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Progressive, neurodegenerative disease characterized by memory loss
Alzheimer disease, Alzheimer's
Drawing comparing a normal aged brain (left) and the brain of a person with Alzheimer's (right). Characteristics that separate the two are pointed out.
No treatments stop or reverse its progression, though some may temporarily improve symptoms. Affected people increasingly rely on others for assistance, often placing a burden on the caregiver. The pressures can include social, psychological, physical, and economic elements. Exercise programs may be beneficial with respect to activities of daily living and can potentially improve outcomes. Behavioral problems or psychosis due to dementia are often treated with antipsychotics, but this is not usually recommended, as there is little benefit and an increased risk of early death.
As of 2015, there were approximately 29.8 million people worldwide with AD with about 50 million of all forms of dementia as of 2020. It most often begins in people over 65 years of age, although up to 10 per cent of cases are early-onset affecting those in their 30's to mid 60's. It affects about 6% of people 65 years and older. In 2015, all forms of dementia resulted in about 1.9 million deaths. The disease is named after German psychiatrist and pathologist Alois Alzheimer, who first described it in 1906. Alzheimer's financial burden on society is large, on par with the costs of cancer and heart disease, costing 200 billion dollars in the US alone.
Signs and symptoms
The course of Alzheimer's is generally described in three stages, with a progressive pattern of cognitive and functionalimpairment. The three stages are described as early or mild, middle or moderate, and late or severe. The disease
is known to target the hippocampus which is associated with memory, and this is responsible for the first symptoms of memory impairment. As the disease progresses so does the degree of memory impairment.
Subtle problems with the executive functions of attentiveness, planning, flexibility, and abstract thinking, or impairments in semantic memory (memory of meanings, and concept relationships) can also be symptomatic of the early stages of AD.Apathy and depression can be seen at this stage, with apathy remaining as the most persistent symptom throughout the course of the disease.
The preclinical stage of the disease has also been termed mild cognitive impairment (MCI). This is often found to be a transitional stage between normal aging and dementia. MCI can present with a variety of symptoms, and when memory loss is the predominant symptom, it is termed amnestic MCI and is frequently seen as a prodromal stage of Alzheimer's disease. Amnestic MCI has a greater than 90% likelihood of being associated with Alzheimer's.
In people with AD, 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. AD does not affect all memory capacities equally. Older memories of the person's life (episodic memory), facts learned (semantic memory), and implicit memory (the memory of the body on how to do things, such as using a fork to eat or how to drink from a glass) are affected to a lesser degree than new facts or memories.
Language problems are mainly characterised by a shrinking vocabulary and decreased word fluency, leading to a general impoverishment of oral and written language. In this stage, the person with Alzheimer's is usually capable of communicating basic ideas adequately. While performing fine motor tasks such as writing, drawing, or dressing, certain movement coordination and planning difficulties (apraxia) may be present, but they are commonly unnoticed. As the disease progresses, people with AD can often continue to perform many tasks independently, but may need assistance or supervision with the most cognitively demanding activities.
Progressive deterioration eventually hinders independence, with subjects being unable to perform most common activities of daily living. Speech difficulties become evident due to an inability to recall vocabulary, which leads to frequent incorrect word substitutions (paraphasias). Reading and writing skills are also progressively lost. Complex motor sequences become less coordinated as time passes and AD progresses, so the risk of falling increases. During this phase, memory problems worsen, and the person may fail to recognise close relatives.Long-term memory, which was previously intact, becomes impaired.
A normal brain on the left and a late stage Alzheimer's brain on the right.
During the final stage, known as the late stage or severe stage, the patient is completely dependent upon caregivers. Language is reduced to simple phrases or even single words, eventually leading to complete loss of speech. Despite the loss of verbal language abilities, people can often understand and return emotional signals. Although aggressiveness can still be present, extreme apathy and exhaustion are much more common symptoms. People with Alzheimer's disease will ultimately not be able to perform even the simplest tasks independently; muscle mass and mobility deteriorates to the point where they are bedridden and unable to feed themselves. The cause of death is usually an external factor, such as infection of pressure ulcers or pneumonia, not the disease itself.
The cause for most Alzheimer's cases is still mostly unknown except for 1-2% of cases where deterministic genetic differences have been identified. Several competing hypotheses exist trying to explain the cause of the disease.
Most cases of Alzheimer's are not inherited and are termed sporadic AD, in which environmental and genetic differences may act as risk factors. Most cases of sporadic AD in contrast to familial AD are late onset AD (LOAD) developing after the age of 65 years. Less than 5% of sporadic AD have an earlier onset. The strongest genetic risk factor for sporadic AD is APOE?4. APOE?4 is one of four alleles of apolipoprotein E (APOE).
APOE plays a major role in lipid-binding proteins in lipoprotein particles and the epsilon4 allele disrupts this function. Between 40 and 80% of people with AD possess at least one APOE?4 allele. The APOE?4 allele increases the risk of the disease by three times in heterozygotes and by 15 times in homozygotes. Like many human diseases, environmental effects and genetic modifiers result in incomplete penetrance. For example, certain Nigerian populations do not show the relationship between dose of APOE?4 and incidence or age-of-onset for Alzheimer's disease seen in other human populations. Early attempts to screen up to 400 candidate genes for association with late-onset sporadic AD (LOAD) resulted in a low yield. More recent genome-wide association studies (GWAS) have found 19 areas in genes that appear to affect the risk. These genes include: CASS4, CELF1, FERMT2, HLA-DRB5, INPP5D, MEF2C, NME8, PTK2B, SORL1, ZCWPW1, SLC24A4, CLU, PICALM, CR1, BIN1, MS4A, ABCA7, EPHA1, and CD2AP.
