This article needs to be updated.(March 2021)
|Drawing comparing a normal aged brain (left) and the brain of a person with Alzheimer's (right). Characteristics that separate the two are pointed out.|
|Symptoms||Difficulty in remembering recent events, problems with language, disorientation, mood swings|
|Complications||Dehydration and Pneumonia in the terminal stage|
|Usual onset||Over 65 years old|
|Risk factors||Genetics, head injuries, depression, hypertension|
|Diagnostic method||Based on symptoms and cognitive testing after ruling out other possible causes|
|Differential diagnosis||Normal aging, Lewy body dementia, Trisomy 21|
|Medication||Acetylcholinesterase inhibitors, NMDA receptor antagonists (small benefit),|
|Prognosis||Life expectancy 3–9 years|
|Frequency||29.8 million (2015)|
|Deaths||For all dementias 1.9 million (2015)|
Alzheimer's disease (AD) is a neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems with language, disorientation (including easily getting lost), mood swings, loss of motivation, self-neglect, and behavioral issues. As a person's condition declines, they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the typical life expectancy following diagnosis is three to nine years.
The cause of Alzheimer's disease is poorly understood. There are many environmental and genetic risk factors associated with its development. The strongest genetic risk factor is from an allele of APOE. Other risk factors include a history of head injury, clinical depression, and high blood pressure. The disease process is largely associated with amyloid plaques, neurofibrillary tangles, and loss of neuronal connections in the brain. A probable diagnosis is based on the history of the illness and cognitive testing with medical imaging and blood tests to rule out other possible causes. Initial symptoms are often mistaken for normal aging. Examination of brain tissue is needed for a definite diagnosis, but this can only take place after death. Good nutrition, physical activity, and engaging socially are known to be of benefit generally in aging, and these may help in reducing the risk of cognitive decline and Alzheimer's; in 2019 clinical trials were underway to look at these possibilities. There are no medications or supplements that have been shown to decrease risk.
No treatments stop or reverse its progression, though some may temporarily improve symptoms. Affected people increasingly rely on others for assistance, often placing a burden on the caregiver. The pressures can include social, psychological, physical, and economic elements. Exercise programs may be beneficial with respect to activities of daily living and can potentially improve outcomes. Behavioral problems or psychosis due to dementia are often treated with antipsychotics, but this is not usually recommended, as there is little benefit and an increased risk of early death.
As of 2020, there were approximately 50 million people worldwide with Alzheimer's disease. It most often begins in people over 65 years of age, although up to 10% of cases are early-onset affecting those in their 30's to mid 60's. Women get sick more often than men. It affects about 6% of people 65 years and older. In 2015, all forms of dementia resulted in about 1.9 million deaths. The disease is named after German psychiatrist and pathologist Alois Alzheimer, who first described it in 1906. Alzheimer's financial burden on society is large, with a estimated global annual cost of US$1 trillion.
Signs and symptoms
The course of Alzheimer's is generally described in three stages, with a progressive pattern of cognitive and functional impairment. The three stages are described as early or mild, middle or moderate, and late or severe. The disease is known to target the hippocampus which is associated with memory, and this is responsible for the first symptoms of memory impairment. As the disease progresses so does the degree of memory impairment.
The first symptoms are often mistakenly attributed to aging or stress. Detailed neuropsychological testing can reveal mild cognitive difficulties up to eight years before a person fulfills the clinical criteria for diagnosis of Alzheimer's disease. These early symptoms can affect the most complex activities of daily living. The most noticeable deficit is short term memory loss, which shows up as difficulty in remembering recently learned facts and inability to acquire new information.
Subtle problems with the executive functions of attentiveness, planning, flexibility, and abstract thinking, or impairments in semantic memory (memory of meanings, and concept relationships) can also be symptomatic of the early stages of Alzheimer's disease. Apathy and depression can be seen at this stage, with apathy remaining as the most persistent symptom throughout the course of the disease. The preclinical stage of the disease has also been termed mild cognitive impairment (MCI). This is often found to be a transitional stage between normal aging and dementia. MCI can present with a variety of symptoms, and when memory loss is the predominant symptom, it is termed amnestic MCI and is frequently seen as a prodromal stage of Alzheimer's disease. Amnestic MCI has a greater than 90% likelihood of being associated with Alzheimer's.
In people with Alzheimer's disease, the increasing impairment of learning and memory eventually leads to a definitive diagnosis. In a small percentage, difficulties with language, executive functions, perception (agnosia), or execution of movements (apraxia) are more prominent than memory problems. Alzheimer's disease does not affect all memory capacities equally. 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 or how to drink from a glass) are affected to a lesser degree than new facts or memories.
Language problems are mainly characterised by a shrinking vocabulary and decreased word fluency, leading to a general impoverishment of oral and written language. In this stage, the person with Alzheimer's is usually capable of communicating basic ideas adequately. While performing fine motor tasks such as writing, drawing, or dressing, certain movement coordination and planning difficulties (apraxia) may be present, but they are commonly unnoticed. As the disease progresses, people with Alzheimer's disease can often continue to perform many tasks independently, but may need assistance or supervision with the most cognitively demanding activities.
Progressive deterioration eventually hinders independence, with subjects being unable to perform most common activities of daily living. Speech difficulties become evident due to an inability to recall vocabulary, which leads to frequent incorrect word substitutions (paraphasias). Reading and writing skills are also progressively lost. Complex motor sequences become less coordinated as time passes and Alzheimer's disease progresses, so the risk of falling increases. During this phase, memory problems worsen, and the person may fail to recognise close relatives. Long-term memory, which was previously intact, becomes impaired.
Behavioral and neuropsychiatric changes become more prevalent. Common manifestations are wandering, irritability and emotional lability, leading to crying, outbursts of unpremeditated aggression, or resistance to caregiving. Sundowning can also appear. Approximately 30% of people with Alzheimer's disease develop illusionary misidentifications and other delusional symptoms. Subjects also lose insight of their disease process and limitations (anosognosia). Urinary incontinence can develop. These symptoms create stress for relatives and caregivers, which can be reduced by moving the person from home care to other long-term care facilities.
During the final stage, known as the late-stage or severe stage, the patient is completely dependent upon caregivers. Language is reduced to simple phrases or even single words, eventually leading to complete loss of speech. Despite the loss of verbal language abilities, people can often understand and return emotional signals. Although aggressiveness can still be present, extreme apathy and exhaustion are much more common symptoms. People with Alzheimer's disease will ultimately not be able to perform even the simplest tasks independently; muscle mass and mobility deteriorates to the point where they are bedridden and unable to feed themselves. The cause of death is usually an external factor, such as infection of pressure ulcers or pneumonia, not the disease itself.
Alzheimer's disease is believed to occur when abnormal amounts of amyloid beta (Aβ), accumulating extracellularly as amyloid plaques, and tau proteins, accumulating intracellularly as neurofibrillary tangles, form in the brain affecting neuronal functioning and connectivity, resulting in a progressive loss of brain function. This altered protein clearance ability is age-related, regulated by brain cholesterol, and associated with other neurodegenerative diseases.
The cause for most Alzheimer's cases is still mostly unknown, except for 1–2% of cases where deterministic genetic differences have been identified. Several competing hypotheses attempt to explain the underlying cause; the two hypotheses that predominate are the amyloid beta (Aβ) hypothesis and the cholinergic hypothesis.
The oldest hypothesis, on which most drug therapies are based, is the cholinergic hypothesis, which proposes that Alzheimer's disease is caused by reduced synthesis of the neurotransmitter acetylcholine.
The 1991 amyloid hypothesis postulated that extracellular amyloid beta (Aβ) deposits are the fundamental cause of the disease. Support for this postulate comes from the location of the gene for the amyloid precursor protein (APP) on chromosome 21, together with the fact that people with trisomy 21 (Down syndrome) who have an extra gene copy almost universally exhibit at least the earliest symptoms of Alzheimer's disease by 40 years of age. Also, a specific isoform of apolipoprotein, APOE4, is a major genetic risk factor for Alzheimer's disease. While apolipoproteins enhance the breakdown of beta amyloid, some isoforms are not very effective at this task (such as APOE4), leading to excess amyloid buildup in the brain.
The tau hypothesis proposes that tau protein abnormalities initiate the disease cascade. In this model, hyperphosphorylated tau begins to pair with other threads of tau as paired helical filaments. Eventually, they form neurofibrillary tangles inside nerve cell bodies. When this occurs, the microtubules disintegrate, destroying the structure of the cell's cytoskeleton which collapses the neuron's transport system. This may result first in malfunctions in biochemical communication between neurons and later in the death of the cells.
Only 1–2% of Alzheimer's cases are inherited (autosomal dominant). These types are known as early onset familial Alzheimer's disease, can have a very early onset, and a faster rate of progression. Early onset familial Alzheimer's disease can be attributed to mutations in one of three genes: those encoding amyloid-beta precursor protein (APP) and presenilins PSEN1 and PSEN2. Most mutations in the APP and presenilin genes increase the production of a small protein called amyloid beta (Aβ)42, which is the main component of amyloid plaques. Some of the mutations merely alter the ratio between Aβ42 and the other major forms—particularly Aβ40—without increasing Aβ42 levels. Two other genes associated with autosomal dominant Alzheimer's disease are ABCA7 and SORL1.
Most cases of Alzheimer's are not inherited and are termed sporadic Alzheimer's disease, in which environmental and genetic differences may act as risk factors. Most cases of sporadic Alzheimer's disease in contrast to familial Alzheimer's disease are late-onset Alzheimer's disease (LOAD) developing after the age of 65 years. Less than 5% of sporadic Alzheimer's disease have an earlier onset. The strongest genetic risk factor for sporadic Alzheimer's disease is APOEε4. APOEε4 is one of four alleles of apolipoprotein E (APOE). APOE plays a major role in lipid-binding proteins in lipoprotein particles and the epsilon4 allele disrupts this function. Between 40 and 80% of people with Alzheimer's disease possess at least one APOEε4 allele. The APOEε4 allele increases the risk of the disease by three times in heterozygotes and by 15 times in homozygotes. Like many human diseases, environmental effects and genetic modifiers result in incomplete penetrance. For example, certain Nigerian populations do not show the relationship between dose of APOEε4 and incidence or age-of-onset for Alzheimer's disease seen in other human populations. Early attempts to screen up to 400 candidate genes for association with late-onset sporadic Alzheimer's disease (LOAD) resulted in a low yield. More recent genome-wide association studies (GWAS) have found 19 areas in genes that appear to affect the risk. These genes include: CASS4, CELF1, FERMT2, HLA-DRB5, INPP5D, MEF2C, NME8, PTK2B, SORL1, ZCWPW1, SLC24A4, CLU, PICALM, CR1, BIN1, MS4A, ABCA7, EPHA1, and CD2AP.
Alleles in the TREM2 gene have been associated with a 3 to 5 times higher risk of developing Alzheimer's disease. A suggested mechanism of action is that in some variants in TREM2, white blood cells in the brain are no longer able to control the amount of amyloid beta present. Many single-nucleotide polymorphisms (SNPs) are associated with Alzheimer's, with a 2018 study adding 30 SNPs by differentiating Alzheimer's disease into six categories, including memory, language, visuospatial, and executive functioning.
A Japanese pedigree of familial Alzheimer's disease was found to be associated with a deletion mutation of codon 693 of APP. This mutation and its association with Alzheimer's disease was first reported in 2008, and is known as the Osaka mutation. Only homozygotes with this mutation develop Alzheimer's disease. This mutation accelerates Aβ oligomerization but the proteins do not form the amyloid fibrils that aggregate into amyloid plaques, suggesting that it is the Aβ oligomerization rather than the fibrils that may be the cause of this disease. Mice expressing this mutation have all the usual pathologies of Alzheimer's disease.
A number of studies connect the misfolded amyloid beta and tau proteins associated with the pathology of Alzheimer's disease, as bringing about oxidative stress that leads to chronic inflammation. Sustained inflammation (neuroinflammation) is also a feature of other neurodegenerative diseases including Parkinson's disease, and ALS. Spirochete infections have also been linked to dementia.
Sleep disturbances are seen as a possible risk factor for inflammation in Alzheimer's disease. Sleep problems have been seen as a consequence of Alzheimer's disease but studies suggest that they may instead be a causal factor. Sleep disturbances are thought to be linked to persistent inflammation. A possible role of chronic periodontal infection and the gut microbiota has been suggested.
Cholesterol signaling hypothesis postulates that amyloid production and tau phosphorylation are regulated by cholesterol and high brain cholesterol contributes to the disease. First, the cholesterol is made in the astrocytes, the astrocytes load the cholesterol into the cholesterol carrier protein apoE, and the apoE loads the cholesterol into the neurons. Once in the neurons, cholesterol causes clustering of amyloid precursor protein (APP) with its hydrolytic enzyme gamma secretase, resulting in amyloid beta production and accumulation of amyloid plaques. Cholesterol regulates amyloid beta production by substrate presentation.
The cellular homeostasis of biometals such as ionic copper, iron, and zinc is disrupted in Alzheimer's disease, though it remains unclear whether this is produced by or causes the changes in proteins. These ions affect and are affected by tau, APP, and APOE, and their dysregulation may cause oxidative stress that may contribute to the pathology. The quality of some of these studies has been criticised, and the link remains controversial. The majority of researchers do not support a causal connection with aluminium.
One hypothesis posits that dysfunction of oligodendrocytes and their associated myelin during aging contributes to axon damage, which then causes amyloid production and tau hyper-phosphorylation as a side effect.
Retrogenesis is a medical hypothesis about the development and progress of Alzheimer's disease proposed by Barry Reisberg in the 1980s. The hypothesis is that just as the fetus goes through a process of neurodevelopment beginning with neurulation and ending with myelination, the brains of people with Alzheimer's disease go through a reverse neurodegeneration process starting with demyelination and death of axons (white matter) and ending with the death of grey matter. Likewise the hypothesis is, that as infants go through states of cognitive development, people with Alzheimer's disease go through the reverse process of progressive cognitive impairment. Reisberg developed the caregiving assessment tool known as "FAST" (Functional Assessment Staging Tool) which he says allows those caring for people with Alzheimer's disease to identify the stages of disease progression and that provides advice about the kind of care needed at each stage.
The association with celiac disease is unclear, with a 2019 study finding no increase in dementia overall in those with CD, while a 2018 review found an association with several types of dementia including Alzheimer's disease.
Kynurenines are a downstream metabolite of tryptophan and have the potential to be neuroactive. This may be associated with the neuropsychiatric symptoms and cognitive prognosis in mild dementia. A five-year study focused on the role of kynurenine in Alzheimer's and Lewy body disease and found its increase to be associated with more hallucinations.
Alzheimer's disease is characterised by loss of neurons and synapses 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. Degeneration is also present in brainstem nuclei particularly the locus coeruleus in the pons. Studies using MRI and PET have documented reductions in the size of specific brain regions in people with Alzheimer's disease as they progressed from mild cognitive impairment to Alzheimer's disease, and in comparison with similar images from healthy older adults.
Both Aβ plaques and neurofibrillary tangles are clearly visible by microscopy in brains of those afflicted by Alzheimer's disease, especially in the hippocampus. However, Alzheimer's disease may occur without neurofibrillary tangles in the neocortex. Plaques are dense, mostly insoluble deposits of beta-amyloid peptide and 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 people with Alzheimer's disease have a greater number of them in specific brain regions such as the temporal lobe. Lewy bodies are not rare in the brains of people with Alzheimer's disease.
Alzheimer's disease has been identified as a protein misfolding disease, a proteopathy, caused by the accumulation of abnormally folded amyloid beta protein into amyloid plaques, and tau protein into neurofibrillary tangles in the brain. Plaques are made up of small peptides, 39–43 amino acids in length, called amyloid beta (Aβ). Amyloid beta is a fragment from the larger amyloid-beta precursor protein (APP) a transmembrane protein that penetrates the neuron's membrane. APP is critical to neuron growth, survival, and post-injury repair. In Alzheimer's disease, gamma secretase and beta secretase act together in a proteolytic process which causes APP to be divided into smaller fragments. One of these fragments gives rise to fibrils of amyloid beta, which then form clumps that deposit outside neurons in dense formations known as amyloid plaques.
