Alzheimer's disease

Alzheimer's disease

Alzheimer's disease
Classification and external resources
Comparison of a normal aged brain (left) and the brain of a person with Alzheimer's (right). Characteristics that separate the two are pointed out.
ICD-10 G30, F00
ICD-9 331.0, 290.1
OMIM 104300
DiseasesDB 490
MedlinePlus 000760
eMedicine neuro/13
MeSH D000544
  • NBK1161

Alzheimer's disease (AD), also known as Alzheimer disease, accounts for 60% to 70% of cases of dementia.[1][2] It is a chronic disease that usually starts slowly and gets worse over time.[2] The most common early symptom is difficulty in remembering recent events (short term memory loss).[1] As the disease advances, symptoms can include: trouble with language, easily getting lost, mood swings, loss of motivation, trouble taking care of themselves, and issues with behavior.[2][1] As a person's condition declines they often withdraw from family and society.[1] Gradually, bodily functions are lost, ultimately leading to death.[3] Although the speed of progression can vary, the average life expectancy following diagnosis is three to nine years.[4] The cause of Alzheimer's disease is poorly understood.[1] About 70% of the risk is believed to be genetic with many genes usually involved.[5] Other risk factors include: a history of head injuries, depression or hypertension.[1] The disease process is associated with plaques and tangles in the brain.[5] A probable diagnosis is based on the history of the illness and cognitive testing with medical imaging and blood work used to rule out other possible causes.[6] Initial symptoms are often mistaken for normal aging.[1] It is not unusual for it to take three to six years before the diagnosis is made.[7] Examination of brain tissue is needed for a definite diagnosis.[5] Engaging in intellectual activities, exercise, and avoiding obesity may decrease the risk of AD.[5] There are no medications or supplements with evidence to support their use.[8] It is classified as a neurodegenerative disorder.[1] No treatments stop or reverse its progression, though some may temporarily improve symptoms.[2] Affected people increasingly relies on others for assistance. It may place a great burden on caregivers; the pressures can include social, psychological, physical, and economic elements.[9] Exercise programs are beneficial with respect to activities of daily living and potentially improve outcomes.[10] Treatment of behavioral problems or psychosis due to dementia with antipsychotics is common but not usually recommended due to there often being little benefit and an increased risks of death.[11][12] In 2010, there were between 21 and 35 million people worldwide with AD.[4][2] It most often begins in people over 65 years of age, although 4% to 5% of cases are early-onset Alzheimer's which begin before this.[13] It affects about 6% of people 65 years and older.[1] In 2010 dementia resulted in about 486,000 deaths.[14] It was first described by German psychiatrist and pathologist Alois Alzheimer in 1906 after who it was later named.[15] In developed countries, AD is one of the most financially costly diseases.[16][17]


  • Characteristics 1
    • Pre-dementia 1.1
    • Early 1.2
    • Moderate 1.3
    • Advanced 1.4
  • Cause 2
    • Genetics 2.1
    • Cholinergic hypothesis 2.2
    • Amyloid hypothesis 2.3
    • Tau hypothesis 2.4
    • Other hypotheses 2.5
  • Pathophysiology 3
    • Neuropathology 3.1
    • Biochemistry 3.2
    • Disease mechanism 3.3
  • Diagnosis 4
    • Criteria 4.1
    • Techniques 4.2
    • Early diagnosis 4.3
  • Prevention 5
    • Medication 5.1
    • Lifestyle 5.2
    • Diet 5.3
  • Management 6
    • Medications 6.1
    • Psychosocial intervention 6.2
    • Caregiving 6.3
    • Feeding tubes 6.4
  • Prognosis 7
  • Epidemiology 8
  • History 9
  • Society and culture 10
    • Social costs 10.1
    • Caregiving burden 10.2
    • Notable cases 10.3
  • Research directions 11
    • Imaging 11.1
  • References 12
  • Further reading 13
  • External links 14


Stages of Alzheimer's disease
Effects of aging on memory but not AD
  • [18]
  • Misplacing items sometimes[18]
  • Minor short-term memory loss[18]
  • Forgetting that memory lapses happened[18]
Early stage Alzheimer's
  • Absent-mindedness[18]
  • Forgetting appointments[18]
  • Slight changes seen by close loved ones[18]
  • Some confusion in situations outside the familiar[18]
Middle stage Alzheimer's
  • Deeper difficulty remembering recently learned information[18]
  • Deepening confusion in many circumstances[18]
  • Speech impairment[18]
  • Repeatedly initiating the same conversation[18]
Late stage Alzheimer's

The disease course is divided into four stages, with a progressive pattern of cognitive and functional impairment.


The first symptoms are often mistakenly attributed to ageing or stress.[19] Detailed neuropsychological testing can reveal mild cognitive difficulties up to eight years before a person fulfills the clinical criteria for diagnosis of AD.[20] These early symptoms can affect the most complex daily living activities.[21] The most noticeable deficit is memory loss, which shows up as difficulty in remembering recently learned facts and inability to acquire new information.[20][22]

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 AD.[20] Apathy can be observed at this stage, and remains the most persistent neuropsychiatric symptom throughout the course of the disease.[23] Depressive symptoms, irritability and reduced awareness of subtle memory difficulties also occur commonly.[24] The preclinical stage of the disease has also been termed mild cognitive impairment,[22] but whether this term corresponds to a different diagnostic stage or identifies the first step of AD is a matter of dispute.[25]


In people with AD the increasing impairment of learning and memory eventually leads to a definitive diagnosis. In a small portion of them, difficulties with language, executive functions, perception (agnosia), or execution of movements (apraxia) are more prominent than memory problems.[26] AD 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) are affected to a lesser degree than new facts or memories.[27][28]

Language problems are mainly characterised by a shrinking vocabulary and decreased word fluency, which lead to a general impoverishment of oral and written language.[26][29] In this stage, the person with Alzheimer's is usually capable of communicating basic ideas adequately.[26][29][30] 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.[26] As the disease progresses, people with AD can often continue to perform many tasks independently, but may need assistance or supervision with the most cognitively demanding activities.[26]


Progressive deterioration eventually hinders independence, with subjects being unable to perform most common activities of daily living.[26] 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.[26][30] Complex motor sequences become less coordinated as time passes and AD progresses, so the risk of falling increases.[26] During this phase, memory problems worsen, and the person may fail to recognise close relatives.[26] Long-term memory, which was previously intact, becomes impaired.[26]

Behavioural and neuropsychiatric changes become more prevalent. Common manifestations are wandering, irritability and labile affect, leading to crying, outbursts of unpremeditated aggression, or resistance to caregiving.[26] Sundowning can also appear.[31] Approximately 30% of people with AD develop illusionary misidentifications and other delusional symptoms.[26] Subjects also lose insight of their disease process and limitations (anosognosia).[26] Urinary incontinence can develop.[26] These symptoms create stress for relatives and caretakers, which can be reduced by moving the person from home care to other long-term care facilities.[26][32]


During the final stages, the patient is completely dependent upon caregivers.[26] Language is reduced to simple phrases or even single words, eventually leading to complete loss of speech.[26][30] 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 deteriorate 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.[26]


The cause for most Alzheimer's cases is still mostly unknown except for 1% to 5% of cases where genetic differences have been identified.[33] Several competing hypotheses exist trying to explain the cause of the disease:


The genetic heritability of Alzheimer's disease (and memory components thereof), based on reviews of twin and family studies, range from 49% to 79%.[34][35] Around 0.1% of the cases are familial forms of autosomal (not sex-linked) dominant inheritance, which usually have an onset before age 65.[36] This form of the disease is known as early onset familial Alzheimer's disease. Most of autosomal dominant familial AD can be attributed to mutations in one of three genes: those encoding amyloid precursor protein (APP) and presenilins 1 and 2.[37] Most mutations in the APP and presenilin genes increase the production of a small protein called Aβ42, which is the main component of senile plaques.[38] Some of the mutations merely alter the ratio between Aβ42 and the other major forms—e.g., Aβ40—without increasing Aβ42 levels.[38][39] This suggests that presenilin mutations can cause disease even if they lower the total amount of Aβ produced and may point to other roles of presenilin or a role for alterations in the function of APP and/or its fragments other than Aβ. There exist variants of the APP gene which are protective.[40]

Most cases of Alzheimer's disease do not exhibit autosomal-dominant inheritance and are termed sporadic AD, in which environmental and genetic differences may act as risk factors. The best known genetic risk factor is the inheritance of the ε4 allele of the apolipoprotein E (APOE).[41][42] Between 40 and 80% of people with AD possess at least one APOEε4 allele.[42] The APOEε4 allele increases the risk of the disease by three times in heterozygotes and by 15 times in homozygotes.[36] 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.[43][44] Early attempts to screen up to 400 candidate genes for association with late-onset sporadic AD (LOAD) resulted in a low yield,[36][37] More recent genome-wide association studies (GWAS) have found 19 areas in genes that appear to affect the risk.[45] These genes include: CASS4, CELF1, FERMT2, HLA-DRB5, INPP5D, MEF2C, NME8, PTK2B, SORL1, ZCWPW1, SlC24A4, CLU, PICALM, CR1, BIN1, MS4A, ABCA7, EPHA1, and CD2AP.[45]

Mutations in the TREM2 gene have been associated with a 3 to 5 times higher risk of developing Alzheimer's disease.[46][47] A suggested mechanism of action is that when TREM2 is mutated, white blood cells in the brain are no longer able to control the amount of beta amyloid present.

Cholinergic hypothesis

The oldest, on which most currently available drug therapies are based, is the cholinergic hypothesis,[48] which proposes that AD is caused by reduced synthesis of the neurotransmitter acetylcholine. The cholinergic hypothesis has not maintained widespread support, largely because medications intended to treat acetylcholine deficiency have not been very effective. Other cholinergic effects have also been proposed, for example, initiation of large-scale aggregation of amyloid,[49] leading to generalised neuroinflammation.[50]

Amyloid hypothesis

In 1991, the transgenic mice that express a mutant form of the human APP gene develop fibrillar amyloid plaques and Alzheimer's-like brain pathology with spatial learning deficits.[56]

An experimental vaccine was found to clear the amyloid plaques in early human trials, but it did not have any significant effect on dementia.[57] Researchers have been led to suspect non-plaque Aβ oligomers (aggregates of many monomers) as the primary pathogenic form of Aβ. These toxic oligomers, also referred to as amyloid-derived diffusible ligands (ADDLs), bind to a surface receptor on neurons and change the structure of the synapse, thereby disrupting neuronal communication.[58] One receptor for Aβ oligomers may be the prion protein, the same protein that has been linked to mad cow disease and the related human condition, Creutzfeldt–Jakob disease, thus potentially linking the underlying mechanism of these neurodegenerative disorders with that of Alzheimer's disease.[59]

In 2009, this theory was updated, suggesting that a close relative of the beta-amyloid protein, and not necessarily the beta-amyloid itself, may be a major culprit in the disease. The theory holds that an amyloid-related mechanism that prunes neuronal connections in the brain in the fast-growth phase of early life may be triggered by ageing-related processes in later life to cause the neuronal withering of Alzheimer's disease.[60] N-APP, a fragment of APP from the peptide's N-terminus, is adjacent to beta-amyloid and is cleaved from APP by one of the same enzymes. N-APP triggers the self-destruct pathway by binding to a neuronal receptor called death receptor 6 (DR6, also known as TNFRSF21).[60] DR6 is highly expressed in the human brain regions most affected by Alzheimer's, so it is possible that the N-APP/DR6 pathway might be hijacked in the ageing brain to cause damage. In this model, beta-amyloid plays a complementary role, by depressing synaptic function.

Tau hypothesis

In Alzheimer's disease, changes in tau protein lead to the disintegration of microtubules in brain cells.

The tau hypothesis proposes that tau protein abnormalities initiate the disease cascade.[52] In this model, hyperphosphorylated tau begins to pair with other threads of tau. Eventually, they form neurofibrillary tangles inside nerve cell bodies.[61] When this occurs, the microtubules disintegrate, collapsing the neuron's transport system.[62] This may result first in malfunctions in biochemical communication between neurons and later in the death of the cells.[63]

Other hypotheses

Herpes simplex virus type 1 has been proposed to play a causative role in people carrying the susceptible versions of the apoE gene.[64]

The cellular homeostasis of ionic copper, iron, and zinc is disrupted in AD, 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.[65] Some studies have shown an increased risk of developing AD with environmental factors such as the intake of metals, particularly aluminium.[66] The quality of some of these studies has been criticised,[67] and other studies have concluded that there is no relationship between these environmental factors and the development of AD.[68] Some have hypothesised that dietary copper may play a causal role.[69]

While some studies suggest that extremely low frequency electromagnetic fields may increase the risk for Alzheimer's disease,[70] reviewers found that further epidemiological and laboratory investigations of this hypothesis are needed.[71] Smoking is a significant AD risk factor.[72] Systemic markers of the innate immune system are risk factors for late-onset AD.[73]

Another hypothesis asserts that the disease may be caused by age-related myelin breakdown in the brain. Iron released during myelin breakdown is hypothesised to cause further damage. Homeostatic myelin repair processes contribute to the development of proteinaceous deposits such as beta-amyloid and tau.[74][75][76]

Oxidative stress and dys-homeostasis of biometal (biology) metabolism may be significant in the formation of the pathology.[77][78][79]

AD individuals show 70% loss of locus coeruleus cells that provide norepinephrine (in addition to its neurotransmitter role) that locally diffuses from "varicosities" as an endogenous anti-inflammatory agent in the microenvironment around the neurons, glial cells, and blood vessels in the neocortex and hippocampus.[80] It has been shown that norepinephrine stimulates mouse microglia to suppress Aβ-induced production of cytokines and their phagocytosis of Aβ.[80] This suggests that degeneration of the locus ceruleus might be responsible for increased Aβ deposition in AD brains.[80]

There is tentative evidence that exposure to air pollution may be a contributing factor to the development of Alzheimer's disease.[81]


Histopathologic image of senile plaques seen in the cerebral cortex of a person with Alzheimer's disease of presenile onset. Silver impregnation.


