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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]

Contents

History

  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]

Etiology

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.

Diagnosis

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]

Pathology

Main article: Biochemistry of Alzheimer's disease

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.

Neuropathology

  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]

Epidemiology

Alzheimer's disease is the most frequent type of dementia in the elderly and affects almost half of all patients with dementia. Correspondingly, advancing age is the primary risk factor for 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]

Prevention

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

Treatment

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 Aβ 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

References

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v • d • e
WHO ICD-10 mental and behavioural disorders (F · 290–319)
Neurological/symptomaticDementia (Alzheimer's disease, multi-infarct dementia, Pick's disease, Creutzfeldt-Jakob disease, Huntington's disease, Parkinson's disease, AIDS dementia complex, Frontotemporal dementia) · Delirium · Post-concussion syndrome
Psychoactive substancealcohol (drunkenness, alcohol dependence, delirium tremens, Korsakoff's syndrome, alcohol abuse) · opiods (opioid dependency) · sedative/hypnotic (benzodiazepine withdrawal) · cocaine (cocaine dependence) · general (Intoxication, Drug abuse, Physical dependence, Withdrawal)
Psychotic disorderSchizophrenia (disorganized schizophrenia) · Schizotypal personality disorder · Delusional disorder · Folie à deux · Schizoaffective disorder
Mood (affective)Mania · Bipolar disorder · Clinical depression · Cyclothymia · Dysthymia
Neurotic, stress-related
and somatoform		Anxiety disorder (Agoraphobia, Panic disorder, Panic attack, Generalized anxiety disorder, Social anxiety) · OCD · Acute stress reaction · PTSD · Adjustment disorder · Conversion disorder (Ganser syndrome) · Somatoform disorder (Somatization disorder, Body dysmorphic disorder, Hypochondriasis, Nosophobia, Da Costa's syndrome, Psychalgia)  · Neurasthenia
Physiological/physical
behavioural		Eating disorder (anorexia nervosa, bulimia nervosa) · Sleep disorder (dyssomnia, insomnia, hypersomnia, parasomnia, night terror, nightmare) ·
Sexual dysfunction (erectile dysfunction, premature ejaculation, vaginismus, dyspareunia, hypersexuality) · Postpartum depression
Adult personality
and behaviour		Personality disorder · Passive-aggressive behavior · Kleptomania · Trichotillomania · Voyeurism · Factitious disorder · Munchausen syndrome · Ego-dystonic sexual orientation
Mental retardationMental retardation
Psychological development
(developmental disorder)		Specific: speech and language (expressive language disorder, aphasia, expressive aphasia, receptive aphasia, Landau-Kleffner syndrome, lisp) · Scholastic skills (dyslexia, dysgraphia, Gerstmann syndrome) · Motor function (developmental dyspraxia)
Pervasive: Autism · Rett syndrome · Asperger syndrome
Behavioural and emotional,
childhood and adolescence onset		ADHD · Conduct disorder · Oppositional defiant disorder · Separation anxiety disorder · Selective mutism · Reactive attachment disorder · Tic disorder · Tourette syndrome · Speech (stuttering · cluttering)
v • d • e
Nervous system pathology, primarily CNS (G00-G47, 320-349)
Inflammatory diseases
of the CNS		Meningitis (Arachnoiditis) - Encephalitis - Myelitis - Encephalomyelitis (Acute disseminated) - Tropical spastic paraparesis
Systemic atrophies
primarily affecting the CNS		Huntington's disease - Spinocerebellar ataxia (Friedreich's ataxia, Ataxia telangiectasia, Hereditary spastic paraplegia)
Spinal muscular atrophy: Werdnig-Hoffman disease - Kugelberg-Welander disease - Fazio Londe syndrome -
MND (Amyotrophic lateral sclerosis (ALS), Progressive muscular atrophy (PMA), Progressive bulbar, Pseudobulbar, PLS)
Extrapyramidal and
movement disorders		Parkinson's disease - Neuroleptic malignant syndrome - Postencephalitic parkinsonism - Pantothenate kinase-associated neurodegeneration - Progressive supranuclear palsy - Striatonigral degeneration - Dystonia (Spasmodic torticollis, Meige's syndrome, Blepharospasm) - Essential tremor - Myoclonus - Chorea (Choreoathetosis) - Restless legs syndrome - Stiff person syndrome
Other degenerative /
demyelinating diseases		Alzheimer's disease - Pick's disease - Alpers' disease - Dementia with Lewy bodies - Leigh's disease - Multiple sclerosis - Devic's disease - Central pontine myelinolysis - Transverse myelitis
Seizure/epilepsyFocal (Simple partial, Complex partial) - Generalised (Tonic-clonic, Absence, Atonic, Benign familial neonatal) - Lennox-Gastaut - West - Epilepsia partialis continua - Status epilepticus (Complex partial status epilepticus)
HeadacheMigraine (Familial hemiplegic) - Cluster - Vascular - Tension
VascularTransient ischemic attack (Amaurosis fugax, Transient global amnesia) - Cerebrovascular disease (MCA, ACA, PCA, Foville's syndrome, Millard-Gubler syndrome, Lateral medullary syndrome, Weber's syndrome, Lacunar stroke)
Sleep disordersInsomnia - Hypersomnia - Sleep apnea (Ondine's curse) - Narcolepsy - Cataplexy - Kleine-Levin syndrome - Circadian rhythm sleep disorder - Delayed sleep phase syndrome - Advanced sleep phase syndrome
OtherHydrocephalus (Normal pressure) - Idiopathic intracranial hypertension - Encephalopathy - Brain herniation - Cerebral edema - Reye's syndrome - Syringomyelia - Syringobulbia - Spinal cord compression
 
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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