Alzheimer's disease 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 stabilises the microtubules when phosphorylated, and is therefore called a microtubule-associated protein. In Alzheimer's disease, tau undergoes chemical changes, becoming hyperphosphorylated; it then begins to pair with other threads, creating neurofibrillary tangles and disintegrating the neuron's transport system. Pathogenic tau can also cause neuronal death through transposable element dysregulation.
Exactly how disturbances of production and aggregation of the beta-amyloid peptide give rise to the pathology of Alzheimer's disease is not known. The amyloid hypothesis traditionally points to the accumulation of beta-amyloid peptides as the central event triggering neuron degeneration. Accumulation of aggregated amyloid fibrils, 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). It is also known that Aβ selectively builds up in the mitochondria in the cells of Alzheimer's-affected brains, and it also inhibits certain enzyme functions and the utilisation of glucose by neurons.
Various inflammatory processes and cytokines may also have a role in the pathology of Alzheimer's disease. Inflammation is a general marker of tissue damage in any disease, and may be either secondary to tissue damage in Alzheimer's disease or a marker of an immunological response. There is increasing evidence of a strong interaction between the neurons and the immunological mechanisms in the brain. Obesity and systemic inflammation may interfere with immunological processes which promote disease progression.
Alterations in the distribution of different neurotrophic factors and in the expression of their receptors such as the brain-derived neurotrophic factor (BDNF) have been described in Alzheimer's disease.
Alzheimer's disease is usually diagnosed based on the person's medical history, history from relatives, and behavioral observations. The presence of characteristic neurological and neuropsychological features and the absence of alternative conditions supports the diagnosis. 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. Moreover, it may predict conversion from prodromal stages (mild cognitive impairment) to Alzheimer's disease. FDA-approved radiopharmaceutical diagnostic agents used in PET for patients with Alzheimer's disease are florbetapir (2012), flutemetamol (2013), florbetaben (2014), and flortaucipir (2020).
Assessment of intellectual functioning including memory testing can further characterise the state of the disease. Medical organizations have created diagnostic criteria to ease and standardise the diagnostic process for practising physicians. The diagnosis can be confirmed with very high accuracy post-mortem when brain material is available and can be examined histologically.
There are three sets of criteria for the clinical diagnoses of the spectrum of Alzheimer's disease: the 2013 fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5); the National Institute on Aging-Alzheimer's Association (NIA-AA) definition as revised in 2011; and the International Working Group criteria as revised in 2010. Three broad time periods, which can span decades, define the progression of AD from the preclinical phase, to mild cognitive impairment (MCI), followed by AD dementia.
Eight intellectual domains are most commonly impaired in AD—memory, language, perceptual skills, attention, motor skills, orientation, problem solving and executive functional abilities, as listed in the fourth text revision of the DSM (DSM-IV-TR).
The DSM-5 defines criteria for probable or possible Alzheimer's for both major and mild neurocognitive disorder. Major or mild neurocognitive disorder must be present along with at least one cognitive deficit for a diagnosis of either probable or possible AD. For major neurocognitive disorder due to Alzheimer's disease, probable Alzheimer's disease can be diagnosed if the individual has genetic evidence of Alzheimer's or if two or more acquired cognitive deficits, and a functional disability that is not from another disorder, are present.[clarification needed] For mild neurocognitive disorder due to Alzheimer's, probable Alzheimer's disease can be diagnosed if there is genetic evidence, whereas possible AD can be met if all of the following are present: no genetic evidence, decline in both learning and memory, two or more cognitive deficits, and a functional disability not from another disorder.
The NIA-AA criteria are used mainly in research rather than in clinical assessments. They define Alzheimer’s disease through three major stages: preclinical, mild cognitive impairment (MCI), and Alzheimer’s dementia. Diagnosis in the preclinical stage is complex and focuses on asymptomatic individuals; the latter two stages describe individuals experiencing symptoms. The core clinical criteria for MCI is used along with identification of biomarkers, predominantly those for neuronal injury (mainly tau-related) and amyloid beta deposition. The core clinical criteria itself rests on the presence of cognitive impairment without the presence of comorbidities. The third stage is divided into probable and possible AD dementia. In probable AD dementia there is steady impairment of cognition over time and a memory-related or non-memory-related cognitive dysfunction. In possible AD dementia, another causal disease such as cerebrovascular disease is present.
Neuropsychological tests including cognitive tests such as the Mini–Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA) and the Mini-Cog are widely used to aid in diagnosis of the cognitive impairments in AD. These tests may not always be accurate, as they lack sensitivity to mild cognitive impairment, and can be biased by language or attention problems; more comprehensive test arrays are necessary for high reliability of results, particularly in the earliest stages of the disease. Neurological examination in early Alzheimer's disease 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.[medical citation needed]
Further neurological examinations are crucial in the differential diagnosis of Alzheimer's disease and other diseases. Interviews with family members are used in assessment; caregivers can supply important information on daily living abilities and on the decrease in the person's mental function. A caregiver's viewpoint is particularly important, since a person with Alzheimer's disease is commonly unaware of their deficits. Many times, families have difficulties in the detection of initial dementia symptoms and may not communicate accurate information to a physician.
Supplemental testing can rule out other potentially treatable diagnoses and help avoid misdiagnoses. Common supplemental tests include blood tests, thyroid function tests, as well as tests to assess vitamin B12 levels, rule out neurosyphilis and rule out metabolic problems (including tests for kidney function, electrolyte levels and for diabetes). MRI or CT scans might also be used to rule out other potential causes of the symptoms – including tumors or strokes. Delirium and depression can be common among older patients and are important to rule out.
Psychological tests for depression are used, since depression can either be concurrent with Alzheimer's disease (see Depression of Alzheimer disease), an early sign of cognitive impairment, or even the cause.
Due to low accuracy, the C-PIB-PET scan is not recommended as an early diagnostic tool or for predicting the development of Alzheimer's disease when people show signs of mild cognitive impairment (MCI). The use of 18F-FDG PET scans, as a single test, to identify people who may develop Alzheimer's disease is not supported by evidence.
There is no evidence that supports any particular measure as being effective in preventing Alzheimer's disease. Global studies of measures to prevent or delay the onset of Alzheimer's disease have often produced inconsistent results. 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 Alzheimer's disease. Further research, including clinical trials, may reveal whether these factors can help to prevent Alzheimer's disease.
Cardiovascular risk factors, such as hypercholesterolaemia, hypertension, diabetes, and smoking, are associated with a higher risk of onset and worsened course of Alzheimer's disease. Blood pressure medications may decrease the risk. A review found that the use of statins, which lower cholesterol may be of benefit in Alzheimer's and other dementias but not in vascular dementia.
Long-term usage of non-steroidal anti-inflammatory drugs (NSAIDs) were thought in 2007 to be associated with a reduced likelihood of developing Alzheimer's disease. Evidence also suggested the notion that NSAIDs could reduce inflammation related to amyloid plaques, but trials were suspended due to high adverse events. No prevention trial has been completed. They do not appear to be useful as a treatment, but as of 2011[update] were thought to be candidates as presymptomatic preventives. Hormone replacement therapy in menopause, although previously used, may increase risk of dementia.
Higher education and occupational attainment, and participation in leisure activities, contribute to a reduced risk of developing Alzheimer's, or of delaying the onset of symptoms. 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. Education delays the onset of Alzheimer's disease syndrome without changing the duration of the disease. Learning a second language later in life seems to delay the onset of Alzheimer's disease.[medical citation needed]
Physical exercise is associated with a decreased rate of dementia, and is effective in reducing symptom severity in those with Alzheimer's disease. Memory and cognitive functions can be improved with aerobic exercises including brisk walking three times weekly for forty minutes. It may also induce neuroplasticity of the brain, supported by animal and human studies.  Calorie restriction may serve as a non-pharmacologic intervention against brain aging in improving metabolic health by neutralizing oxidative damage. Meditation is a helpful lifestyle change to support cognition and well-being, though further research is needed to assess long-term effects.
To further minimize cognitive impairment, lifestyle changes are specific and personalized. Additional research is required to understand the lifestyle effect, such as gaining insight in neuroimaging biomarkers to understand mechanisms.[medical citation needed]
Diet is seen to be a modifiable risk factor for the development of dementia. The Mediterranean diet, and the DASH diet are both associated with less cognitive decline. A different approach has been to incorporate elements of both of these diets into one known as the MIND diet. These diets are generally low in saturated fats while providing a good source of carbohydrates, mainly those that help stabilize blood sugar and insulin levels. Those who eat a diet high in saturated fats and simple carbohydrates (mono- and disaccharide) have a higher risk.
Raised blood sugar levels over a long time, can damage nerves and cause memory problems if they are not managed. Nutritional factors associated with the proposed diets for reducing dementia risk, include unsaturated fatty acids, antioxidants vitamin E, vitamin C, and flavonoids, vitamin B, and vitamin D.
The MIND diet may be more protective but further studies are needed. The Mediterranean diet seems to be more protective against Alzheimer's than DASH but there are no consistent findings against dementia in general. The role of olive oil needs further study as it may be one of the most important components in reducing the risk of cognitive decline and dementia.
In those with celiac disease or non-celiac gluten sensitivity, a strict gluten-free diet may relieve the symptoms given a mild cognitive impairment. Once dementia is advanced no evidence suggests that a gluten free diet is useful.
Conclusions on dietary components have been difficult to ascertain as results have differed between population-based studies and randomised controlled trials. There is limited evidence that light to moderate use of alcohol, particularly red wine, is associated with lower risk of Alzheimer's disease. There is tentative evidence that caffeine may be protective. A number of foods high in flavonoids such as cocoa, red wine, and tea may decrease the risk of Alzheimer's disease. A number of studies have looked at the possible role of minerals such as selenium, zinc, and copper. Omega 3 fatty acid supplements from plants and fish, and dietary docosahexaenoic acid (DHA), do not appear to benefit people with mild to moderate Alzheimer's disease.
Curcumin as of 2010[update] had not shown benefit in people even though there is tentative evidence in animals. There is growing evidence (2020) for the neuroprotection offered by the use of cannabinoids in Alzheimer's and other neurodegenerative disorders. However, further population studies are recommended to see this use beyond experimental.
There is no cure for Alzheimer's disease; available treatments offer relatively small symptomatic benefits but remain palliative in nature. Treatments can be divided into pharmaceutical, psychosocial, and caregiving.
Medications used to treat the cognitive problems of Alzheimer's disease include: four acetylcholinesterase inhibitors (tacrine, rivastigmine, galantamine, and donepezil) and memantine, an NMDA receptor antagonist. The benefit from their use is small.
Reduction in the activity of the cholinergic neurons is a well-known feature of Alzheimer's disease. Acetylcholinesterase inhibitors 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. There is evidence for the efficacy of these medications in mild to moderate Alzheimer's disease, and some evidence for their use in the advanced stage. The use of these drugs in mild cognitive impairment has not shown any effect in a delay of the onset of Alzheimer's disease. The most common side effects are nausea and vomiting, both of which are linked to cholinergic excess. These side effects arise in approximately 10–20% of users, are mild to moderate in severity, and can be managed by slowly adjusting medication doses. Less common secondary effects include muscle cramps, decreased heart rate (bradycardia), decreased appetite and weight, and increased gastric acid production.
Glutamate is an excitatory neurotransmitter of the nervous system, although excessive amounts in the brain can lead to cell death through a process called excitotoxicity which consists of the overstimulation of glutamate receptors. Excitotoxicity occurs not only in Alzheimer's disease, but also in other neurological diseases such as Parkinson's disease and multiple sclerosis. Memantine is a noncompetitive NMDA receptor antagonist first used as an anti-influenza agent. It acts on the glutamatergic system by blocking NMDA receptors and inhibiting their overstimulation by glutamate. Memantine has been shown to have a small benefit in the treatment of moderate to severe Alzheimer's disease. Reported adverse events with memantine are infrequent and mild, including hallucinations, confusion, dizziness, headache and fatigue. The combination of memantine and donepezil has been shown to be "of statistically significant but clinically marginal effectiveness".
An extract of Ginkgo biloba known as EGb 761 has been widely used for treating Alzheimer's and other neuropsychiatric disorders. Its use is approved throughout Europe. The World Federation of Biological Psychiatry guidelines lists EGb 761 with the same weight of evidence (level B) given to acetylcholinesterase inhibitors, and memantine. EGb 761 is the only one that showed improvement of symptoms in both Alzheimer's disease and vascular dementia. EGb 761 is seen as being able to play an important role either on its own or as an add-on particularly when other therapies prove ineffective. EGb 761 is seen to be neuroprotective; it is a free radical scavenger, improves mitochondrial function, and modulates serotonin and dopamine levels. Many studies of its use in mild to moderate dementia have shown it to significantly improve cognitive function, activities of daily living, and neuropsychiatric symptoms. However, its use has not been shown to prevent the progression to dementia.
Atypical antipsychotics are modestly useful in reducing aggression and psychosis in people with Alzheimer's disease, but their advantages are offset by serious adverse effects, such as stroke, movement difficulties or cognitive decline. When used in the long-term, they have been shown to associate with increased mortality. Stopping antipsychotic use in this group of people appears to be safe.
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 Alzheimer's disease, focusing instead on dementia in general.
Behavioral interventions attempt to identify and reduce the antecedents and consequences of problem behaviors. This approach has not shown success in improving overall functioning, but can help to reduce some specific problem behaviors, such as incontinence. There is a lack of high quality data on the effectiveness of these techniques in other behavior problems such as wandering. Music therapy is effective in reducing behavioral and psychological symptoms.
Emotion-oriented interventions include reminiscence therapy, validation therapy, supportive psychotherapy, sensory integration, also called snoezelen, and simulated presence therapy. A Cochrane review has found no evidence that this is effective. Supportive psychotherapy has received little or no formal scientific study, but some clinicians find it useful in helping mildly impaired people 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. A 2018 review of the effectiveness of RT found that effects were inconsistent, small in size and of doubtful clinical significance, and varied by setting. Simulated presence therapy (SPT) is based on 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 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 no evidence to support the usefulness of these therapies.
The aim of cognition-oriented treatments, which include reality orientation and cognitive retraining, is the reduction of cognitive deficits. Reality orientation consists of the presentation of information about time, place, or person 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 exercising mental abilities. Both have shown some efficacy improving cognitive capacities, although in some studies these effects were transient and negative effects, such as frustration, have also been reported.
Stimulation-oriented treatments include art, music and pet therapies, exercise, and any other kind of recreational activities. 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 change in the person's routine.
Since Alzheimer's has no cure and it gradually renders people incapable of tending to their own needs, caregiving is essentially 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. Examples of such modifications are the adherence to simplified routines, the placing of safety locks, the labeling of household items to cue the person with the disease or the use of modified daily life objects. If eating becomes problematic, food will need to be prepared in smaller pieces or even puréed. When swallowing difficulties arise, the use of feeding tubes may be required. In such cases, the medical efficacy and ethics of continuing feeding is an important consideration of the caregivers and family members. 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 Alzheimer's disease or their caregivers.
As the disease progresses, different medical issues can appear, such as oral and dental disease, pressure ulcers, malnutrition, hygiene problems, or respiratory, skin, or eye infections. Careful management can prevent them, while professional treatment is needed when they do arise. During the final stages of the disease, treatment is centred on relieving discomfort until death, often with the help of hospice.
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, especially in the late stages of the disease.
Life expectancy of people with Alzheimer's disease is reduced. The normal life expectancy for 60 to 70 years old is 23 to 15 years; for 90 years old it is 4.5 years. Following Alzheimer's disease diagnosis it ranges from 7 to 10 years for those in their 60s and early 70s (a loss of 13 to 8 years), to only about 3 years or less (a loss of 1.5 years) for those in their 90s. It is about 50% life expectancy with Alzheimer's disease.
