Alzheimer's disease
This article needs to be updated.(March 2021) |
Alzheimer's disease | |
---|---|
Other names | Alzheimer's dementia |
Trisomy 21[10] | |
Medication | Acetylcholinesterase inhibitors, NMDA receptor antagonists[11] |
Prognosis | Life expectancy 3–9 years[12] |
Frequency | 50 million (2020)[13] |
Named after | Alois Alzheimer |
Alzheimer's disease (AD) is a neurodegenerative disease that usually starts slowly and progressively worsens,[2] and is the cause of 60–70% of cases of dementia.[2][14] The most common early symptom is difficulty in remembering recent events.[1] As the disease advances, symptoms can include problems with language, disorientation (including easily getting lost), mood swings, loss of motivation, self-neglect, and behavioral issues.[2] As a person's condition declines, they often withdraw from family and society.[15] Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the average life expectancy following diagnosis is three to twelve years.[16][12]
The cause of Alzheimer's disease is poorly understood.
No treatments can stop or reverse its progression, though some may temporarily improve symptoms.[2] A healthy diet, physical activity, and social engagement are generally beneficial in ageing, and may help in reducing the risk of cognitive decline and Alzheimer's.[19] Affected people become increasingly reliant on others for assistance, often placing a burden on caregivers.[23] The pressures can include social, psychological, physical, and economic elements.[23] Exercise programs may be beneficial with respect to activities of daily living and can potentially improve outcomes.[24] Behavioral problems or psychosis due to dementia are sometimes treated with antipsychotics, but this has an increased risk of early death.[25][26]
As of 2020, there were approximately 50 million people worldwide with Alzheimer's disease.[13] It most often begins in people over 65 years of age, although up to 10% of cases are early-onset impacting those in their 30s to mid-60s.[27][4] It affects about 6% of people 65 years and older,[15] and women more often than men.[28] The disease is named after German psychiatrist and pathologist Alois Alzheimer, who first described it in 1906.[29] Alzheimer's financial burden on society is large, with an estimated global annual cost of US$1 trillion.[13] It is ranked as the seventh leading cause of death worldwide.[30]
Signs and symptoms
The course of Alzheimer's is generally described in three stages, with a progressive pattern of
First symptoms
The first symptoms are often mistakenly attributed to
Subtle problems with the
Early stage
In people with Alzheimer's disease, the increasing impairment of learning and memory eventually leads to a definitive diagnosis. In a small percentage, difficulties with language, executive functions, perception (agnosia), or execution of movements (apraxia) are more prominent than memory problems.[39] Alzheimer's disease does not affect all memory capacities equally. Older memories of the person's life (episodic memory), facts learned (semantic memory), and implicit memory (the memory of the body on how to do things, such as using a fork to eat or how to drink from a glass) are affected to a lesser degree than new facts or memories.[40][41]
Language problems are mainly characterised by a shrinking vocabulary and decreased word fluency, leading to a general impoverishment of oral and written language.[39][42] In this stage, the person with Alzheimer's is usually capable of communicating basic ideas adequately.[39][42][43] While performing fine motor tasks such as writing, drawing, or dressing, certain movement coordination and planning difficulties (apraxia) may be present, but they are commonly unnoticed.[39] As the disease progresses, people with Alzheimer's disease can often continue to perform many tasks independently, but may need assistance or supervision with the most cognitively demanding activities.[39]
Middle stage
Progressive deterioration eventually hinders independence, with subjects being unable to perform most common activities of daily living.[39] Speech difficulties become evident due to an inability to recall vocabulary, which leads to frequent incorrect word substitutions (paraphasias). Reading and writing skills are also progressively lost.[39][43] Complex motor sequences become less coordinated as time passes and Alzheimer's disease progresses, so the risk of falling increases.[39] During this phase, memory problems worsen, and the person may fail to recognise close relatives.[39] Long-term memory, which was previously intact, becomes impaired.[39]
Behavioral and
Late stage
During the final stage, known as the late-stage or severe stage, there is complete dependence on caregivers.