Alleles in the TREM2 gene have been associated with a 3 to 5 times higher risk of developing Alzheimer's disease. A suggested mechanism of action is that in some variants in TREM2, white blood cells in the brain are no longer able to control the amount of amyloid beta present. Many single-nucleotide polymorphisms (SNPs) are associated with Alzheimer's, with a 2018 study adding 30 SNPs by differentiating AD into 6 categories, including memory, language, visuospatial, and executive functioning.
A Japanese pedigree of familial Alzheimer's disease was found to be associated with a deletion mutation of codon 693 of APP. This mutation and its association with Alzheimer's disease was first reported in 2008, and is known as the Osaka mutation. Only homozygotes with this mutation develop Alzheimer's disease. This mutation accelerates A? oligomerization but the proteins do not form the amyloid fibrils that aggregate into amyloid plaques, suggesting that it is the A? oligomerization rather than the fibrils that may be the cause of this disease. Mice expressing this mutation have all usual pathologies of Alzheimer's disease.
The oldest hypothesis, on which most drug therapies are based, is the cholinergic hypothesis, which proposes that AD is caused by reduced synthesis of the neurotransmitteracetylcholine. The cholinergic hypothesis has not maintained widespread support, largely because medications intended to treat acetylcholine deficiency have not been very effective.
The 1991 amyloid hypothesis postulated that extracellular amyloid beta (A?) deposits are the fundamental cause of the disease. Support for this postulate comes from the location of the gene for the amyloid precursor protein (APP) on chromosome 21, together with the fact that people with trisomy 21 (Down syndrome) who have an extra gene copy almost universally exhibit at least the earliest symptoms of AD by 40 years of age. Also, a specific isoform of apolipoprotein, APOE4, is a major genetic risk factor for AD. While apolipoproteins enhance the breakdown of beta amyloid, some isoforms are not very effective at this task (such as APOE4), leading to excess amyloid buildup in the brain.
In Alzheimer's disease, changes in tau protein lead to the disintegration of microtubules in brain cells.
A number of studies connect the misfolded amyloid beta and tau proteins associated with the pathology of AD, as bringing about oxidative stress that leads to chronic inflammation. Sustained inflammation (neuroinflammation) is also a feature of other neurodegenerative diseases including Parkinson's disease, and ALS.Spirochete infections have also been linked to dementia.
Sleep disturbances are seen as a possible risk factor for inflammation in AD. Sleep problems have been seen as a consequence of AD but studies suggest that they may instead be a causal factor. Sleep disturbances are thought to be linked to persistent inflammation. A possible role of chronic periodontal infection and the gut microbiota has been suggested.
This article needs to be updated. Please update this article to reflect recent events or newly available information.(March 2021)
A neurovascular hypothesis stating that poor functioning of the blood-brain barrier may be involved has been proposed.
The cellular homeostasis of biometals such as ionic copper, iron, and zinc is disrupted in AD, though it remains unclear whether this is produced by or causes the changes in proteins. These ions affect and are affected by tau, APP, and APOE, and their dysregulation may cause oxidative stress that may contribute to the pathology. The quality of some of these studies has been criticised, and the link remains controversial. The majority of researchers do not support a causal connection with aluminium.
One hypothesis posits that dysfunction of oligodendrocytes and their associated myelin during aging contributes to axon damage, which then causes amyloid production and tau hyper-phosphorylation as a side effect.
Retrogenesis is a medical hypothesis about the development and progress of Alzheimer's disease proposed by Barry Reisberg in the 1980s. The hypothesis is that just as the fetus goes through a process of neurodevelopment beginning with neurulation and ending with myelination, the brains of people with AD go through a reverse neurodegeneration process starting with demyelination and death of axons (white matter) and ending with the death of grey matter. Likewise the hypothesis is, that as infants go through states of cognitive development, people with AD go through the reverse process of progressive cognitive impairment. Reisberg developed the caregiving assessment tool known as "FAST" (Functional Assessment Staging Tool) which he says allows those caring for people with AD to identify the stages of disease progression and that provides advice about the kind of care needed at each stage.
The association with celiac disease is unclear, with a 2019 study finding no increase in dementia overall in those with CD, while a 2018 review found an association with several types of dementia including AD.
Kynurenines are a downstream metabolite of tryptophan, and have the potential to be neuroactive. This may be associated with the neuropsychiatric symptoms, and cognitive prognosis in mild dementia. A five-year study focused on the role of kynurenine in Alzheimer's and Lewy body disease, and found its increase to be associated with more hallucinations.
Both A?plaques and neurofibrillary tangles are clearly visible by microscopy in brains of those afflicted by AD, especially in the hippocampus. Plaques are dense, mostly insoluble deposits of beta-amyloidpeptide and cellular material outside and around neurons. Tangles (neurofibrillary tangles) are aggregates of the microtubule-associated protein tau which has become hyperphosphorylated and accumulate inside the cells themselves. Although many older individuals develop some plaques and tangles as a consequence of aging, the brains of people with AD have a greater number of them in specific brain regions such as the temporal lobe.Lewy bodies are not rare in the brains of people with AD.