Fewer than 3% of people live more than fourteen years. 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 problems, diabetes or history of alcohol abuse are also related with shortened survival. 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. Men have a less favourable survival prognosis than women.
Two main measures are used in epidemiological studies: incidence and prevalence. 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 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 Alzheimer's disease, which means that half of new dementia cases each year are Alzheimer's disease. Advancing age is a primary risk factor for the disease and incidence rates are not equal for all ages: every 5 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. Females with AD are more common than males, but this difference is likely due to women's' longer life spans. When adjusted for age, both sexes are affected by Alzheimer's at equal rates. In the United States, the risk of dying from Alzheimer's disease in 2010 was 26% higher among the non-Hispanic white population than among the non-Hispanic black population, and the Hispanic population had a 30% lower risk than the non-Hispanic white population.
The prevalence of Alzheimer's disease in populations is dependent upon factors including incidence and survival. Since the incidence of Alzheimer's disease increases with age, prevalence depends on the mean age of the population for which prevalence is given. In the United States in 2020, Alzheimer's dementia prevalence was estimated to be 5.3% for those in the 60–74 age group, with the rate increasing to 13.8% in the 74–84 group and to 34.6% in those greater than 85. Prevalence rates in some less developed regions around the globe are lower. 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. Other studies have reached similar conclusions. As of 2020, 50 million people globally have AD, with this number expected to increase to 152 million by 2050.
The ancient Greek and Roman philosophers and physicians associated old age with increasing dementia. It was not until 1901 that German psychiatrist Alois Alzheimer identified the first case of what became known as Alzheimer's disease, named after him, in a fifty-year-old woman he called Auguste D. He followed her case until she died in 1906 when he first reported publicly on it. During the next five years, eleven similar cases were reported in the medical literature, some of them already using the term Alzheimer's disease. 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. 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 on 15 July, 1910.
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 Alzheimer's disease 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. This eventually led to the diagnosis of Alzheimer's disease independent of age. 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 to describe those who were 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.
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, extensively updated in 2007. 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 Alzheimer's disease. A histopathologic confirmation including a microscopic examination of brain tissue is required for a definitive diagnosis. Good statistical reliability and validity have been shown between the diagnostic criteria and definitive histopathological confirmation.
Society and culture
Dementia, and specifically Alzheimer's disease, may be among the most costly diseases for society in Europe and the United States, while their costs in other countries such as Argentina, and South Korea, are also high and rising. These costs will probably increase with the aging of society, becoming an important 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. Altogether, AD has been estimated to have a worldwide annual cost of US$1 trillion.
The greatest origin of costs for society is the long-term care by health care professionals and particularly institutionalisation, which corresponds to 2/3 of the total costs for society. The cost of living at home is also very high, especially when informal costs for the family, such as caregiving time and caregiver's lost earnings, are taken into account.
Costs increase with dementia severity and the presence of behavioral disturbances, and are related to the increased caregiving time required for the provision of physical care. 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.
The role of the main caregiver is often taken by the spouse or a close relative. Alzheimer's disease is known for placing a great burden on caregivers which includes social, psychological, physical or economic aspects. Home care is usually preferred by people with Alzheimer's disease and their families. This option also delays or eliminates the need for more professional and costly levels of care. Nevertheless, two-thirds of nursing home residents have dementias.
Dementia caregivers are subject to high rates of physical and mental disorders. Factors associated with greater psychosocial problems of the primary caregivers include having an affected person at home, the carer being a spouse, demanding behaviors of the cared person such as depression, behavioral disturbances, hallucinations, sleep problems or walking disruptions and social isolation. Regarding economic problems, family caregivers often give up time from work to spend 47 hours per week on average with the person with Alzheimer's disease, while the costs of caring for them are high. Direct and indirect costs of caring for somebody with Alzheimer's average between $18,000 and $77,500 per year in the United States, depending on the study.
Alzheimer's disease has been portrayed in films such as: Iris (2001), based on John Bayley's memoir of his wife Iris Murdoch; The Notebook (2004), based on Nicholas Sparks' 1996 novel of the same name; A Moment to Remember (2004); Thanmathra (2005); Memories of Tomorrow (Ashita no Kioku) (2006), based on Hiroshi Ogiwara's novel of the same name; Away from Her (2006), based on Alice Munro's short story "The Bear Came over the Mountain"; Still Alice (2014), about a Columbia University professor who has early onset Alzheimer's disease, based on Lisa Genova's 2007 novel of the same name and featuring Julianne Moore in the title role. 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.
Alzheimer's disease has also been portrayed in music by English musician the Caretaker in releases such as Persistent Repetition of Phrases (2008), An Empty Bliss Beyond This World (2011), and Everywhere at the End of Time (2016–2019). Paintings depicting the disorder include the late works by American artist William Utermohlen, who drew self-portraits from 1995 to 2000 as an experiment of showing his disease through art.
Treatment and prevention
In the decade 2002–2012, 244 compounds were assessed in Phase I, Phase II, or Phase III trials, and only one of these (memantine) received FDA approval (though others were still in the pipeline). Solanezumab and aducanumab failed to show effectiveness in people who already had Alzheimer's symptoms.[medical citation needed]
In early 2017, a trial of verubecestat, which inhibits the beta-secretase protein responsible for creating beta-amyloid protein was discontinued as an independent panel found "virtually no chance of finding a positive clinical effect". In 2018 and 2019, more trials, including aducanumab which reduced amyloid beta concentrations, failed, leading some to question the validity of the amyloid hypothesis.[medical citation needed]
The senescence-accelerated mouse (SAMP8) is an Alzheimer's disease (AD) animal model in which amyloid precursor protein (APP) is overproduced. The mice develop early memory disturbances and alterations in the blood-brain barrier, which causes a decreased expulsion of amyloid-β protein from the brain. It has a marked increase in oxidative stress in the brain. Medications that reduce oxidative stress have been shown to improve memory. Treatments that reduce amyloid-β (antisense to APP and antibodies to amyloid-β) not only improve memory but also reduce oxidative stress. It has been shown that the initial deviations in lipid peroxidative damage favor mitochondrial dysfunction as being a trigger for amyloid-β overproduction in this Alzheimer's disease mouse strain. This process begets increased amyloid-beta, which further damages mitochondria.
Research on the effects of meditation on preserving memory and cognitive functions is at an early stage. A 2015 review suggests that mindfulness-based interventions may prevent or delay the onset of mild cognitive impairment and Alzheimer's disease.
The ketogenic diet is a very high-fat, adequate-protein, low-carbohydrate diet that is used to treat refractory epilepsy in children. Designed to mimic some of the effects of fasting, following a ketogenic diet leads to elevated blood levels of molecules called ketone bodies: a metabolic state known as ketosis. These ketone bodies have a neuroprotective effect on aging brain cells, though it is not fully understood why. Limited research in the form of preclinical trials (mice and rats), and small-scale clinical (human) trials, have explored its potential as a therapy for neurodegenerative disorders like Alzheimer's disease.
The herpes simplex virus HSV-1 has been found in the same areas as amyloid plaques. This suggested the possibility that Alzheimer's disease could be treated or prevented with antiviral medication. Studies of antivirals in cell cultures have shown promising results. A 2021 study of 265,172 subjects in Sweden over a 12-year period found that patients with herpes diagnoses not treated with antiviral drugs had a 50% increased risk of dementia over controls, but treatment with antiviral drugs reduced the incidence by 25%.[non-primary source needed]
Fungal infection of Alzheimer's disease brain has also been described. This hypothesis was proposed by the microbiologist L. Carrasco when his group found statistical correlation between disseminated mycoses and Alzheimer's disease. Further work revealed that fungal infection is present in different brain regions of Alzheimer's disease patients, but not in the control individuals. A fungal infection explains the symptoms observed in Alzheimer's disease patients. The slow progression of Alzheimer's disease fits with the chronic nature of some systemic fungal infections, which can be asymptomatic and thus, unnoticed and untreated. The fungal hypotheses are also compatible with some other established Alzheimer's disease hypotheses, like the amyloid hypothesis, that can be explained as an immune system response to an infection in the CNS, as found by R. Moir and R. Tanzi in mouse and worm models of Alzheimer's disease.
Emphasis in Alzheimer's research has been placed on diagnosing the condition before symptoms begin. A number of biochemical tests have been developed to enable earlier detection. Some such tests involve the analysis of cerebrospinal fluid for beta-amyloid, total tau protein and phosphorylated tau181P protein concentrations. Because drawing CSF can be painful, repeated draws are avoided. A blood test for circulatory miRNA and inflammatory biomarkers is a potential alternative indicator.
A series of studies suggest that aging-related breakdown of the blood–brain barrier may be causative of Alzheimer's disease, and conclude that markers for that damage may be an early predictor of the disease.
- Burns A, Iliffe S (February 2009). "Alzheimer's disease". BMJ. 338: b158. doi:10.1136/bmj.b158. PMID 19196745. S2CID 8570146.
- "Dementia Fact sheet". World Health Organization. September 2020.
- Ganguli M, Dodge HH, Shen C, Pandav RS, DeKosky ST (May 2005). "Alzheimer disease and mortality: a 15-year epidemiological study". Archives of Neurology. 62 (5): 779–784. doi:10.1001/archneur.62.5.779. PMID 15883266.
- Mendez MF (November 2012). "Early-onset Alzheimer's disease: nonamnestic subtypes and type 2 AD". Archives of Medical Research. 43 (8): 677–685. doi:10.1016/j.arcmed.2012.11.009. PMC 3532551. PMID 23178565.
- Ballard C, Gauthier S, Corbett A, Brayne C, Aarsland D, Jones E (March 2011). "Alzheimer's disease". Lancet. 377 (9770): 1019–1031. doi:10.1016/S0140-6736(10)61349-9. PMID 21371747. S2CID 20893019.
- "Dementia diagnosis and assessment" (PDF). National Institute for Health and Care Excellence (NICE). Archived from the original (PDF) on 5 December 2014. Retrieved 30 November 2014.
- Gomperts SN (April 2016). "Lewy Body Dementias: Dementia With Lewy Bodies and Parkinson Disease Dementia". Continuum (Review). 22 (2 Dementia): 435–463. doi:10.1212/CON.0000000000000309. PMC 5390937. PMID 27042903.
- Commission de la transparence (June 2012). "Drugs for Alzheimer's disease: best avoided. No therapeutic advantage" [Drugs for Alzheimer's disease: best avoided. No therapeutic advantage]. Prescrire International. 21 (128): 150. PMID 22822592.
- Querfurth HW, LaFerla FM (January 2010). "Alzheimer's disease". The New England Journal of Medicine. 362 (4): 329–344. doi:10.1056/NEJMra0909142. PMID 20107219. S2CID 205115756.
- Vos T, Allen C, Arora M, Barber RM, Bhutta ZA, Brown A, et al. (GBD 2015 Disease Injury Incidence Prevalence Collaborators) (October 2016). "Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1545–1602. doi:10.1016/S0140-6736(16)31678-6. PMC 5055577. PMID 27733282.
- Wang H, Naghavi M, Allen C, Barber RM, Bhutta ZA, Carter A, et al. (GBD 2015 Mortality Causes of Death Collaborators) (October 2016). "Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1459–1544. doi:10.1016/S0140-6736(16)31012-1. PMC 5388903. PMID 27733281.
- Simon RP, Greenberg DA, Aminoff MJ (2018). Clinical neurology (Tenth ed.). [New York]: McGraw Hill. p. 111. ISBN 978-1-259-86173-4. OCLC 1012400314.
- Berkowitz A (2017). Clinical neurology and neuroanatomy: a localization-based approach. New York: McGraw Hill. p. 236. ISBN 978-1-259-83440-0. OCLC 948547621.
- "Alzheimer's Disease Fact Sheet". National Institute on Aging. Retrieved 25 January 2021.
- Todd S, Barr S, Roberts M, Passmore AP (November 2013). "Survival in dementia and predictors of mortality: a review". International Journal of Geriatric Psychiatry. 28 (11): 1109–1124. doi:10.1002/gps.3946. PMID 23526458. S2CID 25445595.
- Long JM, Holtzman DM (October 2019). "Alzheimer Disease: An Update on Pathobiology and Treatment Strategies". Cell. 179 (2): 312–339. doi:10.1016/j.cell.2019.09.001. PMC 6778042. PMID 31564456.
- "Study reveals how APOE4 gene may increase risk for dementia". National Institute on Aging. Retrieved 17 March 2021.
- Hsu D, Marshall GA (2017). "Primary and Secondary Prevention Trials in Alzheimer Disease: Looking Back, Moving Forward". Current Alzheimer Research. 14 (4): 426–440. doi:10.2174/1567205013666160930112125. PMC 5329133. PMID 27697063.
- Thompson CA, Spilsbury K, Hall J, Birks Y, Barnes C, Adamson J (July 2007). "Systematic review of information and support interventions for caregivers of people with dementia". BMC Geriatrics. 7: 18. doi:10.1186/1471-2318-7-18. PMC 1951962. PMID 17662119.
- Forbes D, Forbes SC, Blake CM, Thiessen EJ, Forbes S (April 2015). "Exercise programs for people with dementia". The Cochrane Database of Systematic Reviews (Submitted manuscript). 132 (4): CD006489. doi:10.1002/14651858.CD006489.pub4. PMID 25874613.
- National Institute for Health and Clinical Excellence. "Low-dose antipsychotics in people with dementia". National Institute for Health and Care Excellence (NICE). Archived from the original on 5 December 2014. Retrieved 29 November 2014.
- "Information for Healthcare Professionals: Conventional Antipsychotics". US Food and Drug Administration. 16 June 2008. Archived from the original on 29 November 2014. Retrieved 29 November 2014.
- Breijyeh Z, Karaman R (December 2020). "Comprehensive Review on Alzheimer's Disease: Causes and Treatment". Molecules (Review). 25 (24): 5789. doi:10.3390/molecules25245789. PMC 7764106. PMID 33302541.
- Viña J, Lloret A (2010). "Why women have more Alzheimer's disease than men: gender and mitochondrial toxicity of amyloid-beta peptide". Journal of Alzheimer's Disease. 20 (Suppl 2): S527–S533. doi:10.3233/JAD-2010-100501. PMID 20442496.
- Berchtold NC, Cotman CW (1998). "Evolution in the conceptualization of dementia and Alzheimer's disease: Greco-Roman period to the 1960s". Neurobiology of Aging. 19 (3): 173–189. doi:10.1016/S0197-4580(98)00052-9. PMID 9661992. S2CID 24808582.
- "Alzheimer's disease – Symptoms". nhs.uk. 10 May 2018.
- Waldemar G, Dubois B, Emre M, Georges J, McKeith IG, Rossor M, et al. (January 2007). "Recommendations for the diagnosis and management of Alzheimer's disease and other disorders associated with dementia: EFNS guideline". European Journal of Neurology. 14 (1): e1-26. doi:10.1111/j.1468-1331.2006.01605.x. PMID 17222085. S2CID 2725064.
- Bäckman L, Jones S, Berger AK, Laukka EJ, Small BJ (September 2004). "Multiple cognitive deficits during the transition to Alzheimer's disease". Journal of Internal Medicine. 256 (3): 195–204. doi:10.1111/j.1365-2796.2004.01386.x. PMID 15324363. S2CID 37005854.
- Nygård L (2003). "Instrumental activities of daily living: a stepping-stone towards Alzheimer's disease diagnosis in subjects with mild cognitive impairment?". Acta Neurologica Scandinavica. Supplementum. 179 (s179): 42–46. doi:10.1034/j.1600-0404.107.s179.8.x. PMID 12603250. S2CID 25313065.
- Arnáiz E, Almkvist O (2003). "Neuropsychological features of mild cognitive impairment and preclinical Alzheimer's disease". Acta Neurologica Scandinavica. Supplementum. 179: 34–41. doi:10.1034/j.1600-0404.107.s179.7.x. PMID 12603249. S2CID 22494768.
