 200 different mutations in the presenilin-1 or presenilin-2 genes have been documented in over 500 families. Mutations of presenilin 1 (PS1) lead to the most aggressive form of familial Alzheimer's disease. Over twenty different mutations in the amyloid precursor protein (APP) gene on chromosome 21 can also cause early onset of the disease. The presenilins have been identified as essential components of the proteolytic processing machinery that produces beta amyloid peptides through cleavage of APP. Most mutations in the APP and presenilin genes increase the production of a small protein (peptide) called Abeta42, the main component of senile plaques in brains of AD patients.

Pathophysiology

Main article: Biochemistry of Alzheimer's disease

Neuropathology

File:Alzheimer's disease - MRI.jpg

MRI images of a normal aged brain (right) and an Alzheimer's patient's brain (left). In the Alzheimer brain, atrophy is clearly seen.

At a macroscopic level, AD is characterized by loss of neurons and synapses in the cerebral cortex and certain subcortical regions. This 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.

Both amyloid plaques and neurofibrillary tangles are clearly visible by microscopy in AD brains. Plaques are dense, mostly insoluble deposits of amyloid-beta protein and cellular material outside and around neurons. Tangles are insoluble twisted fibers that build up inside the nerve cell. Though many older people develop some plaques and tangles, the brains of AD patients have them to a much greater extent and in different brain locations.

Biochemical characteristics

Alzheimer's disease has been identified as a protein misfolding disease, or proteopathy, due to the accumulation of abnormally folded A-beta and tau proteins in the brains of AD patients. Plaques are made of a peptide called beta-amyloid (also A-beta or Aβ), a protein fragment snipped from a larger protein called amyloid precursor protein (APP). APP is a transmembrane protein; which means that it sticks through the neuron's membrane; and is believed to help neurons grow, survive and repair themselves after injury. In AD, something causes APP to be divided by enzymes through a mechanism called proteolysis. One of these fragments is beta-amyloid. Beta-amyloid fragments (amyloid fibrils) outside the cell come together into clumps that deposit outside neurons in dense formations known as senile plaques.

AD is also considered a tauopathy due to abnormal aggregation of the tau protein. Healthy neurons have an internal support structure, or cytoskeleton, partly made up of structures called microtubules. These microtubules act like tracks, guiding nutrients and molecules from the body of the cell down to the ends of the axon and back. A special kind of protein, tau, makes the microtubules stable through a process named phosphorylation and is therefore called a microtubule-associated protein. In AD, tau is changed chemically, becoming hyperphosphorylated. Hyperphosphorylated tau begins to pair with other threads of tau and they become tangled up together inside nerve cell bodies in masses known as neurofibrillary tangles. When this happens, the microtubules disintegrate, collapsing the neuron's transport system. This may result first in malfunctions in communication between neurons and later in the death of the cells.

Disease mechanism

Three major competing hypotheses exist to explain the cause of the disease. The oldest, on which most currently available drug therapies are based, is known as the cholinergic hypothesis and suggests that AD is due to reduced biosynthesis of the neurotransmitter acetylcholine. However, the medications that treat acetylcholine deficiency only affect symptoms of the disease and neither halt nor reverse it. The cholinergic hypothesis has not maintained widespread support in the face of this evidence, although cholinergic effects have been proposed to initiate large-scale aggregation, leading to generalized neuroinflammation.

In 1991 the amyloid hypothesis was proposed, while research after 2000 is also centered on tau proteins. The two positions differ with one stating that the tau protein abnormalities initiate the disease cascade, while the other states that amyloid beta (Aβ) deposits are the causative factor in the disease. The tau hypothesis is supported by the long-standing observation that deposition of amyloid plaques does not correlate well with neuron loss, but a majority of researchers support the alternative hypothesis that Aβ is the primary causative agent. The amyloid hypothesis is compelling because the gene for the amyloid beta precursor (APP) is located on chromosome 21, and patients with trisomy 21 (Down Syndrome) who thus have an extra gene copy almost universally exhibit AD-like disorders by 40 years of age. The traditional formulation of the amyloid hypothesis points to the cytotoxicity of mature aggregated amyloid fibrils, which are believed to be the toxic form of the protein responsible for disrupting the cell's calcium ion homeostasis and thus inducing apoptosis. It should be noted further that ApoE4, the major genetic risk factor for AD, leads to excess amyloid build-up in the brain before AD symptoms arise. Thus, Aβ deposition precedes clinical AD. Another strong support for the amyloid hypothesis, which looks at Aβ as the common initiating factor for Alzheimer's disease, is that transgenic mice solely expressing a mutant human APP gene develop fibrillar amyloid plaques.