Causes
Alzheimer's disease is believed to occur when abnormal amounts of amyloid beta (Aβ), accumulating extracellularly as amyloid plaques and tau proteins, or intracellularly as neurofibrillary tangles, form in the brain, affecting neuronal functioning and connectivity, resulting in a progressive loss of brain function.[47][48] This altered protein clearance ability is age-related, regulated by brain cholesterol,[49] and associated with other neurodegenerative diseases.[50][51]
The cause for most Alzheimer's cases is still mostly unknown,
The oldest hypothesis, on which most drug therapies are based, is the
Genetic
Late onset
Late-onset Alzheimer's is about 70%
The strongest genetic risk factor for sporadic Alzheimer's disease is APOEε4.[18] APOEε4 is one of four alleles of apolipoprotein E (APOE). APOE plays a major role in lipid-binding proteins in lipoprotein particles and the ε4 allele disrupts this function.[59] Between 40 and 80% of people with Alzheimer's disease possess at least one APOEε4 allele.[60] The APOEε4 allele increases the risk of the disease by three times in heterozygotes and by 15 times in homozygotes.[61] Like many human diseases, environmental effects and genetic modifiers result in incomplete penetrance. For example, Nigerian Yoruba people do not show the relationship between dose of APOEε4 and incidence or age-of-onset for Alzheimer's disease seen in other human populations.[62][63]
Early onset
Only 1–2% of Alzheimer's cases are
Early onset familial Alzheimer's disease can be attributed to mutations in one of three genes: those encoding
Alleles in the TREM2 gene have been associated with a three to five times higher risk of developing Alzheimer's disease.[68]
A Japanese pedigree of familial Alzheimer's disease was found to be associated with a deletion mutation of codon 693 of APP.[69] This mutation and its association with Alzheimer's disease was first reported in 2008,[70] and is known as the Osaka mutation. Only homozygotes with this mutation have an increased risk of developing Alzheimer's disease. This mutation accelerates Aβ oligomerization but the proteins do not form the amyloid fibrils that aggregate into amyloid plaques, suggesting that it is the Aβ oligomerization rather than the fibrils that may be the cause of this disease. Mice expressing this mutation have all the usual pathologies of Alzheimer's disease.[71]
Hypotheses
Amyloid-beta and tau protein
The
A number of studies connect the misfolded amyloid beta and tau proteins associated with the pathology of Alzheimer's disease, as bringing about
Sleep
Metal toxicity, smoking, neuroinflammation and air pollution
The cellular homeostasis of biometals such as ionic copper, iron, and zinc is disrupted in Alzheimer's disease, though it remains unclear whether this is produced by or causes the changes in proteins.[13][78] Smoking is a significant Alzheimer's disease risk factor.[1] Systemic markers of the innate immune system are risk factors for late-onset Alzheimer's disease.[79] Exposure to air pollution may be a contributing factor to the development of Alzheimer's disease.[13]
Other hypotheses
Retrogenesis is a medical
The association with
According to one theory, dysfunction of oligodendrocytes and their associated myelin during aging contributes to axon damage, which in turn generates in amyloid production and tau hyper-phosphorylation.[84][85]
Studies have shown a potential link between infection with certain viruses and developing Alzheimer's disease later in life.[86] Notably, a large scale study conducted on 6,245,282 patients has shown an increased risk of developing Alzheimer's disease following COVID-19 infection in cognitively normal individuals over 65.[87]
Pathophysiology
Neuropathology
Alzheimer's disease is characterised by loss of
Both
Biochemistry
Alzheimer's disease has been identified as a
Alzheimer's disease is also considered a
Disease mechanism
Exactly how disturbances of production and aggregation of the beta-amyloid peptide give rise to the pathology of Alzheimer's disease is not known.
Iron dyshomeostasis is linked to disease progression, an iron-dependent form of regulated cell death called ferroptosis could be involved. Products of lipid peroxidation are also elevated in AD brain compared with controls.[110]
Various inflammatory processes and cytokines may also have a role in the pathology of Alzheimer's disease. Inflammation is a general marker of tissue damage in any disease, and may be either secondary to tissue damage in Alzheimer's disease or a marker of an immunological response.[111] There is increasing evidence of a strong interaction between the neurons and the immunological mechanisms in the brain. Obesity and systemic inflammation may interfere with immunological processes which promote disease progression.[112]
Alterations in the distribution of different
Diagnosis
Alzheimer's disease (AD) can only be definitively diagnosed with autopsy findings; in the absence of autopsy, clinical diagnoses of AD are "possible" or "probable", based on other findings.[21][22][115] Up to 23% of those clinically diagnosed with AD may be misdiagnosed and may have pathology suggestive of another condition with symptoms that mimic those of AD.[22]
AD is usually clinically diagnosed based on the person's
Assessment of intellectual functioning including memory testing can further characterise the state of the disease.[1] Medical organizations have created diagnostic criteria to ease and standardise the diagnostic process for practising physicians. Definitive diagnosis can only be confirmed with post-mortem evaluations when brain material is available and can be examined histologically for senile plaques and neurofibrillary tangles.[121][122]
Criteria
There are three sets of criteria for the clinical diagnoses of the spectrum of Alzheimer's disease: the 2013 fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5); the National Institute on Aging-Alzheimer's Association (NIA-AA) definition as revised in 2011; and the International Working Group criteria as revised in 2010.[38][121] Three broad time periods, which can span decades, define the progression of Alzheimer's disease from the preclinical phase, to mild cognitive impairment (MCI), followed by Alzheimer's disease dementia.[123]
Eight intellectual domains are most commonly impaired in AD—
The DSM-5 defines criteria for probable or possible Alzheimer's for both major and mild neurocognitive disorder.[125][126][115] Major or mild neurocognitive disorder must be present along with at least one cognitive deficit for a diagnosis of either probable or possible AD.[125][127] For major neurocognitive disorder due to Alzheimer's disease, probable Alzheimer's disease can be diagnosed if the individual has genetic evidence of Alzheimer's[128] or if two or more acquired cognitive deficits, and a functional disability that is not from another disorder, are present.[129] Otherwise, possible Alzheimer's disease can be diagnosed as the diagnosis follows an atypical route.[130] For mild neurocognitive disorder due to Alzheimer's, probable Alzheimer's disease can be diagnosed if there is genetic evidence, whereas possible Alzheimer's disease can be met if all of the following are present: no genetic evidence, decline in both learning and memory, two or more cognitive deficits, and a functional disability not from another disorder.[125][131]