Enzymes act on the APP (amyloid-beta precursor protein) and cut it into fragments. The beta-amyloid fragment is crucial in the formation of amyloid plaques in AD.
Exactly how disturbances of production and aggregation of the beta-amyloid peptide give rise to the pathology of AD is not known.
The amyloid hypothesis traditionally points to the accumulation of beta-amyloid peptides as the central event triggering neuron degeneration. Accumulation of aggregated amyloid fibrils, which are believed to be the toxic form of the protein responsible for disrupting the cell's calciumionhomeostasis, induces programmed cell death (apoptosis). It is also known that A? selectively builds up in the mitochondria in the cells of Alzheimer's-affected brains, and it also inhibits certain enzyme functions and the utilisation of glucose by neurons.
Various inflammatory processes and cytokines may also have a role in the pathology of Alzheimer's disease. Inflammation is a general marker of tissue damage in any disease, and may be either secondary to tissue damage in AD or a marker of an immunological response. There is increasing evidence of a strong interaction between the neurons and the immunological mechanisms in the brain. Obesity and systemic inflammation may interfere with immunological processes which promote disease progression.
Assessment of intellectual functioning including memory testing can further characterise the state of the disease. Medical organizations have created diagnostic criteria to ease and standardise the diagnostic process for practising physicians. The diagnosis can be confirmed with very high accuracy post-mortem when brain material is available and can be examined histologically.
Cognitive tests such as the Mini-Mental State Examination (MMSE) can help in the diagnosis of AD. In this test instructions are given to copy drawings like the one shown, remember some words, read, and subtract numbers serially.
Neuropsychological tests including cognitive tests such as the Mini-Mental State Examination (MMSE) are widely used to evaluate the cognitive impairments needed for diagnosis. More comprehensive test arrays are necessary for high reliability of results, particularly in the earliest stages of the disease.Neurological examination in early AD will usually provide normal results, except for obvious cognitive impairment, which may not differ from that resulting from other diseases processes, including other causes of dementia.
Further neurological examinations are crucial in the differential diagnosis of AD and other diseases. Interviews with family members are also utilised in the assessment of the disease. Caregivers can supply important information on the daily living abilities, as well as on the decrease, over time, of the person's mental function. A caregiver's viewpoint is particularly important, since a person with AD is commonly unaware of their deficits. Many times, families also have difficulties in the detection of initial dementia symptoms and may not communicate accurate information to a physician.
Supplemental testing provides extra information on some features of the disease or is used to rule out other diagnoses. Blood tests can identify other causes for dementia than AD--causes which may, in rare cases, be reversible. It is common to perform thyroid function tests, assess B12, rule out syphilis, rule out metabolic problems (including tests for kidney function, electrolyte levels and for diabetes), assess levels of heavy metals (e.g., lead, mercury) and anaemia. (It is also necessary to rule out delirium).
Due to low accuracy, the C-PIB-PET scan is not recommended to be used as an early diagnostic tool or for predicting the development of Alzheimer's disease when people show signs of mild cognitive impairment (MCI). The use of 18F-FDG PET scans, as a single test, to identify people who may develop Alzheimer's disease is also not supported by evidence.
Intellectual activities such as playing chess or regular social interaction have been linked to a reduced risk of AD in epidemiological studies, although no causal relationship has been found.
There is no evidence that supports any particular measure as being effective in preventing AD. Global studies of measures to prevent or delay the onset of AD have often produced inconsistent results. Epidemiological studies have proposed relationships between certain modifiable factors, such as diet, cardiovascular risk, pharmaceutical products, or intellectual activities, among others, and a population's likelihood of developing AD. Only further research, including clinical trials, will reveal whether these factors can help to prevent AD.
Evidence suggests that higher education and occupational attainment, and participation in leisure activities show a reduced risk of developing Alzheimer's, or of delaying the onset of symptoms. This is compatible with the cognitive reserve theory, which states that some life experiences result in more efficient neural functioning providing the individual a cognitive reserve that delays the onset of dementia manifestations.Education delays the onset of AD syndrome without changing the duration of the disease. Learning a second language even later in life seems to delay the onset of Alzheimer's disease.
Physical exercise is associated with decreased rate of dementia. Physical exercise is also effective in reducing symptom severity in those with Alzheimer's disease.
Diet is seen to be a modifiable risk factor for the development of dementia. The Mediterranean diet, and the DASH diet are both associated with less cognitive decline. A different approach has been to incorporate elements of both of these diets into one known as the MIND diet. These diets are generally low in saturated fats while providing a good source of carbohydrates, mainly those that help stabilize blood sugar and insulin levels. Those who eat a diet high in saturated fats and simple carbohydrates (mono- and disaccharide) have a higher risk.
The MIND diet may be more protective but further studies are needed. The Mediterranean diet seems to be more protective against Alzheimer's than DASH but there are no consistent findings against dementia in general. The role of olive oil needs further study as it may be one of the most important components in reducing the risk of cognitive decline and dementia.
Conclusions on dietary components have been difficult to ascertain as results have differed between population-based studies and randomised controlled trials. There is limited evidence that light to moderate use of alcohol, particularly red wine, is associated with lower risk of AD. There is tentative evidence that caffeine may be protective. A number of foods high in flavonoids such as cocoa, red wine, and tea may decrease the risk of AD. A number of studies have looked at the possible role of minerals such as selenium,zinc, and copper. Omega 3 fatty acid supplements from plants and fish, and dietary docosahexaenoic acid (DHA), do not appear to benefit people with mild to moderate Alzheimer's disease.