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.[50] Degeneration is also present in brainstem nuclei like the locus coeruleus.[82] Studies using MRI and PET have documented reductions in the size of specific brain regions in people with AD as they progressed from mild cognitive impairment to Alzheimer's disease, and in comparison with similar images from healthy older adults.[83][84]

Both amyloid plaques and neurofibrillary tangles are clearly visible by microscopy in brains of those afflicted by AD.[85] 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 ageing, the brains of people with AD have a greater number of them in specific brain regions such as the temporal lobe.[86] Lewy bodies are not rare in the brains of people with AD.[87]


Alzheimer's disease has been identified as a protein misfolding disease (proteopathy), caused by plaque accumulation of abnormally folded beta amyloid and tau amyloid proteins in the brain.[88] Plaques are made up of small peptides, 39–43 amino acids in length, called beta-amyloid (Aβ). Beta-amyloid is a fragment from a larger protein called amyloid precursor protein (APP), a transmembrane protein that penetrates through the neuron's membrane. APP is critical to neuron growth, survival and post-injury repair.[89][90] In Alzheimer's disease, an unknown process causes APP to be divided into smaller fragments by enzymes through proteolysis.[91] One of these fragments gives rise to fibrils of beta-amyloid, which form clumps that deposit outside neurons in dense formations known as senile plaques.[85][92]

AD is also considered a tauopathy due to abnormal aggregation of the tau protein. Every neuron has a cytoskeleton, an internal support structure partly made up of structures called microtubules. These microtubules act like tracks, guiding nutrients and molecules from the body of the cell to the ends of the axon and back. A protein called tau stabilises the microtubules when phosphorylated, and is therefore called a microtubule-associated protein. In AD, tau undergoes chemical changes, becoming hyperphosphorylated; it then begins to pair with other threads, creating neurofibrillary tangles and disintegrating the neuron's transport system.[93]

Disease mechanism

Exactly how disturbances of production and aggregation of the beta-amyloid peptide gives rise to the pathology of AD is not known.[94][95] 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).[96] 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.[97]

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 AD or a marker of an immunological response.[98]

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 AD.[99][100]


PET scan of the brain of a person with AD showing a loss of function in the temporal lobe

Alzheimer's disease is usually diagnosed based on the person's history, history from relatives, and observations of the person's behaviours. The presence of characteristic neurological and neuropsychological features and the absence of alternative conditions is supportive.[101][102] 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.[103] Moreover, it may predict conversion from prodromal stages (mild cognitive impairment) to Alzheimer's disease.[104]

post-mortem when brain material is available and can be examined histologically.[105]


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,[105] extensively updated in 2007.[106] These criteria require that the presence of cognitive impairment, and a suspected dementia syndrome, be confirmed by neuropsychological testing for a clinical diagnosis of possible or probable AD. 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.[107] Eight cognitive domains are most commonly impaired in AD—memory, language, perceptual skills, attention, constructive abilities, orientation, problem solving and functional abilities. These domains are equivalent to the NINCDS-ADRDA Alzheimer's Criteria as listed in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) published by the American Psychiatric Association.[108][109]


Neuropsychological screening tests can help in the diagnosis of AD. In the tests, people are instructed to copy drawings similar to the one shown in the picture, remember words, read, and subtract serial numbers.

Neuropsychological tests such as the mini–mental state examination (MMSE) are widely used to evaluate the cognitive impairments needed for diagnosis. More comprehensive test arrays are necessary for high reliability of results, particularly in the earliest stages of the disease.[110][111] Neurological examination in early AD will usually provide normal results, except for obvious cognitive impairment, which may not differ from that resulting from other diseases processes, including other causes of dementia.

Further neurological examinations are crucial in the differential diagnosis of AD and other diseases.[19] Interviews with family members are also utilised in the assessment of the disease. Caregivers can supply important information on the daily living abilities, as well as on the decrease, over time, of the person's mental function.[104] A caregiver's viewpoint is particularly important, since a person with AD is commonly unaware of his own deficits.[112] Many times, families also have difficulties in the detection of initial dementia symptoms and may not communicate accurate information to a physician.[113]

Supplemental testing provides extra information on some features of the disease or is used to rule out other diagnoses. Blood tests can identify other causes for dementia than AD[19]—causes which may, in rare cases, be reversible.[114] It is common to perform thyroid function tests, assess B12, rule out syphilis, rule out metabolic problems (including tests for kidney function, electrolyte levels and for diabetes), assess levels of heavy metals (e.g. lead, mercury) and anaemia. (See differential diagnosis for Dementia). (It is also necessary to rule out delirium).

Psychological tests for depression are employed, since depression can either be concurrent with AD (see Depression of Alzheimer disease), an early sign of cognitive impairment,[115] or even the cause.[116][117]

Early diagnosis

Emphasis in Alzheimer's research has been placed on diagnosing the condition before symptoms begin.[118] A number of biochemical tests have been developed to allow for early detection. One such test involves the analysis of cerebrospinal fluid for beta-amyloid or tau proteins,[119] both total tau protein and phosphorylated tau181P protein concentrations.[120] Searching for these proteins using a spinal tap can predict the onset of Alzheimer's with a sensitivity of between 94% and 100%.[120] When used in conjunction with existing neuroimaging techniques, doctors can identify people with significant memory loss who are already developing the disease.[120]


Intellectual activities such as playing chess or regular social interaction have been linked to a reduced risk of AD in epidemiological studies, although no causal relationship has been found.

At present, there is no definitive evidence to support that any particular measure is effective in preventing AD.[121] Global studies of measures to prevent or delay the onset of AD 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 AD. Only further research, including clinical trials, will reveal whether these factors can help to prevent AD.[122]


Although cardiovascular risk factors, such as hypercholesterolaemia, hypertension, diabetes, and smoking, are associated with a higher risk of onset and course of AD,[123][124] statins, which are cholesterol lowering drugs, have not been effective in preventing or improving the course of the disease.[125][126]

Long-term usage of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced likelihood of developing AD.[127] Human postmortem studies, in animal models, or in vitro investigations also support the notion that NSAIDs can reduce inflammation related to amyloid plaques.[127] However, trials investigating their use as palliative treatment have failed to show positive results, apparently because the brain NSAID concentration after an oral NSAID dose is exceedingly small.[128] No prevention trial has been completed.[127] Hormone replacement therapy, although previously used, may increase the risk of dementia.[129]


People who engage in intellectual activities such as reading, playing board games, completing crossword puzzles, playing musical instruments, or regular social interaction show a reduced risk for Alzheimer's disease.[130] 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.[130] Education delays the onset of AD syndrome, but is not related to earlier death after diagnosis.[131] Learning a second language even later in life seems to delay getting Alzheimer disease.[132] Physical activity is also associated with a reduced risk of AD.[131]


People who eat a healthy, Japanese or mediterranean diet have a lower risk of AD,[133] and a mediterranean diet may improve outcomes in those with the disease.[134] Those who eat a diet high in saturated fats and simple carbohydrates have a higher risk.[135] The mediterranean diet's beneficial cardiovascular effect has been proposed as the mechanism of action.[136] Conclusions on dietary components have at times been difficult to ascertain as results have differed between population-based studies and randomised controlled trials.[133] There is limited evidence that light to moderate use of alcohol, particularly red wine, is associated with lower risk of AD.[137] There is tentative evidence that caffeine may be protective.[138] A number of foods high in flavonoids such as cocoa, red wine, and tea may decrease the risk of AD.[139][140] Reviews on the use of vitamins and minerals have not found enough consistent evidence to recommend them. This includes vitamin A,[141][142] C,[143][144] E,[144][145] selenium,[146] zinc,[147] and folic acid with or without vitamin B12.[148] Additionally vitamin E is associated with health risks.[144] Trials examining folic acid (B9) and other B vitamins failed to show any significant association with cognitive decline.[149] In those already affected with AD adding docosahexaenoic acid, an Omega 3 fatty acid, to the diet has not been found to slow decline.[150] Curcumin as of 2010 has not shown benefit in people even though there is tentative evidence in animals.[151] There is inconsistent and unconvincing evidence that ginkgo has any positive effect on cognitive impairment and dementia.[152] As of 2008 there is no concrete evidence that cannabinoids are effective in improving the symptoms of AD or dementia.[153] Some research in its early stages however looks promising.[154]


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


Three-dimensional molecular model of donepezil, an acetylcholinesterase inhibitor used in the treatment of AD symptoms
Molecular structure of memantine, a medication approved for advanced AD symptoms

Five medications are currently used to treat the cognitive problems of AD: four are acetylcholinesterase inhibitors (tacrine, rivastigmine, galantamine and donepezil) and the other (memantine) is an NMDA receptor antagonist.[155] The benefit from their use is small.[156][157] No medication has been clearly shown to delay or halt the progression of the disease.

Reduction in the activity of the cholinergic neurons is a well-known feature of Alzheimer's disease.[158] 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.[159] There is evidence for the efficacy of these medications in mild to moderate Alzheimer's disease,[160][161] and some evidence for their use in the advanced stage. Only donepezil is approved for treatment of advanced AD dementia.[162] The use of these drugs in mild cognitive impairment has not shown any effect in a delay of the onset of AD.[163] 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.[164] Less common secondary effects include muscle cramps, decreased heart rate (bradycardia), decreased appetite and weight, and increased gastric acid production.[165]

Glutamate is a useful 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.[166] 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.[166][167] Memantine has been shown to be moderately efficacious in the treatment of moderate to severe Alzheimer's disease. Its effects in the initial stages of AD are unknown.[168] Reported adverse events with memantine are infrequent and mild, including hallucinations, confusion, dizziness, headache and fatigue.[169] The combination of memantine and donepezil has been shown to be "of statistically significant but clinically marginal effectiveness".[170]

Antipsychotic drugs are modestly useful in reducing aggression and psychosis in Alzheimer's disease with behavioural problems, but are associated with serious adverse effects, such as stroke, movement difficulties or cognitive decline, that do not permit their routine use.[171][172] When used in the long-term, they have been shown to associate with increased mortality.[172]

Huperzine A while promising, requires further evidence before it use can be recommended.[173]

Psychosocial intervention

A specifically designed room for sensory integration therapy, also called snoezelen; an emotion-oriented psychosocial intervention for people with dementia

Psychosocial interventions are used as an adjunct to pharmaceutical treatment and can be classified within behaviour-, emotion-, cognition- or stimulation-oriented approaches. Research on efficacy is unavailable and rarely specific to AD, focusing instead on dementia in general.[174]

Behavioural interventions attempt to identify and reduce the antecedents and consequences of problem behaviours. This approach has not shown success in improving overall functioning,[175] but can help to reduce some specific problem behaviours, such as incontinence.[176] There is a lack of high quality data on the effectiveness of these techniques in other behaviour problems such as wandering.[177][178]

Emotion-oriented interventions include reminiscence therapy, validation therapy, supportive psychotherapy, sensory integration, also called snoezelen, and simulated presence therapy. Supportive psychotherapy has received little or no formal scientific study, but some clinicians find it useful in helping mildly impaired people adjust to their illness.[174] Reminiscence therapy (RT) involves the discussion of past experiences individually or in group, many times with the aid of photographs, household items, music and sound recordings, or other familiar items from the past. Although there are few quality studies on the effectiveness of RT, it may be beneficial for cognition and mood.[179] 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 behaviours.[180] 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.[181][182]

The aim of cognition-oriented treatments, which include reality orientation and cognitive retraining, is the reduction of cognitive deficits. Reality orientation consists in 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 exercitation of mental abilities. Both have shown some efficacy improving cognitive capacities,[183][184] although in some studies these effects were transient and negative effects, such as frustration, have also been reported.[174]

Stimulation-oriented treatments include art, music and pet therapies, exercise, and any other kind of recreational activities. Stimulation has modest support for improving behaviour, mood, and, to a lesser extent, function. Nevertheless, as important as these effects are, the main support for the use of stimulation therapies is the change in the person's routine.[174]


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

During the early and moderate stages, modifications to the living environment and lifestyle can increase patient safety and reduce caretaker burden.[185][186] Examples of such modifications are the adherence to simplified routines, the placing of safety locks, the labelling of household items to cue the person with the disease or the use of modified daily life objects.[174][187][188] Patients may also become incapable of feeding themselves, so they require food in smaller pieces or pureed.[189] 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.[190][191] The use of physical restraints is rarely indicated in any stage of the disease, although there are situations when they are necessary to prevent harm to the person with AD or their caregivers.[174]

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.[192][193] During the final stages of the disease, treatment is centred on relieving discomfort until death.[194]

A small recent study in the US concluded that people whose caregivers had a realistic understanding of the prognosis and clinical complications of late dementia were less likely to receive aggressive treatment near the end of life. [195]

Feeding tubes

People with Alzheimer's disease often develop problems with keeping up their oral intake, from difficulties swallowing, reduced appetite or inability to recognise food. Their carers and families often request they have some form of feeding tube. However, there is no evidence that this helps people with advanced Alzheimer's dementia gain weight, regain strength or improve quality of life. In fact, there might be an increased risk of aspiration pneumonia.[196]


Disability-adjusted life year for Alzheimer and other dementias per 100,000 inhabitants in 2004.
  No data
  ≤ 50
  ≥ 250

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.[26]

Life expectancy of the population with the disease is reduced.[197][198][199] The mean life expectancy following diagnosis is approximately seven years.[197] Fewer than 3% of people live more than fourteen years.[200] 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.[198][201][202] 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.[199] Men have a less favourable survival prognosis than women.[200][203]

The disease is the underlying cause of death in 68% of all cases.[197] Pneumonia and dehydration are the most frequent immediate causes of death brought by AD, while cancer is a less frequent cause of death than in the general population.[197][203]


Rates after age 65[204]
Age New affected
per thousand
65–69  3
70–74  6
75–79  9
80–84 23
85–89 40
90–     69

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 AD,[204][205] which means that half of new dementia cases each year are AD. Advancing age is a primary risk factor for the disease and incidence rates are not equal for all ages: every five years after the age of 65, the risk of acquiring the disease approximately doubles, increasing from 3 to as much as 69 per thousand person years.[204][205] There are also sex differences in the incidence rates, women having a higher risk of developing AD particularly in the population older than 85.[205][206] The risk of dying from Alzheimer’s disease is twenty-six percent higher among the non-Hispanic white population than among the non-Hispanic black population, whereas the Hispanic population has a thirty percent lower risk than the non-Hispanic white population.[207]

Prevalence of AD in populations is dependent upon different factors including incidence and survival. Since the incidence of AD increases with age, it is particularly important to include the mean age of the population of interest. In the United States, Alzheimer prevalence was estimated to be 1.6% in 2000 both overall and in the 65–74 age group, with the rate increasing to 19% in the 75–84 group and to 42% in the greater than 84 group.[208] Prevalence rates in less developed regions are lower.[209] The

  • Alzheimer's disease at DMOZ

External links

  • Alzheimer's Disease: Unraveling the Mystery. US Department of Health and Human Services, National Institute on Aging, NIH. 2008. 
  • Can Alzheimer's Disease Be Prevented?. US Department of Health and Human Services, National Institute on Aging, NIH. 2009. 
  • Caring for a Person with Alzheimer's Disease: Your Easy-to-Use Guide from the National Institute on Aging. US Department of Health and Human Services, National Institute on Aging, NIH. 2009. 
  • Russell D, Barston S, White M (19 December 2007). "Alzheimer's Behavior Management: Learn to Manage Common Behavior Problems". Archived from the original on 23 February 2008. Retrieved 29 February 2008. 
  • Irvine K, Laws KR, Gale TM, Kondel TK. Greater cognitive deterioration in women than men with Alzheimer's disease: a meta analysis. Journal of Clinical and Experimental Neuropsychology. 2012;34(9):989–98. doi:10.1080/13803395.2012.712676. PMID 22913619.