The NIA-AA criteria are used mainly in research rather than in clinical assessments.[132] They define Alzheimer's disease through three major stages: preclinical, mild cognitive impairment (MCI), and Alzheimer's dementia.[133][134] Diagnosis in the preclinical stage is complex and focuses on asymptomatic individuals;[134][135] the latter two stages describe individuals experiencing symptoms.[134] The core clinical criteria for MCI is used along with identification of biomarkers,[136] predominantly those for neuronal injury (mainly tau-related) and amyloid beta deposition.[132][134] The core clinical criteria itself rests on the presence of cognitive impairment[134] without the presence of comorbidities.[137][138] The third stage is divided into probable and possible Alzheimer's disease dementia.[138] In probable Alzheimer's disease dementia there is steady impairment of cognition over time and a memory-related or non-memory-related cognitive dysfunction.[138] In possible Alzheimer's disease dementia, another causal disease such as cerebrovascular disease is present.[138]
Techniques
Neuropsychological tests including cognitive tests such as the mini–mental state examination (MMSE), the Montreal Cognitive Assessment (MoCA) and the Mini-Cog are widely used to aid in diagnosis of the cognitive impairments in AD.[139] These tests may not always be accurate, as they lack sensitivity to mild cognitive impairment, and can be biased by language or attention problems;[139] more comprehensive test arrays are necessary for high reliability of results, particularly in the earliest stages of the disease.[140][141]
Further neurological examinations are crucial in the
Supplemental testing can rule out other potentially treatable diagnoses and help avoid misdiagnoses.[145] Common supplemental tests include blood tests, thyroid function tests, as well as tests to assess vitamin B12 levels, rule out neurosyphilis and rule out metabolic problems (including tests for kidney function, electrolyte levels and for diabetes).[145] MRI or CT scans might also be used to rule out other potential causes of the symptoms – including tumors or strokes.[139] Delirium and depression can be common among individuals and are important to rule out.[146]
Psychological tests for depression are used, since depression can either be concurrent with Alzheimer's disease (see Depression of Alzheimer disease), an early sign of cognitive impairment,[147] or even the cause.[148][149]
Due to low accuracy, the C-PIB-PET scan is not recommended as an early diagnostic tool or for predicting the development of Alzheimer's disease when people show signs of mild cognitive impairment (MCI).[150] The use of 18F-FDG PET scans, as a single test, to identify people who may develop Alzheimer's disease is not supported by evidence.[151]
Prevention
There are no disease-modifying treatments available to cure Alzheimer's disease and because of this, AD research has focused on interventions to prevent the onset and progression.[152] There is no evidence that supports any particular measure in preventing Alzheimer's,[1] and studies of measures to prevent the onset or progression have produced inconsistent results. Epidemiological studies have proposed relationships between an individual's likelihood of developing AD and modifiable factors, such as medications, lifestyle, and diet. There are some challenges in determining whether interventions for Alzheimer's disease act as a primary prevention method, preventing the disease itself, or a secondary prevention method, identifying the early stages of the disease.[153] These challenges include duration of intervention, different stages of disease at which intervention begins, and lack of standardization of inclusion criteria regarding biomarkers specific for Alzheimer's disease.[153] Further research is needed to determine factors that can help prevent Alzheimer's disease.[153]
Medication
Cardiovascular risk factors, such as hypercholesterolaemia, hypertension, diabetes, and smoking, are associated with a higher risk of onset and worsened course of AD.[154][155] The use of statins to lower cholesterol may be of benefit in Alzheimer's.[156] Antihypertensive and antidiabetic medications in individuals without overt cognitive impairment may decrease the risk of dementia by influencing cerebrovascular pathology.[1][157] More research is needed to examine the relationship with Alzheimer's disease specifically; clarification of the direct role medications play versus other concurrent lifestyle changes (diet, exercise, smoking) is needed.[1]
Depression is associated with an increased risk for Alzheimer's disease; management with antidepressants may provide a preventative measure.[5]
Historically, long-term usage of
Lifestyle
Certain lifestyle activities, such as physical and cognitive exercises, higher education and occupational attainment, cigarette smoking, stress, sleep, and the management of other comorbidities, including diabetes and hypertension, may affect the risk of developing Alzheimer's.[5]
Physical exercise is associated with a decreased rate of dementia,[6] and is effective in reducing symptom severity in those with AD.[159] Memory and cognitive functions can be improved with aerobic exercises including brisk walking three times weekly for forty minutes.[160] It may also induce neuroplasticity of the brain.[161] Participating in mental exercises, such as reading, crossword puzzles, and chess have shown a potential to be preventative.[5] Meeting the WHO recommendations for physical activity is associated with a lower risk of AD.[162]
Higher education and occupational attainment, and participation in leisure activities, contribute to a reduced risk of developing Alzheimer's,[7] or of delaying the onset of symptoms. This is compatible with the cognitive reserve theory, which states that some life experiences result in more efficient neural functioning providing the individual a cognitive reserve that delays the onset of dementia manifestations.[7] Education delays the onset of Alzheimer's disease syndrome without changing the duration of the disease.[163]
Cessation in smoking may reduce risk of developing Alzheimer's' disease, specifically in those who carry
Alzheimer's disease is associated with sleep disorders but the precise relationship is unclear.[166][167] It was once thought that as people get older, the risk of developing sleep disorders and AD independently increase, but research is examining whether sleep disorders may increase the prevalence of AD.[166] One theory is that the mechanisms to increase clearance of toxic substances, including Aβ, are active during sleep.[166][168] With decreased sleep, a person is increasing Aβ production and decreasing Aβ clearance, resulting in Aβ accumulation.[169][166][167] Receiving adequate sleep (approximately 7–8 hours) every night has become a potential lifestyle intervention to prevent the development of AD.[5]
Stress is a risk factor for the development of Alzheimer's.[5] The mechanism by which stress predisposes someone to development of Alzheimer's is unclear, but it is suggested that lifetime stressors may affect a person's epigenome, leading to an overexpression or under expression of specific genes.[170] Although the relationship of stress and Alzheimer's is unclear, strategies to reduce stress and relax the mind may be helpful strategies in preventing the progression or Alzheimer's disease.[171] Meditation, for instance, is a helpful lifestyle change to support cognition and well-being, though further research is needed to assess long-term effects.[161]
Management
There is no cure for Alzheimer's disease;[172] available treatments offer relatively small symptomatic benefits but remain palliative in nature.[13][173] Treatments can be divided into pharmaceutical, psychosocial, and caregiving.