Curcumin as of 2010[update] had not shown benefit in people even though there is tentative evidence in animals.
There is growing evidence (2020) for the neuroprotection offered by the use of cannabinoids in Alzheimer's and other neurodegenerative disorders. However, further population studies are recommended to see this use beyond experimental.
There is no cure for Alzheimer's disease; available treatments offer relatively small symptomatic benefit but remain palliative in nature. Current treatments can be divided into pharmaceutical, psychosocial and caregiving.
Reduction in the activity of the cholinergic neurons is a well-known feature of Alzheimer's disease. Acetylcholinesterase inhibitors are employed to reduce the rate at which acetylcholine (ACh) is broken down, thereby increasing the concentration of ACh in the brain and combating the loss of ACh caused by the death of cholinergic neurons. There is evidence for the efficacy of these medications in mild to moderate Alzheimer's disease, and some evidence for their use in the advanced stage. The use of these drugs in mild cognitive impairment has not shown any effect in a delay of the onset of AD. The most common side effects are nausea and vomiting, both of which are linked to cholinergic excess. These side effects arise in approximately 10-20% of users, are mild to moderate in severity, and can be managed by slowly adjusting medication doses. Less common secondary effects include muscle cramps, decreased heart rate (bradycardia), decreased appetite and weight, and increased gastric acid production.
An extract of Ginkgo biloba known as EGb 761 has been widely used for treating Alzheimer's and other neuropsychiatric disorders.
Its use is approved throughout Europe. The World Federation of Biological Psychiatry guidelines lists EGb 761 with the same weight of evidence (level B) given to acetylcholinesterase inhibitors, and mementine. EGb 761 is the only one that showed improvement of symptoms in both AD and vascular dementia. EGb 761 is seen as being able to play an important role either on its own or as an add-on particularly when other therapies prove ineffective. EGb 761 is seen to be neuroprotective; it is a free radical scavenger, improves mitochondrial function, and modulates serotonin and dopamine levels. Many studies of its use in mild to moderate dementia have shown it to significantly improve cognitive function, activities of daily living, and neuropsychiatric symptoms. However, its use has not been shown to prevent the progression to dementia.
Psychosocial interventions are used as an adjunct to pharmaceutical treatment and can be classified within behavior-, emotion-, cognition- or stimulation-oriented approaches. Research on efficacy is unavailable and rarely specific to AD, focusing instead on dementia in general.
Behavioral interventions attempt to identify and reduce the antecedents and consequences of problem behaviors. This approach has not shown success in improving overall functioning, but can help to reduce some specific problem behaviors, such as incontinence. There is a lack of high quality data on the effectiveness of these techniques in other behavior problems such as wandering. Music therapy is effective in reducing behavioral and psychological symptoms.
Emotion-oriented interventions include reminiscence therapy, validation therapy, supportive psychotherapy, sensory integration, also called snoezelen, and simulated presence therapy. A Cochrane review has found no evidence that this is effective. Supportive psychotherapy has received little or no formal scientific study, but some clinicians find it useful in helping mildly impaired people adjust to their illness. Reminiscence therapy (RT) involves the discussion of past experiences individually or in group, many times with the aid of photographs, household items, music and sound recordings, or other familiar items from the past. A 2018 review of the effectiveness of RT found that effects were inconsistent, small in size and of doubtful clinical significance, and varied by setting. Simulated presence therapy (SPT) is based on attachment theories and involves playing a recording with voices of the closest relatives of the person with Alzheimer's disease. There is partial evidence indicating that SPT may reduce challenging behaviors.
Finally, validation therapy is based on acceptance of the reality and personal truth of another's experience, while sensory integration is based on exercises aimed to stimulate senses. There is no evidence to support the usefulness of these therapies.
The aim of cognition-oriented treatments, which include reality orientation and cognitive retraining, is the reduction of cognitive deficits. Reality orientation consists in the presentation of information about time, place or person to ease the understanding of the person about its surroundings and his or her place in them. On the other hand, cognitive retraining tries to improve impaired capacities by exercitation of mental abilities. Both have shown some efficacy improving cognitive capacities, although in some studies these effects were transient and negative effects, such as frustration, have also been reported.
Stimulation-oriented treatments include art, music and pet therapies, exercise, and any other kind of recreational activities. Stimulation has modest support for improving behavior, mood, and, to a lesser extent, function. Nevertheless, as important as these effects are, the main support for the use of stimulation therapies is the change in the person's routine.
Since Alzheimer's has no cure and it gradually renders people incapable of tending for their own needs, caregiving is essentially the treatment and must be carefully managed over the course of the disease.
During the early and moderate stages, modifications to the living environment and lifestyle can increase patient safety and reduce caretaker burden. Examples of such modifications are the adherence to simplified routines, the placing of safety locks, the labeling of household items to cue the person with the disease or the use of modified daily life objects. If eating becomes problematic, food will need to be prepared in smaller pieces or even puréed. When swallowing difficulties arise, the use of feeding tubes may be required. In such cases, the medical efficacy and ethics of continuing feeding is an important consideration of the caregivers and family members. The use of physical restraints is rarely indicated in any stage of the disease, although there are situations when they are necessary to prevent harm to the person with AD or their caregivers.
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.