- Deardorff WJ, Grossberg GT (2019). "Behavioral and psychological symptoms in Alzheimer's dementia and vascular dementia". Handbook of Clinical Neurology. 165: 5–32. doi:10.1016/B978-0-444-64012-3.00002-2. ISBN 9780444640123. PMID 31727229. S2CID 208037448.
- Murray ED, Buttner N, Price BH (2012). "Depression and Psychosis in Neurological Practice". In Bradley WG, Daroff RB, Fenichel GM, Jankovic J (eds.). Bradley's neurology in clinical practice (6th ed.). Philadelphia, PA: Elsevier/Saunders. ISBN 978-1-4377-0434-1.
- Petersen RC, Lopez O, Armstrong MJ, Getchius TS, Ganguli M, Gloss D, et al. (January 2018). "Practice guideline update summary: Mild cognitive impairment: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology". Neurology. 90 (3): 126–135. doi:10.1212/WNL.0000000000004826. PMC 5772157. PMID 29282327.
- Atri A (March 2019). "The Alzheimer's Disease Clinical Spectrum: Diagnosis and Management". The Medical Clinics of North America (Review). 103 (2): 263–293. doi:10.1016/j.mcna.2018.10.009. PMID 30704681. S2CID 73432842.
- Förstl H, Kurz A (1999). "Clinical features of Alzheimer's disease". European Archives of Psychiatry and Clinical Neuroscience. 249 (6): 288–290. doi:10.1007/s004060050101. PMID 10653284. S2CID 26142779.
- Carlesimo GA, Oscar-Berman M (June 1992). "Memory deficits in Alzheimer's patients: a comprehensive review". Neuropsychology Review. 3 (2): 119–169. doi:10.1007/BF01108841. PMID 1300219. S2CID 19548915.
- Jelicic M, Bonebakker AE, Bonke B (1995). "Implicit memory performance of patients with Alzheimer's disease: a brief review". International Psychogeriatrics. 7 (3): 385–392. doi:10.1017/S1041610295002134. PMID 8821346.
- Taler V, Phillips NA (July 2008). "Language performance in Alzheimer's disease and mild cognitive impairment: a comparative review". Journal of Clinical and Experimental Neuropsychology. 30 (5): 501–556. doi:10.1080/13803390701550128. PMID 18569251. S2CID 37153159.
- Frank EM (September 1994). "Effect of Alzheimer's disease on communication function". Journal of the South Carolina Medical Association. 90 (9): 417–423. PMID 7967534.
- Volicer L, Harper DG, Manning BC, Goldstein R, Satlin A (May 2001). "Sundowning and circadian rhythms in Alzheimer's disease". The American Journal of Psychiatry. 158 (5): 704–711. doi:10.1176/appi.ajp.158.5.704. PMID 11329390. S2CID 10492607.
- Gold DP, Reis MF, Markiewicz D, Andres D (January 1995). "When home caregiving ends: a longitudinal study of outcomes for caregivers of relatives with dementia". Journal of the American Geriatrics Society. 43 (1): 10–16. doi:10.1111/j.1532-5415.1995.tb06235.x. PMID 7806732. S2CID 29847950.
- Alzheimer's disease – Causes (NHS)
- Tackenberg C, Kulic L, Nitsch RM (2020). "Familial Alzheimer's disease mutations at position 22 of the amyloid β-peptide sequence differentially affect synaptic loss, tau phosphorylation and neuronal cell death in an ex vivo system". PLOS ONE. 15 (9): e0239584. Bibcode:2020PLoSO..1539584T. doi:10.1371/journal.pone.0239584. PMC 7510992. PMID 32966331.
- Wang H, Kulas JA, Wang C, Holtzman DM, Ferris HA, Hansen SB (August 2021). "Regulation of beta-amyloid production in neurons by astrocyte-derived cholesterol". Proceedings of the National Academy of Sciences of the United States of America. 118 (33): e2102191118. doi:10.1073/pnas.2102191118. PMC 8379952. PMID 34385305. S2CID 236998499.
- Vilchez D, Saez I, Dillin A (December 2014). "The role of protein clearance mechanisms in organismal ageing and age-related diseases". Nature Communications. 5: 5659. Bibcode:2014NatCo...5.5659V. doi:10.1038/ncomms6659. PMID 25482515.
- Jacobson M, McCarthy N (2002). Apoptosis. Oxford, OX: Oxford University Press. p. 290. ISBN 0199638497.
- Hardy J, Allsop D (October 1991). "Amyloid deposition as the central event in the aetiology of Alzheimer's disease". Trends in Pharmacological Sciences. 12 (10): 383–388. doi:10.1016/0165-6147(91)90609-V. PMID 1763432.
- Mudher A, Lovestone S (January 2002). "Alzheimer's disease-do tauists and baptists finally shake hands?". Trends in Neurosciences. 25 (1): 22–26. doi:10.1016/S0166-2236(00)02031-2. PMID 11801334. S2CID 37380445.
- Nistor M, Don M, Parekh M, Sarsoza F, Goodus M, Lopez GE, et al. (October 2007). "Alpha- and beta-secretase activity as a function of age and beta-amyloid in Down syndrome and normal brain". Neurobiology of Aging. 28 (10): 1493–1506. doi:10.1016/j.neurobiolaging.2006.06.023. PMC 3375834. PMID 16904243.
- Lott IT, Head E (March 2005). "Alzheimer disease and Down syndrome: factors in pathogenesis". Neurobiology of Aging. 26 (3): 383–389. doi:10.1016/j.neurobiolaging.2004.08.005. PMID 15639317. S2CID 27716613.
- Polvikoski T, Sulkava R, Haltia M, Kainulainen K, Vuorio A, Verkkoniemi A, et al. (November 1995). "Apolipoprotein E, dementia, and cortical deposition of beta-amyloid protein". The New England Journal of Medicine. 333 (19): 1242–1247. doi:10.1056/NEJM199511093331902. PMID 7566000.
- Goedert M, Spillantini MG, Crowther RA (July 1991). "Tau proteins and neurofibrillary degeneration". Brain Pathology. 1 (4): 279–286. doi:10.1111/j.1750-3639.1991.tb00671.x. PMID 1669718. S2CID 33331924.
- Iqbal K, Alonso A, Chen S, Chohan MO, El-Akkad E, Gong CX, et al. (January 2005). "Tau pathology in Alzheimer disease and other tauopathies". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1739 (2–3): 198–210. doi:10.1016/j.bbadis.2004.09.008. PMID 15615638.
- Chun W, Johnson GV (January 2007). "The role of tau phosphorylation and cleavage in neuronal cell death". Frontiers in Bioscience. 12: 733–756. doi:10.2741/2097. PMID 17127334. S2CID 40048768.
- Selkoe DJ (June 1999). "Translating cell biology into therapeutic advances in Alzheimer's disease". Nature. 399 (6738 Suppl): A23–A31. doi:10.1038/19866. PMID 10392577. S2CID 42287088.
- Borchelt DR, Thinakaran G, Eckman CB, Lee MK, Davenport F, Ratovitsky T, et al. (November 1996). "Familial Alzheimer's disease-linked presenilin 1 variants elevate Abeta1-42/1-40 ratio in vitro and in vivo". Neuron. 17 (5): 1005–1013. doi:10.1016/S0896-6273(00)80230-5. PMID 8938131. S2CID 18315650.
- Kim JH (December 2018). "Genetics of Alzheimer's Disease". Dementia and Neurocognitive Disorders. 17 (4): 131–136. doi:10.12779/dnd.2018.17.4.131. PMC 6425887. PMID 30906402.
- Perea JR, Bolós M, Avila J (October 2020). "Microglia in Alzheimer's Disease in the Context of Tau Pathology". Biomolecules. 10 (10): 1439. doi:10.3390/biom10101439. PMC 7602223. PMID 33066368.
- Mahley RW, Weisgraber KH, Huang Y (April 2006). "Apolipoprotein E4: a causative factor and therapeutic target in neuropathology, including Alzheimer's disease". Proceedings of the National Academy of Sciences of the United States of America. 103 (15): 5644–5651. Bibcode:2006PNAS..103.5644M. doi:10.1073/pnas.0600549103. PMC 1414631. PMID 16567625.
- Blennow K, de Leon MJ, Zetterberg H (July 2006). "Alzheimer's disease". Lancet. 368 (9533): 387–403. doi:10.1016/S0140-6736(06)69113-7. PMID 16876668. S2CID 47544338.
- Hall K, Murrell J, Ogunniyi A, Deeg M, Baiyewu O, Gao S, et al. (January 2006). "Cholesterol, APOE genotype, and Alzheimer disease: an epidemiologic study of Nigerian Yoruba". Neurology. 66 (2): 223–227. doi:10.1212/01.wnl.0000194507.39504.17. PMC 2860622. PMID 16434658.
- Gureje O, Ogunniyi A, Baiyewu O, Price B, Unverzagt FW, Evans RM, et al. (January 2006). "APOE epsilon4 is not associated with Alzheimer's disease in elderly Nigerians". Annals of Neurology. 59 (1): 182–185. doi:10.1002/ana.20694. PMC 2855121. PMID 16278853.
- Waring SC, Rosenberg RN (March 2008). "Genome-wide association studies in Alzheimer disease". Archives of Neurology. 65 (3): 329–334. doi:10.1001/archneur.65.3.329. PMID 18332245.
- Lambert JC, Ibrahim-Verbaas CA, Harold D, Naj AC, Sims R, Bellenguez C, et al. (December 2013). "Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease". Nature Genetics. 45 (12): 1452–1458. doi:10.1038/ng.2802. PMC 3896259. PMID 24162737.
- Jonsson T, Stefansson H, Steinberg S, Jonsdottir I, Jonsson PV, Snaedal J, et al. (January 2013). "Variant of TREM2 associated with the risk of Alzheimer's disease". The New England Journal of Medicine. 368 (2): 107–116. doi:10.1056/NEJMoa1211103. PMC 3677583. PMID 23150908.
- Guerreiro R, Wojtas A, Bras J, Carrasquillo M, Rogaeva E, Majounie E, et al. (January 2013). "TREM2 variants in Alzheimer's disease". The New England Journal of Medicine. 368 (2): 117–127. doi:10.1056/NEJMoa1211851. PMC 3631573. PMID 23150934.
- Mukherjee S, Mez J, Trittschuh EH, Saykin AJ, Gibbons LE, Fardo DW, et al. (November 2020). "Genetic data and cognitively defined late-onset Alzheimer's disease subgroups". Molecular Psychiatry. 25 (11): 2942–2951. doi:10.1038/s41380-018-0298-8. PMC 6548676. PMID 30514930.
- Tomiyama T (July 2010). "[Involvement of beta-amyloid in the etiology of Alzheimer's disease]". Brain and Nerve = Shinkei Kenkyu No Shinpo. 62 (7): 691–699. PMID 20675873.
- Tomiyama T, Nagata T, Shimada H, Teraoka R, Fukushima A, Kanemitsu H, et al. (March 2008). "A new amyloid beta variant favoring oligomerization in Alzheimer's-type dementia". Annals of Neurology. 63 (3): 377–387. doi:10.1002/ana.21321. PMID 18300294. S2CID 42311988.
- Tomiyama T, Shimada H (February 2020). "APP Osaka Mutation in Familial Alzheimer's Disease-Its Discovery, Phenotypes, and Mechanism of Recessive Inheritance". International Journal of Molecular Sciences. 21 (4): 1413. doi:10.3390/ijms21041413. PMC 7073033. PMID 32093100.
- Sinyor B, Mineo J, Ochner C (June 2020). "Alzheimer's Disease, Inflammation, and the Role of Antioxidants". Journal of Alzheimer's Disease Reports. 4 (1): 175–183. doi:10.3233/ADR-200171. PMC 7369138. PMID 32715278.
- Kinney JW, Bemiller SM, Murtishaw AS, Leisgang AM, Salazar AM, Lamb BT (2018). "Inflammation as a central mechanism in Alzheimer's disease". Alzheimer's & Dementia. 4: 575–590. doi:10.1016/j.trci.2018.06.014. PMC 6214864. PMID 30406177.
- Miklossy J (August 2011). "Alzheimer's disease - a neurospirochetosis. Analysis of the evidence following Koch's and Hill's criteria". Journal of Neuroinflammation. 8 (1): 90. doi:10.1186/1742-2094-8-90. PMC 3171359. PMID 21816039.
- Allen HB (June 2016). "Alzheimer's Disease: Assessing the Role of Spirochetes, Biofilms, the Immune System, and Amyloid-β with Regard to Potential Treatment and Prevention". Journal of Alzheimer's Disease. 53 (4): 1271–1276. doi:10.3233/JAD-160388. PMC 5008232. PMID 27372648.
- Irwin MR, Vitiello MV (March 2019). "Implications of sleep disturbance and inflammation for Alzheimer's disease dementia". The Lancet. Neurology. 18 (3): 296–306. doi:10.1016/S1474-4422(18)30450-2. PMID 30661858. S2CID 58546748.
- Kamer AR, Craig RG, Dasanayake AP, Brys M, Glodzik-Sobanska L, de Leon MJ (July 2008). "Inflammation and Alzheimer's disease: possible role of periodontal diseases". Alzheimer's & Dementia. 4 (4): 242–250. doi:10.1016/j.jalz.2007.08.004. PMID 18631974. S2CID 8633979.
- Collins SM, Surette M, Bercik P (November 2012). "The interplay between the intestinal microbiota and the brain". Nature Reviews. Microbiology. 10 (11): 735–742. doi:10.1038/nrmicro2876. PMID 23000955. S2CID 36411264.
- Deane R, Zlokovic BV (April 2007). "Role of the blood-brain barrier in the pathogenesis of Alzheimer's disease". Current Alzheimer Research. 4 (2): 191–197. doi:10.2174/156720507780362245. PMID 17430246.
- Xu H, Finkelstein DI, Adlard PA (12 June 2014). "Interactions of metals and Apolipoprotein E in Alzheimer's disease". Frontiers in Aging Neuroscience. 6: 121. doi:10.3389/fnagi.2014.00121. PMC 4054654. PMID 24971061.
Although we still do not know if the metal ion dyshomeostasis present in AD is a cause or consequence of the disease, there is a growing body of evidence showing a direct correlation between metal ions and key AD-related key proteins.
- Su B, Wang X, Nunomura A, Moreira PI, Lee HG, Perry G, et al. (December 2008). "Oxidative stress signaling in Alzheimer's disease". Current Alzheimer Research. 5 (6): 525–532. doi:10.2174/156720508786898451. PMC 2780015. PMID 19075578.
- Kastenholz B, Garfin DE, Horst J, Nagel KA (2009). "Plant metal chaperones: a novel perspective in dementia therapy". Amyloid. 16 (2): 81–83. doi:10.1080/13506120902879392. PMID 20536399. S2CID 37490474.
- "Aluminium and Alzheimer's disease". Facts about dementia. Alzheimer's Society. Archived from the original on 27 October 2005. Retrieved 14 October 2005.
- Bondy SC (January 2016). "Low levels of aluminum can lead to behavioral and morphological changes associated with Alzheimer's disease and age-related neurodegeneration". Neurotoxicology (Submitted manuscript). 52: 222–229. doi:10.1016/j.neuro.2015.12.002. PMID 26687397.
- Kandimalla R, Vallamkondu J, Corgiat EB, Gill KD (March 2016). "Understanding Aspects of Aluminum Exposure in Alzheimer's Disease Development". Brain Pathology. 26 (2): 139–154. doi:10.1111/bpa.12333. PMC 8028870. PMID 26494454. S2CID 40859643.
- Santibáñez M, Bolumar F, García AM (November 2007). "Occupational risk factors in Alzheimer's disease: a review assessing the quality of published epidemiological studies". Occupational and Environmental Medicine. 64 (11): 723–732. doi:10.1136/oem.2006.028209. PMC 2078415. PMID 17525096.
- Lidsky TI (May 2014). "Is the Aluminum Hypothesis dead?". Journal of Occupational and Environmental Medicine. 56 (5 Suppl): S73–S79. doi:10.1097/jom.0000000000000063. PMC 4131942. PMID 24806729.