Pharmaceutical
Medications used to treat the cognitive symptons of Alzheimer's disease rather than the underlying cause include: four acetylcholinesterase inhibitors (tacrine, rivastigmine, galantamine, and donepezil) and memantine, an NMDA receptor antagonist. The acetylcholinesterase inhibitors are intended for those with mild to severe Alzheimer's, whereas memantine is intended for those with moderate or severe Alzheimer's disease.[121] The benefit from their use is small.[174][175][176][14]
Reduction in the activity of the cholinergic neurons is a well-known feature of Alzheimer's disease.[177] Acetylcholinesterase inhibitors are employed to reduce the rate at which acetylcholine (ACh) is broken down, thereby increasing the concentration of ACh in the brain and combating the loss of ACh caused by the death of cholinergic neurons.[178] There is evidence for the efficacy of these medications in mild to moderate Alzheimer's disease,[179][174] and some evidence for their use in the advanced stage.[174] The use of these drugs in mild cognitive impairment has not shown any effect in a delay of the onset of Alzheimer's disease.[180] The most common side effects are nausea and vomiting, both of which are linked to cholinergic excess. These side effects arise in approximately 10–20% of users, are mild to moderate in severity, and can be managed by slowly adjusting medication doses.[181] Less common secondary effects include muscle cramps, decreased heart rate (bradycardia), decreased appetite and weight, and increased gastric acid production.[179]
An extract of Ginkgo biloba known as EGb 761 has been used for treating Alzheimer's and other neuropsychiatric disorders.[189] Its use is approved throughout Europe.[190] The World Federation of Biological Psychiatry guidelines lists EGb 761 with the same weight of evidence (level B) given to acetylcholinesterase inhibitors and memantine. EGb 761 is the only one that showed improvement of symptoms in both Alzheimer's disease and vascular dementia. EGb 761 may have a role either on its own or as an add-on if other therapies prove ineffective.[189] A 2016 review concluded that the quality of evidence from clinical trials on Ginkgo biloba has been insufficient to warrant its use for treating Alzheimer's disease.[191]
Atypical antipsychotics are modestly useful in reducing aggression and psychosis in people with Alzheimer's disease, but their advantages are offset by serious adverse effects, such as stroke, movement difficulties or cognitive decline.[192] When used in the long-term, they have been shown to associate with increased mortality.[193] Stopping antipsychotic use in this group of people appears to be safe.[194]
Psychosocial
Psychosocial interventions are used as an adjunct to pharmaceutical treatment and can be classified within behavior-, emotion-, cognition- or stimulation-oriented approaches.[needs update][195]
Behavioral interventions attempt to identify and reduce the antecedents and consequences of problem behaviors. This approach has not shown success in improving overall functioning,[196] but can help to reduce some specific problem behaviors, such as incontinence.[197] There is a lack of high quality data on the effectiveness of these techniques in other behavior problems such as wandering.[198][199] Music therapy is effective in reducing behavioral and psychological symptoms.[200]
Emotion-oriented interventions include
The aim of cognition-oriented treatments, which include reality orientation and
Stimulation-oriented treatments include art, music and pet therapies, exercise, and any other kind of recreational activities. Stimulation has modest support for improving behavior, mood, and, to a lesser extent, function. Nevertheless, as important as these effects are, the main support for the use of stimulation therapies is the change in the person's routine.[195]
Caregiving
Since Alzheimer's has no cure and it gradually renders people incapable of tending to their own needs, caregiving is essentially the treatment and must be carefully managed over the course of the disease.
During the early and moderate stages, modifications to the living environment and lifestyle can increase safety and reduce caretaker burden.[205][206] Examples of such modifications are the adherence to simplified routines, the placing of safety locks, the labeling of household items to cue the person with the disease or the use of modified daily life objects.[195][207][208] If eating becomes problematic, food will need to be prepared in smaller pieces or even puréed.[209] When swallowing difficulties arise, the use of feeding tubes may be required. In such cases, the medical efficacy and ethics of continuing feeding is an important consideration of the caregivers and family members.[210][211] The use of physical restraints is rarely indicated in any stage of the disease, although there are situations when they are necessary to prevent harm to the person with Alzheimer's disease or their caregivers.[195]
During the final stages of the disease, treatment is centred on relieving discomfort until death, often with the help of hospice.[212]
Diet
Diet may be a modifiable risk factor for the development of Alzheimer's disease. The Mediterranean diet, and the DASH diet are both associated with less cognitive decline. A different approach has been to incorporate elements of both of these diets into one known as the MIND diet.[213] Studies of individual dietary components, minerals and supplements are conflicting as to whether they prevent AD or cognitive decline.[213]
Prognosis
The early stages of Alzheimer's disease are difficult to diagnose. A definitive diagnosis is usually made once cognitive impairment compromises daily living activities, although the person may still be living independently. The symptoms will progress from mild cognitive problems, such as memory loss through increasing stages of cognitive and non-cognitive disturbances, eliminating any possibility of independent living, especially in the late stages of the disease.[39]
Life expectancy of people with Alzheimer's disease is reduced.[214] The normal life expectancy for 60 to 70 years old is 23 to 15 years; for 90 years old it is 4.5 years.[215] Following Alzheimer's disease diagnosis it ranges from 7 to 10 years for those in their 60s and early 70s (a loss of 13 to 8 years), to only about 3 years or less (a loss of 1.5 years) for those in their 90s.[214]
Fewer than 3% of people live more than fourteen years after diagnosis.
