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Alzheimer's disease

Alzheimer's disease
Classification & external resources
Histopathologic image of senile plaques seen in the cerebral cortex in a patient with Alzheimer disease of presenile onset. Silver impregnation.
ICD-10 G30., F00.
ICD-9 331.0, 290.1
OMIM 104300
DiseasesDB 490
MedlinePlus 000760
eMedicine neuro/13 

Alzheimer's disease (AD), also called Alzheimer disease, and simply known as Alzheimer's, is a neurodegenerative disease that, in its most common form, is found in people over the age of 65. Approximately 24 million people worldwide have dementia of which the majority (~60%) is due to Alzheimer's.[1]

Clinical signs of Alzheimer's disease are characterized by progressive cognitive deterioration, together with declining activities of daily living and by neuropsychiatric symptoms or behavioral changes. It is the most common type of dementia. Plaques which contain misfolded peptides called amyloid beta (Aβ) are formed in the brain many years before the clinical signs of Alzheimer's are observed. Together, these plaques and neurofibrillary tangles form the pathological hallmarks of the disease. These features can only be discovered at autopsy and help to confirm the clinical diagnosis. Medications can help reduce the symptoms of the disease, but they cannot change the course of the underlying pathology.

The ultimate cause of Alzheimer's is unknown. Genetic factors are clearly indicated as dominant mutations in three different genes that account for the small number of cases of familial, early-onset AD have been identified. For the more common form of late onset AD, ApoE is the only clearly established susceptibility gene. All four genes can contain mutations or variants that confer increased risk for AD, but account for only 30% of the genetic picture of AD. These four genes have in common the fact that mutations in each lead to the excessive accumulation in the brain of Aβ, the main component of the senile plaques that litter the brains of AD patients.[2]



  Although the origin of the concept of dementia goes as far back as the ancient Greek and Roman philosophers and physicians;[3] it was in 1901 when Alois Alzheimer, a German psychiatrist, identified the first case of what became known as Alzheimer's disease. The patient was a 50-year-old woman called Auguste D. Alois Alzheimer followed her until she died in 1906, when he first reported the case publicly.[4][5][6] In the following five years eleven similar cases were reported in the medical literature; some of them already using the term Alzheimer's disease.[3] However the official consideration of the disease as a distinctive entity is attributed to Emil Kraepelin, who included "Alzheimer’s disease" or presenile dementia as a subtype of senile dementia in the eighth edition of his Textbook of Psychiatry, published in 1910.[7]

Accordingly; for most of the twentieth century, the diagnosis of Alzheimer's disease was reserved for individuals between the ages of 45 and 65 who developed symptoms of dementia. The terminology changed after 1977 when a conference held in that year concluded that the clinical and pathological manifestations of presenile and senile dementia were almost identical, although the authors also added that this did not rule out the possibility of different etiologies. This eventually led to the use of "Alzheimer's disease" independently of onset age of the disease.[8][9] However, the term senile dementia of the Alzheimer type ("SDAT") was often 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.[10]


Most cases of Alzheimer's disease are sporadic, i.e., do not exhibit familial inheritance. Nonetheless, at least 80% of sporadic AD cases most likely involve genetic risk factors. Inheritance of the ε4 allele of the apolipoprotein E (ApoE) gene is regarded as a risk factor for development of up to 50% of late-onset sporadic Alzheimer's. However, genetic experts agree that there are other risk and protective factor genes that influence the development of late onset Alzheimer's disease. Over 400 genes have been tested for association with late-onset sporadic AD.[11]

On the other hand, 5 to 10% of AD cases involve a clear familial pattern of inheritance in which the patient has at least two first-degree relatives with a history of AD. These cases often have an early age of onset (usually <60 years). Nearly 200 different mutations in the presenilin-1 or presenilin-2 genes have been documented in over 500 families. Mutations of presenilin 1 (PS1) lead to the most aggressive form of familial Alzheimer's disease. Over 20 different mutations in the amyloid precursor protein (APP) gene on chromosome 21 can also cause early onset of the disease. The presenilins have been identified as essential components of the proteolytic processing machinery that produces beta amyloid peptides through cleavage of APP. Most mutations in the APP and presenilin genes increase the production of a small protein (peptide) called Abeta42, the main component of senile plaques in brains of AD patients.

Clinical features

Disease course can be divided into stages, having the person with the disease a different pattern of cognitive and functional impairment in each of them. As the disease progresses the patient will advance from mild cognitive impairment, when the disease has not yet been diagnosed, to mild and advanced stages of dementia, finally reaching a severe stage of dementia.[12]

Careful neuropsychological testing can reveal mild cognitive difficulties even eight years before a person fullfils clinical criteria of diagnosis.[13][14][15] Nevertheless it is not yet clear if these difficulties affect their daily living activities, since it was thought they did not but some studies show impairments in the most complex ones.[16] The easiest deficit to notice is short-term memory loss and the consequent problems to acquire new information; but subtle executive problems or semantic memory impairments can also accompany it.[17][18] Humour disturbances such as apathy and depressive symptoms are also common.[19][20] This stage of the disease has also been termed mild cognitive impairment,[21] but there is still a debate on whether this term corresponds to a different diagnostic entity by itself or just a first step of Alzheimer.[22]

These initial symptoms progress from seemingly simple and often fluctuating forgetfulness and difficulty orienting oneself in space such as in a traffic lane while driving, to a more pervasive loss of short-term memory and difficulty navigating through familiar areas such as one's neighborhood. As the disease progresses to the middle stage, patients might still be able to perform tasks independently (such as using the bathroom), but may need assistance with more complicated activities (such as paying bills). As the disease advances there is a loss of well-known skills as well as recognition of objects and persons.[23][24] Other behavioral changes are outbursts of violence in people who have no previous history of such behavior.

In the advanced stage of the disease, deterioration of musculature and mobility, leading to bedfastness, inability to feed oneself, and incontinence, will be seen if death from some external cause (e.g. heart attack or pneumonia) does not intervene. Language becomes severely disorganized, and then is lost altogether. Patients will not be able to perform even simple tasks independently and will require constant supervision.

Once identified, the average life expectancy of patients living with Alzheimer's disease is approximately 7-10 years, although cases are known where reaching the final stage occurs within 4-5 years or at the other extreme they may survive up to 21 years.


Dementia is by definition a clinical condition, and thus can be confidently diagnosed with careful testing. However, a definitive diagnosis of Alzheimer's disease as a particular cause of dementia must await microscopic examination of brain tissue; which generally occurs at autopsy and less often with a pre-mortem brain biopsy.[25] Therefore Alzheimer's disease is usually a clinically diagnosed condition based on the presence of characteristic neurological and neuropsychological features and the absence of alternative diagnoses. In this process, determination of neurological characteristics is made utilizing patient history and clinical observation,[26] while neuropsychological evaluation includes memory testing and assessment of intellectual functioning.[27] Criteria ease and standarize the diagnostic process.