Diagnosis

Dementia is by definition a clinical condition but not an exact diagnosis. Alzheimer's disease is usually diagnosed clinically from the patient history, collateral history from relatives, and clinical observations, based on the presence of characteristic neurological and neuropsychological features and the absence of alternative conditions. Advanced medical imaging with CT or MRI are generally used to help to diagnose the subtype of dementia and exclude other cerebral pathology. Neuropsychological evaluation including memory testing and assessment of intellectual functioning can further characterize the dementia. Medical organizations have created diagnostic criteria to ease and standardize the process for practicing physicians. Sometimes the diagnoses can be confirmed or made at postmortem when brain material is available and can be examined histologically and histochemically.

Diagnostic criteria

The diagnostic criteria for Alzheimer of the NINCDS-ADRDA (NINCDS and the ADRDA) are among the most used. These criteria require that the presence of cognitive impairment and a suspected dementia syndrome be confirmed by neuropsychological testing for a clinical diagnosis of possible or probable AD while they need histopathologic confirmation (microscopic examination of brain tissue) for the definitive diagnosis. They have shown good reliability and validity. They specify as well eight cognitive domains that may be impaired in AD (i.e., memory, language, perceptual skills, attention, constructive abilities, orientation, problem solving and functional abilities). Similar to the NINCDS-ADRDA Alzheimer's Criteria are the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) criteria published by the American Psychiatric Association.

Diagnostic tools

File:InterlockingPentagons.png

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 or sum.

Neuropsychological screening tests as the Mini mental state examination (MMSE) are widely used to evaluate the cognitive impairments needed for diagnosis, but more comprehensive batteries are necessary for high reliability by this method; especially in the earliest stages of the disease. On the other hand neurological examination in early AD will usually be normal, independently of cognitive impairment; but for many of the other dementing disorders is key for diagnosis. Therefore, neurological examination is crucial in the differential diagnosis of Alzheimer and other diseases. In addition, interviews with family members are also utilized 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 patient's mental function. This is especially important since a patient with AD is commonly unaware of his or her own deficits (anosognosia). Many times families also have difficulties in the detection of initial dementia symptoms and in adequately communicating them to a physician. Finally supplemental testing provide extra information on some features of the disease or are utilized to rule out other diagnoses. Examples are blood tests, which can identify other causes for dementia different than AD; which rarely may even be reversible; or psychological tests for depression, as depression can both co-occur with AD or on the contrary be at the origin of the patient's cognitive impairment.

Increasingly, the functional neuroimaging modalities of single photon emission computed tomography (SPECT) and positron emission tomography (PET) are being used to diagnose Alzheimer's, as they have shown similar ability to diagnose Alzheimer's disease as methods involving mental status examination. Furthermore, the ability of SPECT to differentiate Alzheimer's disease from other possible causes, in a given patient already known to be suffering from dementia, appears to be superior to attempts to differentiate the cause of dementia cause by mental testing and history. Another recent objective marker of the disease is the analysis of cerebrospinal fluid for amyloid beta or tau proteins. Both advances (neuroimaging and cerebrospinal fluid analysis) have led to the proposal of new diagnostic criteria.

Prevention

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.

Different epidemiological studies have shown relationships between certain modifiable factors, such as diet, cardiovascular risk, pharmaceutical products, or intellectual activities among others, and a population's likelihood of developing Alzheimer. Only further research, including clinical trials, will reveal whether, in fact, these factors can help to prevent AD. At present contradictory results in global studies, incapacity to prove causal relationships between risk factors and the disease, and possible secondary effects indicate a lack of specific measures to prevent or delay the onset of AD.

The components of a Mediterranean diet, which include fruit and vegetables, bread, wheat and other cereals, olive oil, fish, and red wine, may all individually or together reduce the risk and course of Alzheimer's disease. Vitamins E, B, and C, or folic acid have appeared to be related to a reduced risk of Alzheimer, but other studies indicate that they do not have any significant effect on the onset or course of the disease, while at the same time may have important secondary effects in conjunction with other therapies. Curcumin in curry has shown some effectiveness in preventing brain damage in mouse models.