Fewer than 3% of people live more than fourteen years. Disease features significantly associated with reduced survival are an increased severity of cognitive impairment, decreased functional level, history of falls, and disturbances in the neurological examination. Other coincident diseases such as heart problems, diabetes or history of alcohol abuse are also related with shortened survival. While the earlier the age at onset the higher the total survival years, life expectancy is particularly reduced when compared to the healthy population among those who are younger. Men have a less favourable survival prognosis than women.
Pneumonia and dehydration are the most frequent immediate causes of death brought by AD, while cancer is a less frequent cause of death than in the general population.
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.
Deaths per million persons in 2012 due to dementias including Alzheimer's disease
Regarding incidence, cohortlongitudinal studies (studies where a disease-free population is followed over the years) provide rates between 10 and 15 per thousand person-years for all dementias and 5-8 for AD, which means that half of new dementia cases each year are AD. Advancing age is a primary risk factor for the disease and incidence rates are not equal for all ages: every five years after the age of 65, the risk of acquiring the disease approximately doubles, increasing from 3 to as much as 69 per thousand person years. There are also sex differences in the incidence rates, women having a higher risk of developing AD particularly in the population older than 85. In the United States, the risk of dying from Alzheimer's disease is 26% higher among the non-Hispanic white population than among the non-Hispanic black population, whereas the Hispanic population has a 30% lower risk than the non-Hispanic white population.
Prevalence of AD in populations is dependent upon different factors including incidence and survival. Since the incidence of AD increases with age, it is particularly important to include the mean age of the population of interest. In the United States, Alzheimer prevalence was estimated to be 1.6% in 2000 both overall and in the 65-74 age group, with the rate increasing to 19% in the 75-84 group and to 42% in the greater than 84 group. Prevalence rates in less developed regions are lower. The World Health Organization estimated that in 2005, 0.379% of people worldwide had dementia, and that the prevalence would increase to 0.441% in 2015 and to 0.556% in 2030. Other studies have reached similar conclusions. Another study estimated that in 2006, 0.40% of the world population (range 0.17-0.89%; absolute number , range ) were afflicted by AD, and that the prevalence rate would triple and the absolute number would quadruple by 2050.
Alois Alzheimer's patient Auguste Deter in 1902. Hers was the first described case of what became known as Alzheimer's disease.
The ancient Greek and Romanphilosophers and physicians associated old age with increasing dementia. It was not until 1901 that German psychiatristAlois Alzheimer identified the first case of what became known as Alzheimer's disease, named after him, in a fifty-year-old woman he called Auguste D. He followed her case until she died in 1906, when he first reported publicly on it. During the next five years, eleven similar cases were reported in the medical literature, some of them already using the term Alzheimer's disease. The disease was first described as a distinctive disease by Emil Kraepelin after suppressing some of the clinical (delusions and hallucinations) and pathological features (arteriosclerotic changes) contained in the original report of Auguste D. He included Alzheimer's disease, also named preseniledementia by Kraepelin, as a subtype of senile dementia in the eighth edition of his Textbook of Psychiatry, published on 1910.
For most of the 20th century, the diagnosis of Alzheimer's disease was reserved for individuals between the ages of 45 and 65 who developed symptoms of dementia. The terminology changed after 1977 when a conference on AD concluded that the clinical and pathological manifestations of presenile and senile dementia were almost identical, although the authors also added that this did not rule out the possibility that they had different causes. This eventually led to the diagnosis of Alzheimer's disease independent of age. The term senile dementia of the Alzheimer type (SDAT) was used for a time to describe the condition in those over 65, with classical Alzheimer's disease being used to describe those who were younger. Eventually, the term Alzheimer's disease was formally adopted in medical nomenclature to describe individuals of all ages with a characteristic common symptom pattern, disease course, and neuropathology.
Society and culture
Dementia, and specifically Alzheimer's disease, may be among the most costly diseases for society in Europe and the United States, while their costs in other countries such as Argentina, and South Korea, are also high and rising. These costs will probably increase with the aging of society, becoming an important social problem. AD-associated costs include direct medical costs such as nursing home care, direct nonmedical costs such as in-home day care, and indirect costs such as lost productivity of both patient and caregiver. Numbers vary between studies but dementia costs worldwide have been calculated around $160 billion, while costs of Alzheimer's disease in the United States may be $100 billion each year.
The greatest origin of costs for society is the long-term care by health care professionals and particularly institutionalisation, which corresponds to 2/3 of the total costs for society. The cost of living at home is also very high, especially when informal costs for the family, such as caregiving time and caregiver's lost earnings, are taken into account.
Costs increase with dementia severity and the presence of behavioral disturbances, and are related to the increased caregiving time required for the provision of physical care. Therefore, any treatment that slows cognitive decline, delays institutionalisation or reduces caregivers' hours will have economic benefits. Economic evaluations of current treatments have shown positive results.
The role of the main caregiver is often taken by the spouse or a close relative. Alzheimer's disease is known for placing a great burden on caregivers which includes social, psychological, physical or economic aspects. Home care is usually preferred by people with AD and their families. This option also delays or eliminates the need for more professional and costly levels of care. Nevertheless, two-thirds of nursing home residents have dementias.
Dementia caregivers are subject to high rates of physical and mental disorders. Factors associated with greater psychosocial problems of the primary caregivers include having an affected person at home, the carer being a spouse, demanding behaviors of the cared person such as depression, behavioral disturbances, hallucinations, sleep problems or walking disruptions and social isolation. Regarding economic problems, family caregivers often give up time from work to spend 47 hours per week on average with the person with AD, 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.