Diagnostic criteria

The diagnostic criteria for Alzheimer of the NINCDS-ADRDA (NINCDS and the ADRDA) are among the most used.[25] These criteria require that the presence of cognitive impairment and a suspected dementia syndrome be confirmed by neuropsychological testing for a clinical diagnosis of possible or probable AD while they need histopathologic confirmation (microscopic examination of brain tissue) for the definitive diagnosis. They have shown good reliability and validity.[28] They specify as well eight cognitive domains that may be impaired in AD (i.e., memory, language, perceptual skills, attention, constructive abilities, orientation, problem solving and functional abilities). Similar to the NINCDS-ADRDA Alzheimer's Criteria are the DSM-IV-TR criteria published by the American Psychiatric Association.[29][30]

Diagnostic tools

Neuropsychological screening tests as the Mini mental state examination (MMSE) are widely used to evaluate the cognitive impairments needed for diagnosis, but more comprenhensive batteries are necessary for high reliability by this method; specially in the earliest stages of the disease.[31][32] On the other hand neurological examination in early AD will usually be normal, independently of cognitive impairment; but for many of the other dementing disorders is key for diagnosis. Therefore neurological examination is crucial in the differential diagnosis of Alzheimer and other diseases.[27] In addition, interviews with family members are also utilized in the assessment of the disease. Caregivers can supply important information on the daily living abilities, as well as on the decrease over time of the patient's mental function.[33] This is specially important since unawareness of own's deficits (anosognosia) is common in AD.[34] However many times families have difficulties in the detection of initial dementia symptoms and in adequately transmitting them to physician.[35] Finally supplemental testing provide extra information on some features of the disease or are utilized to rule out other diagnoses. Examples are blood tests, which can identificate other causes for dementia different than AD;[27] some of which may even be reversible;[36] or psychological tests for depression, as depression can both co-occur with AD or on the contrary be at the origin of the patient's cognitive impairment.[37][38]

Increasingly, the functional neuroimaging modalities of SPECT and PET are being used to diagnose Alzheimer's, as they have shown similar ability to diagnose Alzheimer's disease as methods involving mental status examination.[39] Furthermore, the ability of SPECT to differentiate Alzheimer's disease from other possible causes, in a given patient already known to be suffering from dementia, appears to be superior to attempts to differentiate the cause of dementia cause by mental testing and history.[40] Another recent objective marker of the disease is the analysis of cerebrospinal fluid for amyloid beta or tau proteins .[41] Both advances (neuroimaging and cerebrospinal fluid analysis) have led to the proposal of new diagnostic criteria.[42][27]


Biochemical characteristics

Alzheimer's disease has been identified as a protein misfolding disease, or proteopathy, due to the accumulation of abnormally folded A-beta and tau proteins in the brains of AD patients.[43] A-beta, also written Aβ, is a short peptide that is a proteolytic byproduct of the transmembrane protein amyloid precursor protein (APP), whose function is unclear but thought to be involved in neuronal development. The presenilins are components of a proteolytic complex involved in APP processing and degradation.[44] Although amyloid beta monomers are soluble and harmless, they undergo a dramatic conformational change at sufficiently high concentration to form a beta sheet-rich tertiary structure that aggregates to form amyloid fibrils[45] that deposit outside neurons in dense formations known as senile plaques or neuritic plaques, in less dense aggregates as diffuse plaques, and sometimes in the walls of small blood vessels in the brain in a process called amyloid angiopathy or congophilic angiopathy.

AD is also considered a tauopathy due to abnormal aggregation of the tau protein, a microtubule-associated protein expressed in neurons that normally acts to stabilize microtubules in the cell cytoskeleton. Like most microtubule-associated proteins, tau is normally regulated by phosphorylation; however, in AD patients, hyperphosphorylated tau accumulates as paired helical filaments[46] that in turn aggregate into masses inside nerve cell bodies known as neurofibrillary tangles and as dystrophic neurites associated with amyloid plaques.


  Both amyloid plaques and neurofibrillary tangles are clearly visible by microscopy in AD brains.[47] At an anatomical level, AD is characterized by gross diffuse atrophy of the brain and loss of neurons, neuronal processes and synapses in the cerebral cortex and certain subcortical regions. This results in gross atrophy of the affected regions, including degeneration in the temporal lobe and parietal lobe, and parts of the frontal cortex and cingulate gyrus.[48] Levels of the neurotransmitter acetylcholine are reduced. Levels of the neurotransmitters serotonin, norepinephrine, and somatostatin are also often reduced. Glutamate levels are usually elevated.[49]

Disease mechanism

Three major competing hypotheses exist to explain the cause of the disease. The oldest, on which most currently available drug therapies are based, is known as the "cholinergic hypothesis" and suggests that AD is due to reduced biosynthesis of the neurotransmitter acetylcholine. The medications that treat acetylcholine deficiency have served to only treat symptoms of the disease and have neither halted nor reversed it.[50] The cholinergic hypothesis has not maintained widespread support in the face of this evidence, although cholingeric effects have been proposed to initiate large-scale aggregation[51] leading to generalized neuroinflammation.[48]

Research after 2000 includes hypotheses centered on the effects of the misfolded and aggregated proteins, amyloid beta and tau. The two positions differ with one stating that the tau protein abnormalities initiate the disease cascade, while the other states that amyloid beta (Aβ) deposits are the causative factor in the disease.[52] The tau hypothesis is supported by the long-standing observation that deposition of amyloid plaques do not correlate well with neuron loss;[53] however, a majority of researchers support the alternative hypothesis that Aβ is the primary causative agent.[52]

The amyloid hypothesis is compelling because the gene for the amyloid beta precursor (APP) is located on chromosome 21, and patients with trisomy 21 (Down Syndrome) who thus have an extra gene copy almost universally exhibit AD-like disorders by 40 years of age.[54][55] The traditional formulation of the amyloid hypothesis points to the cytotoxicity of mature aggregated amyloid fibrils, which are believed to be the toxic form of the protein responsible for disrupting the cell's calcium ion homeostasis and thus inducing apoptosis.[56] A more recent and widely supported hypothesis suggests that the cytotoxic species is an intermediate misfolded form of Aβ, neither a soluble monomer nor a mature aggregated polymer but an oligomeric species.[57] Relevantly, much early development work on lead compounds has focused on the inhibition of fibrillization,[58][59][60] but the toxic-oligomer theory would imply that prevention of oligomeric assembly is the more important process[61] or that a better target lies upstream, for example in the inhibition of APP processing to amyloid beta.[62]

It should be noted further that ApoE4, the major genetic risk factor for AD, leads to excess amyloid build up in the brain before AD symptoms arise. Thus, Aβ deposition precedes clinical AD.[63] Another strong support for the amyloid hypothesis, which looks at Aβ as the common initiating factor for Alzheimer's disease, is that transgenic mice solely expressing a mutant human APP gene develop first diffuse and then fibrillar amyloid plaques, associated with neuronal and microglial damage.[64][65][66]


Alzheimer's disease is the most frequent type of dementia in the elderly and affects almost half of all patients with dementia. Correspondingly, advancing age is the primary risk factor for Alzheimer's. Among people aged 65, 2-3% show signs of the disease, while 25–50% of people aged 85 have symptoms of Alzheimer's and an even greater number have some of the pathological hallmarks of the disease without the characteristic symptoms. Every five years after the age of 65, the probability of having the disease doubles.[67] The share of Alzheimer's patients over the age of 85 is the fastest growing segment of the Alzheimer's disease population in the US, although current estimates suggest the 75-84 population has about the same number of patients as the over 85 population.[68]


Although aging itself cannot be prevented, the senescence of it can be mitigated. However, the evidence relating certain behaviors, dietary intakes, environmental exposures, and diseases to the likelihood of developing Alzheimer's varies in quality and its acceptance by the medical community.[69] It is important to understand that interventions that reduce the risk of developing the disease in the first place may not alter its progression after symptoms become apparent.[citation needed] Due to their observational design, studies examining disease risk factors are often at risk from confounding variables. Several recent large randomized controlled trials—in particular the Women's Health Initiative—have called into question preventive measures based on cross-sectional studies.