Aspiration pneumonia is the most frequent immediate cause of death brought by Alzheimer's disease.[3] While the reasons behind the lower prevalence of cancer in Alzheimer's patients remain unclear, some researchers hypothesize that biological mechanisms shared by both diseases might play a role. However, this requires further investigation.[222]
Epidemiology
Two main measures are used in epidemiological studies: incidence and prevalence. Incidence is the number of new cases per unit of person-time at risk (usually number of new cases per thousand person-years); while prevalence is the total number of cases of the disease in the population at any given time.
Regarding incidence,
The prevalence of Alzheimer's disease in populations is dependent upon factors including incidence and survival. Since the incidence of Alzheimer's disease increases with age, prevalence depends on the mean age of the population for which prevalence is given. In the United States in 2020, Alzheimer's dementia prevalence was estimated to be 5.3% for those in the 60–74 age group, with the rate increasing to 13.8% in the 74–84 group and to 34.6% in those greater than 85.[230] Prevalence rates in some less developed regions around the globe are lower.[231][232] As the incidence and prevalence are steadily increasing, the prevalence itself is projected to triple by 2050.[clarification needed][233] As of 2020, 50 million people globally have AD, with this number expected to increase to 152 million by 2050.[13]
History
The
For most of the 20th century, the diagnosis of Alzheimer's disease was reserved for individuals between the ages of 45 and 65 who developed symptoms of dementia. The terminology changed after 1977 when a conference on Alzheimer's disease concluded that the clinical and
The
Society and culture
Social costs
Dementia, and specifically Alzheimer's disease, may be among the most costly diseases for societies worldwide.
In the United States as of 2019[update], informal (family) care is estimated to constitute nearly three-fourths of caregiving for people with AD at a cost of US$234 billion per year and approximately 18.5 billion hours of care.[243] The cost to society worldwide to care for individuals with AD is projected to increase nearly ten-fold, and reach about US$9.1 trillion by 2050.[245]
Costs for those with more severe dementia or behavioral disturbances are higher and are related to the additional caregiving time to provide physical care.[246]
Caregiving burden
This section needs to be updated.(February 2022) |
Individuals with Alzheimer's will require assistance in their lifetime, and care will most likely come in the form of a full-time caregiver which is often a role that is taken on by the spouse or a close relative. Caregiving tends to include physical and emotional burdens as well as time and financial strain at times on the person administering the aid.[247][248] Alzheimer's disease is known for placing a great burden on caregivers which includes social, psychological, physical, or economic aspects.[23][249][250] Home care is usually preferred by both those people with Alzheimer's disease as well as their families.[251] This option also delays or eliminates the need for more professional and costly levels of care.[251][252] Nevertheless, two-thirds of nursing home residents have dementias.[195]
Dementia caregivers are subject to high rates of physical and mental disorders.[253] Factors associated with greater psychosocial problems of the primary caregivers include having an affected person at home, the carer being a spouse, demanding behaviors of the cared person such as depression, behavioral disturbances, hallucinations, sleep problems or walking disruptions and social isolation.[254][255] Regarding economic problems, family caregivers often give up time from work to spend 47 hours per week on average with the person with Alzheimer's disease, while the costs of caring for them are high. Direct and indirect costs of caring for somebody with Alzheimer's average between $18,000 and $77,500 per year in the United States, depending on the study.[256][248]
Media
Alzheimer's disease has been portrayed in films such as:
Alzheimer's disease has also been portrayed in music by English musician the Caretaker in releases such as Persistent Repetition of Phrases (2008), An Empty Bliss Beyond This World (2011), and Everywhere at the End of Time (2016–2019).[266][267][268] Paintings depicting the disorder include the late works by American artist William Utermohlen, who drew self-portraits from 1995 to 2000 as an experiment of showing his disease through art.[269][270]
Research directions
Additional research on the lifestyle effect may provide insight into neuroimaging biomarkers and better understanding of the mechanisms causing both Alzheimer's disease and early-onset AD.[271]
Emerging hypotheses
Alzheimer's disease is associated with neuroinflammation and loss of function of microglia, the resident immune cells of the central nervous system.[272] Microglia become progressively dysfunctional following exposure to amyloid plaques, and exposure to pro-inflammatory cytokines (e.g., TNFα, IL-1β, IL-12) has been hypothesized to sustain this dysfunction. Aberrant synaptic pruning via microglial phagocytosis may also contribute to AD pathology.[273] The complement system, which is involved in some forms of typical microglial pruning during development,[274] is implicated in animal models of AD by way of dysregulation of the activation (e.g. C1q; C3b) and terminal (e.g. MAC) pathways in synapses with proximity to amyloid plaques.[275]
Detection, prevention and treatment
Antibodies may have the ability to alter the disease course by targeting amyloid beta with immunotherapy medications such as
Specific medications that may reduce the risk or progression of Alzheimer's disease have been studied.
Machine learning algorithms with electronic health records are being studied as a way to predict AD earlier.[293]
References
- ^ PMID 33986301.