In the decade 2002-2012, 244 compounds were assessed in Phase I, Phase II, or Phase III trials, and only one of these (memantine) received FDA approval (though others were still in the pipeline).Solanezumab and aducanumab failed to show effectiveness in people who already had Alzheimer's symptoms.[medical ]
In early 2017, a trial of verubecestat, which inhibits the beta-secretase protein responsible for creating beta-amyloid protein was discontinued as an independent panel found "virtually no chance of finding a positive clinical effect". In 2018 and 2019, more trials, including aducanumab which reduced amyloid beta concentrations, failed, leading some to question the validity of the amyloid hypothesis.[medical ]
The senescence accelerated mouse (SAMP8) is an Alzheimer's disease (AD) animal model in which amyloid precursor protein (APP) is overproduced. The mice develops early memory disturbances and alters the blood-brain barrier, which causes a decreased expulsion of amyloid-? protein from the brain. It has a marked increase in oxidative stress in the brain. Medications that reduce oxidative stress have been shown to improve memory. Treatments that reduce amyloid-? (antisense to APP and antibodies to amyloid-?) not only improve memory but also reduce oxidative stress. It has been shown that the initial deviations in lipid peroxidative damage favor mitochondrial dysfunction as being a trigger for amyloid-? overproduction in this AD mouse strain. This process begets increased amyloid-beta, which further damages mitochondria.
Research on the effects of meditation on preserving memory and cognitive functions is at an early stage. A 2015 review suggests that mindfulness-based interventions may prevent or delay the onset of mild cognitive impairment and Alzheimer's disease.
The ketogenic diet is a very high-fat, adequate protein, low-carbohydrate diet that is used to treat refractory epilepsy in children. Designed to mimic some of the effects of fasting, following a ketogenic diet leads to elevated blood-levels of molecules called ketone bodies: a metabolic state known as ketosis. These ketone bodies have a neuroprotective effect on aging brain cells, though it is not fully understood why. Limited research in the form of preclinical trials (mice and rats), and small-scale clinical (human) trials, have explored its potential as a therapy for neurodegenerative disorders like Alzheimer's disease.
The herpes simplex virus HSV-1 has been found in the same areas as amyloid plaques. This suggested the possibility that AD could be treated or prevented with antiviral medication. Studies of antivirals in cell cultures have shown promising results. A 2021 study of 265,172 subjects in Sweden over a 12 year period found that patients with herpes diagnoses not treated with antiviral drugs had a 50% increased risk of dementia over controls, but treatment with antiviral drugs reduced the incidence by 25%.[non-primary source needed]
Fungal infection of AD brain has also been described.
This hypothesis was proposed by the microbiologist L. Carrasco when his group found statistical correlation between disseminated mycoses and AD.
Further work revealed that fungal infection is present in different brain regions of AD patients, but not in the control individuals.
A fungal infection explains the symptoms observed in AD patients. The slow progression of AD fits with the chronic nature of some systemic fungal infections, which can be asymptomatic and thus, unnoticed and untreated.
The fungal hypotheses are also compatible with some other established AD hypotheses, like the amyloid hypothesis, that can be explained as an immune system response to an infection in the CNS, as found by R. Moir and R. Tanzi in mouse and worm models of AD.
Emphasis in Alzheimer's research has been placed on diagnosing the condition before symptoms begin. A number of biochemical tests have been developed to enable earlier detection. Some such tests involve the analysis of cerebrospinal fluid for beta-amyloid, total tau protein and phosphorylated tau181P protein concentrations. Because drawing CSF can be painful, repeated draws are avoided. A blood test for circulatory miRNA and inflammatory biomarkers is a potential alternative indicator.
A series of studies suggest that aging-related breakdown of the blood-brain barrier may be causative of AD, and conclude that markers for that damage may be an early predictor of the disease.
^Commission de la transparence (June 2012). "Drugs for Alzheimer's disease: best avoided. No therapeutic advantage" [Drugs for Alzheimer's disease: best avoided. No therapeutic advantage]. Prescrire International. 21 (128): 150. PMID22822592.
^Todd S, Barr S, Roberts M, Passmore AP (November 2013). "Survival in dementia and predictors of mortality: a review". International Journal of Geriatric Psychiatry. 28 (11): 1109-24. doi:10.1002/gps.3946. PMID23526458. S2CID25445595.
^Jelicic M, Bonebakker AE, Bonke B (1995). "Implicit memory performance of patients with Alzheimer's disease: a brief review". International Psychogeriatrics. 7 (3): 385-92. doi:10.1017/S1041610295002134. PMID8821346.
^Tomiyama T (2010). "Involvement of beta-amyloid in the etiology of Alzheimer's disease". Brain Nerve. 62 (7): 691-699. PMID20675873.
^Tomiyama T, Nagata T, Shimada H, Teraoka R, Fukushima A, Kanemitsu H, Takuma H, Kuwano R, Imagawa M, Ataka S, Wada Y, Yoshioka E, Nishizaki T, Watanabe Y, Mori H (2008). "A new amyloid beta variant favoring oligomerization in Alzheimer's-type dementia". Ann Neurol. 63 (3): 377-387. doi:10.1002/ana.21321. PMID18300294. S2CID42311988.CS1 maint: multiple names: authors list (link)
^Hardy J, Allsop D (October 1991). "Amyloid deposition as the central event in the aetiology of Alzheimer's disease". Trends in Pharmacological Sciences. 12 (10): 383-88. doi:10.1016/0165-6147(91)90609-V. PMID1763432.