Risk reducers

  • Adults with damaged blood vessels in the brain or atrophy in their temporal lobe are more likely to develop Alzheimer's disease. It is known that blood vessel damage in the brain is more likely to occur in patients with high blood pressure, high cholesterol or diabetes. Therefore, prevention of these conditions can lower the risk of developing Alzheimer's, as well as heart attack and stroke.
  • Intellectual stimulation (e.g., playing chess or doing crosswords).[70]
  • Regular physical exercise.[71]
  • Regular social interaction.[72] Lonely individuals may be twice as likely to develop the type of dementia linked to Alzheimer’s disease in late life as those who are not lonely.
  • A Mediterranean diet with fruits and vegetables and low in saturated fat,[73] supplemented in particular with:
    • B vitamins,[74] in particular folic acid.[75][76][77][78]
    • Curcumin in Curry (from the yellow spice Turmeric).[79]
    • Omega-3 fatty acids, especially Docosahexaenoic acid (DHA, often found in fish oil).[80][81][82]
    • Fresh fruit and vegetables high in the Polyphenol antioxidant (berries, apples, grapes, broccoli, legumes like kidney beans, etc).[83][84]
    • Vitamin E. High doses (up to 2000IU, especially in combination with vitamin C to aid absorption) have been shown to reduce Alzheimer's risk in cross sectional studies, but not in a randomized trial.[85][86] Randomized trials have shown Vitamin E increases the risk of cardiovascular events and these risks should be considered.[87]
    • The moderate consumption of alcohol (beer, wine or distilled spirits).[88] Other research is consistent with the finding that moderate alcohol consumption is associated with lower risk of Alzheimer’s and other forms of dementia: [89][90][91][92][93][94][95][96]
  • avoiding high blood pressure prevents or delays Alzheimers [97]
  • preventing a high level of Cholesterol by avoiding obesity and exercising reduces the risk of Alzheimers[98]
  • Cholesterol-lowering drugs (statins) reduce Alzheimer's risk in observational studies but so far not in randomized controlled trials.[99]
  • Female Hormone replacement therapy is no longer thought to prevent dementia based on data from the Women's Health Initiative.
  • Long-term usage of non-steroidal anti-inflammatory drugs (NSAIDs), used to reduce joint inflammation and pain, are associated with a reduced likelihood of developing AD, according to some observational studies.[100][101] The risks appear to outweigh the drugs' benefit as a method of primary prevention.[102]

Risk factors


There is currently no cure for Alzheimer's disease. Currently available medications offer relatively small symptomatic benefit for some patients but do not slow disease progression. The American Association for Geriatric Psychiatry published a consensus statement on Alzheimer's treatment in 2006.[102]

Acetylcholinesterase inhibitors

There is a reduction in activity of the cholinergic neurons in AD. Acetylcholinesterase inhibitors reduce the rate at which acetylcholine (ACh) is broken down and hence increase the concentration of ACh in the brain (combatting the loss of ACh caused by the death of the cholinergin neurons). Acetylcholinesterase-inhibitors seem to modestly moderate symptoms but do not alter the course of the underlying dementing process.[112][113][114] Examples currently marketed include donepezil (Trade name Aricept), galantamine (trade names Reminylin and Nivalin, U.S. trade name Razadyne) and rivastigmine (Exelon). The three products come in an oral form taken once or twice a day. Rivastigmine is also available as a once-daily transdermal patch.

There is some question as to the effectiveness of cholinesterase inhibitors. A number of recent articles have criticized the design of studies reporting benefit from these drugs, concluding that they have doubtful clinical utility, are costly, and confer many side effects.[115][116] The pharmaceutical companies, but also some independent clinicians, dispute the conclusions of these articles.

Ginkgo biloba

Examining over 52 studies conducted on Ginkgo for the treatment of "cognitive impairment and dementia," a Cochrane Review concludes that "there is promising evidence of improvement in cognition and function associated with Ginkgo." According to this review, the two randomized controlled studies that focused on Alzheimer's patients both showed significant improvement in these areas. [117] The AAGP review[102] did not recommend Ginkgo, nor did it warn against its use. A large, randomized clinical study in the U.S. called the GEM study is now underway (fully enrolled), which examines the effect (or effects) of Ginkgo to prevent dementia. Results are expected in late 2007 or early 2008. [118]

NMDA antagonists

Recent evidence of the involvement of glutamatergic neuronal excitotoxicity in Alzheimer's disease led to the development and introduction of memantine. Memantine is a novel NMDA receptor antagonist, and has been shown to be moderately clinically efficacious.[119] Memantine is marketed as Akatinol, Axura, Ebixa and Namenda.

Psychosocial interventions

Cognitive and behavioral interventions and rehabilitation strategies may be used as an adjunct to pharmacological treatment, especially in the early to moderately advanced stages of disease. Treatment modalities include counseling, psychotherapy (if cognitive functioning is adequate), reminiscent therapy, reality orientation therapy, and behavioral reinforcements as well as cognitive rehabilitation training.[120][121][122]

Treatments in clinical development

A large number of potential treatments for Alzheimer's disease are currently under investigation, including two compounds being studied in phase 3 clinical trials. Tarenflurbil (MPC-7869, formerly R-flubiprofen) is a gamma secretase modulator sometimes called a selective amyloid beta 42 lowering agent. It is believed to reduce the production of the toxic amyloid beta in favor of shorter forms of the peptide.[123][124] Tramiprosate (3APS or Alzhemed) is a GAG-mimetic molecule that is believed to act by binding to soluble amyloid beta to prevent the accumulation of the toxic plaques. Its initial Phase 3 trial did not show significant effects on clinical measures of disease progression, but a second trial is underway. The European underway trial was modified in consequence to the results of the USA phase 3 trial.
4 Nov 2007: Memory Pharmaceuticals announced positive phase 2a results for MEM 3454. For the eight hour post-dose time points over the treatment period, subjects receiving 5 mg and 15 mg of MEM 3454 demonstrated a statistically significant effect according to results with tests of episodic memory (QESM) compared to placebo (p=0.023 and p=0.050, respectively) [9].

  • Vaccines or immunotherapy for Alzheimer's, unlike typical vaccines, would be used to treat diagnosed patients rather than for disease prevention. Ongoing efforts are based on the idea that, by training the immune system to recognize and attack beta-amyloid, the immune system might reverse deposition of amyloid and thus stop the disease. Initial results using this approach in animals were promising, and clinical trials of the drug candidate AN-1792 showed results in 20% of patients. However, in 2002 it was reported that 6% of multi-dosed participants (18 of 300) developed symptoms resembling meningoencephalitis, and the trials were stopped. Participants in the halted trials continued to be followed, and 20% "developed high levels of antibodies to beta-amyloid" and some showed slower progression of the disease, maintaining memory-test levels while placebo-patients worsened. Microcerebral haemorrhages with passive immunisation and meningoencephalitis with active immunisation still remain potent threats to this strategy.[125] Work is continuing on less toxic vaccines.
  • The statin simvastatin has been found to reduce the incidence of Alzheimer's disease and Parkinsons disease by almost 50 percent by researchers from Boston University School of Medicine (BUSM).[126][127]
  • Proposed alternative treatments for Alzheimer's include a range of herbal compounds and dietary supplements. In the AAGP review from 2006,[102] Vitamin E in doses below 400 IU was mentioned as having conflicting evidence in efficacy to prevent AD. Higher doses were discouraged as these may be linked with higher mortality related to cardiac events.