Further reading

  1. ^ a b c d e f g h i Burns, A; Iliffe, S (5 February 2009). "Alzheimer's disease.". BMJ (Clinical research ed.) 338: b158.  
  2. ^ a b c d e "Dementia Fact sheet N°362". April 2012. Retrieved 28 November 2014. 
  3. ^ "About Alzheimer's Disease: Symptoms". National Institute on Aging. Retrieved 28 December 2011. 
  4. ^ a b Querfurth, HW; LaFerla, FM (28 January 2010). "Alzheimer's disease.". The New England journal of medicine 362 (4): 329–44.  
  5. ^ a b c d Ballard, C; Gauthier, S; Corbett, A; Brayne, C; Aarsland, D; Jones, E (19 March 2011). "Alzheimer's disease.". Lancet 377 (9770): 1019–31.  
  6. ^ "Dementia diagnosis and assessment". Retrieved 30 November 2014. 
  7. ^ 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): 1109–24.  
  8. ^ "More research needed on ways to prevent Alzheimer's, panel finds" (PDF). National Institute on Aging. 29 August 2006. Retrieved 29 February 2008. 
  9. ^ a b c Thompson CA, Spilsbury K, Hall J, Birks Y, Barnes C, Adamson J. Systematic Review of Information and Support Interventions for Caregivers of People with Dementia. BMC Geriatrics. 2007;7:18. doi:10.1186/1471-2318-7-18. PMID 17662119.
  10. ^ Forbes, D.; Thiessen, E.J.; Blake, C.M.; Forbes, S.C.; Forbes, S. (4 December 2013). "Exercise programs for people with dementia.". The Cochrane database of systematic reviews 12: CD006489.  
  11. ^ National Institute for Health and Clinical Excellence. "Low-dose antipsychotics in people with dementia". Retrieved 29 November 2014. 
  12. ^ "Information for Healthcare Professionals: Conventional Antipsychotics". 2008-06-16. Retrieved 29 November 2014. 
  13. ^ Mendez, MF (November 2012). "Early-onset Alzheimer's disease: nonamnestic subtypes and type 2 AD.". Archives of medical research 43 (8): 677–85.  
  14. ^ Lozano, R; Naghavi, M; Foreman, Ktitle=Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. (15 December 2012). Lancet 380 (9859): 2095–128.  
  15. ^ a b c Berchtold NC, Cotman CW. Evolution in the Conceptualization of Dementia and Alzheimer's Disease: Greco-Roman Period to the 1960s. Neurobiology of Aging. 1998;19(3):173–89. doi:10.1016/S0197-4580(98)00052-9. PMID 9661992.
  16. ^ a b c d Bonin-Guillaume S, Zekry D, Giacobini E, Gold G, Michel JP. Impact économique de la démence (English: The Economical Impact of Dementia). Presse Médicale. 2005;34(1):35–41. French. PMID 15685097.
  17. ^ a b c d e Meek PD, McKeithan K, Schumock GT. Economic Considerations in Alzheimer's Disease. Pharmacotherapy. 1998;18(2 Pt 2):68–73; discussion 79–82. PMID 9543467.
  18. ^ a b c d e f g h i j k l m n o p Consumer Reports; Drug Effectiveness Review Project. Evaluating Prescription Drugs Used to Treat: Alzheimer's Disease Comparing Effectiveness, Safety, and Price. May 2012 [Retrieved 1 May 2013]:2., which claims Alzheimer’s Association guidance as a source
  19. ^ a b c d e Waldemar G, Dubois B, Emre M, Georges J, McKeith IG, Rossor M, Scheltens P, Tariska P, Winblad B. Recommendations for the Diagnosis and Management of Alzheimer's Disease and Other Disorders Associated with Dementia: EFNS Guideline. European Journal of Neurology. 2007;14(1):e1–26. doi:10.1111/j.1468-1331.2006.01605.x. PMID 17222085.
  20. ^ a b c Bäckman L, Jones S, Berger AK, Laukka EJ, Small BJ. Multiple Cognitive Deficits During the Transition to Alzheimer's Disease. Journal of Internal Medicine. 2004;256(3):195–204. doi:10.1111/j.1365-2796.2004.01386.x. PMID 15324363.
  21. ^ Nygård L. Instrumental Activities of Daily Living: A Stepping-stone Towards Alzheimer's Disease Diagnosis in Subjects with Mild Cognitive Impairment?. Acta Neurologica Scandinavica. 2003;Suppl(179):42–6. doi:10.1034/j.1600-0404.107.s179.8.x. PMID 12603250.
  22. ^ a b Arnáiz E, Almkvist O. Neuropsychological Features of Mild Cognitive Impairment and Preclinical Alzheimer's Disease. Acta Neurologica Scandinavica. 2003;179:34–41. doi:10.1034/j.1600-0404.107.s179.7.x. PMID 12603249.
  23. ^ Landes AM, Sperry SD, Strauss ME, Geldmacher DS. Apathy in Alzheimer's Disease. Journal of the American Geriatrics Society. 2001;49(12):1700–7. doi:10.1046/j.1532-5415.2001.49282.x. PMID 11844006.
  24. ^ Murray ED, Buttner N, Price BH (2012). "Depression and Psychosis in Neurological Practice". In Bradley WG, Daroff RB, Fenichel GM, Jankovic J. Bradley's neurology in clinical practice. (6th ed.). Philadelphia, PA: Elsevier/Saunders.  
  25. ^ Petersen RC. The Current Status of Mild Cognitive Impairment—What Do We Tell Our Patients?. Nature Clinical Practice. Neurology. 2007;3(2):60–1. doi:10.1038/ncpneuro0402. PMID 17279076.
  26. ^ a b c d e f g h i j k l m n o p q r s Förstl H, Kurz A. Clinical Features of Alzheimer's Disease. European Archives of Psychiatry and Clinical Neuroscience. 1999;249(6):288–290. doi:10.1007/s004060050101. PMID 10653284.
  27. ^ Carlesimo GA, Oscar-Berman M. Memory Deficits in Alzheimer's Patients: A Comprehensive Review. Neuropsychology Review. 1992;3(2):119–69. doi:10.1007/BF01108841. PMID 1300219.
  28. ^ Jelicic M, Bonebakker AE, Bonke B. Implicit Memory Performance of Patients with Alzheimer's Disease: A Brief Review. International Psychogeriatrics. 1995;7(3):385–392. doi:10.1017/S1041610295002134. PMID 8821346.
  29. ^ a b Taler V, Phillips NA. Language Performance in Alzheimer's Disease and Mild Cognitive Impairment: a comparative review. Journal of Clinical and Experimental Neuropsychology. July 2008;30(5):501–56. doi:10.1080/13803390701550128. PMID 18569251.
  30. ^ a b c Frank EM. Effect of Alzheimer's Disease on Communication Function. Journal of the South Carolina Medical Association. 1994;90(9):417–23. PMID 7967534.
  31. ^ Volicer L, Harper DG, Manning BC, Goldstein R, Satlin A. Sundowning and Circadian Rhythms in Alzheimer's Disease. The American Journal of Psychiatry. 2001 [Retrieved 27 August 2008];158(5):704–11. doi:10.1176/appi.ajp.158.5.704. PMID 11329390.
  32. ^ Gold DP, Reis MF, Markiewicz D, Andres D. When Home Caregiving Ends: A Longitudinal Study of Outcomes for Caregivers of Relatives with Dementia. Journal of the American Geriatrics Society. 1995;43(1):10–6. PMID 7806732.
  33. ^ "What We Know Today About Alzheimer's Disease". Alzheimer's Association. Retrieved 1 October 2011. While scientists know Alzheimer's disease involves progressive brain cell failure, the reason cells fail isn't clear. 
  34. ^ Wilson RS, Barral S, Lee JH, Leurgans SE, Foroud TM, Sweet RA, Graff-Radford N, Bird TD, Mayeux R, Bennett DA. Heritability of different forms of memory in the Late Onset Alzheimer's Disease Family Study.. J Alzheimers Dis.. 2011;23(2):249-55. doi:doi:10.3233/JAD-2010-101515. PMID 20930268.
  35. ^ Gatz M, Reynolds CA, Fratiglioni L, Johansson B, Mortimer JA, Berg S, Fiske A, Pedersen NL. Role of genes and environments for explaining Alzheimer disease. Arch Gen Psychiatry. 2006;63(2):168-74. doi:doi:10.1001/archpsyc.63.2.168. PMID 16461860.
  36. ^ a b c Blennow K, de Leon MJ, Zetterberg H. Alzheimer's Disease. Lancet. 2006;368(9533):387–403. doi:10.1016/S0140-6736(06)69113-7. PMID 16876668.
  37. ^ a b Waring SC, Rosenberg RN. Genome-wide association studies in Alzheimer disease. Archives of Neurology. 2008;65(3):329–34. doi:10.1001/archneur.65.3.329. PMID 18332245.
  38. ^ a b Selkoe DJ. Translating cell biology into therapeutic advances in Alzheimer's disease. Nature. 1999;399(6738 Suppl):A23–31. doi:10.1038/19866. PMID 10392577.
  39. ^ Shioi J, Georgakopoulos A, Mehta P, Kouchi Z, Litterst CM, Baki L, Robakis NK. FAD mutants unable to increase neurotoxic Aβ 42 suggest that mutation effects on neurodegeneration may be independent of effects on Abeta. Journal of Neurochemistry. 2007;101(3):674–81. doi:10.1111/j.1471-4159.2006.04391.x. PMID 17254019.
  40. ^ Jonsson T, Atwal JK, Steinberg S, Snaedal J, Jonsson PV, Bjornsson S, Stefansson H, Sulem P, Gudbjartsson D, Maloney J, Hoyte K, Gustafson A, Liu Y, Lu Y, Bhangale T, Graham RR, Huttenlocher J, Bjornsdottir G, Andreassen OA, Jönsson EG, Palotie A, Behrens TW, Magnusson OT, Kong A, Thorsteinsdottir U, Watts RJ, Stefansson K. A mutation in APP protects against Alzheimer's disease and age-related cognitive decline.. Nature. 2 August 2012;488(7409):96–9. doi:10.1038/nature11283. PMID 22801501.
  41. ^ Strittmatter WJ, Saunders AM, Schmechel D, Pericak-Vance M, Enghild J, Salvesen GS, Roses AD. Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proceedings of the National Academy of Sciences of the United States of America. 1993;90(5):1977–81. doi:10.1073/pnas.90.5.1977. PMID 8446617.
  42. ^ a b Mahley RW, Weisgraber KH, Huang Y. 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. 2006;103(15):5644–51. doi:10.1073/pnas.0600549103. PMID 16567625.
  43. ^ Hall K, Murrell J, Ogunniyi A, Deeg M, Baiyewu O, Gao S, Gureje O, Dickens J, Evans R, Smith-Gamble V, Unverzagt FW, Shen J, Hendrie H. Cholesterol, APOE genotype, and Alzheimer disease: an epidemiologic study of Nigerian Yoruba. Neurology. 2006;66(2):223–227. doi:10.1212/01.wnl.0000194507.39504.17. PMID 16434658.
  44. ^ Gureje O, Ogunniyi A, Baiyewu O, Price B, Unverzagt FW, Evans RM, Smith-Gamble V, Lane KA, Gao S, Hall KS, Hendrie HC, Murrell JR. APOE ε4 is not associated with Alzheimer's disease in elderly Nigerians. Annals of Neurology. 2006;59(1):182–185. doi:10.1002/ana.20694. PMID 16278853.
  45. ^ a b Lambert, JC (Dec 2013). "Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease.". Nature Genetics 45 (12): 1452–8.  
  46. ^ Jonsson T, Stefansson H, Steinberg S, Jonsdottir I, Jonsson PV, Snaedal J, Bjornsson S, Huttenlocher J, Levey AI, Lah JJ, Rujescu D, Hampel H, Giegling I, Andreassen OA, Engedal K, Ulstein I, Djurovic S, Ibrahim-Verbaas C, Hofman A, Ikram MA, van Duijn CM, Thorsteinsdottir U, Kong A, Stefansson K. Variant of TREM2 associated with the risk of Alzheimer's disease. The New England Journal of Medicine. 2012;368(2):107–16. doi:10.1056/NEJMoa1211103. PMID 23150908.
  47. ^ Guerreiro R, Wojtas A, Bras J, Carrasquillo M, Rogaeva E, Majounie E, Cruchaga C, Sassi C, Kauwe JS, Younkin S, Hazrati L, Collinge J, Pocock J, Lashley T, Williams J, Lambert JC, Amouyel P, Goate A, Rademakers R, Morgan K, Powell J, St George-Hyslop P, Singleton A, Hardy J. TREM2 variants in Alzheimer's disease. The New England Journal of Medicine. 2012;368(2):117–27. doi:10.1056/NEJMoa1211851. PMID 23150934.
  48. ^ Francis PT, Palmer AM, Snape M, Wilcock GK. The Cholinergic Hypothesis of Alzheimer's Disease: a Review of Progress. Journal of Neurology, Neurosurgery, and Psychiatry. 1999;66(2):137–47. doi:10.1136/jnnp.66.2.137. PMID 10071091.
  49. ^ Shen ZX. Brain Cholinesterases: II. The Molecular and Cellular Basis of Alzheimer's Disease. Medical Hypotheses. 2004;63(2):308–21. doi:10.1016/j.mehy.2004.02.031. PMID 15236795.
  50. ^ a b Wenk GL. Neuropathologic Changes in Alzheimer's Disease. The Journal of Clinical Psychiatry. 2003;64 Suppl 9:7–10. PMID 12934968.
  51. ^ Hardy J, Allsop D. Amyloid Deposition as the Central Event in the Aetiology of Alzheimer's Disease. Trends in Pharmacological Sciences. 1991;12(10):383–88. doi:10.1016/0165-6147(91)90609-V. PMID 1763432.
  52. ^ a b Mudher A, Lovestone S. Alzheimer's disease-do tauists and baptists finally shake hands?. Trends in Neurosciences. 2002;25(1):22–26. doi:10.1016/S0166-2236(00)02031-2. PMID 11801334.
  53. ^ Nistor M, Don M, Parekh M, Sarsoza F, Goodus M, Lopez GE, Kawas C, Leverenz J, Doran E, Lott IT, Hill M, Head E. Alpha- and Beta-secretase Activity as a Function of Age and Beta-amyloid in Down Syndrome and Normal Brain. Neurobiology of Aging. 2007;28(10):1493–1506. doi:10.1016/j.neurobiolaging.2006.06.023. PMID 16904243.
  54. ^ Lott IT, Head E. Alzheimer Disease and Down Syndrome: Factors in Pathogenesis. Neurobiology of Aging. 2005;26(3):383–89. doi:10.1016/j.neurobiolaging.2004.08.005. PMID 15639317.
  55. ^ Polvikoski T, Sulkava R, Haltia M, Kainulainen K, Vuorio A, Verkkoniemi A, Niinistö L, Halonen P, Kontula K. Apolipoprotein E, Dementia, and Cortical Deposition of Beta-amyloid Protein. The New England Journal of Medicine. 1995;333(19):1242–47. doi:10.1056/NEJM199511093331902. PMID 7566000.
  56. ^ Transgenic mice:
    • Games D, Adams D, Alessandrini R, Barbour R, Berthelette P, Blackwell C, Carr T, Clemens J, Donaldson T, Gillespie F. Alzheimer-type Neuropathology in Transgenic Mice Overexpressing V717F Beta-amyloid Precursor Protein. Nature. 1995;373(6514):523–27. doi:10.1038/373523a0. PMID 7845465.
    • Masliah E, Sisk A, Mallory M, Mucke L, Schenk D, Games D. Comparison of Neurodegenerative Pathology in Transgenic Mice Overexpressing V717F Beta-amyloid Precursor Protein and Alzheimer's Disease. The Journal of Neuroscience. 1996;16(18):5795–811. PMID 8795633.
    • Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, Yang F, Cole G. Correlative Memory Deficits, Abeta Elevation, and Amyloid Plaques in Transgenic Mice. Science. 1996;274(5284):99–102. doi:10.1126/science.274.5284.99. PMID 8810256.