^Polvikoski T, Sulkava R, Haltia M, Kainulainen K, Vuorio A, Verkkoniemi A, Niinistö L, Halonen P, Kontula K (November 1995). "Apolipoprotein E, dementia, and cortical deposition of beta-amyloid protein". The New England Journal of Medicine. 333 (19): 1242-47. doi:10.1056/NEJM199511093331902. PMID7566000.
^Iqbal K, Alonso A, Chen S, Chohan MO, El-Akkad E, Gong CX, Khatoon S, Li B, Liu F, Rahman A, Tanimukai H, Grundke-Iqbal I (January 2005). "Tau pathology in Alzheimer disease and other tauopathies". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1739 (2-3): 198-210. doi:10.1016/j.bbadis.2004.09.008. PMID15615638.
^Eikelenboom P, van Exel E, Hoozemans JJ, Veerhuis R, Rozemuller AJ, van Gool WA (2010). "Neuroinflammation - an early event in both the history and pathogenesis of Alzheimer's disease". Neuro-Degenerative Diseases. 7 (1-3): 38-41. doi:10.1159/000283480. PMID20160456. S2CID40048333.
^ abcReisberg B, Franssen EH, Hasan SM, et al. (1999). "Retrogenesis: clinical, physiologic, and pathologic mechanisms in brain aging, Alzheimer's and other dementing processes". European Archives of Psychiatry and Clinical Neuroscience. 249 Suppl 3 (3): 28-36. doi:10.1007/pl00014170. PMID10654097. S2CID23410069.
^ abMakhlouf S, Messelmani M, Zaouali J, Mrissa R (March 2018). "Cognitive impairment in celiac disease and non-celiac gluten sensitivity: review of literature on the main cognitive impairments, the imaging and the effect of gluten free diet". Acta Neurologica Belgica (Review). 118 (1): 21-27. doi:10.1007/s13760-017-0870-z. PMID29247390. S2CID3943047.
^Hashimoto M, Rockenstein E, Crews L, Masliah E (2003). "Role of protein aggregation in mitochondrial dysfunction and neurodegeneration in Alzheimer's and Parkinson's diseases". Neuromolecular Medicine. 4 (1-2): 21-36. doi:10.1385/NMM:4:1-2:21. PMID14528050. S2CID20760249.
^Hooper NM (April 2005). "Roles of proteolysis and lipid rafts in the processing of the amyloid precursor protein and prion protein". Biochemical Society Transactions. 33 (Pt 2): 335-38. doi:10.1042/BST0330335. PMID15787600. S2CID14269634.
^Van Broeck B, Van Broeckhoven C, Kumar-Singh S (2007). "Current insights into molecular mechanisms of Alzheimer disease and their implications for therapeutic approaches". Neuro-Degenerative Diseases. 4 (5): 349-65. doi:10.1159/000105156. PMID17622778. S2CID7949658.
^Blacker D, Albert MS, Bassett SS, Go RC, Harrell LE, Folstein MF (December 1994). "Reliability and validity of NINCDS-ADRDA criteria for Alzheimer's disease. The National Institute of Mental Health Genetics Initiative". Archives of Neurology. 51 (12): 1198-204. doi:10.1001/archneur.1994.00540240042014. PMID7986174.
^American Psychiatric Association (2000). Diagnostic and statistical manual of mental disorders: DSM-IV-TR (4th Edition Text Revision ed.). Washington, DC: American Psychiatric Association. ISBN978-0-89042-025-6.
^Ito N (May 1996). "[Clinical aspects of dementia]". [Hokkaido Igaku Zasshi] the Hokkaido Journal of Medical Science (in Japanese). 71 (3): 315-20. PMID8752526.
^Cunnane SC, Chouinard-Watkins R, Castellano CA, Barberger-Gateau P (January 2013). "Docosahexaenoic acid homeostasis, brain aging and Alzheimer's disease: Can we reconcile the evidence?". Prostaglandins, Leukotrienes, and Essential Fatty Acids. 88 (1): 61-70. doi:10.1016/j.plefa.2012.04.006. PMID22575581.
^Fink HA, Linskens EJ, MacDonald R, et al. (May 2020). "Benefits and Harms of Prescription Drugs and Supplements for Treatment of Clinical Alzheimer-Type Dementia". Annals of Internal Medicine. 172 (10): 656-668. doi:10.7326/M19-3887. PMID32340037. S2CID216595473.
^Stahl SM (November 2000). "The new cholinesterase inhibitors for Alzheimer's disease, Part 2: illustrating their mechanisms of action". The Journal of Clinical Psychiatry. 61 (11): 813-14. doi:10.4088/JCP.v61n1101. PMID11105732.
^Alldredge BK, Corelli RL, Ernst ME, Guglielmo BJ, Jacobson PA, Kradjan WA, Williams BR (2013). Applied therapeutics : the clinical use of drugs (10th ed.). Baltimore: Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 2385. ISBN978-1-60913-713-7.
^Raina P, Santaguida P, Ismaila A, Patterson C, Cowan D, Levine M, Booker L, Oremus M (March 2008). "Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline". Annals of Internal Medicine. 148 (5): 379-97. doi:10.7326/0003-4819-148-5-200803040-00009. PMID18316756. S2CID22235353.