Although cardiovascular risk factors, such as hypercholesterolemia, hypertension, diabetes, and smoking, are associated with a higher risk of onset and course of AD, statins, which are cholesterol lowering drugs, have not been effective in preventing or improving the course of the disease. However long-term usage of non-steroidal anti-inflammatory drug (NSAIDs), is associated with a reduced likelihood of developing AD. Other pharmaceutical therapies such as female hormone replacement therapy are no longer thought to prevent dementia, while a 2007 systematic review concluded that there was inconsistent and unconvincing evidence that ginkgo has any positive effect on dementia or cognitive impairment.

Intellectual activities such as playing chess, completing crossword puzzles or regular social interaction, may also delay the onset or reduce the severity of Alzheimer's disease. Bilingualism is also related to a later onset of Alzheimer.

Treatment

There is currently no cure for Alzheimer's disease. Currently available medications offer relatively small symptomatic benefit for some patients and some may even slow disease progression but in essence remain palliative care.

Pharmaceutical

3d molecular spacefill of donepezil, an acetylcholinesterase inhibitor used in the treatment of AD.

AS of 2008 only four medications are approved for AD by regulatory agencies as the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMEA) and the Japanese PMDA. Three are acetylcholinesterase inhibitors and the other is memantine, an NMDA receptor antagonist.

A reduction in the activity of the cholinergic neurons in the disease is well known. Acetylcholinesterase inhibitors reduce the rate at which acetylcholine (ACh) is broken down and hence increase the concentration of ACh in the brain, combatting the loss of ACh caused by the death of the cholinergin neurons. Cholinesterase inhibitors currently approved include donepezil (Brand name Aricept), galantamine (Razadyne), and rivastigmine (Marketed as Exelon and Exelon Patch). There is substantial evidence for the efficacy of these medications in mild to moderate Alzheimer’s disease, and some evidence for their use in the advanced stage, being only donepezil approved for this stage. Their use in mild cognitive impairment has not been associated with any delay in the onset of AD. Donepezil and galantamine are taken orally while rivastigmine has oral forms and a once-daily transdermal patch.

Involvement of glutamatergic neuronal excitotoxicity in Alzheimer's disease led to the development and introduction of memantine (Brand names Akatinol, Axura, Ebixa/Abixa, Memox and Namenda). Memantine is a novel NMDA receptor antagonist, and has been shown to be moderately clinically efficacious.

Psychosocial intervention

A specifically designed room for sensory integration therapy, or 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 behavior, emotion, cognition or stimulation oriented approaches. Research on efficacy is unavailable and rarely specific to the disease, focusing instead on dementia.

Behavioral interventions attempt to identify and reduce the antecedents and consequences of problem behaviors. This approach has not shown success in the overall functioning of patients, but can help to reduce some specific problem behaviors, such as incontinence. There is still a lack of high quality data on the effectiveness of these techniques in other behavior problems such as wandering.

Emotion-oriented interventions include reminiscence therapy, validation therapy, supportive psychotherapy, sensory integration or 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. 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. Simulated presence therapy (SPT) is based on attachment theories and is normally carried out playing a recording with voices of the closests relatives of the patient. There is preliminary evidence indicating that SPT may reduce anxiety and challenging behaviors. 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 senses. There is little evidence to support the usefulness of these therapies.

The aim of cognition-oriented treatments, which include reality orientation and cognitive retraining is the restoration of cognitive deficits. 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 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, although in some works these effects were transient and negative effects, such as frustation, have also been reported.

Stimulation-oriented treatments include art, music and pet therapies, exercise, and any other kind of recreational activities for patients. Stimulation has modest support for improving behavior, 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 improvement in the patient daily life routine they suppose.

Treatments in clinical development

Several potential treatments for Alzheimer's disease are currently under investigation, including two compounds being studied in phase 3 clinical trials. Tarenflurbil (MPC-7869, formerly R-flubiprofen) is a gamma secretase modulator sometimes called a selective amyloid beta 42 lowering agent. It is believed to reduce the production of the toxic amyloid beta in favor of shorter forms of the peptide.

Vaccines or immunotherapy for Alzheimer's, unlike typical vaccines, would be used to treat diagnosed patients rather than for disease prevention. Ongoing efforts are based on the idea that, by training the immune system to recognize and attack beta-amyloid, the immune system might reverse deposition of amyloid and thus stop the disease. Initial results using this approach in animals were promising, and clinical trials of the drug candidate AN-1792 showed results in 20% of patients. In 2002 it was reported that 6% of multi-dosed participants (18 of 300) developed symptoms resembling meningoencephalitis, and the trials were stopped. Participants in the halted trials continued to be followed, and 20% "developed high levels of antibodies to beta-amyloid" and some showed slower progression of the disease, maintaining memory-test levels while placebo-patients worsened. Micro-cererebral hemorrhages during passive immunisation and meningoencephalitis with active immunisation still remain potent threats to this strategy.