- Yegambaram M, Manivannan B, Beach TG, Halden RU (2015). "Role of environmental contaminants in the etiology of Alzheimer's disease: a review". Current Alzheimer Research. 12 (2): 116–146. doi:10.2174/1567205012666150204121719. PMC 4428475. PMID 25654508.
- Rabins PV (2020). Is it Alzheimer's? : 101 answers to your most pressing questions about memory loss and dementia. Baltimore, Maryland: Johns Hopkins University Press. ISBN 978-1-4214-3639-5. OCLC 1097463155.
- Cataldo JK, Prochaska JJ, Glantz SA (2010). "Cigarette smoking is a risk factor for Alzheimer's Disease: an analysis controlling for tobacco industry affiliation". Journal of Alzheimer's Disease. 19 (2): 465–480. doi:10.3233/JAD-2010-1240. PMC 2906761. PMID 20110594.
- Eikelenboom P, van Exel E, Hoozemans JJ, Veerhuis R, Rozemuller AJ, van Gool WA (2010). "Neuroinflammation – an early event in both the history and pathogenesis of Alzheimer's disease". Neuro-Degenerative Diseases. 7 (1–3): 38–41. doi:10.1159/000283480. PMID 20160456. S2CID 40048333.
- Moulton PV, Yang W (2012). "Air pollution, oxidative stress, and Alzheimer's disease". Journal of Environmental and Public Health (Review). 2012: 472751. doi:10.1155/2012/472751. PMC 3317180. PMID 22523504.
- Paul KC, Haan M, Mayeda ER, Ritz BR (April 2019). "Ambient Air Pollution, Noise, and Late-Life Cognitive Decline and Dementia Risk". Annual Review of Public Health. 40: 203–220. doi:10.1146/annurev-publhealth-040218-044058. PMC 6544148. PMID 30935305.
- Bartzokis G (August 2011). "Alzheimer's disease as homeostatic responses to age-related myelin breakdown". Neurobiology of Aging. 32 (8): 1341–1371. doi:10.1016/j.neurobiolaging.2009.08.007. PMC 3128664. PMID 19775776.
- Cai Z, Xiao M (2016). "Oligodendrocytes and Alzheimer's disease". The International Journal of Neuroscience. 126 (2): 97–104. doi:10.3109/00207454.2015.1025778. PMID 26000818. S2CID 21448714.
- Reisberg B, Franssen EH, Hasan SM, Monteiro I, Boksay I, Souren LE, et al. (1999). "Retrogenesis: clinical, physiologic, and pathologic mechanisms in brain aging, Alzheimer's and other dementing processes". European Archives of Psychiatry and Clinical Neuroscience. 249 (3): 28–36. doi:10.1007/pl00014170. PMID 10654097. S2CID 23410069.
- Alves GS, Oertel Knöchel V, Knöchel C, Carvalho AF, Pantel J, Engelhardt E, Laks J (2015). "Integrating retrogenesis theory to Alzheimer's disease pathology: insight from DTI-TBSS investigation of the white matter microstructural integrity". BioMed Research International. 2015: 291658. doi:10.1155/2015/291658. PMC 4320890. PMID 25685779.
- Carson VB (2015). Caregiving for Alzheimer's Disease. New York: Springer New York Academy of Sciences. pp. 1–9. ISBN 978-1-4939-2406-6.
- Zis P, Hadjivassiliou M (February 2019). "Treatment of Neurological Manifestations of Gluten Sensitivity and Coeliac Disease". Current Treatment Options in Neurology. 21 (3): 10. doi:10.1007/s11940-019-0552-7. PMID 30806821. S2CID 73466457.
- Makhlouf S, Messelmani M, Zaouali J, Mrissa R (March 2018). "Cognitive impairment in celiac disease and non-celiac gluten sensitivity: review of literature on the main cognitive impairments, the imaging and the effect of gluten free diet". Acta Neurologica Belgica (Review). 118 (1): 21–27. doi:10.1007/s13760-017-0870-z. PMID 29247390. S2CID 3943047.
- Solvang SH, Nordrehaug JE, Aarsland D, Lange J, Ueland PM, McCann A, et al. (2019). "Kynurenines, Neuropsychiatric Symptoms, and Cognitive Prognosis in Patients with Mild Dementia". International Journal of Tryptophan Research. 12: 1178646919877883. doi:10.1177/1178646919877883. PMC 6769202. PMID 31632053.
- Wenk GL (2003). "Neuropathologic changes in Alzheimer's disease". The Journal of Clinical Psychiatry. 64 (Suppl 9): 7–10. PMID 12934968.
- Braak H, Del Tredici K (December 2012). "Where, when, and in what form does sporadic Alzheimer's disease begin?". Current Opinion in Neurology. 25 (6): 708–714. doi:10.1097/WCO.0b013e32835a3432. PMID 23160422.
- Desikan RS, Cabral HJ, Hess CP, Dillon WP, Glastonbury CM, Weiner MW, et al. (August 2009). "Automated MRI measures identify individuals with mild cognitive impairment and Alzheimer's disease". Brain. 132 (Pt 8): 2048–2057. doi:10.1093/brain/awp123. PMC 2714061. PMID 19460794.
- Moan R (20 July 2009). "MRI Software Accurately IDs Preclinical Alzheimer's Disease". Diagnostic Imaging. Archived from the original on 16 May 2016. Retrieved 7 January 2013.
- Tiraboschi P, Hansen LA, Thal LJ, Corey-Bloom J (June 2004). "The importance of neuritic plaques and tangles to the development and evolution of AD". Neurology. 62 (11): 1984–1989. doi:10.1212/01.WNL.0000129697.01779.0A. PMID 15184601. S2CID 25017332.
- DeTure MA, Dickson DW (August 2019). "The neuropathological diagnosis of Alzheimer's disease". Molecular Neurodegeneration. 14 (1): 32. doi:10.1186/s13024-019-0333-5. PMC 6679484. PMID 31375134.
- Tiraboschi P, Sabbagh MN, Hansen LA, Salmon DP, Merdes A, Gamst A, et al. (April 2004). "Alzheimer disease without neocortical neurofibrillary tangles: "a second look"". Neurology. 62 (7): 1141–1147. doi:10.1212/01.wnl.0000118212.41542.e7. PMID 15079014. S2CID 22832110.
- Bouras C, Hof PR, Giannakopoulos P, Michel JP, Morrison JH (1994). "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". Cerebral Cortex. 4 (2): 138–150. doi:10.1093/cercor/4.2.138. PMID 8038565.
- Kotzbauer PT, Trojanowsk JQ, Lee VM (October 2001). "Lewy body pathology in Alzheimer's disease". Journal of Molecular Neuroscience. 17 (2): 225–232. doi:10.1385/JMN:17:2:225. PMID 11816795. S2CID 44407971.
- Hashimoto M, Rockenstein E, Crews L, Masliah E (2003). "Role of protein aggregation in mitochondrial dysfunction and neurodegeneration in Alzheimer's and Parkinson's diseases". Neuromolecular Medicine. 4 (1–2): 21–36. doi:10.1385/NMM:4:1-2:21. PMID 14528050. S2CID 20760249.
- Priller C, Bauer T, Mitteregger G, Krebs B, Kretzschmar HA, Herms J (July 2006). "Synapse formation and function is modulated by the amyloid precursor protein". The Journal of Neuroscience. 26 (27): 7212–7221. doi:10.1523/JNEUROSCI.1450-06.2006. PMC 6673945. PMID 16822978.
- Turner PR, O'Connor K, Tate WP, Abraham WC (May 2003). "Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory". Progress in Neurobiology. 70 (1): 1–32. doi:10.1016/S0301-0082(03)00089-3. PMID 12927332. S2CID 25376584.
- Hooper NM (April 2005). "Roles of proteolysis and lipid rafts in the processing of the amyloid precursor protein and prion protein". Biochemical Society Transactions. 33 (Pt 2): 335–338. doi:10.1042/BST0330335. PMID 15787600. S2CID 14269634.
- Ohnishi S, Takano K (March 2004). "Amyloid fibrils from the viewpoint of protein folding". Cellular and Molecular Life Sciences. 61 (5): 511–524. doi:10.1007/s00018-003-3264-8. PMID 15004691. S2CID 25739126.
- Hernández F, Avila J (September 2007). "Tauopathies". Cellular and Molecular Life Sciences. 64 (17): 2219–2233. doi:10.1007/s00018-007-7220-x. PMID 17604998.
- Sun W, Samimi H, Gamez M, Zare H, Frost B (August 2018). "Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies". Nature Neuroscience. 21 (8): 1038–1048. doi:10.1038/s41593-018-0194-1. PMC 6095477. PMID 30038280.
- Van Broeck B, Van Broeckhoven C, Kumar-Singh S (2007). "Current insights into molecular mechanisms of Alzheimer disease and their implications for therapeutic approaches". Neuro-Degenerative Diseases. 4 (5): 349–365. doi:10.1159/000105156. PMID 17622778. S2CID 7949658.
- Huang Y, Mucke L (March 2012). "Alzheimer mechanisms and therapeutic strategies". Cell. 148 (6): 1204–1222. doi:10.1016/j.cell.2012.02.040. PMC 3319071. PMID 22424230.
- Yankner BA, Duffy LK, Kirschner DA (October 1990). "Neurotrophic and neurotoxic effects of amyloid beta protein: reversal by tachykinin neuropeptides". Science. 250 (4978): 279–282. Bibcode:1990Sci...250..279Y. doi:10.1126/science.2218531. PMID 2218531.
- Chen X, Yan SD (December 2006). "Mitochondrial Abeta: a potential cause of metabolic dysfunction in Alzheimer's disease". IUBMB Life. 58 (12): 686–694. doi:10.1080/15216540601047767. PMID 17424907. S2CID 85423830.
- Greig NH, Mattson MP, Perry T, Chan SL, Giordano T, Sambamurti K, et al. (December 2004). "New therapeutic strategies and drug candidates for neurodegenerative diseases: p53 and TNF-alpha inhibitors, and GLP-1 receptor agonists". Annals of the New York Academy of Sciences. 1035: 290–315. doi:10.1196/annals.1332.018. PMID 15681814. S2CID 84659695.
- Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL, et al. (April 2015). "Neuroinflammation in Alzheimer's disease". The Lancet. Neurology. 14 (4): 388–405. doi:10.1016/S1474-4422(15)70016-5. PMC 5909703. PMID 25792098.
- Tapia-Arancibia L, Aliaga E, Silhol M, Arancibia S (November 2008). "New insights into brain BDNF function in normal aging and Alzheimer disease". Brain Research Reviews. 59 (1): 201–220. doi:10.1016/j.brainresrev.2008.07.007. hdl:10533/142174. PMID 18708092. S2CID 6589846.
- Schindowski K, Belarbi K, Buée L (February 2008). "Neurotrophic factors in Alzheimer's disease: role of axonal transport". Genes, Brain, and Behavior. 7 (Suppl 1): 43–56. doi:10.1111/j.1601-183X.2007.00378.x. PMC 2228393. PMID 18184369.
- Mendez MF (2006). "The accurate diagnosis of early-onset dementia". International Journal of Psychiatry in Medicine. 36 (4): 401–412. doi:10.2190/Q6J4-R143-P630-KW41. PMID 17407994. S2CID 43715976.
- Klafki HW, Staufenbiel M, Kornhuber J, Wiltfang J (November 2006). "Therapeutic approaches to Alzheimer's disease". Brain. 129 (Pt 11): 2840–2855. doi:10.1093/brain/awl280. PMID 17018549.
- Dementia: Quick Reference Guide (PDF). London: (UK) National Institute for Health and Clinical Excellence. November 2006. ISBN 978-1-84629-312-2. Archived from the original (PDF) on 27 February 2008. Retrieved 22 February 2008.
- Schroeter ML, Stein T, Maslowski N, Neumann J (October 2009). "Neural correlates of Alzheimer's disease and mild cognitive impairment: a systematic and quantitative meta-analysis involving 1351 patients". NeuroImage. 47 (4): 1196–1206. doi:10.1016/j.neuroimage.2009.05.037. PMC 2730171. PMID 19463961.
- Jie CV, Treyer V, Schibli R, Mu L (January 2021). "Tauvid™: The First FDA-Approved PET Tracer for Imaging Tau Pathology in Alzheimer's Disease". Pharmaceuticals. 14 (2): 110. doi:10.3390/ph14020110. PMC 7911942. PMID 33573211.
- McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (July 1984). "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". Neurology. 34 (7): 939–944. doi:10.1212/wnl.34.7.939. PMID 6610841. S2CID 11646075.
- Weller J, Budson A (2018). "Current understanding of Alzheimer's disease diagnosis and treatment". F1000Research (Review). 7: 1161. doi:10.12688/f1000research.14506.1. PMC 6073093. PMID 30135715.
- Hane FT, Robinson M, Lee BY, Bai O, Leonenko Z, Albert MS (2017). "Recent Progress in Alzheimer's Disease Research, Part 3: Diagnosis and Treatment". Journal of Alzheimer's Disease (Review). 57 (3): 645–665. doi:10.3233/JAD-160907. PMC 5389048. PMID 28269772.
- Diagnostic and statistical manual of mental disorders: DSM-IV-TR (4th Text Revision ed.). Washington, DC: American Psychiatric Association. 2000. ISBN 978-0-89042-025-6.
- Diagnostic and statistical manual of mental disorders: DSM-5. Washington, D.C: American Psychiatric Association. 2013. p. 611. ISBN 978-0890425558.
- Sachs-Ericsson N, Blazer DG (January 2015). "The new DSM-5 diagnosis of mild neurocognitive disorder and its relation to research in mild cognitive impairment". Aging & Mental Health. 19 (1): 2–12. doi:10.1080/13607863.2014.920303. PMID 24914889. S2CID 46244321.
- Sachdev PS, Blacker D, Blazer DG, Ganguli M, Jeste DV, Paulsen JS, Petersen RC (November 2014). "Classifying neurocognitive disorders: the DSM-5 approach". Nature Reviews. Neurology. 10 (11): 634–642. doi:10.1038/nrneurol.2014.181. PMID 25266297. S2CID 20635070.
- Stokin GB, Krell-Roesch J, Petersen RC, Geda YE (2015). "Mild Neurocognitive Disorder: An Old Wine in a New Bottle". Harvard Review of Psychiatry (Review). 23 (5): 368–376. doi:10.1097/HRP.0000000000000084. PMC 4894762. PMID 26332219.
- Sperry L, Carlson J, Sauerheber J, Sperry J, eds. (6 August 2014). Psychopathology and Psychotherapy: DSM-5 Diagnosis, Case Conceptualization, and Treatment (3 ed.). New York: Routledge. pp. 342–43. doi:10.4324/9780203772287. ISBN 978-0-203-77228-7.
- Fink HA, Hemmy LS, Linskens EJ, et al. (2020). Diagnosis and Treatment of Clinical Alzheimer's-Type Dementia: A Systematic Review. AHRQ Comparative Effectiveness Reviews. Rockville (MD): Agency for Healthcare Research and Quality (US). PMID 32369312.
- Bradfield NI, Ames D (April 2020). "Mild cognitive impairment: narrative review of taxonomies and systematic review of their prediction of incident Alzheimer's disease dementia". BJPsych Bulletin (Review). 44 (2): 67–74. doi:10.1192/bjb.2019.77. PMC 7283119. PMID 31724527.
- Vega JN, Newhouse PA (October 2014). "Mild cognitive impairment: diagnosis, longitudinal course, and emerging treatments". Current Psychiatry Reports. SpringerLink. 16 (10): 490. doi:10.1007/s11920-014-0490-8. PMC 4169219. PMID 25160795.
- Parnetti L, Chipi E, Salvadori N, D'Andrea K, Eusebi P (January 2019). "Prevalence and risk of progression of preclinical Alzheimer's disease stages: a systematic review and meta-analysis". Alzheimer's Research & Therapy. Springer Nature. 11 (1): 7. doi:10.1186/s13195-018-0459-7. PMC 6334406. PMID 30646955.