^Ballard C, Waite J (January 2006). Ballard CG (ed.). "The effectiveness of atypical antipsychotics for the treatment of aggression and psychosis in Alzheimer's disease". The Cochrane Database of Systematic Reviews (1): CD003476. doi:10.1002/14651858.CD003476.pub2. PMID16437455.
^Ballard C, Hanney ML, Theodoulou M, Douglas S, McShane R, Kossakowski K, Gill R, Juszczak E, Yu LM, Jacoby R (February 2009). "The dementia antipsychotic withdrawal trial (DART-AD): long-term follow-up of a randomised placebo-controlled trial". The Lancet Neurology. 8 (2): 151-57. doi:10.1016/S1474-4422(08)70295-3. PMID19138567. S2CID23000439. Lay summary.
^ abcdefgRabins PV, Blacker D, Rovner BW, et al. (Steering Committee on Practice Guidelines) (December 2007). "American Psychiatric Association practice guideline for the treatment of patients with Alzheimer's disease and other dementias. Second edition". The American Journal of Psychiatry. 164 (12 Suppl): 5-56. PMID18340692.
^Chung JC, Lai CK, Chung PM, French HP (2002). Chung JC (ed.). "Snoezelen for dementia". The Cochrane Database of Systematic Reviews (4): CD003152. doi:10.1002/14651858.CD003152. PMID12519587. (up to date as of 2009)
Friedlander AH, Norman DC, Mahler ME, Norman KM, Yagiela JA (September 2006). "Alzheimer's disease: psychopathology, medical management and dental implications". Journal of the American Dental Association. 137 (9): 1240-51. doi:10.14219/jada.archive.2006.0381. PMID16946428.
Belmin J (2007). "Practical guidelines for the diagnosis and management of weight loss in Alzheimer's disease: a consensus from appropriateness ratings of a large expert panel". The Journal of Nutrition, Health & Aging. 11 (1): 33-37. PMID17315078.
McCurry SM, Gibbons LE, Logsdon RG, Vitiello M, Teri L (October 2003). "Training caregivers to change the sleep hygiene practices of patients with dementia: the NITE-AD project". Journal of the American Geriatrics Society. 51 (10): 1455-60. doi:10.1046/j.1532-5415.2003.51466.x. PMID14511168. S2CID24065377.
^Jagger C, Clarke M, Stone A (January 1995). "Predictors of survival with Alzheimer's disease: a community-based study". Psychological Medicine. 25 (1): 171-77. doi:10.1017/S0033291700028191. PMID7792352.
^ abBermejo-Pareja F, Benito-León J, Vega S, Medrano MJ, Román GC (January 2008). "Incidence and subtypes of dementia in three elderly populations of central Spain". Journal of the Neurological Sciences. 264 (1-2): 63-72. doi:10.1016/j.jns.2007.07.021. PMID17727890. S2CID34341344.
^ abcDi Carlo A, Baldereschi M, Amaducci L, Lepore V, Bracco L, Maggi S, Bonaiuto S, Perissinotto E, Scarlato G, Farchi G, Inzitari D (January 2002). "Incidence of dementia, Alzheimer's disease, and vascular dementia in Italy. The ILSA Study". Journal of the American Geriatrics Society. 50 (1): 41-48. doi:10.1046/j.1532-5415.2002.50006.x. PMID12028245. S2CID22576935.
^Andersen K, Launer LJ, Dewey ME, et al. (December 1999). "Gender differences in the incidence of AD and vascular dementia: The EURODEM Studies. EURODEM Incidence Research Group". Neurology. 53 (9): 1992-97. doi:10.1212/wnl.53.9.1992. PMID10599770. S2CID22725252.
"Highlights"(PDF). World Population Prospects: The 2006 Revision. Working Paper No. ESA/P/WP.202. Population Division, Department of Economic and Social Affairs, United Nations. 2007. Archived from the original(PDF) on 19 August 2008. Retrieved 2008.
Alzheimer A (1907). "Über eine eigenartige Erkrankung der Hirnrinde" [About a peculiar disease of the cerebral cortex]. Allgemeine Zeitschrift für Psychiatrie und Psychisch-Gerichtlich Medizin (in German). 64 (1-2): 146-48.
Alzheimer A (1987). Translated by H. Greenson. "About a peculiar disease of the cerebral cortex. By Alois Alzheimer, 1907 (Translated by L. Jarvik and H. Greenson)". Alzheimer Disease and Associated Disorders. 1 (1): 3-8. PMID3331112.
^Amaducci LA, Rocca WA, Schoenberg BS (November 1986). "Origin of the distinction between Alzheimer's disease and senile dementia: how history can clarify nosology". Neurology. 36 (11): 1497-9. doi:10.1212/wnl.36.11.1497. PMID3531918. S2CID7689479.
^Jönsson L, Eriksdotter Jönhagen M, et al. (May 2006). "Determinants of costs of care for patients with Alzheimer's disease". International Journal of Geriatric Psychiatry. 21 (5): 449-59. doi:10.1002/gps.1489. PMID16676288. S2CID20193233.
^Wozniak MA, Mee AP, Itzhaki RF (January 2009). "Herpes simplex virus type 1 DNA is located within Alzheimer's disease amyloid plaques". The Journal of Pathology (Original study). 217 (1): 131-38. doi:10.1002/path.2449. PMID18973185. S2CID5176764.