Laboratory studies with cells and animals continually fuel the pipeline of potential treatments. Some currently approved drugs such as statins and thiazolidinediones[128] have also been under investigation for the treatment and prevention of Alzheimer’s. Recent clinical trials for Phase 2 and Phase 3 in this category have taken 12 to 18 months under study drug, plus additional months for patient enrollment and analysis. Compounds that are just entering into human trials or are in pre-clinical trials would be at least 4 years from being available to the public and would be available only if they can demonstrate safety and efficacy in human trials.

Occupational and lifestyle therapies

Modifications to the living environment and lifestyle of the Alzheimer's patient can improve functional performance and ease caretaker burden. Assessment by an occupational therapist is often indicated. Adherence to simplified routines and labeling of household items to cue the patient can aid with activities of daily living, while placing safety locks on cabinets, doors, and gates and securing hazardous chemicals and guns can prevent accidents and wandering. Changes in routine or environment can trigger or exacerbate agitation, whereas well-lit rooms, adequate rest, and avoidance of excess stimulation all help prevent such episodes.[129] Appropriate social and visual stimulation, however, can improve function by increasing awareness and orientation. For instance, boldly colored tableware aids those with severe AD, helping people overcome a diminished sensitivity to visual contrast to increase food and beverage intake.[130]

Social issues

Alzheimer's is a major public health challenge since the median age of the industrialized world's population is increasing gradually.[131] Indeed, much of the concern about the solvency of governmental social safety nets is founded on estimates of the costs of caring for baby boomers, assuming that they develop Alzheimer's in the same proportions as earlier generations. For this reason, money spent informing the public of available effective prevention methods may yield disproportionate benefits.

The role of family caregivers has also become more prominent, as care in the familiar surroundings of home may delay onset of some symptoms and delay or eliminate the need for more professional and costly levels of care. However, home-based care may entail tremendous economic, emotional, and even psychological costs as well (see elderly care). Family caregivers often give up time from work and forego pay to spend 47 hours per week on average with an affected loved one who frequently cannot be left alone. From a survey of patients with long term care insurance, direct and indirect costs of caring for an Alzheimer's patient average $77,500 per year.[132]

Statistics on Alzheimer's disease

  • In the United States of America, AD was the 7th leading cause of death in 2004, with 65,829 number of deaths (and rising).[133]
  • At over $100 billion per year, AD is the third most costly disease in the U.S., after heart disease and cancer.[134]
  • There are an estimated 24 million people with dementia worldwide.[135] By 2040, it is projected that this figure will have increased to 81 million.
  • More than 5 million Americans are estimated to have Alzheimer’s disease.[136] It is projected that 14.3 million Americans will have the disease by mid-century: a 350 percent increase from 2000.[137]
  • The U.S. federal government estimates spending approximately $647 million for Alzheimer’s disease research in fiscal year 2005.[136]

Notable cases

Notable cases of Alzheimer's disease have included Aaron Copland, Ronald Reagan, Harold Wilson, Iris Murdoch, Eddie Robinson, Ferenc Puskas, Rita Hayworth,[138] Eddie Albert, Charlton Heston, James Doohan, Claude Shannon, A.E. van Vogt, Hazel Hawke and Terry Pratchett.

Alzheimer's in the media

  • TV documentaries Malcolm and Barbara - A Love Story(1999) and Malcolm and Barbara: Love’s Farewell (2007), featured Malcolm Pointon who was diagnosed with Alzheimer's at the age of 51. Over a period of 14 years Paul Watson followed Malcolm and Barbara Pointon's lives. The documentary follows the couple as Malcolm succumbs to the disease and shows the harsh reality faced by caregivers. The 2007 programme was the target of controversy when initial media claims that the finale purported to show Malcolm's death from the disease, but insider sources revealed that in the closing shots of the documentary actually show Malcolm slipping into a coma from which he never recovered. The argument overshadowed the importance of the documentary, and when it aired on 8th August 2007 the narrator informs us that "Malcolm is in a coma, and dies three days later."[139]
  • Iris is a 2001 film that tells the story of Irish novelist Iris Murdoch and her relationship with John Bayley. The film contrasts the start of their relationship and their later life, when Murdoch (played by Dame Judi Dench) was suffering from Alzheimer's disease. The film is based on Bayley's memoir Elegy for Iris.
  • The 2004 American film The Notebook is a fictional story about a woman with Alzheimer's and how her husband copes with the disease. Ryan Gosling and Rachel McAdams star in this film adapted from Nicholas Sparks' novel.
  • Thanmathra (Malayalam:Molecule) (2005) is a Malayalam film directed by Blessy which portrays the effects of Alzheimer's disease on the life of an individual and his family.
  • The 2006 Japanese film Memories of tomorrow (Ashita no Kioku), starring Ken Watanabe, tells a story of a 49-year-old man suffering from Alzheimer's disease and burden of care put on his wife.
  • In the American TV show Grey's Anatomy the mother of the main character Meredith Grey dies after battling Alzheimer's disease.
  • Away From Her is the feature-length directorial debut of English Canadian actor Sarah Polley. The film is based on Alice Munro's short story "The Bear Came Over the Mountain", from the 2001 collection Hateship, Friendship, Courtship, Loveship, Marriage. The film stars Gordon Pinsent and Julie Christie as a couple whose marriage is tested when Christie's character begins to suffer from Alzheimer's and moves into a nursing home, where she loses virtually all memory of her husband and begins to develop a romance with another nursing home resident.
  • Grace is a documentary that profiles the life of Grace Kirkland, beginning shortly after her diagnosis of Alzheimer’s disease and ending at her death seven years later. The documentary tracks Grace through the progression of her symptoms and the changing role of her caregiver husband, Glenn Kirkland. This Whiteford-Hadary production was aired on American public television stations in 1991 and has received a regional Emmy Award (1992).

Further reading

Clinical guidelines: clinical guidelines are documents with the aim of guiding decisions and criteria in specific areas of healthcare, as defined by an authoritative examination of current evidence (evidence-based medicine).

  • Waldemar G, Dubois B, Emre M, et al (2007). "Recommendations for the diagnosis and management of Alzheimer's disease and other disorders associated with dementia: EFNS guideline". Eur. J. Neurol. 14 (1): e1–26. doi:10.1111/j.1468-1331.2006.01605.x. PMID 17222085.
  • Cummings JL, Frank JC, Cherry D, et al (2002). "Guidelines for managing Alzheimer's disease: part I. Assessment". Am Fam Physician 65 (11): 2263–72. PMID 12074525. Free full text (2002-06-01). Retrieved on 2007-12-09.
  • Cummings JL, Frank JC, Cherry D, et al (2002). "Guidelines for managing Alzheimer's disease: Part II. Treatment". Am Fam Physician 65 (12): 2525–34. PMID 12086242. Free full text (2002-06-15). Retrieved on 2007-12-09.