Simvastatin, a statin, stimulates brain vascular endothelial cells to create a beta-amyloid ejector. The use of this statin may be have a causal relationship to decreased development of the disease.

Several other pharmaceuticals are under investigation to treat Alzheimer's disease. A 2006 pilot study showed small but significant improvements in various cognitive rating scales in patients with Alzheimer's disease after treatment with etanercept, Tumor necrosis factor-alpha receptor fusion protein, which binds to tumor necrosis factor-alpha, and decreases its role in inflammation of nervous tissue. A further study, administering to a single AD patient via perispinal infusion, showed rapid and significant improvement in Alzheimer's symptoms. Laboratory studies with cells and animals continually fuel the pipeline of potential treatments. Some currently approved drugs such as statins and thiazolidinediones have also been under investigation for the treatment and prevention of Alzheimer’s.

Caregiving

Further information: [[:Caregiving and dementia]]

Since there is no cure for Alzheimer's, caregiving is an essential part of the treatment. Due to the eventual inability for the sufferer to self-care, Alzheimer's has to be carefully care-managed. Home care in the familiar surroundings of home may delay onset of some symptoms and delay or eliminate the need for more professional and costly levels of care. Many family members choose to look after their relative, but two-thirds of nursing home residents have dementias.

Modifications to the living environment and lifestyle of the Alzheimer's patient can improve functional performance and ease caretaker burden. Assessment by an occupational therapist is often indicated. Adherence to simplified routines and labeling of household items to cue the patient can aid with activities of daily living, while placing safety locks on cabinets, doors, and gates and securing hazardous chemicals can prevent accidents and wandering. Changes in routine or environment can trigger or exacerbate agitation, whereas well-lit rooms, adequate rest, and avoidance of excess stimulation all help prevent such episodes. Appropriate social and visual stimulation can improve function by increasing awareness and orientation. For instance, boldly colored tableware aids those with severe AD, helping people overcome a diminished sensitivity to visual contrast to increase food and beverage intake.

Prognosis

As the disease progresses the patient will advance from mild cognitive impairment, when the disease has not yet been diagnosed, to mild and advanced stages of dementia, finally reaching a severe stage of dementia. It is important to note there is also an important individual variability in the presentation and development of the symptoms; being sometimes difficult to classify the person in one of the described stages. Once Alzheimer's has been diagnosed, the average life expectancy of patients living with the disease is approximately 7 years, while less than 3% of the patients live more than 14 years.

Social costs

Because the median age of the industrialized world's population is increasing gradually, Alzheimer's is a major public health challenge. Much of the concern about the solvency of governmental social safety nets is founded on estimates of the costs of caring for baby boomers, assuming that they develop Alzheimer's in the same proportions as earlier generations. For this reason, money spent informing the public of available effective prevention methods may yield disproportionate benefits.

Caregiving burden

Further information: [[:Caregiving and dementia]]

The role of family caregivers has become more prominent in both reducing the social cost of care and improving the quality of life of the patient. Home-based care also can have economic, emotional, and psychological costs to the patient's family. Although family members in particular often express the desire to care for the sufferer to the end, Alzheimer's disease is known for effecting a high burden on caregivers.

Alzheimer's disease can incur a variety of stresses on the caregivers: typical complaints are stress, depression, and an inability to cope. Reasons for these complaints can include: high-demands on the caregiver's concentration, as Alzheimer's sufferers have a decreasing regard for their own safety (and can wander when unattended, for example); the lack of gratitude received when the sufferer is unaware of the help being given; and the lack of satisfaction when the sufferer's condition does not abate. Alzheimer's sufferers can be verbally and physically aggressive, and can stubbornly refuse to be helped. Aggression in particular can lead to a temptation to retaliate, which can put both the sufferer and carer at risk. It is additionally stressful for caregivers who are friends and family to witness a sufferer lose his or her identity, and eventually be unable to recognise them.

Family caregivers often give up time from work and forego pay to spend 47 hours per week on average with the person with AD. From a 2006 survey of US patients with long term care insurance, direct and indirect costs of caring for an Alzheimer's patient average $77,500 per year.