- Jack CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. (April 2018). "NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease". Alzheimer's & Dementia. Wiley Online Library. 14 (4): 535–562. doi:10.1016/j.jalz.2018.02.018. PMC 5958625. PMID 29653606.
- Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, et al. (May 2011). "Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease". Alzheimer's & Dementia. Wiley Online Library. 7 (3): 280–292. doi:10.1016/j.jalz.2011.03.003. PMC 3220946. PMID 21514248.
- Cheng YW, Chen TF, Chiu MJ (16 February 2017). "From mild cognitive impairment to subjective cognitive decline: conceptual and methodological evolution". Neuropsychiatric Disease and Treatment. Dove Medical Press Limited. 13: 491–498. doi:10.2147/NDT.S123428. PMC 5317337. PMID 28243102.
- Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, et al. (May 2011). "The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease". Alzheimer's & Dementia. Wiley Online Library. 7 (3): 270–279. doi:10.1016/j.jalz.2011.03.008. PMC 3312027. PMID 21514249.
- Chertkow H, Feldman HH, Jacova C, Massoud F (July 2013). "Definitions of dementia and predementia states in Alzheimer's disease and vascular cognitive impairment: consensus from the Canadian conference on diagnosis of dementia". Alzheimer's Research & Therapy. BMC. 5 (Suppl 1): S2. doi:10.1186/alzrt198. PMC 3981054. PMID 24565215.
- Papadakis MA, McPhee SJ, Rabow MW (2021). Current medical diagnosis & treatment 2021 (Sixtieth ed.). New York: McGraw Hill. p. 1760. ISBN 978-1-260-46986-8. OCLC 1195972209.
- Tombaugh TN, McIntyre NJ (September 1992). "The mini-mental state examination: a comprehensive review". Journal of the American Geriatrics Society. 40 (9): 922–935. doi:10.1111/j.1532-5415.1992.tb01992.x. PMID 1512391. S2CID 25169596.
- Pasquier F (January 1999). "Early diagnosis of dementia: neuropsychology". Journal of Neurology. 246 (1): 6–15. doi:10.1007/s004150050299. PMID 9987708. S2CID 2108587.
- Harvey PD, Moriarty PJ, Kleinman L, Coyne K, Sadowsky CH, Chen M, Mirski DF (2005). "The validation of a caregiver assessment of dementia: the Dementia Severity Scale". Alzheimer Disease and Associated Disorders. 19 (4): 186–194. doi:10.1097/01.wad.0000189034.43203.60. PMID 16327345. S2CID 20238911.
- Antoine C, Antoine P, Guermonprez P, Frigard B (2004). "[Awareness of deficits and anosognosia in Alzheimer's disease]". L'Encephale (in French). 30 (6): 570–577. doi:10.1016/S0013-7006(04)95472-3. PMID 15738860.
- Cruz VT, Pais J, Teixeira A, Nunes B (2004). "[The initial symptoms of Alzheimer disease: caregiver perception]". Acta Medica Portuguesa (in Portuguese). 17 (6): 435–444. PMID 16197855.
- Stern SD (2020). Symptom to diagnosis: an evidence-based guide. Adam S. Cifu, Diane Altkorn (4th ed.). [New York]. pp. 209–10. ISBN 9781260121117. OCLC 1121597721.
- Jha A, Mukhopadhaya K (2021). Alzheimer's disease: diagnosis and treatment guide. Cham, Switzerland: Springer. p. 32. ISBN 978-3-030-56739-2. OCLC 1202472277.
- Sun X, Steffens DC, Au R, Folstein M, Summergrad P, Yee J, et al. (May 2008). "Amyloid-associated depression: a prodromal depression of Alzheimer disease?". Archives of General Psychiatry. 65 (5): 542–550. doi:10.1001/archpsyc.65.5.542. PMC 3042807. PMID 18458206.
- Geldmacher DS, Whitehouse PJ (May 1997). "Differential diagnosis of Alzheimer's disease". Neurology. 48 (5 Suppl 6): S2–S9. doi:10.1212/WNL.48.5_Suppl_6.2S. PMID 9153154. S2CID 30018544.
- Potter GG, Steffens DC (May 2007). "Contribution of depression to cognitive impairment and dementia in older adults". The Neurologist. 13 (3): 105–117. doi:10.1097/01.nrl.0000252947.15389.a9. PMID 17495754. S2CID 24569198.
- Zhang S, Smailagic N, Hyde C, Noel-Storr AH, Takwoingi Y, McShane R, Feng J (July 2014). "(11)C-PIB-PET for the early diagnosis of Alzheimer's disease dementia and other dementias in people with mild cognitive impairment (MCI)". The Cochrane Database of Systematic Reviews (7): CD010386. doi:10.1002/14651858.CD010386.pub2. PMC 6464750. PMID 25052054.
- Smailagic N, Vacante M, Hyde C, Martin S, Ukoumunne O, Sachpekidis C (January 2015). "¹⁸F-FDG PET for the early diagnosis of Alzheimer's disease dementia and other dementias in people with mild cognitive impairment (MCI)". The Cochrane Database of Systematic Reviews. 1: CD010632. doi:10.1002/14651858.CD010632.pub2. PMC 7081123. PMID 25629415.
- Patterson C, Feightner JW, Garcia A, Hsiung GY, MacKnight C, Sadovnick AD (February 2008). "Diagnosis and treatment of dementia: 1. Risk assessment and primary prevention of Alzheimer disease". CMAJ. 178 (5): 548–556. doi:10.1503/cmaj.070796. PMC 2244657. PMID 18299540.
- Rosendorff C, Beeri MS, Silverman JM (2007). "Cardiovascular risk factors for Alzheimer's disease". The American Journal of Geriatric Cardiology. 16 (3): 143–149. doi:10.1111/j.1076-7460.2007.06696.x. PMID 17483665.
- Ding J, Davis-Plourde KL, Sedaghat S, Tully PJ, Wang W, Phillips C, et al. (January 2020). "Antihypertensive medications and risk for incident dementia and Alzheimer's disease: a meta-analysis of individual participant data from prospective cohort studies". The Lancet. Neurology. 19 (1): 61–70. doi:10.1016/S1474-4422(19)30393-X. PMC 7391421. PMID 31706889.
- Chu CS, Tseng PT, Stubbs B, Chen TY, Tang CH, Li DJ, et al. (April 2018). "Use of statins and the risk of dementia and mild cognitive impairment: A systematic review and meta-analysis". Scientific Reports. 8 (1): 5804. Bibcode:2018NatSR...8.5804C. doi:10.1038/s41598-018-24248-8. PMC 5895617. PMID 29643479.
- Szekely CA, Town T, Zandi PP (2007). NSAIDs for the chemoprevention of Alzheimer's disease. Subcellular Biochemistry. 42. pp. 229–48. doi:10.1007/1-4020-5688-5_11. ISBN 978-1-4020-5687-1. PMID 17612054.
- Hoozemans JJ, Veerhuis R, Rozemuller JM, Eikelenboom P (February 2011). "Soothing the inflamed brain: effect of non-steroidal anti-inflammatory drugs on Alzheimer's disease pathology". CNS & Neurological Disorders Drug Targets. 10 (1): 57–67. doi:10.2174/187152711794488665. PMID 21143138.
- Marjoribanks J, Farquhar C, Roberts H, Lethaby A, Lee J (January 2017). "Long-term hormone therapy for perimenopausal and postmenopausal women". The Cochrane Database of Systematic Reviews. 1: CD004143. doi:10.1002/14651858.CD004143.pub5. PMC 6465148. PMID 28093732.
- Viña J, Sanz-Ros J (October 2018). "Alzheimer's disease: Only prevention makes sense". European Journal of Clinical Investigation (Review). 48 (10): e13005. doi:10.1111/eci.13005. PMID 30028503. S2CID 51703879.
- Imtiaz B, Tolppanen AM, Kivipelto M, Soininen H (April 2014). "Future directions in Alzheimer's disease from risk factors to prevention". Biochemical Pharmacology (Review). 88 (4): 661–670. doi:10.1016/j.bcp.2014.01.003. PMID 24418410.
- Cheng ST (September 2016). "Cognitive Reserve and the Prevention of Dementia: the Role of Physical and Cognitive Activities". Current Psychiatry Reports (Review). 18 (9): 85. doi:10.1007/s11920-016-0721-2. PMC 4969323. PMID 27481112.
- Farina N, Rusted J, Tabet N (January 2014). "The effect of exercise interventions on cognitive outcome in Alzheimer's disease: a systematic review". International Psychogeriatrics (Review). 26 (1): 9–18. doi:10.1017/S1041610213001385. PMID 23962667. S2CID 24936334.
- Barnard ND, Bush AI, Ceccarelli A, Cooper J, de Jager CA, Erickson KI, et al. (September 2014). "Dietary and lifestyle guidelines for the prevention of Alzheimer's disease". Neurobiology of Aging (Review). 35 (Suppl 2): S74–S78. doi:10.1016/j.neurobiolaging.2014.03.033. PMID 24913896. S2CID 8265377.
- Bhatti GK, Reddy AP, Reddy PH, Bhatti JS (2019). "Lifestyle Modifications and Nutritional Interventions in Aging-Associated Cognitive Decline and Alzheimer's Disease". Frontiers in Aging Neuroscience (Review). 11: 369. doi:10.3389/fnagi.2019.00369. PMC 6966236. PMID 31998117.
- Dominguez LJ, Barbagallo M (June 2018). "Nutritional prevention of cognitive decline and dementia". Acta Bio-Medica. 89 (2): 276–290. doi:10.23750/abm.v89i2.7401. PMC 6179018. PMID 29957766.
- Goodman B. "Diet Affects Markers of Alzheimer's Disease". WebMD. Retrieved 13 December 2020.
- Kanoski SE, Davidson TL (April 2011). "Western diet consumption and cognitive impairment: links to hippocampal dysfunction and obesity". Physiology & Behavior (Review). 103 (1): 59–68. doi:10.1016/j.physbeh.2010.12.003. PMC 3056912. PMID 21167850.
- Editor (15 January 2019). "Memory loss can be caused by a number of factors, from short term causes such as low blood sugar or medication side effects to long term health issues such as dementia". Diabetes. Retrieved 13 December 2020.CS1 maint: extra text: authors list (link)
- Cao L, Tan L, Wang HF, Jiang T, Zhu XC, Lu H, et al. (November 2016). "Dietary Patterns and Risk of Dementia: a Systematic Review and Meta-Analysis of Cohort Studies". Molecular Neurobiology. 53 (9): 6144–6154. doi:10.1007/s12035-015-9516-4. OCLC 6947867710. PMID 26553347. S2CID 8188716.
- Canevelli M, Lucchini F, Quarata F, Bruno G, Cesari M (March 2016). "Nutrition and Dementia: Evidence for Preventive Approaches?". Nutrients. MDPI. 8 (3): 144. doi:10.3390/nu8030144. OCLC 8147564576. PMC 4808873. PMID 26959055.
- Omar SH (June 2019). "Mediterranean and MIND Diets Containing Olive Biophenols Reduces the Prevalence of Alzheimer's Disease". International Journal of Molecular Sciences. 20 (11): 2797. doi:10.3390/ijms20112797. PMC 6600544. PMID 31181669.
- Zis P, Hadjivassiliou M (February 2019). "Treatment of Neurological Manifestations of Gluten Sensitivity and Coeliac Disease". Current Treatment Options in Neurology (Review). 21 (3): 10. doi:10.1007/s11940-019-0552-7. PMID 30806821.
- Hu N, Yu JT, Tan L, Wang YL, Sun L, Tan L (2013). "Nutrition and the risk of Alzheimer's disease". BioMed Research International (Review). 2013: 524820. doi:10.1155/2013/524820. PMC 3705810. PMID 23865055.
- Santos C, Costa J, Santos J, Vaz-Carneiro A, Lunet N (2010). "Caffeine intake and dementia: systematic review and meta-analysis". Journal of Alzheimer's Disease. 20 (Suppl 1): S187–S204. doi:10.3233/JAD-2010-091387. PMID 20182026.
- Nehlig A (March 2013). "The neuroprotective effects of cocoa flavanol and its influence on cognitive performance". British Journal of Clinical Pharmacology (Review). 75 (3): 716–727. doi:10.1111/j.1365-2125.2012.04378.x. PMC 3575938. PMID 22775434.
- Stoclet JC, Schini-Kerth V (March 2011). "[Dietary flavonoids and human health]". Annales Pharmaceutiques Francaises. 69 (2): 78–90. doi:10.1016/j.pharma.2010.11.004. PMID 21440100.
- Loef M, Schrauzer GN, Walach H (2011). "Selenium and Alzheimer's disease: a systematic review". Journal of Alzheimer's Disease (Review). 26 (1): 81–104. doi:10.3233/JAD-2011-110414. PMID 21593562. S2CID 30661765.
- Loef M, von Stillfried N, Walach H (September 2012). "Zinc diet and Alzheimer's disease: a systematic review". Nutritional Neuroscience (Review). 15 (5): 2–12. doi:10.1179/1476830512Y.0000000010. PMID 22583839. S2CID 23381337.
- Avan A, Hoogenraad TU (2015). "Zinc and Copper in Alzheimer's Disease". Journal of Alzheimer's Disease (Review). 46 (1): 89–92. doi:10.3233/JAD-150186. PMID 25835420.
- Cunnane SC, Chouinard-Watkins R, Castellano CA, Barberger-Gateau P (January 2013). "Docosahexaenoic acid homeostasis, brain aging and Alzheimer's disease: Can we reconcile the evidence?". Prostaglandins, Leukotrienes, and Essential Fatty Acids. 88 (1): 61–70. doi:10.1016/j.plefa.2012.04.006. PMID 22575581.
- Burckhardt M, Herke M, Wustmann T, Watzke S, Langer G, Fink A (April 2016). "Omega-3 fatty acids for the treatment of dementia". The Cochrane Database of Systematic Reviews. 4: CD009002. doi:10.1002/14651858.CD009002.pub3. PMC 7117565. PMID 27063583.
- Hamaguchi T, Ono K, Yamada M (October 2010). "REVIEW: Curcumin and Alzheimer's disease". CNS Neuroscience & Therapeutics (review). 16 (5): 285–297. doi:10.1111/j.1755-5949.2010.00147.x. PMC 6493893. PMID 20406252.
- Bahji A, Meyyappan AC, Hawken ER (June 2020). "Cannabinoids for the Neuropsychiatric Symptoms of Dementia: A Systematic Review and Meta-Analysis". Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie. 65 (6): 365–376. doi:10.1177/0706743719892717. PMC 7265608. PMID 31835954.
- Drislane F, Hovauimian A, Tarulli A, Boegle AK, McIiduff C, Caplan LR (2019). Blueprints neurology (Fifth ed.). Philadelphia: Wolters Kluwer. p. 146. ISBN 978-1-4963-8739-4. OCLC 1048659425.
- Birks JS, Harvey RJ (June 2018). "Donepezil for dementia due to Alzheimer's disease". The Cochrane Database of Systematic Reviews. 2018 (6): CD001190. doi:10.1002/14651858.CD001190.pub3. PMC 6513124. PMID 29923184.
- Birks JS, Grimley Evans J (April 2015). Birks JS (ed.). "Rivastigmine for Alzheimer's disease". The Cochrane Database of Systematic Reviews (4): CD001191. doi:10.1002/14651858.CD001191.pub3. PMID 25858345.
- Fink HA, Linskens EJ, MacDonald R, Silverman PC, McCarten JR, Talley KM, et al. (May 2020). "Benefits and Harms of Prescription Drugs and Supplements for Treatment of Clinical Alzheimer-Type Dementia". Annals of Internal Medicine. 172 (10): 656–668. doi:10.7326/M19-3887. PMID 32340037. S2CID 216595473.