- ^ a b c d e f "Dementia Fact sheet". World Health Organization. 15 March 2023. Retrieved 10 July 2023.
- ^ a b c "Ask the Doctors - What is the cause of death in Alzheimer's disease?". www.uclahealth.org. Retrieved 18 March 2024.
- ^ PMID 23178565.
- ^ PMID 32690803.
- ^ PMID 27481112.
- ^ S2CID 51703879.
- ^ a b "Dementia diagnosis and assessment" (PDF). National Institute for Health and Care Excellence (NICE). Archived from the original (PDF) on 5 December 2014. Retrieved 30 November 2014.
- PMID 27042903.
- ^ PMID 30733618.
- ^ "How Alzheimer's drugs help manage symptoms". Mayo Clinic. 30 August 2023. Retrieved 19 March 2024.
- ^ a b "Life Span After Alzheimer's Diagnosis: What Factors Matter Most - Health Encyclopedia - University of Rochester Medical Center". www.urmc.rochester.edu. Retrieved 19 March 2024.
- ^ PMID 33302541.
- ^ OCLC 1012400314.
- ^ S2CID 8570146.
- ^ "Alzheimer's stages: How the disease progresses". Mayo Clinic. Retrieved 19 March 2024.
- ^ PMID 31564456.
- ^ a b "Study reveals how APOE4 gene may increase risk for dementia". National Institute on Aging. 16 March 2021. Archived from the original on 17 March 2021. Retrieved 17 March 2021.
- ^ a b c d "Alzheimer's Disease Fact Sheet". National Institute on Aging. Archived from the original on 23 March 2022. Retrieved 23 March 2022.
- ^ Dementia: assessment, management and support for people living with dementia and their carers (Report). National Institute for Health and Care Excellence (NICE). 20 June 2018. NG97. Retrieved 8 July 2023.
- ^ PMID 32484110.
- ^ PMID 32186726.
- ^ PMID 17662119.
- PMID 25874613.
- ^ "Low-dose antipsychotics in people with dementia". National Institute for Health and Care Excellence (NICE). Archived from the original on 5 December 2014. Retrieved 29 November 2014.
- ^ "Information for Healthcare Professionals: Conventional Antipsychotics". US Food and Drug Administration. 16 June 2008. Archived from the original on 29 November 2014. Retrieved 29 November 2014.
- ^ a b "Alzheimer's Disease Fact Sheet". National Institute on Aging. Archived from the original on 24 January 2021. Retrieved 25 January 2021.
- PMID 33844047.
- ^ S2CID 24808582.
- ^ "The top 10 causes of death". www.who.int. Retrieved 19 March 2024.
- ^ a b c "Alzheimer's disease – Symptoms". National Health Service (NHS). 10 May 2018. Archived from the original on 30 January 2021. Retrieved 25 January 2021.
- ^ S2CID 2725064.
- ^ S2CID 37005854.
- S2CID 25313065.
- S2CID 208037448.
- ISBN 978-1-4377-0434-1.
- ^ PMID 29282327.
- ^ S2CID 73432842.
- ^ S2CID 26142779.
- S2CID 19548915.
- S2CID 9419442.
- ^ S2CID 37153159.
- ^ PMID 7967534.
- S2CID 10492607.
- S2CID 29847950.
- S2CID 195063786.
- ^ "Alzheimer's disease – Causes". National Health Service (NHS). 24 April 2023. Archived from the original on 29 September 2020. Retrieved 10 July 2023.
- PMID 32966331.
- S2CID 236998499.
- PMID 25482515.
- ISBN 0199638497.
- PMID 1763432.
- ^ S2CID 37380445.
- PMID 7566000.
- ^ PMID 36907103.
- ^ PMID 33667416.
- S2CID 256839971.
- PMID 23276979.
- PMID 33066368.
- PMID 16567625.
- S2CID 47544338.
- PMID 16434658.
- PMID 16278853.
- PMID 23276979.
- S2CID 42287088.
- S2CID 18315650.
- PMID 30906402.
- from the original on 27 March 2022. Retrieved 21 February 2022.
- PMID 20675873.
- S2CID 42311988.
- PMID 32093100.
- S2CID 33331924.
- PMID 15615638.
- PMID 32715278.
- PMID 30406177.
- PMID 32121304.
- S2CID 58546748.
- PMID 30664867.
- S2CID 40048333.
- PMID 25685779.
- S2CID 23410069.
- S2CID 73466457.
- S2CID 3943047.
- PMID 19775776.
- S2CID 21448714.
- PMID 23724961.
- S2CID 260132167.
- PMID 12934968.
- PMID 23160422.
- PMID 19460794.
- ^ Moan R (July 2009). "MRI Software Accurately IDs Preclinical Alzheimer's Disease". Diagnostic Imaging. Archived from the original on 21 February 2022. Retrieved 21 February 2022.
- ^ S2CID 25017332.
- PMID 31375134.
- S2CID 22832110.
- PMID 8038565.
- S2CID 44407971.
- S2CID 20760249.
- PMID 16822978.
- S2CID 25376584.
- S2CID 14269634.
- S2CID 25739126.
- S2CID 261121643.
- PMID 30038280.
- PMID 37708272
- ^ "Scientists discover how brain cells die in Alzheimer's". BBC News. 15 September 2023. Retrieved 27 September 2023.
- S2CID 7949658.
- PMID 22424230.
- PMID 2218531.
- S2CID 85423830.
- PMID 37657967.