See also


  1. ^ Ferri CP, Prince M, Brayne C, et al (2005). "Global prevalence of dementia: a Delphi consensus study". Lancet 366 (9503): 2112-7. doi:10.1016/S0140-6736(05)67889-0. PMID 16360788.
  2. ^ "Decoding Darkness: The Search for the Genetics Causes of Alzheimer's Disease", Rudolph Tanzi and Ann Parson, Perseus Press, 2000
  3. ^ a b Berchtold NC, Cotman CW (1998). "Evolution in the conceptualization of dementia and Alzheimer's disease: Greco-Roman period to the 1960s". Neurobiol. Aging 19 (3): 173–89. PMID 9661992.
  4. ^ Alzheimer, A. (1907). "Uber eine eigenartige Erkrankung der Hirnrinde.". Allg. Z. Psychiat. Psych.-Gerichtl. Med. 64 (1-2): 146–148.
  5. ^ Maurer, Konrad; Maurer, Ulrike (2003). Alzheimer: the life of a physician and the career of a disease. New York: Columbia University Press. ISBN 0-231-11896-1. 
  6. ^ Hochberg, Fred H.; Rottenberg, David (1977). Neurological classics in modern translation. New York: Hafner Press. ISBN 0-02-851180-8. 
  7. ^ Kraepelin, Emil (1910). Textbook of Psychiatry. 
  8. ^ Boller F, Forbes MM (1998). "History of dementia and dementia in history: an overview". J. Neurol. Sci. 158 (2): 125–33. PMID 9702682.
  9. ^ Katzman; Terry, Bick (1978). Alzheimer's disease: senile dementia and related disorders. New York: Raven Press. 
  10. ^ Amaducci LA, Rocca WA, Schoenberg BS (1986). "Origin of the distinction between Alzheimer's disease and senile dementia: how history can clarify nosology". Neurology 36 (11): 1497–9. PMID 3531918.
  11. ^ . Alzheimer's Disease Genetics Fact Sheet. From the National Institute of Health
  12. ^ Förstl H, Kurz A (1999). "Clinical features of Alzheimer's disease". Eur Arch Psychiatry Clin Neurosci 249 (6): 288–90. PMID 10653284.
  13. ^ Linn RT, Wolf PA, Bachman DL, et al (1995). "The 'preclinical phase' of probable Alzheimer's disease. A 13-year prospective study of the Framingham cohort". Arch. Neurol. 52 (5): 485–90. PMID 7733843.
  14. ^ Saxton J, Lopez OL, Ratcliff G, et al (2004). "Preclinical Alzheimer disease: neuropsychological test performance 1.5 to 8 years prior to onset". Neurology 63 (12): 2341–7. PMID 15623697.
  15. ^ Twamley EW, Ropacki SA, Bondi MW (2006). "Neuropsychological and neuroimaging changes in preclinical Alzheimer's disease". J Int Neuropsychol Soc 12 (5): 707–35. doi:10.1017/S1355617706060863. PMID 16961952.
  16. ^ Perneczky R, Pohl C, Sorg C, et al (2006). "Complex activities of daily living in mild cognitive impairment: conceptual and diagnostic issues". Age Ageing 35 (3): 240–5. doi:10.1093/ageing/afj054. PMID 16513677.
  17. ^ Rapp MA, Reischies FM (2005). "Attention and executive control predict Alzheimer disease in late life: results from the Berlin Aging Study (BASE)". Am J Geriatr Psychiatry 13 (2): 134–41. doi:10.1176/appi.ajgp.13.2.134. PMID 15703322.
  18. ^ Spaan PE, Raaijmakers JG, Jonker C (2003). "Alzheimer's disease versus normal ageing: a review of the efficiency of clinical and experimental memory measures". J Clin Exp Neuropsychol 25 (2): 216–33. PMID 12754679.
  19. ^ Robert PH, Berr C, Volteau M, et al (2006). "Apathy in patients with mild cognitive impairment and the risk of developing dementia of Alzheimer's disease: a one-year follow-up study". Clin Neurol Neurosurg 108 (8): 733–6. doi:10.1016/j.clineuro.2006.02.003. PMID 16567037.
  20. ^ Palmer K, Berger AK, Monastero R, Winblad B, Bäckman L, Fratiglioni L (2007). "Predictors of progression from mild cognitive impairment to Alzheimer disease". Neurology 68 (19): 1596–602. doi:10.1212/01.wnl.0000260968.92345.3f. PMID 17485646.
  21. ^ Small BJ, Gagnon E, Robinson B (2007). "Early identification of cognitive deficits: preclinical Alzheimer's disease and mild cognitive impairment". Geriatrics 62 (4): 19–23. PMID 17408315.
  22. ^ Petersen RC (2007). "The current status of mild cognitive impairment--what do we tell our patients?". Nat Clin Pract Neurol 3 (2): 60–1. doi:10.1038/ncpneuro0402. PMID 17279076.
  23. ^ Kumru, Liz. Getting Lost in Alzheimer's UNMC. Accessed 22 July 2007.
  24. ^ Rickey, Tom. (31 January 2002) Road Skills Hint at "Motion Blindness" of Alzheimer's Accessed 21 July 2007.
  25. ^ a b McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984). "Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease". Neurology 34 (7): 939–44. PMID 6610841.
  26. ^ Lopera F (2001). "[Clinical history in the study of a patient with dementia]" (in Spanish; Castilian). Rev Neurol 32 (12): 1187–91. PMID 11708253.
  27. ^ a b c d Waldemar G, Dubois B, Emre M, et al (2007). "Recommendations for the diagnosis and management of Alzheimer's disease and other disorders associated with dementia: EFNS guideline". Eur. J. Neurol. 14 (1): e1–26. doi:10.1111/j.1468-1331.2006.01605.x. PMID 17222085.
  28. ^ Blacker D, Albert MS, Bassett SS, Go RC, Harrell LE, Folstein MF (1994). "Reliability and validity of NINCDS-ADRDA criteria for Alzheimer's disease. The National Institute of Mental Health Genetics Initiative". Arch. Neurol. 51 (12): 1198–204. PMID 7986174.
  29. ^ American Psychiatric Association (2000). Diagnostic and Statistical Manual of Mental disorders, 4th Edition Text Revision. 
  30. ^ Ito N (1996). "[Clinical aspects of dementia]" (in Japanese). Hokkaido Igaku Zasshi 71 (3): 315–20. PMID 8752526.
  31. ^ Tombaugh TN, McIntyre NJ (1992). "The mini-mental state examination: a comprehensive review". J Am Geriatr Soc 40 (9): 922–35. PMID 1512391.
  32. ^ Pasquier F (1999). "Early diagnosis of dementia: neuropsychology". J. Neurol. 246 (1): 6–15. PMID 9987708.
  33. ^ Harvey PD, Moriarty PJ, Kleinman L, et al (2005). "The validation of a caregiver assessment of dementia: the Dementia Severity Scale". Alzheimer Dis Assoc Disord 19 (4): 186–94. PMID 16327345.
  34. ^ Antoine C, Antoine P, Guermonprez P, Frigard B (2004). "[Awareness of deficits and anosognosia in Alzheimer's disease.]" (in French). Encephale 30 (6): 570–7. PMID 15738860.
  35. ^ Cruz VT, Pais J, Teixeira A, Nunes B (2004). "[The initial symptoms of Alzheimer disease: caregiver perception]" (in Portuguese). Acta Med Port 17 (6): 435–44. PMID 16197855.
