Alzheimer's disease (AD), also called Alzheimer disease or simply Alzheimer's, is the most common cause of dementia. Alzheimer's is a degenerative and terminal disease for which there is no known cure. In its most common form, it afflicts individuals over 65 years old, although a less prevalent early-onset form also exists. It is estimated that 26.6 million people worldwide were afflicted by AD in 2006, which could quadruple by 2050,[1] although estimations vary greatly.[2]
Each individual experiences the symptoms of AD in unique ways.[3] The symptoms of Alzheimer's disease are generally reported to a physician when memory loss becomes apparent. If AD is suspected as the cause, the physician or healthcare specialist will confirm the diagnosis with behavioral assessments and cognitive tests, often followed by a brain scan, if available.[4] A prognosis for Alzheimer's is hard to make, as the duration of the disease varies per individual, and the disease can develop for an indeterminate time before becoming fully apparent, sometimes escaping diagnosis for years. Generally, life with Alzheimer's disease lasts between 5 and 20 years.[5][6] In the early stages, the most commonly recognised symptom is memory loss, such as the difficulty to remember recently learned facts. Earliest occurring symptoms are often mistaken as being noncritical age-related complaints, or forms of stress.[7] As the disease advances, progressive symptoms include confusion, anger, mood swings, language breakdown, long-term memory loss, and the general withdrawal of the sufferer as his or her senses decline.[7][8] Gradually, minor and major bodily functions are lost, leading ultimately to death.[9]
The cause and progression of Alzheimer's disease are not well understood. Research indicates that the disease is associated with plaques and tangles in the brain.[10] No treatment has been found to stop or reverse the disease, and it is not known whether current treatments slow the progression, or simply manage the symptoms. Many preventive measures have been suggested for Alzheimer's disease, but their value is unproven in reducing the course and severity of the disease. Mental stimulation, exercise and a balanced diet are often recommended, both as a possible prevention and as a sensible way of managing the disease
Characteristics
The disease course is divided into four stages, with a progressive pattern of cognitive and functional impairment expressed during each stage.
Predementia
Detailed neuropsychological testing can reveal mild cognitive difficulties up to eight years before a person fulfills the clinical criteria of diagnosis.[16] These early symptoms can have an effect on the most complex daily living activities.[17] The most noticeable deficit is memory loss , shown as a difficulty to remember recently learned facts and an inability to acquire new information.[18][19] In addition, subtle executive function problems (attention, planning, flexibility, abstraction...) or impairments in semantic memory (memory of meanings and concept relationships) can also occur.[20][21] Apathy can be observed at this stage, and is the most common and persistent neuropsychiatric symptom throughout the course of the disease.[22][23][24] This stage of the disease has also been termed mild cognitive impairment,[25] but there is still a debate on whether this term corresponds to a different diagnostic entity by itself or just a first step of the disease.[26]
Early dementia
In 1994 the former United States president R. Reagan informed the country of his AD diagnosis via a hand-written letter. Writing is usually affected in the first stages of the disease.
In 1994 the former United States president R. Reagan informed the country of his AD diagnosis via a hand-written letter. Writing is usually affected in the first stages of the disease.
In most people with the disease the increasing impairments in learning and memory will lead to diagnosis, while in a small proportion of them difficulties with language, executive functions, recognition of perceptions (agnosia) or execution of movements (apraxia) will be more salient.[27] Nevertheless, memory problems do not affect all memory subcapacities equally. Older memories of the patient's life (episodic memory), facts learned (semantic memory), and implicit memory (the memory of the body on how to do things, such as using a fork to eat) are affected to a much lesser degree than the capacities needed to learn new facts or make new memories.[28][29] Language problems are mainly characterised by a shrinking vocabulary and a decreased word fluency which leads to a general impoverishment of oral and written language. The Alzheimer's patient is usually capable of adequately communicating basic ideas.] While performing fine motor tasks such as writing, drawing or dressing, certain visoconstructional difficulties, or apraxia, may be present, which may appear as clumsiness. As the disease progresses to the middle stage, patients might still be able to live and perform tasks independently for most of the time, but may need assistance or supervision with the most complicated activities.[27]
Moderate dementia
In the early stage, people with Alzheimer's can usually care for themselves. At the moderate stage, progressive deterioration seriously hinders the possibility of independence.[27]