- from the original on 3 June 2020. Retrieved 19 July 2019.
- PMID 25792098.
- S2CID 6589846.
- PMID 18184369.
- ^ from the original on 20 March 2022. Retrieved 27 November 2021.
- from the original on 3 June 2020. Retrieved 25 May 2020.
- PMID 17018549.
- ISBN 978-1-84629-312-2. Archived from the original(PDF) on 27 February 2008. Retrieved 22 February 2008.
- PMID 19463961.
- PMID 33573211.
- ^ PMID 30135715.
- PMID 31072403.
- PMID 28269772.
- ISBN 978-0-89042-025-6.
- ^ ISBN 978-0890425558.
- S2CID 46244321.
- PMID 26332219.
- ISBN 978-0-203-77228-7. Archivedfrom the original on 16 November 2021. Retrieved 16 November 2021.
- from the original on 7 July 2023. Retrieved 16 November 2021.
- PMID 26332219.
- PMID 31724527.
- ^ PMID 25160795.
- PMID 30646955.
- ^ PMID 29653606.
- PMID 21514248.
- PMID 28243102.
- PMID 21514249.
- ^ PMID 24565215.
- ^ OCLC 1195972209.
- S2CID 25169596.
- S2CID 2108587.
- S2CID 20238911.
- PMID 15738860.
- PMID 16197855.
- ^ OCLC 1121597721.)
{{cite book}}
: CS1 maint: location missing publisher (link - OCLC 1202472277.
- PMID 18458206.
- S2CID 30018544.
- S2CID 24569198.
- PMID 25052054.
- PMID 25629415.
- S2CID 51703879.
- ^ PMID 27697063.
- PMID 18299540.
- PMID 17483665.
- PMID 29643479.
- PMID 34127835.
- PMID 18254016.
- S2CID 24936334.
- S2CID 8265377.
- ^ PMID 31998117.
- S2CID 253382289.
- PMID 24418410.
- PMID 24418410.
- S2CID 52925352.
- ^ S2CID 209327994.
- ^ S2CID 212729131.
- PMID 30353860.
- S2CID 58546748.
- PMID 29458203.
- PMID 32150066.
- PMID 37451163.
- OCLC 1048659425.
- ^ PMID 29923184.
- S2CID 216595473.
- OCLC 948547621.
- PMID 8534419.
- PMID 11105732.
- ^ PMID 16437532.
- PMID 18044984.
- ISBN 978-1-60913-713-7.
- ^ S2CID 21379258.
- ^ "Memantine". US National Library of Medicine (Medline). 4 January 2004. Archived from the original on 22 February 2010. Retrieved 3 February 2010.
- PMID 30891742.
- ^ "Namenda- memantine hydrochloride tablet Namenda- memantine hydrochloride kit". DailyMed. 15 November 2018. Archived from the original on 27 January 2022. Retrieved 20 February 2022.
- ^ "Namenda XR- memantine hydrochloride capsule, extended release Namenda XR- memantine hydrochloride kit". DailyMed. 15 November 2019. Archived from the original on 21 February 2022. Retrieved 20 February 2022.
- ^ "Namzaric- memantine hydrochloride and donepezil hydrochloride capsule Namzaric- memantine hydrochloride and donepezil hydrochloride kit". DailyMed. 22 January 2019. Archived from the original on 20 January 2022. Retrieved 20 February 2022.
- S2CID 22235353.
- ^ PMID 30648358.
- PMID 30546253.
- PMID 26268332.
- PMID 16437455.
- S2CID 23000439. See lay summary, January 2009.
- PMID 23543555.
- ^ PMID 18340692.
- S2CID 21290731.
- S2CID 10711725.
- PMID 17253573.
- S2CID 45660235.
- PMID 28302633.
- PMID 12519587.
- PMID 29493789.
- S2CID 39529938.
- PMID 12948999.
- PMID 11220813.
- PMID 15860476.
- ^ "Treating Behavioral and Psychiatric Symptoms". Alzheimer's Association. 2006. Archived from the original on 25 September 2006. Retrieved 25 September 2006.
- PMID 15297089.
- ISBN 978-0-7817-6651-7. Retrieved 19 August 2008.
- PMID 16415742.
- S2CID 20841502.
- S2CID 6072807.
- ^ PMID 29957766.
- ^ PMID 19836639.
- ^ "United States Life Tables, 2017" (PDF). National Vital Statistics Reports, CDC. Archived (PDF) from the original on 24 May 2021. Retrieved 10 June 2021.
- ^ S2CID 19724937.
- S2CID 24961809.
- S2CID 27410149.
- S2CID 34066330.
- PMID 12580712.
- PMID 15883266.
- PMID 32382138.
- ^ S2CID 34341344.
- ^ S2CID 22576935.
- ^ Tejada-Vera B. (2013). Mortality from Alzheimer's Disease in the United States: Data for 2000 and 2010. Hyattsville, MD: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics.
- PMID 33225065.
- ^ PMID 23296339.
- S2CID 234745473.
- PMID 28373857.
- S2CID 235215290.
- PMID 25089278.
- PMID 16360788.
- S2CID 235735045.
- ^ Auguste D.:
- Alzheimer A (1907). "Über eine eigenartige Erkrankung der Hirnrinde" [About a peculiar disease of the cerebral cortex]. Allgemeine Zeitschrift für Psychiatrie und Psychisch-Gerichtlich Medizin (in German). 64 (1–2): 146–148.