    • Lalonde R, Dumont M, Staufenbiel M, Sturchler-Pierrat C, Strazielle C. Spatial Learning, Exploration, Anxiety, and Motor Coordination in Female APP23 Transgenic Mice with the Swedish Mutation. Brain Research. 2002;956(1):36–44. doi:10.1016/S0006-8993(02)03476-5. PMID 12426044.
  57. ^ Holmes C, Boche D, Wilkinson D, Yadegarfar G, Hopkins V, Bayer A, Jones RW, Bullock R, Love S, Neal JW, Zotova E, Nicoll JA. Long-term Effects of Abeta42 Immunisation in Alzheimer's Disease: Follow-up of a Randomised, Placebo-controlled Phase I Trial. Lancet. 2008;372(9634):216–23. doi:10.1016/S0140-6736(08)61075-2. PMID 18640458.
  58. ^ Lacor PN, Buniel MC, Furlow PW, Clemente AS, Velasco PT, Wood M, Viola KL, Klein WL. Aß Oligomer-Induced Aberrations in Synapse Composition, Shape, and Density Provide a Molecular Basis for Loss of Connectivity in Alzheimer's Disease. The Journal of Neuroscience. 2007;27(4):796–807. doi:10.1523/JNEUROSCI.3501-06.2007. PMID 17251419.
  59. ^ Laurén J, Gimbel DA, Nygaard HB, Gilbert JW, Strittmatter SM. Cellular Prion Protein Mediates Impairment of Synaptic Plasticity by Amyloid-β Oligomers. Nature. 2009;457(7233):1128–32. doi:10.1038/nature07761. PMID 19242475.
  60. ^ a b Nikolaev A, McLaughlin T, O'Leary DD, Tessier-Lavigne M. APP Binds DR6 to Cause Axon Pruning and Neuron Death via Distinct Caspases. Nature. 19 February 2009;457(7232):981–989. doi:10.1038/nature07767. PMID 19225519.
  61. ^ Goedert M, Spillantini MG, Crowther RA. Tau Proteins and Neurofibrillary Degeneration. Brain Pathology (Zurich, Switzerland). 1991;1(4):279–86. doi:10.1111/j.1750-3639.1991.tb00671.x. PMID 1669718.
  62. ^ Iqbal K, Alonso Adel C, Chen S, Chohan MO, El-Akkad E, Gong CX, Khatoon S, Li B, Liu F, Rahman A, Tanimukai H, Grundke-Iqbal I. Tau Pathology in Alzheimer Disease and Other Tauopathies. Biochimica Et Biophysica Acta. 2005;1739(2–3):198–210. doi:10.1016/j.bbadis.2004.09.008. PMID 15615638.
  63. ^ Chun W, Johnson GV. The Role of Tau Phosphorylation and Cleavage in Neuronal Cell Death. Frontiers in Bioscience: A Journal and Virtual Library. 2007;12:733–56. doi:10.2741/2097. PMID 17127334.
  64. ^ Itzhaki RF, Wozniak MA. Herpes Simplex Virus Type 1 in Alzheimer's Disease: The Enemy Within. Journal of Alzheimer's Disease. 2008 [Retrieved 5 February 2011];13(4):393–405. PMID 18487848.
  65. ^ Xu H, Finkelstein DI, Adlard PA. Interactions of metals and Apolipoprotein E in Alzheimer's disease. Front Aging Neurosci.. 2014 Jun 12;6:121. doi:10.3389/fnagi.2014.00121. 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."
  66. ^ Shcherbatykh I, Carpenter DO. The Role of Metals in the Etiology of Alzheimer's Disease. Journal of Alzheimer's Disease. 2007;11(2):191–205. PMID 17522444.
  67. ^ Santibáñez M, Bolumar F, García AM. Occupational Risk Factors in Alzheimer's Disease: A Review Assessing the Quality of Published Epidemiological Studies. Occupational and Environmental Medicine. 2007;64(11):723–732. doi:10.1136/oem.2006.028209. PMID 17525096.
  68. ^ Rondeau V. A Review of Epidemiologic Studies on Aluminum and Silica in Relation to Alzheimer's Disease and Associated Disorders. Reviews on Environmental Health. 2002;17(2):107–21. doi:10.1515/REVEH.2002.17.2.107. PMID 12222737.
  69. ^ Brewer GJ. Copper excess, zinc deficiency, and cognition loss in Alzheimer's disease. BioFactors (Oxford, England). March 2012;38(2):107–113. doi:10.1002/biof.1005. PMID 22438177.
  70. ^ Kheifets L, Bowman JD, Checkoway H, Feychting M, Harrington JM, Kavet R, Marsh G, Mezei G, Renew DC, van Wijngaarden E. Future needs of occupational epidemiology of extremely low frequency electric and magnetic fields: review and recommendations. Occupational and Environmental Medicine. February 2009;66(2):72–80. doi:10.1136/oem.2007.037994. PMID 18805878.
  71. ^ Scientific Committee on Emerging and Newly Identified Health Risks-SCENIHR. Health Effects of Exposure to EMF. January 2009 [Retrieved 27 April 2010]:4–5.
  72. ^ Cataldo JK, Prochaska JJ, Glantz SA. Cigarette smoking is a risk factor for Alzheimer's disease: An analysis controlling for tobacco industry affiliation. Journal of Alzheimer's Disease. 2010;19(2):465–80. doi:10.3233/JAD-2010-1240. PMID 20110594.
  73. ^ Eikelenboom P, van Exel E, Hoozemans JJ, Veerhuis R, Rozemuller AJ, van Gool WA. Neuroinflammation – An Early Event in Both the History and Pathogenesis of Alzheimer's Disease. Neuro-Degenerative Diseases. 2010;7(1–3):38–41. doi:10.1159/000283480. PMID 20160456.
  74. ^ Bartzokis G. Alzheimer's Disease as Homeostatic Responses to Age-related Myelin Breakdown. Neurobiology of Aging. August 2011;32(8):1341–71. doi:10.1016/j.neurobiolaging.2009.08.007. PMID 19775776.
  75. ^ Bartzokis G, Lu PH, Mintz J. Quantifying Age-Related Myelin Breakdown with MRI: Novel Therapeutic Targets for Preventing Cognitive Decline and Alzheimer's Disease. Journal of Alzheimer's Disease. December 2004;6(6 Suppl):S53–9. PMID 15665415.
  76. ^ Bartzokis G, Lu PH, Mintz J. Human Brain Myelination and Beta-amyloid Deposition in Alzheimer's Disease. Alzheimer's & Dementia. April 2007;3(2):122–5. doi:10.1016/j.jalz.2007.01.019. PMID 18596894.
  77. ^ Su B, Wang X, Nunomura A, Moreira PI, Lee HG, Perry G, Smith MA, Zhu X. Oxidative Stress Signaling in Alzheimer's Disease. Current Alzheimer Research. December 2008;5(6):525–32. doi:10.2174/156720508786898451. PMID 19075578.
  78. ^ Kastenholz B, Garfin DE, Horst J, Nagel KA. Plant Metal Chaperones: A Novel Perspective in Dementia Therapy. Amyloid: The International Journal of Experimental and Clinical Investigation: The Official Journal of the International Society of Amyloidosis. 2009;16(2):81–3. doi:10.1080/13506120902879392. PMID 20536399.
  79. ^ Pohanka M. Alzheimer´s Disease and Oxidative Stress: A Review. Current Medicinal Chemistry. 2013;21(3):356–64. doi:10.2174/09298673113206660258. PMID 24059239.
  80. ^ a b c Heneka MT, Nadrigny F, Regen T, Martinez-Hernandez A, Dumitrescu-Ozimek L, Terwel D, Jardanhazi-Kurutz D, Walter J, Kirchhoff F, Hanisch UK, Kummer MP. (2010). Locus ceruleus controls Alzheimer's disease pathology by modulating microglial functions through norepinephrine. Proceedings of the National Academy of Sciences of the United States of America 107:6058–6063 doi:10.1073/pnas.0909586107 PMID 20231476
  81. ^ Moulton PV, Yang W. Air Pollution, Oxidative Stress, and Alzheimer's Disease. Journal of Environmental and Public Health. 2012;2012:472751. doi:10.1155/2012/472751. PMID 22523504.
  82. ^ Braak H, Del Tredici K. Where, when, and in what form does sporadic Alzheimer's disease begin?. Current Opinion in Neurology. December 2012;25(Pt 6):708–14. doi:10.1097/WCO.0b013e32835a3432. PMID 23160422.
  83. ^ Desikan RS, Cabral HJ, Hess CP, Dillon WP, Glastonbury CM, Weiner MW, Schmansky NJ, Greve DN, Salat DH, Buckner RL, Fischl B. Automated MRI Measures Identify Individuals with Mild Cognitive Impairment and Alzheimer's Disease. Brain. August 2009;132(Pt 8):2048–57. doi:10.1093/brain/awp123. PMID 19460794.
  84. ^ Moan R. MRI Software Accurately IDs Preclinical Alzheimer's Disease. Diagnostic Imaging. 20 July 2009.
  85. ^ a b Tiraboschi P, Hansen LA, Thal LJ, Corey-Bloom J. The Importance of Neuritic Plaques and Tangles to the Development and Evolution of AD. Neurology. 2004;62(11):1984–9. doi:10.1212/01.WNL.0000129697.01779.0A. PMID 15184601.
  86. ^ Bouras C, Hof PR, Giannakopoulos P, Michel JP, Morrison JH. 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. 1994;4(2):138–50. doi:10.1093/cercor/4.2.138. PMID 8038565.
  87. ^ Kotzbauer PT, Trojanowsk JQ, Lee VM. Lewy Body Pathology in Alzheimer's Disease. Journal of Molecular Neuroscience. 2001;17(2):225–32. doi:10.1385/JMN:17:2:225. PMID 11816795.
  88. ^ Hashimoto M, Rockenstein E, Crews L, Masliah E. Role of Protein Aggregation in Mitochondrial Dysfunction and Neurodegeneration in Alzheimer's and Parkinson's Diseases. Neuromolecular Medicine. 2003;4(1–2):21–36. doi:10.1385/NMM:4:1-2:21. PMID 14528050.
  89. ^ Priller C, Bauer T, Mitteregger G, Krebs B, Kretzschmar HA, Herms J. Synapse Formation and Function is Modulated by the Amyloid Precursor Protein. The Journal of Neuroscience. 2006;26(27):7212–21. doi:10.1523/JNEUROSCI.1450-06.2006. PMID 16822978.
  90. ^ Turner PR, O'Connor K, Tate WP, Abraham WC. Roles of Amyloid Precursor Protein and its Fragments in Regulating Neural Activity, Plasticity and Memory. Progress in Neurobiology. 2003;70(1):1–32. doi:10.1016/S0301-0082(03)00089-3. PMID 12927332.
  91. ^ Hooper NM. Roles of Proteolysis and Lipid Rafts in the Processing of the Amyloid Precursor Protein and Prion Protein. Biochemical Society Transactions. 2005;33(Pt 2):335–8. doi:10.1042/BST0330335. PMID 15787600.
  92. ^ Ohnishi S, Takano K. Amyloid Fibrils from the Viewpoint of Protein Folding. Cellular and Molecular Life Sciences. 2004;61(5):511–24. doi:10.1007/s00018-003-3264-8. PMID 15004691.
  93. ^ Hernández F, Avila J. Tauopathies. Cellular and Molecular Life Sciences. 2007;64(17):2219–33. doi:10.1007/s00018-007-7220-x. PMID 17604998.
  94. ^ Van Broeck B, Van Broeckhoven C, Kumar-Singh S. Current Insights into Molecular Mechanisms of Alzheimer Disease and Their Implications for Therapeutic Approaches. Neuro-Degenerative Diseases. 2007;4(5):349–65. doi:10.1159/000105156. PMID 17622778.
  95. ^ Huang Y, Mucke L. Alzheimer Mechanisms and Therapeutic strategies. Cell. 2012;148(6):1204-22. doi:10.1016/j.cell.2012.02.040. PMID 22424230.
  96. ^ Yankner BA, Duffy LK, Kirschner DA. Neurotrophic and Neurotoxic Effects of Amyloid Beta Protein: Reversal by Tachykinin Neuropeptides. Science. 1990;250(4978):279–82. doi:10.1126/science.2218531. PMID 2218531.
  97. ^ Chen X, Yan SD. Mitochondrial Abeta: A Potential Cause of Metabolic Dysfunction in Alzheimer's Disease. IUBMB Life. 2006;58(12):686–94. doi:10.1080/15216540601047767. PMID 17424907.
  98. ^ Greig NH, Mattson MP, Perry T, Chan SL, Giordano T, Sambamurti K, Rogers JT, Ovadia H, Lahiri DK. 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. 2004;1035:290–315. doi:10.1196/annals.1332.018. PMID 15681814.
  99. ^ Tapia-Arancibia L, Aliaga E, Silhol M, Arancibia S. New insights into brain BDNF function in normal aging and Alzheimer disease. Brain Research Reviews. 2008;59(1):201–20. doi:10.1016/j.brainresrev.2008.07.007. PMID 18708092.
  100. ^ Schindowski K, Belarbi K, Buée L. Neurotrophic factors in Alzheimer's disease: role of axonal transport. Genes, Brain, and Behavior. 2008;7(Suppl 1):43–56. doi:10.1111/j.1601-183X.2007.00378.x. PMID 18184369.
  101. ^ Mendez MF. The Accurate Diagnosis of Early-onset Dementia. International Journal of Psychiatry in Medicine. 2006;36(4):401–412. doi:10.2190/Q6J4-R143-P630-KW41. PMID 17407994.
  102. ^ Klafki HW, Staufenbiel M, Kornhuber J, Wiltfang J. Therapeutic Approaches to Alzheimer's Disease. Brain. 2006;129(Pt 11):2840–55. doi:10.1093/brain/awl280. PMID 17018549.
  103. ^ Dementia: Quick Reference Guide (PDF). London: (UK)  
  104. ^ a b Schroeter ML, Stein T, Maslowski N, Neumann J. Neural Correlates of Alzheimer's Disease and Mild Cognitive Impairment: A Systematic and Quantitative Meta-Analysis involving 1,351 Patients. NeuroImage. 2009;47(4):1196–1206. doi:10.1016/j.neuroimage.2009.05.037. PMID 19463961.
  105. ^ a b McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. 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. 1984;34(7):939–44. doi:10.1212/wnl.34.7.939. PMID 6610841.
  106. ^ a b Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P, Cummings J, Delacourte A, Galasko D, Gauthier S, Jicha G, Meguro K, O'brien J, Pasquier F, Robert P, Rossor M, Salloway S, Stern Y, Visser PJ, Scheltens P. Research Criteria for the Diagnosis of Alzheimer's Disease: Revising the NINCDS-ADRDA Criteria. Lancet Neurology. 2007;6(8):734–46. doi:10.1016/S1474-4422(07)70178-3. PMID 17616482.
  107. ^ Blacker D, Albert MS, Bassett SS, Go RC, Harrell LE, Folstein MF. Reliability and validity of NINCDS-ADRDA criteria for Alzheimer's disease. The National Institute of Mental Health Genetics Initiative. Archives of Neurology. 1994;51(12):1198–204. doi:10.1001/archneur.1994.00540240042014. PMID 7986174.
  108. ^ American Psychiatric Association (2000). Diagnostic and statistical manual of mental disorders: DSM-IV-TR (4th Edition Text Revision ed.). Washington, DC: American Psychiatric Association.  
  109. ^ Ito N. [Clinical aspects of dementia]. [Hokkaido Igaku Zasshi] the Hokkaido Journal of Medical Science. 1996;71(3):315–20. Japanese. PMID 8752526.
  110. ^ Tombaugh TN, McIntyre NJ. The mini-mental state examination: a comprehensive review. Journal of the American Geriatrics Society. 1992;40(9):922–35. PMID 1512391.
  111. ^ Pasquier F. Early diagnosis of dementia: neuropsychology. Journal of Neurology. 1999;246(1):6–15. doi:10.1007/s004150050299. PMID 9987708.
  112. ^ Antoine C, Antoine P, Guermonprez P, Frigard B. Awareness of Deficits and Anosognosia in Alzheimer's Disease.. L'Encéphale. 2004;30(6):570–7. French. doi:10.1016/S0013-7006(04)95472-3. PMID 15738860.