  36. ^ Sellal F, Becker H (2007). "[Potentially reversible dementia]" (in French). Presse Med 36 (2 Pt 2): 289–98. doi:10.1016/j.lpm.2006.11.005. PMID 17258677.
  37. ^ Geldmacher DS, Whitehouse PJ (1997). "Differential diagnosis of Alzheimer's disease". Neurology 48 (5 Suppl 6): S2–9. PMID 9153154.
  38. ^ Potter GG, Steffens DC (2007). "Contribution of depression to cognitive impairment and dementia in older adults". Neurologist 13 (3): 105–17. doi:10.1097/01.nrl.0000252947.15389.a9. PMID 17495754.
  39. ^ Bonte FJ, Harris TS, Hynan LS, Bigio EH, White CL (2006). "Tc-99m HMPAO SPECT in the differential diagnosis of the dementias with histopathologic confirmation". Clinical nuclear medicine 31 (7): 376–8. doi:10.1097/01.rlu.0000222736.81365.63. PMID 16785801.
  40. ^ Dougall NJ, Bruggink S, Ebmeier KP (2004). "Systematic review of the diagnostic accuracy of 99mTc-HMPAO-SPECT in dementia". The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry 12 (6): 554–70. doi:10.1176/appi.ajgp.12.6.554. PMID 15545324.
  41. ^ Marksteiner J, Hinterhuber H, Humpel C (2007). "Cerebrospinal fluid biomarkers for diagnosis of Alzheimer's disease: beta-amyloid(1-42), tau, phospho-tau-181 and total protein". Drugs Today 43 (6): 423–31. doi:10.1358/dot.2007.43.6.1067341. PMID 17612711.
  42. ^ Dubois B, Feldman HH, Jacova C, et al (2007). "Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria". Lancet Neurol 6 (8): 734–46. doi:10.1016/S1474-4422(07)70178-3. PMID 17616482.
  43. ^ Hashimoto M, Rockenstein E, Crews L, Masliah E (2003). "Role of protein aggregation in mitochondrial dysfunction and neurodegeneration in Alzheimer's and Parkinson's diseases.". Neuromolecular Med 4 (1-2): 21-36. PMID 14528050.
  44. ^ Cai D, Netzer W, Zhong M, Lin Y, Du G, Frohman M, Foster D, Sisodia S, Xu H, Gorelick F, Greengard P (2006). "Presenilin-1 uses phospholipase D1 as a negative regulator of beta-amyloid formation.". Proc Natl Acad Sci U S A 103 (6): 1941-6. PMID 16449386.
  45. ^ Ohnishi S, Takano K (2004). "Amyloid fibrils from the viewpoint of protein folding.". Cell Mol Life Sci 61 (5): 511-24. PMID 15004691.
  46. ^ Goedert M, Klug A, Crowther R (2006). "Tau protein, the paired helical filament and Alzheimer's disease.". J Alzheimers Dis 9 (3 Suppl): 195-207. PMID 16914859.
  47. ^ Tiraboschi P, Hansen L, Thal L, Corey-Bloom J (2004). "The importance of neuritic plaques and tangles to the development and evolution of AD.". Neurology 62 (11): 1984-9. PMID 15184601.
  48. ^ a b Wenk G. "Neuropathologic changes in Alzheimer's disease.". J Clin Psychiatry 64 Suppl 9: 7-10. PMID 12934968.
  49. ^ Baskys. Receptor found that could lead to better treatments for stroke, alzheimer's disease. UCI Medical Center. Retrieved on 2006-11-04.
  50. ^ Walker LC, Rosen RF (2006). "Alzheimer therapeutics: What after the cholinesterase inhibitors?". Age Ageing 35: 332-335. PMID 16644763.
  51. ^ Shen Z (2004). "Brain cholinesterases: II. The molecular and cellular basis of Alzheimer's disease.". Med Hypotheses 63 (2): 308-21. PMID 15236795.
  52. ^ a b Mudher A, Lovestone S (2002). "Alzheimer's disease-do tauists and baptists finally shake hands?". Trends Neurosci 25 (1): 22-6. PMID 11801334.
  53. ^ Schmitz C, Rutten B, Pielen A, Schäfer S, Wirths O, Tremp G, Czech C, Blanchard V, Multhaup G, Rezaie P, Korr H, Steinbusch H, Pradier L, Bayer T (2004). "Hippocampal neuron loss exceeds amyloid plaque load in a transgenic mouse model of Alzheimer's disease.". Am J Pathol 164 (4): 1495-502. PMID 15039236.
  54. ^ Nistor M, Don M, Parekh M, Sarsoza F, Goodus M, Lopez GE, Kawas C, Leverenz J, Doran E, Lott IT, Hill M, Head E (2006). "Alpha- and beta-secretase activity as a function of age and Aβ in Down syndrome and normal brain.". Neurobiol Aging (epub). PMID 16904243.
  55. ^ Lott I, Head E (2005). "Alzheimer disease and Down syndrome: factors in pathogenesis.". Neurobiol Aging 26 (3): 383-9. PMID 15639317.
  56. ^ Yankner B, Duffy L, Kirschner D (1990). "Neurotrophic and neurotoxic effects of amyloid beta protein: reversal by tachykinin neuropeptides.". Science 250 (4978): 279-82. PMID 2218531.
  57. ^ Blanchard BJ, Hiniker AE, Lu CC, Margolin Y, Yu AS, Ingram VM (2000). "Elimination of Amyloid beta Neurotoxicity.". J Alzheimers Dis 2 (2): 137-149. PMID 12214104.
  58. ^ Blanchard B, Chen A, Rozeboom L, Stafford K, Weigele P, Ingram V (2004). "Efficient reversal of Alzheimer's disease fibril formation and elimination of neurotoxicity by a small molecule.". Proc Natl Acad Sci U S A 101 (40): 14326-32. PMID 15388848.
  59. ^ Porat Y, Abramowitz A, Gazit E (2006). "Inhibition of amyloid fibril formation by polyphenols: structural similarity and aromatic interactions as a common inhibition mechanism.". Chem Biol Drug Des 67 (1): 27-37. PMID 16492146.
  60. ^ Kanapathipillai M, Lentzen G, Sierks M, Park C (2005). "Ectoine and hydroxyectoine inhibit aggregation and neurotoxicity of Alzheimer's beta-amyloid.". FEBS Lett 579 (21): 4775-80. PMID 16098972.
  61. ^ Lee K, Shin B, Shin K, Kim D, Yu J (2005). "A hybrid molecule that prohibits amyloid fibrils and alleviates neuronal toxicity induced by beta-amyloid (1-42).". Biochem Biophys Res Commun 328 (4): 816-23. PMID 15707952.
  62. ^ Espeseth A, Xu M, Huang Q, Coburn C, Jones K, Ferrer M, Zuck P, Strulovici B, Price E, Wu G, Wolfe A, Lineberger J, Sardana M, Tugusheva K, Pietrak B, Crouthamel M, Lai M, Dodson E, Bazzo R, Shi X, Simon A, Li Y, Hazuda D (2005). "Compounds that bind APP and inhibit Abeta processing in vitro suggest a novel approach to Alzheimer disease therapeutics.". J Biol Chem 280 (18): 17792-7. PMID 15737955.
  63. ^ Polvikoski T, Sulkava R, Haltia M, Kainulainen K, Vuorio A, Verkkoniemi A, Niinistö L, Halonen P, Kontula K (1995). "Apolipoprotein E, dementia, and cortical deposition of beta-amyloid protein.". N Engl J Med 333 (19): 1242-7. PMID 7566000.
  64. ^ Games D, Adams D, Alessandrini R, Barbour R, Berthelette P, Blackwell C, Carr T, Clemens J, Donaldson T, Gillespie F (1995). "Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein.". Nature 373 (6514): 523-7. PMID 7845465.