Epidemiology

Alzheimer's disease is the most frequent type of dementia in the elderly and affects almost half of all patients with dementia. Correspondingly, advancing age is the primary risk factor for the disease. Among people aged 65, 2–3% show signs of the disease, while 25–50% of people aged 85 have symptoms of Alzheimer's and an even greater number have some of the pathological hallmarks of the disease without the characteristic symptoms. Every five years after the age of 65, the probability of having the disease doubles. The share of Alzheimer's patients over the age of 85 is the fastest growing segment of the Alzheimer's disease population in the US, although current estimates suggest the 75–84 population has about the same number of patients as the over 85 population.

The World Health Organization estimates that globally the total disability adjusted life years (DALY) for AD and other dementias exceeded eleven million in 2005, with a projected 3.4% annual increase.

A study in Denmark found that women aged 65 are at significantly higher risk (22 percent) of developing AD by age 95 than their male counterparts (9 percent), while vascular dementias were nearly equal.

Some studies have shown a relationship between Alzheimer's Disease and magnetic field exposure, although the mechanism is unknown. Other research does not confirm this link. The role of metals in the disease is also controversial.

History

Auguste D, first described patient with AD.

Although the concept of dementia goes as far back as the ancient Greek and Roman philosophers and physicians, it was in 1901 when Alöis Alzheimer, a German psychiatrist, identified the first case of what became known as Alzheimer's disease. The patient was a 50-year-old woman called Auguste D. Alöis Alzheimer followed her until she died in 1906, when he first reported the case publicly. In the following five years, 11 similar cases were reported in the medical literature, some of them already using the term Alzheimer's disease. The official consideration of the disease as a distinctive entity is attributed to Emil Kraepelin, who included Alzheimer’s disease or presenile dementia as a subtype of senile dementia in the eighth edition of his Textbook of Psychiatry, published in 1910.

For most of the twentieth 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 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 of different etiologies. This eventually led to the use of Alzheimer's disease independently of onset age of the disease. 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.

Cultural references

Further information: [[:Alzheimer's in the media]]

As a result of the prevalence of the disease, many notable people have contracted it. Well-known examples are former United States President Ronald Reagan and Irish writer Iris Murdoch, both of whom have scientific articles on how their cognitive capacities deteriorated with the disease. Other cases include the retired footballer Ferenc Puskas, the former British Prime Minister Harold Wilson, the actress Rita Hayworth, the actor Charlton Heston, etc. The media attention to the cases of these prominent individuals has helped to make society even more aware of the problem of the disease.

Alzheimers has also been portrayed in films such as Iris (2001), (based on John Baley's memoir of his wife Iris Murdoch) The Notebook (2004), Thanmathra (2005), Memories of tomorrow (Ashita no Kioku) (2006), and Away From Her (2006), (based on Alice Munro's short story The Bear Came Over the Mountain), in documentaries, such as Malcolm and Barbara: A Love Story (1999) and Malcolm and Barbara: Love’s Farewell (2007) both featuring Malcolm Pointon, and in television series.

Further reading

• Cummings JL, Frank JC, Cherry D, Kohatsu ND, Kemp B, Hewett L, Mittman B (2002). "Guidelines for managing Alzheimer's disease: Part I. Assessment". American Family Physician. 65 (11): 2263–2272. PMID 12074525.{{cite journal}}: CS1 maint: multiple names: authors list (link)
• Cummings JL, Frank JC, Cherry D, Kohatsu ND, Kemp B, Hewett L, Mittman B (2002). "Guidelines for managing Alzheimer's disease: Part II. Treatment". American Family Physician. 65 (12): 2525–2534. PMID 12086242.{{cite journal}}: CS1 maint: multiple names: authors list (link)
• "Genes, lifestyles, and crossword puzzles: Can Alzheimer's disease be prevented" (PDF). US Department of Health and Human Services, National Institute of Aging. Retrieved 2008-02-29.
• Russell D, Barston S, White M (2007-12-19). "Alzheimer's Behavior Management: Learn to manage common behavior problems". helpguide.org. Retrieved 2008-02-29.{{cite web}}: CS1 maint: multiple names: authors list (link)
• Warner Mark J (2006). In Search of the Alzheimer's Wanderer: A Workbook to Protect Your Loved One. West Lafayette, Indiana: Purdue University Press. p. 145. ISBN 9781557533999. OCLC 63807670.