  113. ^ Cruz VT, Pais J, Teixeira A, Nunes B. The Initial Symptoms of Alzheimer Disease: Caregiver Perception. Acta Médica Portuguesa. 2004;17(6):435–44. Portuguese. PMID 16197855.
  114. ^ Clarfield AM. The Decreasing Prevalence of Reversible Dementias: An Updated Meta-analysis. Archives of Internal Medicine. 2003;163(18):2219–29. doi:10.1001/archinte.163.18.2219. PMID 14557220.
  115. ^ Sun X, Steffens DC, Au R, Folstein M, Summergrad P, Yee J, Rosenberg I, Mwamburi DM, Qiu WQ. Amyloid-Associated Depression: A Prodromal Depression of Alzheimer Disease?. Archives of General Psychiatry. 2008;65(5):542–550. doi:10.1001/archpsyc.65.5.542. PMID 18458206. PMC 3042807.
  116. ^ Geldmacher DS, Whitehouse PJ. Differential Diagnosis of Alzheimer's Disease. Neurology. 1997;48(5 Suppl 6):S2–9. PMID 9153154.
  117. ^ Potter GG, Steffens DC. Contribution of Depression to Cognitive Impairment and Dementia in Older adults. The Neurologist. 2007;13(3):105–17. doi:10.1097/01.nrl.0000252947.15389.a9. PMID 17495754.
  118. ^ Chong MS, Sahadevan S. Preclinical Alzheimer's disease: diagnosis and prediction of progression.. Lancet Neurology. 1 Sep 2005 [Retrieved 7 April 2014];4(9):576–9. doi:10.1016/s1474-4422(05)70168-x. PMID 16109364.
  119. ^ Marksteiner J, Hinterhuber H, Humpel C. Cerebrospinal Fluid Biomarkers for Diagnosis of Alzheimer's Disease: Beta-amyloid(1–42), Tau, Phospho-tau-181 and Total Protein. Drugs of Today. 2007;43(6):423–31. doi:10.1358/dot.2007.43.6.1067341. PMID 17612711.
  120. ^ a b c De Meyer G, Shapiro F, Vanderstichele H, Vanmechelen E, Engelborghs S, De Deyn PP, Coart E, Hansson O, Minthon L, Zetterberg H, Blennow K, Shaw L, Trojanowski JQ. Diagnosis-Independent Alzheimer Disease Biomarker Signature in Cognitively Normal Elderly People. Archives of Neurology. 2010;67(8):949–56. doi:10.1001/archneurol.2010.179. PMID 20697045.
  121. ^ Prevention recommendations not supported:
    • Kawas CH. Medications and Diet: Protective Factors for AD?. Alzheimer Disease and Associated Disorders. 2006;20(3 Suppl 2):S89–96. PMID 16917203.
    • Luchsinger JA, Mayeux R. Dietary Factors and Alzheimer's Disease. Lancet Neurology. 2004;3(10):579–87. doi:10.1016/S1474-4422(04)00878-6. PMID 15380154.
    • Luchsinger JA, Noble JM, Scarmeas N. Diet and Alzheimer's Disease. Current Neurology and Neuroscience Reports. 2007;7(5):366–72. doi:10.1007/s11910-007-0057-8. PMID 17764625.
    • "Independent Panel Finds Insufficient Evidence to Support Preventive Measures for Alzheimer's Disease" (Press release).  
    • Daviglus ML et al. (26–28 April 2010). "NIH State-of-the-Science Conference: Preventing Alzheimer's Disease and Cognitive Decline". 
  122. ^ Szekely CA, Breitner JC, Zandi PP. Prevention of Alzheimer's Disease. International Review of Psychiatry (Abingdon, England). 2007;19(6):693–706. doi:10.1080/09540260701797944. PMID 18092245.
  123. ^ Patterson C, Feightner JW, Garcia A, Hsiung GY, MacKnight C, Sadovnick AD. Diagnosis and Treatment of Dementia: 1. Risk Assessment and Primary Prevention of Alzheimer Disease. Canadian Medical Association Journal. 2008;178(5):548–56. doi:10.1503/cmaj.070796. PMID 18299540.
  124. ^ Rosendorff C, Beeri MS, Silverman JM. Cardiovascular Risk Factors for Alzheimer's Disease. The American Journal of Geriatric Cardiology. 2007;16(3):143–9. doi:10.1111/j.1076-7460.2007.06696.x. PMID 17483665.
  125. ^ Reiss AB, Wirkowski E. Role of HMG-CoA Reductase Inhibitors in Neurological Disorders: Progress to Date. Drugs. 2007;67(15):2111–20. doi:10.2165/00003495-200767150-00001. PMID 17927279.
  126. ^ Kuller LH. Statins and Dementia. Current Atherosclerosis Reports. 2007;9(2):154–61. doi:10.1007/s11883-007-0012-9. PMID 17877925.
  127. ^ a b c Szekely CA, Town T, Zandi PP. NSAIDs for the Chemoprevention of Alzheimer's Disease. Sub-Cellular Biochemistry. 2007;42:229–48. doi:10.1007/1-4020-5688-5_11. PMID 17612054.
  128. ^ Lehrer S. Nasal NSAIDs for Alzheimer's Disease. Am J Alzheimers Dis Other Demen. 2014 Jan 9. [Epub ahead of print].
  129. ^ Marjoribanks J, Farquhar C, Roberts H, Lethaby A. Long term hormone therapy for perimenopausal and postmenopausal women. The Cochrane Database of Systematic Reviews. 2012;7:CD004143. doi:10.1002/14651858.CD004143.pub4. PMID 22786488.
  130. ^ a b Stern Y. Cognitive reserve and Alzheimer disease. Alzheimer Disease and Associated Disorders. July 2006;20(2):112–117. doi:10.1097/01.wad.0000213815.20177.19. PMID 16917199.
  131. ^ a b Paradise M, Cooper C, Livingston G. Systematic Review of the Effect of Education on Survival in Alzheimer's Disease. International Psychogeriatrics. 2009;21(1):25–32. doi:10.1017/S1041610208008053. PMID 19026089.
  132. ^ Neergaard, Lauran (19 February 2011). "Speaking 2 Languages May Delay Getting Alzheimer's". The Denver Post. Associated Press. 
  133. ^ a b Hu N, Yu JT, Tan L, Wang Y-L, Sun L, Tan L. Nutrition and the Risk of Alzheimer's Disease. BioMed Research International. 2013;2013. doi:10.1155/2013/524820. 524820.
  134. ^ Solfrizzi V, Panza F, Frisardi V, Seripa D, Logroscino G, Imbimbo BP, Pilotto A. Diet and Alzheimer's disease risk factors or prevention: the current evidence.. Expert Review of Neurotherapeutics. May 2011;11(5):677–708. doi:10.1586/ern.11.56. PMID 21539488.
  135. ^ Kanoski SE, Davidson TL. Western diet consumption and cognitive impairment: links to hippocampal dysfunction and obesity. Physiology & Behavior. 18 April 2011;103(1):59–68. doi:10.1016/j.physbeh.2010.12.003. PMID 21167850.
  136. ^ Solfrizzi V, Capurso C, D'Introno A, Colacicco AM, Santamato A, Ranieri M, Fiore P, Capurso A, Panza F. Lifestyle-related Factors in Predementia and Dementia Syndromes. Expert Review of Neurotherapeutics. 2008;8(1):133–58. doi:10.1586/14737175.8.1.133. PMID 18088206.
  137. ^ Panza F, Capurso C, D'Introno A, Colacicco AM, Frisardi V, Lorusso M, Santamato A, Seripa D, Pilotto A, Scafato E, Vendemiale G, Capurso A, Solfrizzi V. Alcohol Drinking, Cognitive Functions in Older Age, Predementia, and Dementia Syndromes. Journal of Alzheimer's Disease. May 2009;17(1):7–31. doi:10.3233/JAD-2009-1009. PMID 19494429.
  138. ^ Santos C, Costa J, Santos J, Vaz-Carneiro A, Lunet N. Caffeine intake and dementia: systematic review and meta-analysis. Journal of Alzheimer's Disease. 2010;20 Suppl 1:S187–204. doi:10.3233/JAD-2010-091387. PMID 20182026.
  139. ^ Nehlig A. The neuroprotective effects of cocoa flavanol and its influence on cognitive performance. British Journal of Clinical Pharmacology. July 2012;75(3):n/a–n/a. doi:10.1111/j.1365-2125.2012.04378.x. PMID 22775434.
  140. ^ Stoclet JC, Schini-Kerth V. [Dietary flavonoids and human health].. Annales Pharmaceutiques Françaises. March 2011;69(2):78–90. doi:10.1016/j.pharma.2010.11.004. PMID 21440100.
  141. ^ Ono K, Yamada M. Vitamin A and Alzheimer's disease. Geriatrics & Gerontology International. April 2012;12(2):180–8. doi:10.1111/j.1447-0594.2011.00786.x. PMID 22221326.
  142. ^ Lerner AJ, Gustaw-Rothenberg K, Smyth S, Casadesus G. Retinoids for treatment of Alzheimer's disease.. BioFactors (Oxford, England). Mar–Apr 2012;38(2):84–9. doi:10.1002/biof.196. PMID 22419567.
  143. ^ Heo JH, Lee KM. The possible role of antioxidant vitamin C in Alzheimer's disease treatment and prevention. American Journal of Alzheimer's Disease and Other Dementias. March 2013;28(2):120–5. doi:10.1177/1533317512473193. PMID 23307795.
  144. ^ a b c Boothby LA, Doering PL. Vitamin C and Vitamin E for Alzheimer's Disease. The Annals of Pharmacotherapy. 2005;39(12):2073–80. doi:10.1345/aph.1E495. PMID 16227450.
  145. ^ Isaac MG, Quinn R, Tabet N. Vitamin E for Alzheimer's Disease and Mild Cognitive Impairment. The Cochrane Database of Systematic Reviews. 2008;(3):CD002854. doi:10.1002/14651858.CD002854.pub2. PMID 18646084.
  146. ^ Loef M, Schrauzer GN, Walach H. Selenium and Alzheimer's disease: a systematic review. Journal of Alzheimer's Disease. 2011;26(1):81–104. doi:10.3233/JAD-2011-110414. PMID 21593562.
  147. ^ Loef M, von Stillfried N, Walach H. Zinc diet and Alzheimer's disease: a systematic review. Nutritional Neuroscience. 1 September 2012;15(5):2–12. doi:10.1179/1476830512Y.0000000010. PMID 22583839.
  148. ^ Malouf R, Grimley Evans J. Folic Acid with or without Vitamin B12 for the Prevention and Treatment of Healthy Elderly and Demented people. The Cochrane Database of Systematic Reviews. 2008;(4):CD004514. doi:10.1002/14651858.CD004514.pub2. PMID 18843658.
  149. ^ Wald DS, Kasturiratne A, Simmonds M. Effect of Folic Acid, with or without other B vitamins, on Cognitive Decline: Meta-analysis of Randomized trials. The American Journal of Medicine. June 2010;123(6):522–527.e2. doi:10.1016/j.amjmed.2010.01.017. PMID 20569758.
  150. ^ Cunnane SC, Chouinard-Watkins R, Castellano CA, Barberger-Gateau P. Docosahexaenoic acid homeostasis, brain aging and Alzheimer's disease: Can we reconcile the evidence?. Prostaglandins, Leukotrienes, and Essential Fatty Acids. January 2013;88(1):61–70. doi:10.1016/j.plefa.2012.04.006. PMID 22575581.
  151. ^ Hamaguchi T, Ono K, Yamada M. REVIEW: Curcumin and Alzheimer's disease. CNS Neuroscience & Therapeutics. October 2010;16(5):285–97. doi:10.1111/j.1755-5949.2010.00147.x. PMID 20406252.
  152. ^ Birks J, Grimley Evans J. Ginkgo Biloba for Cognitive Impairment and Dementia. The Cochrane Database of Systematic Reviews. 2009;(1):CD003120. doi:10.1002/14651858.CD003120.pub3. PMID 19160216.
  153. ^ Krishnan S, Cairns R, Howard R. Cannabinoids for the treatment of dementia. The Cochrane Database of Systematic Reviews. 2009;(2):CD007204. doi:10.1002/14651858.CD007204.pub2. PMID 19370677.
  154. ^ Bilkei-Gorzo A. The endocannabinoid system in normal and pathological brain ageing. Philos. Trans. R. Soc. Lond., B, Biol. Sci.. 2012;367(1607):3326–41. doi:10.1098/rstb.2011.0388. PMID 23108550.
  155. ^ Pohanka M. Cholinesterases, a target of pharmacology and toxicology. Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czech Republic. 2011;155(3):219–229. doi:10.5507/bp.2011.036. PMID 22286807.
  156. ^ Commission de la transparence. Médicaments de la maladie d'Alzheimer [Drugs for Alzheimer's disease: best avoided. No therapeutic advantage]. Prescrire International. June 2012;21(128):150. PMID 22822592.
  157. ^ Birks J, Harvey RJ. Donepezil for dementia due to Alzheimer's disease.. The Cochrane Database of Systematic Reviews. 25 January 2006;(1):CD001190. doi:10.1002/14651858.CD001190.pub2. PMID 16437430.
  158. ^ Geula C, Mesulam MM. Cholinesterases and the pathology of Alzheimer disease. Alzheimer Disease and Associated Disorders. 1995;9 Suppl 2:23–28. doi:10.1097/00002093-199501002-00005. PMID 8534419.
  159. ^ Stahl SM. The new cholinesterase inhibitors for Alzheimer's disease, part 2: illustrating their mechanisms of action. The Journal of Clinical Psychiatry. 2000;61(11):813–814. doi:10.4088/JCP.v61n1101. PMID 11105732.
  160. ^ Birks J. Cholinesterase inhibitors for Alzheimer's disease. The Cochrane Database of Systematic Reviews. 2006;(1):CD005593. doi:10.1002/14651858.CD005593. PMID 16437532.
  161. ^ Birks J, Grimley Evans J, Iakovidou V, Tsolaki M, Holt FE. Rivastigmine for Alzheimer's disease. The Cochrane Database of Systematic Reviews. 15 April 2009;(2):CD001191. doi:10.1002/14651858.CD001191.pub2. PMID 19370562.
  162. ^ Birks J, Harvey RJ. Donepezil for dementia due to Alzheimer's disease. The Cochrane Database of Systematic Reviews. 25 January 2006;(1):CD001190. doi:10.1002/14651858.CD001190.pub2. PMID 16437430.
  163. ^ Raschetti R, Albanese E, Vanacore N, Maggini M. Cholinesterase inhibitors in mild cognitive impairment: a systematic review of randomised trials. PLoS Medicine. 2007;4(11):e338. doi:10.1371/journal.pmed.0040338. PMID 18044984.
  164. ^ al.], edited by Brian K. Alldredge ... [et (2013). Applied therapeutics : the clinical use of drugs. (10th ed. ed.). Baltimore: Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 2385.  
  165. ^ Birks J. Cholinesterase inhibitors for Alzheimer's disease. The Cochrane Database of Systematic Reviews. 2006;(1):CD005593. doi:10.1002/14651858.CD005593. PMID 16437532.
  166. ^ a b Lipton SA. Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond. Nature Reviews. Drug Discovery. 2006;5(2):160–170. doi:10.1038/nrd1958. PMID 16424917.
  167. ^ "Memantine". US National Library of Medicine (Medline). 4 January 2004. Archived from the original on 22 February 2010. Retrieved 3 February 2010. 
  168. ^ Areosa Sastre A, McShane R, Sherriff F. Memantine for Dementia. The Cochrane Database of Systematic Reviews. 2004;(4):CD003154. doi:10.1002/14651858.CD003154.pub2. PMID 15495043.
  169. ^ "Namenda prescribing information" (PDF).   (primary source)
  170. ^ Raina P, Santaguida P, Ismaila A, Patterson C, Cowan D, Levine M, Booker L, Oremus M. Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline. Annals of Internal Medicine. 2008;148(5):379–397. doi:10.7326/0003-4819-148-5-200803040-00009. PMID 18316756.
  171. ^ Antipsychotics use:
    • Ballard C, Waite J. The Effectiveness of Atypical Antipsychotics for the Treatment of Aggression and Psychosis in Alzheimer's Disease. The Cochrane Database of Systematic Reviews. 2006;(1):CD003476. doi:10.1002/14651858.CD003476.pub2. PMID 16437455.