- "About a peculiar disease of the cerebral cortex. By Alois Alzheimer, 1907 (Translated by L. Jarvik and H. Greenson)". Alzheimer Disease and Associated Disorders. 1 (1). Translated by H. Greenson: 3–8. 1987. PMID 3331112.
- Maurer U, Maurer K (2003). Alzheimer: The Life of a Physician and the Career of a Disease. New York: Columbia University Press. p. 270. ISBN 978-0-231-11896-5.
- S2CID 145155424.
- ISBN 978-1-4325-0833-3.
- ISBN 978-0-89004-225-0.
- S2CID 42399340.
- S2CID 7689479.
- S2CID 11646075.
- S2CID 7356809.
- PMID 7986174.
- ^ PMID 31256142.
- ^ from the original on 25 February 2022. Retrieved 17 March 2022.
- ^ S2CID 247014076.
- ^ S2CID 233403683.
- PMID 37222859.
- ^ a b "The MetLife study of Alzheimer's disease: The caregiving experience" (PDF). MetLife Mature Market Institute. August 2006. Archived from the original (PDF) on 8 January 2011. Retrieved 5 February 2011.
- S2CID 27346798.
- S2CID 41741923.
- ^ PMID 18044111.
- PMID 15799982.
- S2CID 21404062.
- S2CID 11788466.
- S2CID 22187694.
- PMID 11445614.
- S2CID 32517015.
- OCLC 41960006.
- ISBN 978-0-7862-0821-0.
- ^ "Thanmathra". Webindia123.com. Archived from the original on 6 November 2007. Retrieved 24 January 2008.
- OCLC 57352130.
- OCLC 46929223.
- ^ "Malcolm and Barbara: A love story". Dfgdocs. Archived from the original on 24 May 2008. Retrieved 24 January 2008.
- ^ "Malcolm and Barbara: A love story". BBC Cambridgeshire. Archived from the original on 10 November 2012. Retrieved 2 March 2008.
- ^ Plunkett J (7 August 2007). "Alzheimer's film-maker to face ITV lawyers". London: Guardian Media. Archived from the original on 15 January 2008. Retrieved 24 January 2008.
- ^ "The Caretaker: Persistent Repetition of Phrases". Fact. 26 August 2009. Archived from the original on 15 April 2021. Retrieved 9 April 2021.
- ^ Powell M (14 June 2011). "The Caretaker: An Empty Bliss Beyond This World Album Review". Pitchfork. Archived from the original on 18 June 2011. Retrieved 19 February 2021.
- ^ Ezra M (23 October 2020). "Why Are TikTok Teens Listening to an Album About Dementia?". The New York Times. Archived from the original on 23 October 2020. Retrieved 21 April 2021.
- ^ Gerrard N (19 July 2015). "Words fail us: dementia and the arts". The Guardian. Archived from the original on 19 July 2015. Retrieved 14 June 2021.
- ^ Grady D (24 October 2006). "Self-Portraits Chronicle a Descent Into Alzheimer's". The New York Times. Archived from the original on 24 October 2006. Retrieved 14 June 2021.
- PMID 26321944.
- S2CID 6116253.
- PMID 29563239.
- PMID 22632727.
- PMID 35794654.
- PMID 35493943.
- PMID 37251912.
- ^ "How Is Alzheimer's Disease Treated?". U.S. National Institute on Aging. 1 April 2023. Retrieved 10 July 2023.
- PMID 35611326.
- PMID 35197360.
- from the original on 8 July 2023. Retrieved 7 July 2023.
- ^ Belluck P, Robbins R (10 June 2021). "Three F.D.A. Advisers Resign Over Agency's Approval of Alzheimer's Drug". The New York Times. Archived from the original on 14 November 2021. Retrieved 7 July 2023.
- PMID 34881080.
- S2CID 257568052.
- ^ "FDA Grants Accelerated Approval for Alzheimer's Disease Treatment" (Press release). U.S. Food and Drug Administration (FDA). 6 January 2023. Archived from the original on 7 January 2023. Retrieved 7 January 2023. This article incorporates text from this source, which is in the public domain.
- ^ "Lecanemab Summary Review" (PDF). U.S. Food and Drug Administration (FDA). Archived (PDF) from the original on 7 January 2023. Retrieved 7 January 2023.
- ^ "FDA Converts Novel Alzheimer's Disease Treatment to Traditional Approval". U.S. Food and Drug Administration (FDA) (Press release). 6 July 2023. Retrieved 6 July 2023. This article incorporates text from this source, which is in the public domain.
- ^ "FDA Makes Alzheimer's Drug Leqembi Widely Accessible". The New York Times. 6 July 2023. Archived from the original on 7 July 2023. Retrieved 8 July 2023.
- PMID 36973044.
- ^ PMID 34289882.
- PMID 30386171.
- S2CID 214784366.
- S2CID 257101613.
Further reading
- Van Acker ZP, Perdok A, Bretou M, Annaert W (November 2021). "The microglial lysosomal system in Alzheimer's disease: Guardian against proteinopathy". Ageing Research Reviews. 71: 101444. S2CID 236994329.
- Xi Y, Chen Y, Jin Y, Han G, Song M, Song T, et al. (May 2022). "Versatile nanomaterials for Alzheimer's disease: Pathogenesis inspired disease-modifying therapy". Journal of Controlled Release. 345: 38–61. S2CID 247285338.
External links
- "Alzheimer's Disease Research Timeline – Alzforum". www.alzforum.org.
- "Alzheimer's Disease Brain Cell Atlas- brain-map.org". portal.brain-map.org.