- Geula C, Mesulam MM (1995). "Cholinesterases and the pathology of Alzheimer disease". Alzheimer Disease and Associated Disorders. 9 (Suppl 2): 23–28. doi:10.1097/00002093-199501002-00005. PMID 8534419.
- Stahl SM (November 2000). "The new cholinesterase inhibitors for Alzheimer's disease, Part 2: illustrating their mechanisms of action". The Journal of Clinical Psychiatry. 61 (11): 813–814. doi:10.4088/JCP.v61n1101. PMID 11105732.
- Birks J (January 2006). Birks J (ed.). "Cholinesterase inhibitors for Alzheimer's disease". The Cochrane Database of Systematic Reviews (1): CD005593. doi:10.1002/14651858.CD005593. PMID 16437532.
- Raschetti R, Albanese E, Vanacore N, Maggini M (November 2007). "Cholinesterase inhibitors in mild cognitive impairment: a systematic review of randomised trials". PLOS Medicine. 4 (11): e338. doi:10.1371/journal.pmed.0040338. PMC 2082649. PMID 18044984.
- Alldredge BK, Corelli RL, Ernst ME, Guglielmo BJ, Jacobson PA, Kradjan WA, Williams BR (2013). Applied therapeutics : the clinical use of drugs (10th ed.). Baltimore: Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 2385. ISBN 978-1-60913-713-7.
- Lipton SA (February 2006). "Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond". Nature Reviews. Drug Discovery. 5 (2): 160–170. doi:10.1038/nrd1958. PMID 16424917. S2CID 21379258.
- "Memantine". US National Library of Medicine (Medline). 4 January 2004. Archived from the original on 22 February 2010. Retrieved 3 February 2010.
- McShane R, Westby MJ, Roberts E, Minakaran N, Schneider L, Farrimond LE, et al. (March 2019). "Memantine for dementia". The Cochrane Database of Systematic Reviews. 3 (3): CD003154. doi:10.1002/14651858.CD003154.pub6. PMC 6425228. PMID 30891742.
- "Namenda prescribing information" (PDF). Forest Pharmaceuticals. Archived from the original (PDF) on 27 February 2008. Retrieved 19 February 2008. (primary source)
- Raina P, Santaguida P, Ismaila A, Patterson C, Cowan D, Levine M, et al. (March 2008). "Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline". Annals of Internal Medicine. 148 (5): 379–397. doi:10.7326/0003-4819-148-5-200803040-00009. PMID 18316756. S2CID 22235353.
- Kandiah N, Ong PA, Yuda T, Ng LL, Mamun K, Merchant RA, et al. (February 2019). "Treatment of dementia and mild cognitive impairment with or without cerebrovascular disease: Expert consensus on the use of Ginkgo biloba extract, EGb 761®". CNS Neuroscience & Therapeutics. 25 (2): 288–298. doi:10.1111/cns.13095. PMC 6488894. PMID 30648358.
- McKeage K, Lyseng-Williamson KA (2018). "Ginkgo biloba extract EGb 761® in the symptomatic treatment of mild-to-moderate dementia: a profile of its use". Drugs & Therapy Perspectives. 34 (8): 358–366. doi:10.1007/s40267-018-0537-8. PMC 6267544. PMID 30546253.
- Ballard C, Waite J (January 2006). Ballard CG (ed.). "The effectiveness of atypical antipsychotics for the treatment of aggression and psychosis in Alzheimer's disease". The Cochrane Database of Systematic Reviews (1): CD003476. doi:10.1002/14651858.CD003476.pub2. PMID 16437455.
- Ballard C, Hanney ML, Theodoulou M, Douglas S, McShane R, Kossakowski K, et al. (February 2009). "The dementia antipsychotic withdrawal trial (DART-AD): long-term follow-up of a randomised placebo-controlled trial". The Lancet. Neurology. 8 (2): 151–157. doi:10.1016/S1474-4422(08)70295-3. PMID 19138567. S2CID 23000439. Lay summary.
- Declercq T, Petrovic M, Azermai M, Vander Stichele R, De Sutter AI, van Driel ML, Christiaens T (March 2013). "Withdrawal versus continuation of chronic antipsychotic drugs for behavioural and psychological symptoms in older people with dementia". The Cochrane Database of Systematic Reviews. 3 (3): CD007726. doi:10.1002/14651858.CD007726.pub2. hdl:1854/LU-3109108. PMID 23543555.
- Rabins PV, Blacker D, Rovner BW, Rummans T, Schneider LS, Tariot PN, et al. (Steering Committee on Practice Guidelines) (December 2007). "American Psychiatric Association practice guideline for the treatment of patients with Alzheimer's disease and other dementias. Second edition". The American Journal of Psychiatry. 164 (12 Suppl): 5–56. PMID 18340692.
- Bottino CM, Carvalho IA, Alvarez AM, Avila R, Zukauskas PR, Bustamante SE, et al. (December 2005). "Cognitive rehabilitation combined with drug treatment in Alzheimer's disease patients: a pilot study". Clinical Rehabilitation. 19 (8): 861–869. doi:10.1191/0269215505cr911oa. PMID 16323385. S2CID 21290731.
- Doody RS, Stevens JC, Beck C, Dubinsky RM, Kaye JA, Gwyther L, et al. (May 2001). "Practice parameter: management of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology". Neurology. 56 (9): 1154–1166. doi:10.1212/WNL.56.9.1154. PMID 11342679. S2CID 10711725.
- Hermans DG, Htay UH, McShane R (January 2007). "Non-pharmacological interventions for wandering of people with dementia in the domestic setting". The Cochrane Database of Systematic Reviews (1): CD005994. doi:10.1002/14651858.CD005994.pub2. PMC 6669244. PMID 17253573.
- Robinson L, Hutchings D, Dickinson HO, Corner L, Beyer F, Finch T, et al. (January 2007). "Effectiveness and acceptability of non-pharmacological interventions to reduce wandering in dementia: a systematic review". International Journal of Geriatric Psychiatry. 22 (1): 9–22. doi:10.1002/gps.1643. PMID 17096455. S2CID 45660235.
- Abraha I, Rimland JM, Trotta FM, Dell'Aquila G, Cruz-Jentoft A, Petrovic M, et al. (March 2017). "Systematic review of systematic reviews of non-pharmacological interventions to treat behavioural disturbances in older patients with dementia. The SENATOR-OnTop series". BMJ Open. 7 (3): e012759. doi:10.1136/bmjopen-2016-012759. PMC 5372076. PMID 28302633.
- Chung JC, Lai CK, Chung PM, French HP (2002). "Snoezelen for dementia". The Cochrane Database of Systematic Reviews (4): CD003152. doi:10.1002/14651858.CD003152. PMID 12519587.
- Woods B, O'Philbin L, Farrell EM, Spector AE, Orrell M (March 2018). "Reminiscence therapy for dementia". The Cochrane Database of Systematic Reviews. 2018 (3): CD001120. doi:10.1002/14651858.CD001120.pub3. PMC 6494367. PMID 29493789.
- Zetteler J (November 2008). "Effectiveness of simulated presence therapy for individuals with dementia: a systematic review and meta-analysis". Aging & Mental Health. 12 (6): 779–785. doi:10.1080/13607860802380631. PMID 19023729. S2CID 39529938.
- Neal M, Barton Wright P (2003). Neal M (ed.). "Validation therapy for dementia". The Cochrane Database of Systematic Reviews (3): CD001394. doi:10.1002/14651858.CD001394. PMID 12917907.
- Chung JC, Lai CK, Chung PM, French HP (2002). Chung JC (ed.). "Snoezelen for dementia". The Cochrane Database of Systematic Reviews (4): CD003152. doi:10.1002/14651858.CD003152. PMID 12519587. (up to date as of 2009)
- Spector A, Thorgrimsen L, Woods B, Royan L, Davies S, Butterworth M, Orrell M (September 2003). "Efficacy of an evidence-based cognitive stimulation therapy programme for people with dementia: randomised controlled trial". The British Journal of Psychiatry. 183 (3): 248–254. doi:10.1192/bjp.183.3.248. PMID 12948999.
- Gitlin LN, Corcoran M, Winter L, Boyce A, Hauck WW (February 2001). "A randomized, controlled trial of a home environmental intervention: effect on efficacy and upset in caregivers and on daily function of persons with dementia". The Gerontologist. 41 (1): 4–14. doi:10.1093/geront/41.1.4. PMID 11220813.
- Gitlin LN, Hauck WW, Dennis MP, Winter L (March 2005). "Maintenance of effects of the home environmental skill-building program for family caregivers and individuals with Alzheimer's disease and related disorders". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 60 (3): 368–374. doi:10.1093/gerona/60.3.368. PMID 15860476.
- "Treating Behavioral and Psychiatric Symptoms". Alzheimer's Association. 2006. Archived from the original on 25 September 2006. Retrieved 25 September 2006.
- Dunne TE, Neargarder SA, Cipolloni PB, Cronin-Golomb A (August 2004). "Visual contrast enhances food and liquid intake in advanced Alzheimer's disease". Clinical Nutrition. 23 (4): 533–538. doi:10.1016/j.clnu.2003.09.015. PMID 15297089.
- Dudek SB (2007). Nutrition Essentials for Nursing Practice. Hagerstown, Maryland: Lippincott Williams & Wilkins. p. 360. ISBN 978-0-7817-6651-7. Retrieved 19 August 2008.
- Dennehy C (2006). "Analysis of patients' rights: dementia and PEG insertion". British Journal of Nursing. 15 (1): 18–20. doi:10.12968/bjon.2006.15.1.20303. PMID 16415742.
- Chernoff R (April 2006). "Tube feeding patients with dementia". Nutrition in Clinical Practice. 21 (2): 142–146. doi:10.1177/0115426506021002142. PMID 16556924.
- Gambassi G, Landi F, Lapane KL, Sgadari A, Mor V, Bernabei R (July 1999). "Predictors of mortality in patients with Alzheimer's disease living in nursing homes". Journal of Neurology, Neurosurgery, and Psychiatry. 67 (1): 59–65. doi:10.1136/jnnp.67.1.59. PMC 1736445. PMID 10369823.
- Medical issues:
- Head B (January 2003). "Palliative care for persons with dementia". Home Healthcare Nurse. 21 (1): 53–60, quiz 61. doi:10.1097/00004045-200301000-00012. PMID 12544465.
- Friedlander AH, Norman DC, Mahler ME, Norman KM, Yagiela JA (September 2006). "Alzheimer's disease: psychopathology, medical management and dental implications". Journal of the American Dental Association. 137 (9): 1240–1251. doi:10.14219/jada.archive.2006.0381. PMID 16946428.
- Belmin J (2007). "Practical guidelines for the diagnosis and management of weight loss in Alzheimer's disease: a consensus from appropriateness ratings of a large expert panel". The Journal of Nutrition, Health & Aging. 11 (1): 33–37. PMID 17315078.
- McCurry SM, Gibbons LE, Logsdon RG, Vitiello M, Teri L (October 2003). "Training caregivers to change the sleep hygiene practices of patients with dementia: the NITE-AD project". Journal of the American Geriatrics Society. 51 (10): 1455–1460. doi:10.1046/j.1532-5415.2003.51466.x. PMID 14511168. S2CID 24065377.
- Perls TT, Herget M (December 1995). "Higher respiratory infection rates on an Alzheimer's special care unit and successful intervention". Journal of the American Geriatrics Society. 43 (12): 1341–1344. doi:10.1111/j.1532-5415.1995.tb06611.x. PMID 7490383. S2CID 30067677.
- Shega JW, Levin A, Hougham GW, Cox-Hayley D, Luchins D, Hanrahan P, et al. (April 2003). "Palliative Excellence in Alzheimer Care Efforts (PEACE): a program description". Journal of Palliative Medicine. 6 (2): 315–320. doi:10.1089/109662103764978641. PMID 12854952. S2CID 6072807.
- Zanetti O, Solerte SB, Cantoni F (2009). "Life expectancy in Alzheimer's disease (AD)". Archives of Gerontology and Geriatrics. 49 (Suppl 1): 237–243. doi:10.1016/j.archger.2009.09.035. PMID 19836639.
- "United States Life Tables, 2017" (PDF). National Vital Statistics Reports, CDC. Retrieved 10 June 2021.
- Mölsä PK, Marttila RJ, Rinne UK (March 1995). "Long-term survival and predictors of mortality in Alzheimer's disease and multi-infarct dementia". Acta Neurologica Scandinavica. 91 (3): 159–164. doi:10.1111/j.1600-0404.1995.tb00426.x. PMID 7793228. S2CID 19724937.
- Bowen JD, Malter AD, Sheppard L, Kukull WA, McCormick WC, Teri L, Larson EB (August 1996). "Predictors of mortality in patients diagnosed with probable Alzheimer's disease". Neurology. 47 (2): 433–439. doi:10.1212/wnl.47.2.433. PMID 8757016. S2CID 24961809.
- Larson EB, Shadlen MF, Wang L, McCormick WC, Bowen JD, Teri L, Kukull WA (April 2004). "Survival after initial diagnosis of Alzheimer disease". Annals of Internal Medicine. 140 (7): 501–509. doi:10.7326/0003-4819-140-7-200404060-00008. PMID 15068977. S2CID 27410149.
- Jagger C, Clarke M, Stone A (January 1995). "Predictors of survival with Alzheimer's disease: a community-based study". Psychological Medicine. 25 (1): 171–177. doi:10.1017/S0033291700028191. PMID 7792352.
- Dodge HH, Shen C, Pandav R, DeKosky ST, Ganguli M (February 2003). "Functional transitions and active life expectancy associated with Alzheimer disease". Archives of Neurology. 60 (2): 253–259. doi:10.1001/archneur.60.2.253. PMID 12580712.
- Bermejo-Pareja F, Benito-León J, Vega S, Medrano MJ, Román GC (January 2008). "Incidence and subtypes of dementia in three elderly populations of central Spain". Journal of the Neurological Sciences. 264 (1–2): 63–72. doi:10.1016/j.jns.2007.07.021. PMID 17727890. S2CID 34341344.
- Di Carlo A, Baldereschi M, Amaducci L, Lepore V, Bracco L, Maggi S, et al. (January 2002). "Incidence of dementia, Alzheimer's disease, and vascular dementia in Italy. The ILSA Study". Journal of the American Geriatrics Society. 50 (1): 41–48. doi:10.1046/j.1532-5415.2002.50006.x. PMID 12028245. S2CID 22576935.
- Tejada-Vera B. (2013). Mortality from Alzheimer's Disease in the United States: Data for 2000 and 2010. Hyattsville, MD: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics.
- Rajan KB, Weuve J, Barnes LL, McAninch EA, Wilson RS, Evans DA (May 2021). "Population estimate of people with clinical Alzheimer's disease and mild cognitive impairment in the United States (2020-2060)". Alzheimers Dement. doi:10.1002/alz.12362. PMID 34043283. S2CID 235215290.
- Rizzi L, Rosset I, Roriz-Cruz M (2014). "Global epidemiology of dementia: Alzheimer's and vascular types". Biomed Res Int. 2014: 908915. doi:10.1155/2014/908915. PMC 4095986. PMID 25089278.
- Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, et al. (December 2005). "Global prevalence of dementia: a Delphi consensus study". Lancet. 366 (9503): 2112–2117. doi:10.1016/S0140-6736(05)67889-0. PMC 2850264. PMID 16360788.
- World Health Organization (2006). Neurological Disorders: Public Health Challenges. Switzerland: World Health Organization. pp. 204–07. ISBN 978-92-4-156336-9. Archived from the original on 10 February 2010.
- Auguste D.:
- Alzheimer A (1907). "Über eine eigenartige Erkrankung der Hirnrinde" [About a peculiar disease of the cerebral cortex]. Allgemeine Zeitschrift für Psychiatrie und Psychisch-Gerichtlich Medizin (in German). 64 (1–2): 146–48.
- . Translated by H. Greenson. "About a peculiar disease of the cerebral cortex. By Alois Alzheimer, 1907 (Translated by L. Jarvik and H. Greenson)". Alzheimer Disease and Associated Disorders. 1 (1): 3–8. 1987. PMID 3331112.