    • Ballard C, Lana MM, Theodoulou M, Douglas S, McShane R, Jacoby R, Kossakowski K, Yu LM, Juszczak E. A Randomised, Blinded, Placebo-Controlled Trial in Dementia Patients Continuing or Stopping Neuroleptics (The DART-AD Trial). PLoS Medicine. 2008;5(4):e76. doi:10.1371/journal.pmed.0050076. PMID 18384230.
    • Sink KM, Holden KF, Yaffe K. Pharmacological Treatment of Neuropsychiatric Symptoms of Dementia: A Review of the Evidence. JAMA. 2005;293(5):596–608. doi:10.1001/jama.293.5.596. PMID 15687315.
  172. ^ a b Ballard C, Hanney ML, Theodoulou M, Douglas S, McShane R, Kossakowski K, Gill R, Juszczak E, Yu LM, Jacoby R. The Dementia Antipsychotic Withdrawal Trial (DART-AD): Long-term Follow-up of a Randomised Placebo-controlled Trial. Lancet Neurology. 9 January 2009;8(2):151–7. doi:10.1016/S1474-4422(08)70295-3. PMID 19138567. Lay summary.
  173. ^ Li J, Wu HM, Zhou RL, Liu GJ, Dong BR. Huperzine A for Alzheimer's disease. The Cochrane Database of Systematic Reviews. 2008;(2):CD005592. doi:10.1002/14651858.CD005592.pub2. PMID 18425924.
  174. ^ a b c d e f g Rabins PV, Blacker D, Rovner BW, Rummans T, Schneider LS, Tariot PN, Blass DM, McIntyre JS, Charles SC, Anzia DJ, Cook IA, Finnerty MT, Johnson BR, Nininger JE, Schneidman B, Summergrad P, Woods SM, Berger J, Cross CD, Brandt HA, Margolis PM, Shemo JP, Blinder BJ, Duncan DL, Barnovitz MA, Carino AJ, Freyberg ZZ, Gray SH, Tonnu T, Kunkle R, Albert AB, Craig TJ, Regier DA, Fochtmann LJ. American Psychiatric Association practice guideline for the treatment of patients with Alzheimer's disease and other dementias. The American Journal of Psychiatry. December 2007;164(12 Suppl):5–56. PMID 18340692.
  175. ^ Bottino CM, Carvalho IA, Alvarez AM, Avila R, Zukauskas PR, Bustamante SE, Andrade FC, Hototian SR, Saffi F, Câmargo CH. Cognitive rehabilitation combined with drug treatment in Alzheimer's disease patients: a pilot study. Clinical Rehabilitation. 2005;19(8):861–869. doi:10.1191/0269215505cr911oa. PMID 16323385.
  176. ^ Doody RS, Stevens JC, Beck C, Dubinsky RM, Kaye JA, Gwyther L, Mohs RC, Thal LJ, Whitehouse PJ, DeKosky ST, Cummings JL. Practice parameter: management of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2001;56(9):1154–1166. doi:10.1212/WNL.56.9.1154. PMID 11342679.
  177. ^ Hermans DG, Htay UH, McShane R. Non-pharmacological interventions for wandering of people with dementia in the domestic setting. The Cochrane Database of Systematic Reviews. 2007;(1):CD005994. doi:10.1002/14651858.CD005994.pub2. PMID 17253573.
  178. ^ Robinson L, Hutchings D, Dickinson HO, Corner L, Beyer F, Finch T, Hughes J, Vanoli A, Ballard C, Bond J. Effectiveness and acceptability of non-pharmacological interventions to reduce wandering in dementia: a systematic review. International Journal of Geriatric Psychiatry. 2007;22(1):9–22. doi:10.1002/gps.1643. PMID 17096455.
  179. ^ Woods B, Spector A, Jones C, Orrell M, Davies S. Reminiscence therapy for dementia. The Cochrane Database of Systematic Reviews. 2005;(2):CD001120. doi:10.1002/14651858.CD001120.pub2. PMID 15846613.
  180. ^ Zetteler J. Effectiveness of simulated presence therapy for individuals with dementia: a systematic review and meta-analysis. Aging & Mental Health. November 2008;12(6):779–85. doi:10.1080/13607860802380631. PMID 19023729.
  181. ^ Neal M, Briggs M. Validation therapy for dementia. The Cochrane Database of Systematic Reviews. 2003;(3):CD001394. doi:10.1002/14651858.CD001394. PMID 12917907.
  182. ^ Chung JC, Lai CK, Chung PM, French HP. Snoezelen for dementia. The Cochrane Database of Systematic Reviews. 2002;(4):CD003152. doi:10.1002/14651858.CD003152. PMID 12519587. (up to date as of 2009)
  183. ^ Spector A, Orrell M, Davies S, Woods B. Withdrawn: reality orientation for dementia. The Cochrane Database of Systematic Reviews. 2000;(3):CD001119. doi:10.1002/14651858.CD001119.pub2. PMID 17636652.
  184. ^ Spector A, Thorgrimsen L, Woods B, Royan L, Davies S, Butterworth M, Orrell M. Efficacy of an evidence-based cognitive stimulation therapy programme for people with dementia: randomised controlled trial. The British Journal of Psychiatry. 2003;183(3):248–254. doi:10.1192/bjp.183.3.248. PMID 12948999.
  185. ^ Gitlin LN, Corcoran M, Winter L, Boyce A, Hauck WW. 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. 1 February 2001 [Retrieved 15 July 2008];41(1):4–14. doi:10.1093/geront/41.1.4. PMID 11220813.
  186. ^ Gitlin LN, Hauck WW, Dennis MP, Winter L. 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. 2005;60(3):368–74. doi:10.1093/gerona/60.3.368. PMID 15860476.
  187. ^ "Treating Behavioral and Psychiatric Symptoms". Alzheimer's Association. 2006. Archived from the original on 25 September 2006. Retrieved 25 September 2006. 
  188. ^ Dunne TE, Neargarder SA, Cipolloni PB, Cronin-Golomb A. Visual Contrast Enhances Food and Liquid Intake in Advanced Alzheimer's Disease. Clinical Nutrition (Edinburgh, Scotland). 2004;23(4):533–538. doi:10.1016/j.clnu.2003.09.015. PMID 15297089.
  189. ^ Dudek, Susan G. (2007). Nutrition Essentials for Nursing Practice. Hagerstown, Maryland: Lippincott Williams & Wilkins. p. 360.  
  190. ^ Dennehy C. Analysis of Patients' Rights: Dementia and PEG Insertion. British Journal of Nursing (Mark Allen Publishing). 2006;15(1):18–20. PMID 16415742.
  191. ^ Chernoff R. Tube Feeding Patients with Dementia. Nutrition in Clinical Practice. 2006;21(2):142–6. doi:10.1177/0115426506021002142. PMID 16556924.
  192. ^ Gambassi G, Landi F, Lapane KL, Sgadari A, Mor V, Bernabei R. Predictors of Mortality in Patients with Alzheimer's Disease Living in Nursing Homes. Journal of Neurology, Neurosurgery, and Psychiatry. 1999;67(1):59–65. doi:10.1136/jnnp.67.1.59. PMID 10369823.
  193. ^ Medical issues:
    • Head B. Palliative Care for Persons with Dementia. Home Healthcare Nurse. 2003;21(1):53–60; quiz 61. doi:10.1097/00004045-200301000-00012. PMID 12544465.
    • Friedlander AH, Norman DC, Mahler ME, Norman KM, Yagiela JA. Alzheimer's Disease: Psychopathology, Medical Management and Dental Implications. Journal of the American Dental Association (1939). 2006;137(9):1240–51. PMID 16946428.
    • Belmin J. 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. 2007;11(1):33–7. PMID 17315078.
    • McCurry SM, Gibbons LE, Logsdon RG, Vitiello M, Teri L. Training Caregivers to Change the Sleep Hygiene Practices of Patients with Dementia: The NITE-AD Project. Journal of the American Geriatrics Society. 2003;51(10):1455–60. doi:10.1046/j.1532-5415.2003.51466.x. PMID 14511168.
    • Perls TT, Herget M. Higher Respiratory Infection Rates on an Alzheimer's Special Care Unit and successful intervention. Journal of the American Geriatrics Society. 1995;43(12):1341–4. PMID 7490383.
  194. ^ Shega JW, Levin A, Hougham GW, Cox-Hayley D, Luchins D, Hanrahan P, Stocking C, Sachs GA. Palliative Excellence in Alzheimer Care Efforts (PEACE): A Program Description. Journal of Palliative Medicine. 2003;6(2):315–20. doi:10.1089/109662103764978641. PMID 12854952.
  195. ^ Mitchell SL, Teno JM, Kiely DK, Shaffer ML, Jones RN, Prigerson HG, Volicer L, Givens JL, Hamel MB. The Clinical Course of Advanced Dementia. The New England Journal of Medicine. 2009;361(16):1529–38. doi:10.1056/NEJMoa0902234. PMID 19828530.
  196. ^ Sampson EL, Candy B, Jones L (2009). "Enteral tube feeding for older people with advanced dementia (Intervention Review)". The Cochrane Library (2): CD007209.  
  197. ^ a b c d Mölsä PK, Marttila RJ, Rinne UK. Survival and Cause of Death in Alzheimer's Disease and Multi-Infarct Dementia. Acta Neurologica Scandinavica. 1986;74(2):103–7. doi:10.1111/j.1600-0404.1986.tb04634.x. PMID 3776457.
  198. ^ a b Bowen JD, Malter AD, Sheppard L, Kukull WA, McCormick WC, Teri L, Larson EB. Predictors of Mortality in Patients Diagnosed with Probable Alzheimer's Disease. Neurology. 1996;47(2):433–9. PMID 8757016.
  199. ^ a b Dodge HH, Shen C, Pandav R, DeKosky ST, Ganguli M. Functional Transitions and Active Life Expectancy Associated with Alzheimer Disease. Archives of Neurology. 2003;60(2):253–9. doi:10.1001/archneur.60.2.253. PMID 12580712.
  200. ^ a b Mölsä PK, Marttila RJ, Rinne UK. Long-Term Survival and Predictors of Mortality in Alzheimer's Disease and Multi-Infarct Dementia. Acta Neurologica Scandinavica. 1995;91(3):159–64. PMID 7793228.
  201. ^ Larson EB, Shadlen MF, Wang L, McCormick WC, Bowen JD, Teri L, Kukull WA. Survival after Initial Diagnosis of Alzheimer Disease. Annals of Internal Medicine. 2004;140(7):501–9. PMID 15068977.
  202. ^ Jagger C, Clarke M, Stone A. Predictors of Survival with Alzheimer's Disease: A Community-based Study. Psychological Medicine. 1995;25(1):171–7. doi:10.1017/S0033291700028191. PMID 7792352.
  203. ^ a b Ganguli M, Dodge HH, Shen C, Pandav RS, DeKosky ST. Alzheimer Disease and Mortality: A 15-year Epidemiological Study. Archives of Neurology. 2005;62(5):779–84. doi:10.1001/archneur.62.5.779. PMID 15883266.
  204. ^ a b c Bermejo-Pareja F, Benito-León J, Vega S, Medrano MJ, Román GC. Incidence and subtypes of dementia in three elderly populations of central Spain. Journal of the Neurological Sciences. 2008;264(1–2):63–72. doi:10.1016/j.jns.2007.07.021. PMID 17727890.
  205. ^ a b c Di Carlo A, Baldereschi M, Amaducci L, Lepore V, Bracco L, Maggi S, Bonaiuto S, Perissinotto E, Scarlato G, Farchi G, Inzitari D. Incidence of dementia, Alzheimer's disease, and vascular dementia in Italy. The ILSA Study. Journal of the American Geriatrics Society. 2002;50(1):41–8. doi:10.1046/j.1532-5415.2002.50006.x. PMID 12028245.
  206. ^ Andersen K, Launer LJ, Dewey ME, Letenneur L, Ott A, Copeland JR, Dartigues JF, Kragh-Sorensen P, Baldereschi M, Brayne C, Lobo A, Martinez-Lage JM, Stijnen T, Hofman A. Gender Differences in the Incidence of AD and Vascular Dementia: The EURODEM Studies. EURODEM Incidence Research Group. Neurology. 1999;53(9):1992–7. PMID 10599770.
  207. ^ 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.
  208. ^ 2000 U.S. estimates:
    • Hebert LE, Scherr PA, Bienias JL, Bennett DA, Evans DA. Alzheimer Disease in the US population: Prevalence Estimates Using the 2000 census. Archives of Neurology. 2003;60(8):1119–22. doi:10.1001/archneur.60.8.1119. PMID 12925369.
    • "Profiles of General Demographic Characteristics, 2000 Census of Population and Housing, United States" (PDF). U.S. Census Bureau. 2001. Archived from the original on 19 August 2008. Retrieved 27 August 2008. 
  209. ^ a b Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, Hall K, Hasegawa K, Hendrie H, Huang Y, Jorm A, Mathers C, Menezes PR, Rimmer E, Scazufca M. Global Prevalence of Dementia: A Delphi Consensus Study. Lancet. 2005;366(9503):2112–7. doi:10.1016/S0140-6736(05)67889-0. PMID 16360788.
  210. ^ World Health Organization (2006). Neurological Disorders: Public Health Challenges. Switzerland: World Health Organization. pp. 204–207.  
  211. ^ 2006 prevalence estimate:
    • Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM. Forecasting the global burden of Alzheimer's disease. Alzheimer's & Dementia. 2007 [Retrieved 18 June 2008];3(3):186–91. doi:10.1016/j.jalz.2007.04.381. PMID 19595937.
    • World population prospects: the 2006 revision, highlights [PDF]. 2007 [Retrieved 27 August 2008].
  212. ^ Auguste D.:
    • Alzheimer Alois. Über eine eigenartige Erkrankung der Hirnrinde [About a peculiar disease of the cerebral cortex]. Allgemeine Zeitschrift fur Psychiatrie und Psychisch-Gerichtlich Medizin. 1907;64(1–2):146–148. (German).
    • Alzheimer Alois. About a Peculiar Disease of the Cerebral Cortex. Alzheimer Disease and Associated Disorders. 1987;1(1):3–8. PMID 3331112.
    • Maurer Ulrike, Maurer Konrad (2003). Alzheimer: The Life of a Physician and the Career of a Disease. New York: Columbia University Press. p. 270.  
  213. ^ Berrios G E. Alzheimer's Disease: A Conceptual History. Int. J. Ger. Psychiatry. 1990;5(6):355–365. doi:10.1002/gps.930050603.
  214. ^ Kraepelin Emil, Diefendorf A. Ross (translated by) (17 January 2007). Clinical Psychiatry: A Textbook For Students And Physicians (Reprint). Kessinger Publishing. p. 568.  
  215. ^ Katzman Robert, Terry Robert D, Bick Katherine L (editors) (1978). Alzheimer's Disease: Senile Dementia and Related Disorders. New York: Raven Press. p. 595.  
  216. ^ Boller F, Forbes MM. History of Dementia and Dementia in History: An Overview. Journal of the Neurological Sciences. 1998;158(2):125–33. doi:10.1016/S0022-510X(98)00128-2. PMID 9702682.
  217. ^ Amaducci LA, Rocca WA, Schoenberg BS. Origin of the Distinction between Alzheimer's Disease and Senile Dementia: How History Can Clarify Nosology. Neurology. 1986;36(11):1497–9. PMID 3531918.
  218. ^ Allegri RF, Butman J, Arizaga RL, Machnicki G, Serrano C, Taragano FE, Sarasola D, Lon L. Economic Impact of Dementia in Developing Countries: An Evaluation of Costs of Alzheimer-type Dementia in Argentina. International Psychogeriatrics. 2007;19(4):705–18. doi:10.1017/S1041610206003784. PMID 16870037.