  65. ^ Masliah E, Sisk A, Mallory M, Mucke L, Schenk D, Games D (1996). "Comparison of neurodegenerative pathology in transgenic mice overexpressing V717F beta-amyloid precursor protein and Alzheimer's disease.". J Neurosci 16 (18): 5795-811. PMID 8795633.
  66. ^ Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, Yang F, Cole G (1996). "Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice.". Science 274 (5284): 99-102. PMID 8810256.
  67. ^ Gorelick P (2004). "Risk factors for vascular dementia and Alzheimer disease.". Stroke 35 (11 Suppl 1): 2620-2. PMID 15375299.
  68. ^ Hebert L, Scherr P, Bienias J, Bennett D, Evans D (2003). "Alzheimer disease in the U.S. population: prevalence estimates using the 2000 census.". Arch Neurol 60 (8): 1119-22. PMID 12925369.
  69. ^ Small, Gary W (2002-06-22). "What we need to know about age related memory loss". British Medical Journal: 1502-1507. Retrieved on 2006-11-05.
  70. ^ Verghese J, Lipton R, Katz M, Hall C, Derby C, Kuslansky G, Ambrose A, Sliwinski M, Buschke H (2003). "Leisure activities and the risk of dementia in the elderly.". N Engl J Med 348 (25): 2508-16. PMID 12815136.
  71. ^ Larson E, Wang L, Bowen J, McCormick W, Teri L, Crane P, Kukull W (2006). "Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older.". Ann Intern Med 144 (2): 73-81. PMID 16418406.
  72. ^ Loneliness link with Alzheimer's. Retrieved on 30 October, 2007.
  73. ^ Scarmeas N, Stern Y, Mayeux R, Luchsinger J (2006). "Mediterranean diet, Alzheimer disease, and vascular mediation.". Arch Neurol 63 (12): 1709-17. PMID 17030648.
  74. ^ Morris M, Schneider J, Tangney C (2006). "Thoughts on B-vitamins and dementia.". J Alzheimers Dis 9 (4): 429-33. PMID 16917152.
  75. ^ Inna I. Kruman1, T. S. Kumaravel2, Althaf Lohani2, Ward A. Pedersen1, Roy G. Cutler1, Yuri Kruman1, Norman Haughey1, Jaewon Lee1, Michele Evans2, and Mark P. Mattson1, 3 (March 1, 2002). "Folic Acid Deficiency and Homocysteine Impair DNA Repair in Hippocampal Neurons and Sensitize Them to Amyloid Toxicity in Experimental Models of Alzheimer's Disease .". The Journal of Neuroscience, 22 (5). A simplified report can be found at:
  76. ^ CBS news, reporting from WebMD Folate May Lower Alzheimer's Risk
  77. ^ National Institute of Health - Folic Acid Possibly A Key Factor In Alzheimer's Disease Prevention
  78. ^ Alzheimer's and Dementia journal, reported at USA today[1]
  79. ^ Giselle P. Lim1, Teresa Chu1, Fusheng Yang, Walter Beech1, Sally A. Frautschy1, and Greg M. Cole1 (2001). "The Curry Spice Curcumin Reduces Oxidative Damage and Amyloid Pathology in an Alzheimer Transgenic Mouse". The Journal of Neuroscience 21 (4): 8370-8377. PMID 11606625.
  80. ^ Lim W, Gammack J, Van Niekerk J, Dangour A. "Omega 3 fatty acid for the prevention of dementia.". Cochrane Database Syst Rev: CD005379. PMID 16437528.
  81. ^ Morris M, Evans D, Tangney C, Bienias J, Wilson R (2005). "Fish consumption and cognitive decline with age in a large community study.". Arch Neurol 62 (12): 1849-53. PMID 16216930.
  82. ^ Docosahexaenoic acid may protect against the accumulation of a protein believed to be linked to Alzheimer's disease
  83. ^ Dai Q, Borenstein A, Wu Y, Jackson J, Larson E (2006). "Fruit and vegetable juices and Alzheimer's disease: the Kame Project.". Am J Med 119 (9): 751-9. PMID 16945610.
  84. ^ Joseph J, Fisher D, Carey A (2004). "Fruit extracts antagonize Abeta- or DA-induced deficits in Ca2+ flux in M1-transfected COS-7 cells.". J Alzheimers Dis 6 (4): 403-11; discussion 443-9. PMID 15345811.
  85. ^ Petersen R, Thomas R, Grundman M, Bennett D, Doody R, Ferris S, Galasko D, Jin S, Kaye J, Levey A, Pfeiffer E, Sano M, van Dyck C, Thal L (2005). "Vitamin E and donepezil for the treatment of mild cognitive impairment.". N Engl J Med 352 (23): 2379-88. PMID 15829527.
  86. ^ Zandi P, Anthony J, Khachaturian A, Stone S, Gustafson D, Tschanz J, Norton M, Welsh-Bohmer K, Breitner J (2004). "Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study.". Arch Neurol 61 (1): 82-8. PMID 14732624.
  87. ^ Lonn E, Bosch J, Yusuf S, et al (2005). "Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial". JAMA 293 (11): 1338–47. doi:10.1001/jama.293.11.1338. PMID 15769967.
  88. ^ Scarmeas, N., et al. Mediterranean diet and risk for Alzheimer’s disease. Annals of Neurology, 2006 (published online April 18, 2006).
  89. ^ Mulkamal, K.J., et al. Prospective study of alcohol consumption and risk of dementia in older adults. Journal of the American Medical Association, 2003 (March 19), 289, 1405-1413;
  90. ^ Ganguli, M., et al. Alcohol consumption and cognitive function in late life: A longitudinal community study. Neurology, 2005, 65, 1210-12-17
  91. ^ Huang, W., et al. Alcohol consumption and incidence of dementia in a community sample aged 75 years and older. Journal of Clinical Epidemiology, 2002, 55(10), 959-964
  92. ^ Rodgers, B., et al. Non-linear relationships between cognitive function and alcohol consumption in young, middle-aged and older adults: The PATH Through Life Project. Addiction, 2005, 100(9), 1280-1290
  93. ^ Anstey, K. J., et al. Lower cognitive test scores observed in alcohol are associated with demographic, personality, and biological factors: The PATH Through Life Project. Addiction, 2005, 100(9), 1291-1301
  94. ^ Espeland, M., et al. Association between alcohol intake and domain-specific cognitive function in older women. Neuroepidemiology, 2006, 1(27), 1-12
  95. ^ Stampfer, M.J., et al. Effects of moderate alcohol consumption on cognitive function in women. New England Journal of Medicine, 2005, 352, 245-253;
  96. ^ Ruitenberg, A., et al. Alcohol consumption and risk of dementia: the Rotterdam Study. Lancet, 2002, 359(9303), 281-286.
  97. ^
  98. ^
  99. ^ Rockwood K. "Epidemiological and clinical trials evidence about a preventive role for statins in Alzheimer's disease.". Acta Neurol Scand Suppl 185: 71-7. PMID 16866914.
  100. ^ Zandi P, Anthony J, Hayden K, Mehta K, Mayer L, Breitner J (2002). "Reduced incidence of AD with NSAID but not H2 receptor antagonists: the Cache County Study". Neurology 59 (6): 880-6. PMID 12297571.