- Maurer U, Maurer K (2003). Alzheimer: The Life of a Physician and the Career of a Disease. New York: Columbia University Press. p. 270. ISBN 978-0-231-11896-5.
- Berrios GE (1990). "Alzheimer's Disease: A Conceptual History". Int. J. Geriatr. Psychiatry. 5 (6): 355–65. doi:10.1002/gps.930050603. S2CID 145155424.
- Kraepelin Emil (2007). Clinical Psychiatry: A Textbook For Students And Physicians (Reprint). Translated by Diefendorf A. Ross. Kessinger Publishing. p. 568. ISBN 978-1-4325-0833-3.
- Katzman R, Terry RD, Bick KL, eds. (1978). Alzheimer's Disease: Senile Dementia and Related Disorders. New York: Raven Press. p. 595. ISBN 978-0-89004-225-0.
- Boller F, Forbes MM (June 1998). "History of dementia and dementia in history: an overview". Journal of the Neurological Sciences. 158 (2): 125–133. doi:10.1016/S0022-510X(98)00128-2. PMID 9702682. S2CID 42399340.
- Amaducci LA, Rocca WA, Schoenberg BS (November 1986). "Origin of the distinction between Alzheimer's disease and senile dementia: how history can clarify nosology". Neurology. 36 (11): 1497–1499. doi:10.1212/wnl.36.11.1497. PMID 3531918. S2CID 7689479.
- Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P, Cummings J, et al. (August 2007). "Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria". The Lancet. Neurology. 6 (8): 734–746. doi:10.1016/S1474-4422(07)70178-3. PMID 17616482. S2CID 7356809.
- Blacker D, Albert MS, Bassett SS, Go RC, Harrell LE, Folstein MF (December 1994). "Reliability and validity of NINCDS-ADRDA criteria for Alzheimer's disease. The National Institute of Mental Health Genetics Initiative". Archives of Neurology. 51 (12): 1198–1204. doi:10.1001/archneur.1994.00540240042014. PMID 7986174.
- Bonin-Guillaume S, Zekry D, Giacobini E, Gold G, Michel JP (January 2005). "[The economical impact of dementia]". Presse Médicale (in French). 34 (1): 35–41. doi:10.1016/s0755-4982(05)83882-5. PMID 15685097.
- Meek PD, McKeithan K, Schumock GT (1998). "Economic considerations in Alzheimer's disease". Pharmacotherapy. 18 (2 Pt 2): 68–73, discussion 79–82. doi:10.1002/j.1875-9114.1998.tb03880.x. PMID 9543467. S2CID 44496161.
- Allegri RF, Butman J, Arizaga RL, Machnicki G, Serrano C, Taragano FE, et al. (August 2007). "Economic impact of dementia in developing countries: an evaluation of costs of Alzheimer-type dementia in Argentina". International Psychogeriatrics. 19 (4): 705–718. doi:10.1017/S1041610206003784. PMID 16870037. S2CID 41247271.
- Suh GH, Knapp M, Kang CJ (August 2006). "The economic costs of dementia in Korea, 2002". International Journal of Geriatric Psychiatry. 21 (8): 722–728. doi:10.1002/gps.1552. PMID 16858741. S2CID 24138151.
- Moore MJ, Zhu CW, Clipp EC (July 2001). "Informal costs of dementia care: estimates from the National Longitudinal Caregiver Study". The Journals of Gerontology. Series B, Psychological Sciences and Social Sciences. 56 (4): S219–S228. doi:10.1093/geronb/56.4.S219. PMID 11445614.
- Jönsson L, Eriksdotter Jönhagen M, Kilander L, Soininen H, Hallikainen M, Waldemar G, et al. (May 2006). "Determinants of costs of care for patients with Alzheimer's disease". International Journal of Geriatric Psychiatry. 21 (5): 449–459. doi:10.1002/gps.1489. PMID 16676288. S2CID 20193233.
- "The MetLife study of Alzheimer's disease: The caregiving experience" (PDF). MetLife Mature Market Institute. August 2006. Archived from the original (PDF) on 8 January 2011. Retrieved 5 February 2011.
- Schneider J, Murray J, Banerjee S, Mann A (August 1999). "EUROCARE: a cross-national study of co-resident spouse carers for people with Alzheimer's disease: I—Factors associated with carer burden". International Journal of Geriatric Psychiatry. 14 (8): 651–661. doi:10.1002/(SICI)1099-1166(199908)14:8<651::AID-GPS992>3.0.CO;2-B. PMID 10489656.
- Murray J, Schneider J, Banerjee S, Mann A (August 1999). "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". International Journal of Geriatric Psychiatry. 14 (8): 662–667. doi:10.1002/(SICI)1099-1166(199908)14:8<662::AID-GPS993>3.0.CO;2-4. PMID 10489657.
- Zhu CW, Sano M (2006). "Economic considerations in the management of Alzheimer's disease". Clinical Interventions in Aging. 1 (2): 143–154. doi:10.2147/ciia.2006.1.2.143. PMC 2695165. PMID 18044111.
- Gaugler JE, Kane RL, Kane RA, Newcomer R (April 2005). "Early community-based service utilization and its effects on institutionalization in dementia caregiving". The Gerontologist. 45 (2): 177–185. doi:10.1093/geront/45.2.177. PMID 15799982.
- Ritchie K, Lovestone S (November 2002). "The dementias". Lancet. 360 (9347): 1759–1766. doi:10.1016/S0140-6736(02)11667-9. PMID 12480441. S2CID 21404062.
- Brodaty H, Hadzi-Pavlovic D (September 1990). "Psychosocial effects on carers of living with persons with dementia". The Australian and New Zealand Journal of Psychiatry. 24 (3): 351–361. doi:10.3109/00048679009077702. PMID 2241719. S2CID 11788466.
- Donaldson C, Tarrier N, Burns A (April 1998). "Determinants of carer stress in Alzheimer's disease". International Journal of Geriatric Psychiatry. 13 (4): 248–256. doi:10.1002/(SICI)1099-1166(199804)13:4<248::AID-GPS770>3.0.CO;2-0. PMID 9646153.
- Pusey H, Richards D (May 2001). "A systematic review of the effectiveness of psychosocial interventions for carers of people with dementia". Aging & Mental Health. 5 (2): 107–119. doi:10.1080/13607860120038302. PMID 11511058. S2CID 32517015.
- Bayley J (2000). Iris: A Memoir of Iris Murdoch. London: Abacus. ISBN 978-0-349-11215-2. OCLC 41960006.
- Sparks N (1996). The notebook. Thorndike, Maine: Thorndike Press. p. 268. ISBN 978-0-7862-0821-0.
- "Thanmathra". Webindia123.com. Archived from the original on 6 November 2007. Retrieved 24 January 2008.
- Ogiwara H (2004). Ashita no Kioku (in Japanese). Tōkyō: Kōbunsha. ISBN 978-4-334-92446-1. OCLC 57352130.
- Munro A (2001). Hateship, Friendship, Courtship, Loveship, Marriage: Stories. New York: A.A. Knopf. ISBN 978-0-375-41300-1. OCLC 46929223.
- "Malcolm and Barbara: A love story". Dfgdocs. Archived from the original on 24 May 2008. Retrieved 24 January 2008.
- "Malcolm and Barbara: A love story". BBC Cambridgeshire. Archived from the original on 10 November 2012. Retrieved 2 March 2008.
- Plunkett J (7 August 2007). "Alzheimer's film-maker to face ITV lawyers". London: Guardian Media. Archived from the original on 15 January 2008. Retrieved 24 January 2008.
- "The Caretaker: Persistent Repetition of Phrases". Fact. 26 August 2009. Archived from the original on 15 April 2021. Retrieved 9 April 2021.
- Powell M (14 June 2011). "The Caretaker: An Empty Bliss Beyond This World Album Review". Pitchfork. Archived from the original on 18 June 2011. Retrieved 19 February 2021.
- Ezra M (23 October 2020). "Why Are TikTok Teens Listening to an Album About Dementia?". The New York Times. Archived from the original on 23 October 2020. Retrieved 21 April 2021.
- Gerrard N (19 July 2015). "Words fail us: dementia and the arts". The Guardian. Archived from the original on 19 July 2015. Retrieved 14 June 2021.
- Grady D (24 October 2006). "Self-Portraits Chronicle a Descent Into Alzheimer's". The New York Times. Archived from the original on 24 October 2006. Retrieved 14 June 2021.
- Cummings JL, Morstorf T, Zhong K (July 2014). "Alzheimer's disease drug-development pipeline: few candidates, frequent failures". Alzheimer's Research & Therapy. 6 (4): 37. doi:10.1186/alzrt269. PMC 4095696. PMID 25024750.
- Gutis PS (22 March 2019). "An Alzheimer's Drug Trial Gave Me Hope, and Then It Ended". The New York Times. Retrieved 25 March 2019.
- Feuerstein A (14 February 2017). "Merck Alzheimer's Drug Study Halted Early for Futility". New York City: TheStreet, Inc. Archived from the original on 16 February 2017. Merck Alzheimer's Drug Study Halted Early for Futility Independent study monitors concluded that there was "virtually no chance of finding a positive clinical effect."
- "After A Big Failure, Scientists And Patients Hunt For A New Type Of Alzheimer's Drug". NPR.org. Retrieved 17 May 2019.
- Gallagher J (2 May 2019). "Dementia is 'greatest health challenge'". Retrieved 17 May 2019.
- Morley JE, Armbrecht HJ, Farr SA, Kumar VB (May 2012). "The senescence accelerated mouse (SAMP8) as a model for oxidative stress and Alzheimer's disease". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1822 (5): 650–656. doi:10.1016/j.bbadis.2011.11.015. PMID 22142563.
- Marciniak R, Sheardova K, Cermáková P, Hudeček D, Sumec R, Hort J (2014). "Effect of meditation on cognitive functions in context of aging and neurodegenerative diseases". Frontiers in Behavioral Neuroscience. 8: 17. doi:10.3389/fnbeh.2014.00017. PMC 3903052. PMID 24478663.
- Larouche E, Hudon C, Goulet S (January 2015). "Potential benefits of mindfulness-based interventions in mild cognitive impairment and Alzheimer's disease: an interdisciplinary perspective". Behavioural Brain Research. 276 (276): 199–212. doi:10.1016/j.bbr.2014.05.058. hdl:20.500.11794/39836. PMID 24893317. S2CID 36235259.
- Rusek M, Pluta R, Ułamek-Kozioł M, Czuczwar SJ (August 2019). "Ketogenic Diet in Alzheimer's Disease". International Journal of Molecular Sciences. 20 (16): 3892. doi:10.3390/ijms20163892. PMC 6720297. PMID 31405021.
- Martin C, Solís L, Concha MI, Otth C (June 2011). "[Herpes simplex virus type 1 as risk factor associated to Alzheimer disease]" [Herpes Simplex Virus Type 1 as Risk Factor Associated to Alzheimer Disease]. Revista Medica de Chile (in Spanish). 139 (6): 779–786. doi:10.4067/S0034-98872011000600013. PMID 22051760.
- Wozniak MA, Mee AP, Itzhaki RF (January 2009). "Herpes simplex virus type 1 DNA is located within Alzheimer's disease amyloid plaques". The Journal of Pathology (Original study). 217 (1): 131–138. doi:10.1002/path.2449. PMID 18973185. S2CID 5176764.
- Itzhaki RF (2014). "Herpes simplex virus type 1 and Alzheimer's disease: increasing evidence for a major role of the virus". Frontiers in Aging Neuroscience. 6: 202. doi:10.3389/fnagi.2014.00202. PMC 4128394. PMID 25157230.
- Lopatko Lindman K, Hemmingsson ES, Weidung B, Brännström J, Josefsson M, Olsson J, et al. (2021). "Herpesvirus infections, antiviral treatment, and the risk of dementia-a registry-based cohort study in Sweden". Alzheimer's & Dementia. 7 (1): e12119. doi:10.1002/trc2.12119. PMC 7882534. PMID 33614892.
- Itzhaki RF, Lathe R, Balin BJ, Ball MJ, Bearer EL, Braak H, et al. (2016). "Microbes and Alzheimer's Disease". Journal of Alzheimer's Disease. 51 (4): 979–984. doi:10.3233/JAD-160152. PMC 5457904. PMID 26967229.
- Alonso R, Pisa D, Rábano A, Carrasco L (July 2014). "Alzheimer's disease and disseminated mycoses". European Journal of Clinical Microbiology & Infectious Diseases. 33 (7): 1125–1132. doi:10.1007/s10096-013-2045-z. PMID 24452965. S2CID 14780610.
- Pisa D, Alonso R, Rábano A, Rodal I, Carrasco L (October 2015). "Different Brain Regions are Infected with Fungi in Alzheimer's Disease". Scientific Reports. 5: 15015. Bibcode:2015NatSR...515015P. doi:10.1038/srep15015. PMC 4606562. PMID 26468932.
- "Fungus, the bogeyman". The Economist. 22 October 2015. Archived from the original on 8 August 2017.
- Kumar DK, Choi SH, Washicosky KJ, Eimer WA, Tucker S, Ghofrani J, et al. (May 2016). "Amyloid-β peptide protects against microbial infection in mouse and worm models of Alzheimer's disease". Science Translational Medicine. 8 (340): 340ra72. doi:10.1126/scitranslmed.aaf1059. PMC 5505565. PMID 27225182.
- Kolata G (25 May 2016). "Could Alzheimer's Stem From Infections? It Makes Sense, Experts Say". The New York Times. Archived from the original on 4 February 2017.
- "Alzheimer's culprit may fight other diseases". Science News. 16 June 2016. Archived from the original on 26 May 2016.
- Chong MS, Sahadevan S (September 2005). "Preclinical Alzheimer's disease: diagnosis and prediction of progression". The Lancet. Neurology. 4 (9): 576–579. doi:10.1016/s1474-4422(05)70168-x. PMID 16109364. S2CID 45448888.
- Sharma N, Singh AN (July 2016). "Exploring Biomarkers for Alzheimer's Disease". Journal of Clinical and Diagnostic Research (Review). 10 (7): KE01–KE06. doi:10.7860/JCDR/2016/18828.8166. PMC 5020308. PMID 27630867.
- Montagne A, Barnes SR, Sweeney MD, Halliday MR, Sagare AP, Zhao Z, et al. (January 2015). "Blood-brain barrier breakdown in the aging human hippocampus". Neuron. 85 (2): 296–302. doi:10.1016/j.neuron.2014.12.032. PMC 4350773. PMID 25611508.
- Nation DA, Sweeney MD, Montagne A, Sagare AP, D'Orazio LM, Pachicano M, et al. (February 2019). "Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction". Nature Medicine. 25 (2): 270–276. doi:10.1038/s41591-018-0297-y. PMC 6367058. PMID 30643288.
- Montagne A, Nation DA, Sagare AP, Barisano G, Sweeney MD, Chakhoyan A, et al. (May 2020). "APOE4 leads to blood-brain barrier dysfunction predicting cognitive decline". Nature. 581 (7806): 71–76. Bibcode:2020Natur.581...71M. doi:10.1038/s41586-020-2247-3. PMC 7250000. PMID 32376954.
|Library resources about |
- Irvine K, Laws KR, Gale TM, Kondel TK (2012). "Greater cognitive deterioration in women than men with Alzheimer's disease: a meta analysis". Journal of Clinical and Experimental Neuropsychology (Meta-analysis). 34 (9): 989–998. doi:10.1080/13803395.2012.712676. PMID 22913619. S2CID 28300240.
- Harilal S, Jose J, Parambi DG, Kumar R, Mathew GE, Uddin MS, et al. (September 2019). "Advancements in nanotherapeutics for Alzheimer's disease: current perspectives". The Journal of Pharmacy and Pharmacology. 71 (9): 1370–1383. doi:10.1111/jphp.13132. PMID 31304982. S2CID 196616758.
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