  219. ^ Suh GH, Knapp M, Kang CJ. The Economic Costs of Dementia in Korea, 2002. International Journal of Geriatric Psychiatry. 2006;21(8):722–8. doi:10.1002/gps.1552. PMID 16858741.
  220. ^ Wimo A, Jonsson L, Winblad B. An Estimate of the Worldwide Prevalence and Direct Costs of Dementia in 2003. Dementia and Geriatric Cognitive Disorders. 2006;21(3):175–81. doi:10.1159/000090733. PMID 16401889.
  221. ^ a b c Moore MJ, Zhu CW, Clipp EC. Informal Costs of Dementia Care: Estimates from the National Longitudinal Caregiver Study. The Journals of Gerontology. Series B, Psychological Sciences and Social Sciences. 2001;56(4):S219–28. doi:10.1093/geronb/56.4.S219. PMID 11445614.
  222. ^ Jönsson L, Eriksdotter Jönhagen M, Kilander L, Soininen H, Hallikainen M, Waldemar G, Nygaard H, Andreasen N, Winblad B, Wimo A. Determinants of Costs of Care for Patients with Alzheimer's Disease. International Journal of Geriatric Psychiatry. 2006;21(5):449–59. doi:10.1002/gps.1489. PMID 16676288.
  223. ^ a b "The MetLife study of Alzheimer's disease: The caregiving experience" (PDF). MetLife Mature Market Institute. August 2006. Archived from the original on 8 January 2011. Retrieved 5 February 2011. 
  224. ^ Schneider J, Murray J, Banerjee S, Mann A. 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. 1999;14(8):651–661. doi:10.1002/(SICI)1099-1166(199908)14:8<651::AID-GPS992>3.0.CO;2-B. PMID 10489656.
  225. ^ Murray J, Schneider J, Banerjee S, Mann A. 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. 1999;14(8):662–7. doi:10.1002/(SICI)1099-1166(199908)14:8<662::AID-GPS993>3.0.CO;2-4. PMID 10489657.
  226. ^ a b Zhu CW, Sano M. Economic Considerations in the Management of Alzheimer's Disease. Clinical Interventions in Aging. 2006;1(2):143–54. doi:10.2147/ciia.2006.1.2.143. PMID 18044111.
  227. ^ Gaugler JE, Kane RL, Kane RA, Newcomer R. Early Community-based Service Utilization and Its Effects on Institutionalization in Dementia Caregiving. The Gerontologist. 2005;45(2):177–85. doi:10.1093/geront/45.2.177. PMID 15799982.
  228. ^ Ritchie K, Lovestone S. The Dementias. Lancet. 2002;360(9347):1759–66. doi:10.1016/S0140-6736(02)11667-9. PMID 12480441.
  229. ^ Brodaty H, Hadzi-Pavlovic D. Psychosocial Effects on Carers of Living with Persons with Dementia. The Australian and New Zealand Journal of Psychiatry. 1990;24(3):351–61. doi:10.3109/00048679009077702. PMID 2241719.
  230. ^ Donaldson C, Tarrier N, Burns A. Determinants of Carer Stress in Alzheimer's Disease. International Journal of Geriatric Psychiatry. 1998;13(4):248–56. doi:10.1002/(SICI)1099-1166(199804)13:4<248::AID-GPS770>3.0.CO;2-0. PMID 9646153.
  231. ^ Pusey H, Richards D. A Systematic Review of the Effectiveness of Psychosocial Interventions for Carers of People with Dementia. Aging & Mental Health. 2001;5(2):107–19. doi:10.1080/13607860120038302. PMID 11511058.
  232. ^ Garrard P, Maloney LM, Hodges JR, Patterson K. The Effects of Very Early Alzheimer's Disease on the Characteristics of Writing by a Renowned Author. Brain. 2005;128(Pt 2):250–60. doi:10.1093/brain/awh341. PMID 15574466.
  233. ^ Sherman FT. Did President Reagan Have Mild cognitive Impairment While in Office? Living Longer with Alzheimer's Disease. Geriatrics. 2004;59(9):11, 15. PMID 15461232.
  234. ^ Venneri A, Forbes-Mckay KE, Shanks MF. Impoverishment of Spontaneous Language and the Prediction of Alzheimer's Disease. Brain. 2005;128(Pt 4):E27. doi:10.1093/brain/awh419. PMID 15788549.
  235. ^ "Hungary Legend Puskas Dies at 79". BBC News. 17 November 2006. Retrieved 25 January 2008. 
  236. ^ "Prime Ministers in History: Harold Wilson". London: 10 Downing Street. Archived from the original on 25 August 2008. Retrieved 18 August 2008. 
  237. ^ "Mi padre no reconoció al Rey pero notó el cariño". Madrid: El País. 2008. Retrieved 1 October 2008. 
  238. ^ "Chicago Rita Hayworth Gala". Alzheimer's Association. 2007. Retrieved 3 February 2010. 
  239. ^ "Charlton Heston has Alzheimer's Symptoms". CNN. 9 August 2002. Archived from the original on 1 February 2008. Retrieved 25 January 2008. 
  240. ^ Pauli Michelle (12 December 2007). "Pratchett Announces He Has Alzheimer's". London: Guardian News and Media. Archived from the original on 29 September 2008. Retrieved 18 August 2008. 
  241. ^ "Harnett T. Kane, 73, Author of Books About the South".  
  242. ^ "George Fernandes Being treated for Alzheimer's by Yoga Guru Ramdev".  
  243. ^ "Nobel Winner Kao Coping with Fame and Alzheimer's". China Daily. 9 October 2009. Archived from the original on 24 January 2011. Retrieved 6 February 2011. 
  244. ^ Bayley John (2000). Iris: A Memoir of Iris Murdoch. London: Abacus.  
  245. ^ Sparks Nicholas (1996). The notebook. Thorndike, Maine: Thorndike Press. p. 268.  
  246. ^ "Thanmathra". Retrieved 24 January 2008. 
  247. ^ Ogiwara Hiroshi (2004). Ashita no Kioku (in jp). Tōkyō: Kōbunsha.  
  248. ^ Munro Alice (2001).  
  249. ^ Malcolm and Barbara:
    • "Malcolm and Barbara: A love story". Dfgdocs. Retrieved 24 January 2008. 
    • "Malcolm and Barbara: A love story". BBC Cambridgeshire. 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. 
  250. ^ "Clinical Trials. Found 1504 studies with search of: alzheimer". US National Institutes of Health. Retrieved 30 October 2014. 
  251. ^ Lashuel HA, Hartley DM, Balakhaneh D, Aggarwal A, Teichberg S, Callaway DJ. New Class of Inhibitors of Beta-amyloid Fibril Formation. Implications for the Mechanism of Pathogenesis in Alzheimer's Disease. The Journal of Biological Chemistry. 2002;277(45):42881–42890. doi:10.1074/jbc.M206593200. PMID 12167652.
  252. ^ Dodel R, Neff F, Noelker C, Pul R, Du Y, Bacher M, Oertel W. Intravenous Immunoglobulins as a Treatment for Alzheimer's Disease: Rationale and Current Evidence. Drugs. 2010;70(5):513–528. doi:10.2165/11533070-000000000-00000. PMID 20329802.
  253. ^ Vaccination:
    • Hawkes CA, McLaurin J. Immunotherapy as Treatment for Alzheimer's Disease. Expert Review of Neurotherapeutics. 2007;7(11):1535–48. doi:10.1586/14737175.7.11.1535. PMID 17997702.
    • Solomon B. Clinical Immunologic Approaches for the Treatment of Alzheimer's Disease. Expert Opinion on Investigational Drugs. 2007;16(6):819–28. doi:10.1517/13543784.16.6.819. PMID 17501694.
    • Woodhouse A, Dickson TC, Vickers JC. Vaccination Strategies for Alzheimer's Disease: A New Hope?. Drugs & Aging. 2007;24(2):107–19. doi:10.2165/00002512-200724020-00003. PMID 17313199.
  254. ^ "Study Evaluating ACC-001 in Mild to Moderate Alzheimers Disease Subjects". Clinical Trial. US National Institutes of Health. 11 March 2008. Retrieved 5 June 2008. 
  255. ^ "Study Evaluating Safety, Tolerability, and Immunogenicity of ACC-001 in Subjects with Alzheimer's Disease". US National Institutes of Health. Retrieved 5 June 2008. 
  256. ^ "Alzheimer's Disease Vaccine Trial Suspended on Safety Concern". Medpage Today. 18 April 2008. Retrieved 14 June 2008. 
  257. ^ "Bapineuzumab in Patients with Mild to Moderate Alzheimer's Disease/ Apo_e4 Non-carriers" (Clinical Trial). US National Institutes of Health. 29 February 2008. Archived from the original on 22 March 2008. Retrieved 23 March 2008. 
  258. ^ "Safety, Tolerability and Efficacy Study to Evaluate Subjects with Mild Cognitive Impairment" (Clinical Trial). US National Institutes of Health. 11 March 2008. Retrieved 23 March 2008. 
  259. ^ "Study Evaluating the Safety, Tolerability and Efficacy of PBT2 in Patients with Early Alzheimer's Disease" (Clinical Trial). US National Institutes of Health. 13 January 2008. Retrieved 23 March 2008. 
  260. ^ Etanercept research:
    • Tobinick E. Tumour necrosis factor modulation for treatment of Alzheimer's disease: rationale and current evidence. CNS Drugs. 2009 Sep;23(9):713-25. doi:10.2165/11310810-000000000-00000. PMID 19689163.
    • Tobinick E, Gross H, Weinberger A, Cohen H. TNF-alpha Modulation for Treatment of Alzheimer's Disease: A 6-Month Pilot Study. MedGenMed. 2006;8(2):25. PMID 16926764.
    • Griffin WS. Perispinal etanercept: Potential as an Alzheimer Therapeutic. Journal of Neuroinflammation. 2008;5:3. doi:10.1186/1742-2094-5-3. PMID 18186919.
    • Tobinick E. Perispinal Etanercept for Treatment of Alzheimer's Disease. Current Alzheimer Research. 2007;4(5):550–2. doi:10.2174/156720507783018217. PMID 18220520.
    • Cheng X, Shen Y, Li R. Targeting TNF: a therapeutic strategy for Alzheimer's disease. Drug Discov Today. 2014 Jul 4. doi:10.1016/j.drudis.2014.06.029. PMID 24998784.
  261. ^ Wischik Claude M, Bentham Peter, Wischik Damon J, Seng Kwang Meng. Tau aggregation inhibitor (TAI) therapy with remberTM arrests disease progression in mild and moderate Alzheimer's disease over 50 weeks. Alzheimer's & Dementia. 2008 [Retrieved 30 July 2008];4(4):T167. doi:10.1016/j.jalz.2008.05.438.
  262. ^ Harrington Charles. Methylthioninium chloride (MTC) acts as a tau aggregation inhibitor (TAI) in a cellular model and reverses tau pathology in transgenic mouse models of Alzheimer's disease. Alzheimer's & Dementia. 2008;4(4):T120–T121. doi:10.1016/j.jalz.2008.05.259.
  263. ^ Doody RS, Gavrilova SI, Sano M, Thomas RG, Aisen PS, Bachurin SO, Seely L, Hung D. Effect of dimebon on cognition, activities of daily living, behaviour, and global function in patients with mild-to-moderate Alzheimer's disease: a randomised, double-blind, placebo-controlled study. Lancet. 2008;372(9634):207–15. doi:10.1016/S0140-6736(08)61074-0. PMID 18640457.
  264. ^ Bezprozvanny I. The rise and fall of Dimebon. Drug News & Perspectives. October 2010;23(8):518–23. doi:10.1358/dnp.2010.23.8.1500435. PMID 21031168.
  265. ^ "Pfizer And Medivation announce results from two phase 3 studies in Dimebon (latrepirdine*) Alzheimer's disease clinical development program (NASDAQ:MDVN)" (Press release). Retrieved 16 November 2012. 
  266. ^ Wendler A, Wehling M. Translatability scoring in drug development: eight case studies. Journal of Translational Medicine. 2012;10(10):39. doi:10.1186/1479-5876-10-39. PMID 22397594.
  267. ^ Baddeley TC, McCaffrey J, Storey JM, Cheung JK, Melis V, Horsley D, Harrington CR, Wischik CM (Oct 15, 2014). "Complex disposition of methylthioninium redox forms determines efficacy in tau aggregation inhibitor therapy for Alzheimer's disease". J Pharmacol Exp Ther 352 (1): 110–118.  
  268. ^ Wischik CM, Harrington CR, Storey JM. Tau-aggregation inhibitor therapy for Alzheimer's disease. Biochem Pharmacol. 2014 Apr 15;88(4):529-39. doi:10.1016/j.bcp.2013.12.008. PMID 24361915.
  269. ^ a b Martin C, Solís L, Concha MI, Otth C. Herpes simplex virus tipo 1 como factor de riesgo asociado con la enfermedad de Alzheimer [Herpes Simplex Virus Type 1 as Risk Factor Associated to Alzheimer Disease]. Revista Médica De Chile. June 2011;139(6):779–86. Spanish. doi:10.4067/S0034-98872011000600013. PMID 22051760.
  270. ^ Wozniak MA, Mee AP, Itzhaki RF. Herpes Simplex Virus type 1 DNA Is Located within Alzheimer's Disease Amyloid Plaques. The Journal of Pathology. 2008;217(1):131–138. doi:10.1002/path.2449. PMID 18973185.
  271. ^ Newberg AB, Wintering N, Khalsa DS, Roggenkamp H, Waldman MR. Meditation Effects on Cognitive Function and Cerebral Blood Flow in Subjects with Memory Loss: A Preliminary Study. Journal of Alzheimer's Disease. 2010;20(2):517–26. doi:10.3233/JAD-2010-1391. PMID 20164557.
  272. ^ Clark CM, Schneider JA, Bedell BJ, Beach TG, Bilker WB, Mintun MA, Pontecorvo MJ, Hefti F, Carpenter AP, Flitter ML, Krautkramer MJ, Kung HF, Coleman RE, Doraiswamy PM, Fleisher AS, Sabbagh MN, Sadowsky CH, Reiman EP, Reiman PE, Zehntner SP, Skovronsky DM. FDA Recommends Approval of New Compound in Alzheimer's Detection. JAMA. 19 January 2011;305(3):275–83. doi:10.1001/jama.2010.2008. PMID 21245183.
  273. ^ Dougall NJ, Bruggink S, Ebmeier KP. Systematic Review of the Diagnostic Accuracy of 99mTc-HMPAO-SPECT in Dementia. The American Journal of Geriatric Psychiatry. 2004;12(6):554–70. doi:10.1176/appi.ajgp.12.6.554. PMID 15545324.
  274. ^ Carpenter AP, Pontecorvo MJ, Hefti FF, Skovronsky DM. The Use of the Exploratory IND in the Evaluation and Development of18F-PET Radiopharmaceuticals for Amyloid Imaging in the Brain: A Review of One Company's Experience. The Quarterly Journal of Nuclear Medicine and Molecular Imaging. August 2009;53(4):387–93. PMID 19834448.
  275. ^ Leung K (8 April 2010). F]AV-45] ]]"18F-fluoroethoxy)ethoxy)ethoxy)pyridin-3-yl)vinyl)-N-methyl benzenamine [[18"(E)-4-(2-(6-(2-(2-(2-(. Molecular Imaging and Contrast Agent Database. Retrieved 24 June 2010. 
  276. ^ Rabinovici GD, Jagust WJ. Amyloid Imaging in Aging and Dementia: Testing the Amyloid Hypotheses in Vivo. Behavioural Neurology. 2009;21(1):117–28. doi:10.3233/BEN-2009-0232. PMID 19847050. PMC 2804478.
  277. ^ O'Brien JT. Role of Imaging Techniques in the Diagnosis of Dementia. The British Journal of Radiology. December 2007;80(Spec No 2):S71–7. doi:10.1259/bjr/33117326. PMID 18445747.