  101. ^ in t' Veld B, Ruitenberg A, Hofman A, Launer L, van Duijn C, Stijnen T, Breteler M, Stricker B (2001). "Nonsteroidal antiinflammatory drugs and the risk of Alzheimer's disease". N Engl J Med 345 (21): 1515-21. PMID 11794217.
  102. ^ a b c d Lyketsos C, Colenda C, Beck C, Blank K, Doraiswamy M, Kalunian D, Yaffe K (2006). "Position statement of the American Association for Geriatric Psychiatry (AAGP) regarding principles of care for patients with dementia resulting from Alzheimer disease.". Am J Geriatr Psychiatry 14 (7): 561-72. PMID 16816009. [2]
  103. ^
  104. ^ Mayeux R, Ottman R, Tang M, Noboa-Bauza L, Marder K, Gurland B, Stern Y (1993). "Genetic susceptibility and head injury as risk factors for Alzheimer's disease among community-dwelling elderly persons and their first-degree relatives". Ann. Neurol. 33 (5): 494-501. PMID 8498827.
  105. ^ Kofman OS, MacMillan VH (1970). "Diffuse Cerebral Atrophy.". Applied Therapeutics 12 (4): 24-26.
  106. ^ Kehoe P, Wilcock G (2007). "Is inhibition of the renin-angiotensin system a new treatment option for Alzheimer's disease?". Lancet neurology 6 (4): 373-8. PMID 17362841.
  107. ^ Crisby M, Carlson L, Winblad B (2002). "Statins in the prevention and treatment of Alzheimer disease". Alzheimer disease and associated disorders 16 (3): 131-6. PMID 12218642.
  108. ^ BBC Why stroke ups Alzheimer's risk 4 June 2007
  109. ^ Anstey KJ, von Sanden C, Salim A, O'kearney R (2007). "Smoking as a risk factor for dementia and cognitive decline: a meta-analysis of prospective studies". Am. J. Epidemiol. 166 (4): 367-78. doi:10.1093/aje/kwm116. PMID 17573335.
  110. ^ BMJ. 1991 Aug 10;303(6798):361. Relation between nicotine intake and Alzheimer's disease.van Duijn CM, Hofman A.
  111. ^
  112. ^ Ortho-McNeil Neurologics, “Razadyne ER U.S. Product Insert”, May 2006. [3]
  113. ^ Novartis Pharmaceuticals Corporation “Exelon Product Insert” June 2006. [4]
  114. ^ Eisai Inc, “Aricept and Aricept ODT Product Insert”, March 2005. [5]
  115. ^ Courtney C, Farrell D, Gray R, Hills R, Lynch L, Sellwood E, Edwards S, Hardyman W, Raftery J, Crome P, Lendon C, Shaw H, Bentham P (2004). "Long-term donepezil treatment in 565 patients with Alzheimer's disease (AD2000): randomised double-blind trial.". Lancet 363 (9427): 2105-15. PMID 15220031.
  116. ^ Kaduszkiewicz H, Zimmermann T, Beck-Bornholdt H, van den Bussche H (2005). "Cholinesterase inhibitors for patients with Alzheimer's disease: systematic review of randomised clinical trials.". BMJ 331 (7512): 321-7. PMID 16081444.
  117. ^ Birks J, Grimley E, Van Dongen M. "Ginkgo biloba for cognitive impairment and dementia.". Cochrane Database Syst Rev: CD003120. PMID 12519586..
  118. ^ DeKosky S, Fitzpatrick A, Ives D, Saxton J, Williamson J, Lopez O, Burke G, Fried L, Kuller L, Robbins J, Tracy R, Woolard N, Dunn L, Kronmal R, Nahin R, Furberg C (2006). "The Ginkgo Evaluation of Memory (GEM) study: design and baseline data of a randomized trial of Ginkgo biloba extract in prevention of dementia.". Contemp Clin Trials 27 (3): 238-53. PMID 16627007..
  119. ^ Areosa Sastre A, McShane R, Sherriff F. "Memantine for dementia.". Cochrane Database Syst Rev: CD003154. PMID 15495043.
  120. ^ Olazarán J, Muñiz R, Reisberg B, Peña-Casanova J, del Ser T, Cruz-Jentoft A, Serrano P, Navarro E, García de la Rocha M, Frank A, Galiano M, Fernández-Bullido Y, Serra J, González-Salvador M, Sevilla C (2004). "Benefits of cognitive-motor intervention in MCI and mild to moderate Alzheimer disease.". Neurology 63 (12): 2348-53. PMID 15623698.
  121. ^ Clare L, Woods R, Moniz Cook E, Orrell M, Spector A. "Cognitive rehabilitation and cognitive training for early-stage Alzheimer's disease and vascular dementia.". Cochrane Database Syst Rev: CD003260. PMID 14583963.
  122. ^ Practice Guideline for the Treatment of Patients with Alzheimer's disease and Other Dementias (PDF). American Psychiatry Association (October 2007). Retrieved on December 28, 2007.
  123. ^ Zamrini E (2006). "Emerging Drug Therapies for Dementia.". Geriatrics Aging 9 (2): 107,110-113. [6].
  124. ^ Eriksen J, Sagi S, Smith T, Weggen S, Das P, McLendon D, Ozols V, Jessing K, Zavitz K, Koo E, Golde T (2003). "NSAIDs and enantiomers of flurbiprofen target gamma-secretase and lower Abeta 42 in vivo.". J Clin Invest 112 (3): 440-9. PMID 12897211..
  125. ^ Alzheimer’s Association Fact Sheet: AN-1792 (2006, on Retrieved on 2006-11-06..
  126. ^ Researchers Find Specific Statin Significantly Reduces Alzheimer's and Parkinson's Disease Risk. Retrieved on 2007-08-06..
  127. ^ Simvastatin is associated with a reduced incidence of dementia and Parkinson's disease. Retrieved on 2007-09-10..
  128. ^ Landreth G (2006). "PPARgamma agonists as new therapeutic agents for treatment of Alzheimer's disease.". Exp Neurol 199 (2): 245-8. PMID 16733054.
  129. ^ Treating behavioral and psychiatric symptoms. Alzheimer's Association. Accessed Oct. 15, 2006.[7]
  130. ^ Dunne TE, Neargarder SA, Cipolloni PB, Cronin-Golomb A. (2004). "Visual contrast enhances food and liquid intake in advanced Alzheimer's disease". Clin Nutr 23 (4): 533-8. PMID 15297089.
  131. ^ Sloane P, Zimmerman S, Suchindran C, Reed P, Wang L, Boustani M, Sudha S. "The public health impact of Alzheimer's disease, 2000-2050: potential implication of treatment advances.". Annu Rev Public Health 23: 213-31. PMID 11910061.
  132. ^ "The MetLife Study of Alzheimer’s Disease: The Caregiving Experience". MetLife Mature Market Institute ® (August 2006). [8]
  133. ^ Faststats – Alzheimer's Disease National Center for Health Statistics
  134. ^ Alzheimer's Drug Discovery Foundation 2005 Annual Report
  135. ^ Statistics - Alzheimer's Disease International
  136. ^ a b Alzheimer's Facts and Figures Alzheimer's Association
  137. ^ Diagnostic Center for Alzheimer's Disease
  138. ^ Shenk, David (2003). The Forgetting Alzheimer’s: Portrait of an Epidemic. New York: Anchor Books. ISBN 0-385-49838-1. 
  139. ^ Alzheimer's film-maker to face ITV lawyers.
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Alzheimer's_disease". A list of authors is available in Wikipedia.
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