Amyloid imaging is likely to be used in conjunction with other markers rather than as an alternative.[276] Volumetric MRI can detect changes in the size of brain regions. Measuring those regions that atrophy during the progress of Alzheimer's disease is showing promise as a diagnostic indicator. It may prove less expensive than other imaging methods currently under study.[277]

PiB PET remains investigational, but a similar PET scanning radiopharmaceutical called florbetapir, containing the longer-lasting radionuclide fluorine-18, has recently been tested as a diagnostic tool in Alzheimer's disease, and given FDA approval for this use.[274][275]

In a person already having dementia, single photon emission computed tomography (SPECT) appears to be superior in differentiating Alzheimer's disease from other possible causes, compared with the usual attempts employing mental testing and medical history analysis.[273] Advances have led to the proposal of new diagnostic criteria.[19][106]


An FDA panel voted unanimously to recommend approval of florbetapir, which is currently used in an investigational study. The imaging agent can help to detect Alzheimer's brain plaques, but will require additional clinical research before it can be made available commercially.[272]

Preliminary research on the effects of meditation on retrieving memory and cognitive functions have been encouraging. Limitations of this research can be addressed in future studies with more detailed analyses.[271]

The common herpes simplex virus HSV-1 has been found to colocate with amyloid plaques.[269] This suggested the possibility that AD could be treated or prevented with antiviral medication.[269][270]

In 2008, two separate clinical trials showed positive results in modifying the course of disease in mild to moderate AD with methylthioninium chloride (trade name rember), a drug that inhibits tau aggregation,[261][262] and dimebon, an antihistamine.[263] The consecutive phase-III trial of dimebon failed to show positive effects in the primary and secondary endpoints.[264][265][266] Work with methylthioninium chloride showed that bioavailability of methylthioninium from the gut was affected by feeding and by stomach acidity, leading to unexpectedly variable dosing.[267] A new stabilized formulation, as the prodrug LMTX, is in phase-III trials.[268]

One area of clinical research is focused on treating the underlying disease pathology. Reduction of beta-amyloid levels is a common target of compounds[251] (such as apomorphine) under investigation. Immunotherapy or vaccination for the amyloid protein is one treatment modality under study.[252] Unlike preventative vaccination, the putative therapy would be used to treat people already diagnosed. It is based upon the concept of training the immune system to recognise, attack, and reverse deposition of amyloid, thereby altering the course of the disease.[253] An example of such a vaccine under investigation was ACC-001,[254][255] although the trials were suspended in 2008.[256] Another similar agent is bapineuzumab, an antibody designed as identical to the naturally induced anti-amyloid antibody.[257] Other approaches are neuroprotective agents, such as AL-108,[258] and metal-protein interaction attenuation agents, such as PBT2.[259] A TNFα receptor-blocking fusion protein, etanercept has showed encouraging results.[260]

As of 2014, the safety and efficacy of more than 400 pharmaceutical treatments had been or were being investigated in over 1,500 clinical trials worldwide, and approximately a quarter of these compounds are in Phase III trials, the last step prior to review by regulatory agencies.[250]

Research directions

AD has also been portrayed in films such as: Iris (2001), based on John Bayley's memoir of his wife Iris Murdoch;[244] The Notebook (2004), based on Nicholas Sparks' 1996 novel of the same name;[245] A Moment to Remember (2004);Thanmathra (2005);[246] Memories of Tomorrow (Ashita no Kioku) (2006), based on Hiroshi Ogiwara's novel of the same name;[247] Away from Her (2006), based on Alice Munro's short story "The Bear Came over the Mountain".[248] 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.[249]

[243].Charles K. Kao in Physics recipient Nobel Prize and the 2009 [242] As Alzheimer's disease is highly prevalent, many notable people have developed it. Well-known examples are former

Charlton Heston and Ronald Reagan at a meeting in the White House. Both of them would later be diagnosed with Alzheimer's disease.

Notable cases

Cognitive behavioural therapy and the teaching of coping strategies either individually or in group have demonstrated their efficacy in improving caregivers' psychological health.[9][231]

Dementia caregivers are subject to high rates of physical and mental disorders.[228] Factors associated with greater psychosocial problems of the primary caregivers include having an affected person at home, the carer being a spouse, demanding behaviours of the cared person such as depression, behavioural disturbances, hallucinations, sleep problems or walking disruptions and social isolation.[229][230] Regarding economic problems, family caregivers often give up time from work to spend 47 hours per week on average with the person with AD, while the costs of caring for them are high. Direct and indirect costs of caring for an Alzheimer's patient average between $18,000 and $77,500 per year in the United States, depending on the study.[223][221]

The role of the main caregiver is often taken by the spouse or a close relative.[223] Alzheimer's disease is known for placing a great burden on caregivers which includes social, psychological, physical or economic aspects.[9][224][225] Home care is usually preferred by people with AD and their families.[226] This option also delays or eliminates the need for more professional and costly levels of care.[226][227] Nevertheless two-thirds of nursing home residents have dementias.[174]

Caregiving burden

Costs increase with dementia severity and the presence of behavioural disturbances,[222] and are related to the increased caregiving time required for the provision of physical care.[221] 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.[17]

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.[16] The cost of living at home is also very high,[16] especially when informal costs for the family, such as caregiving time and caregiver's lost earnings, are taken into account.[221]

Dementia, and specifically Alzheimer's disease, may be among the most costly diseases for society in Europe and the United States,[16][17] while their cost in other countries such as Argentina,[218] or South Korea,[219] is also high and rising. These costs will probably increase with the ageing 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.[17] Numbers vary between studies but dementia costs worldwide have been calculated around $160 billion,[220] while costs of Alzheimer's disease in the United States may be $100 billion each year.[17]

Social costs

Society and culture

For most of the 20th century, the diagnosis of Alzheimer's disease was reserved for individuals between the ages of 45 and 65 who developed symptoms of dementia. The terminology changed after 1977 when a conference on AD concluded that the clinical and pathological manifestations of presenile and senile dementia were almost identical, although the authors also added that this did not rule out the possibility that they had different causes.[215] This eventually led to the diagnosis of Alzheimer's disease independently of age.[216] The term senile dementia of the Alzheimer type (SDAT) was used for a time to describe the condition in those over 65, with classical Alzheimer's disease being used for those younger. Eventually, the term Alzheimer's disease was formally adopted in medical nomenclature to describe individuals of all ages with a characteristic common symptom pattern, disease course, and neuropathology.[217]

The ancient Greek and Roman philosophers and physicians associated old age with increasing dementia.[15] It was not until 1901 that German psychiatrist Alois Alzheimer identified the first case of what became known as Alzheimer's disease in a fifty-year-old woman he called Auguste D. He followed her case until she died in 1906, when he first reported publicly on it.[212] During the next five years, eleven similar cases were reported in the medical literature, some of them already using the term Alzheimer's disease.[15] 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.[213] 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.[214]

Alois Alzheimer's patient Auguste Deter in 1902. Hers was the first described case of what became known as Alzheimer's disease.


[211]) were afflicted by AD, and that the prevalence rate would triple and the absolute number would quadruple by 2050.11.4–59.4 million, range 26.6 million Another study estimated that in 2006, 0.40% of the world population (range 0.17–0.89%; absolute number [209] Other studies have reached similar conclusions.[210]