Speech difficulties become clearly noticeable: due to difficulties in finding words the person makes frequent incorrect substitutions (paraphasias) , and content is poor. Reading and writing are also progressively forgotten.[30][34] As time passes, complex motor sequences become less coordinated, costing the patient most of their daily-living abilities.[35] Memory problems worsen, and the person may not recognize close relatives.[36] Long-term memory, which was previously left intact, is now also impaired.[37] At this stage, behavior changes are the norm. Common neuropsychiatric manifestations in this stage are irritability and labile affect, leading to crying or outbursts of unpremeditated aggression and physical violence, even in patients whose life-long behavior has been peaceful. Approximately 30% of the patients also develop illusionary misidentifications and other delusional symptoms.[22][38] Often urinary incontinence develops.[39] Because of the communication deficit along with delusions, patients often resist when caregivers attempt to provide care.[40] It is important to prevent escalation of resistiveness to care into combativeness when patient might strike out. All these symptoms create stress for relatives and caretakers, increasing the likelihood of moving the patient from home care to other long-term care facilities.[27][41]
Advanced
In the last stage of Alzheimer's disease the subject with the disease is fully dependent. Language is reduced to simple phrases or even single words before being lost altogether.[30] Nevertheless many patients can receive and return emotional signals long after the loss of verbal language.[42] Although aggressiveness can still be present, extreme apathy and exhaustion are much more common.[27] Patients will ultimately not be able to perform even the most simple tasks independently. Finally, deterioration of muscle and mobility will develop, leading the patient to become bedridden,[43] and to lose the ability to feed oneself,[44] if death from some external cause, such as infection due to pressure ulcers or pneumonia, does not occur first.[45][46]
Causes
Three major competing hypotheses exist to explain the cause of the disease. The oldest, on which most currently available drug therapies are based, is known as the cholinergic hypothesis and suggests that AD is due to reduced biosynthesis of the neurotransmitter acetylcholine. However, the medications that treat acetylcholine deficiency only affect symptoms of the disease and neither halt nor reverse it.[47] The cholinergic hypothesis has not maintained widespread support in the face of this evidence, although cholinergic effects have been proposed to initiate large-scale aggregation,[48] leading to generalised neuroinflammation.[49]
In 1991 the amyloid hypothesis was proposed,[50] while research after 2000 is also centered on tau proteins. The two positions differ with one stating that the tau protein abnormalities initiate the disease cascade, while the other states that amyloid beta (Aβ) deposits are the causative factor in the disease.[51]
The tau hypothesis is supported by the long-standing observation that deposition of amyloid plaques does not correlate well with neuron loss.[52] In this model, hyperphosphorylated tau begins to pair with other threads of tau and they become tangled up together inside nerve cell bodies in masses known as neurofibrillary tangles.[53] When this happens, the microtubules disintegrate, collapsing the neuron's transport system. This may result first in malfunctions in communication between neurons and later in the death of the cells.[54]
A majority of researchers support the alternative hypothesis that Aβ is the primary causative agent.[51] The amyloid hypothesis is compelling because the gene for the amyloid beta precursor (APP) is located on chromosome 21, and patients with trisomy 21 (Down Syndrome) who thus have an extra gene copy almost universally exhibit AD-like disorders by 40 years of age. It should be noted further that APOE4, the major genetic risk factor for AD, leads to excess amyloid build-up in the brain before AD symptoms arise. Thus, Aβ deposition precedes clinical AD.[57] It is known that some types of inherited AD involve only mutations in the APP gene (although this is not the most common type—others involve genes for "pre-senilin" proteins which process APP and may also have still-unknown functions).[58] However, another strong support for the amyloid hypothesis, which looks at Aβ as the common initiating factor for Alzheimer's disease, is that transgenic mice solely expressing a mutant human APP gene develop fibrillar amyloid plaques.[59]
Pathophysiology
Main article: Biochemistry of Alzheimer's disease
Neuropathology
MRI images of a normal aged brain (right) and an Alzheimer's patient's brain (left). In the Alzheimer brain, atrophy is clearly seen.
MRI images of a normal aged brain (right) and an Alzheimer's patient's brain (left). In the Alzheimer brain, atrophy is clearly seen.
At a macroscopic level, AD is characterised by loss of neurons and synapses in the cerebral cortex and certain subcortical regions. This results in gross atrophy of the affected regions, including degeneration in the temporal lobe and parietal lobe, and parts of the frontal cortex and cingulate gyrus.[49]
Both amyloid plaques and neurofibrillary tangles are clearly visible by microscopy in AD brains.[10] Plaques are dense, mostly insoluble deposits of amyloid-beta protein and cellular material outside and around neurons. Tangles are insoluble twisted fibers that build up inside the nerve cell. Though many older people develop some plaques and tangles, the brains of AD patients have them to a much greater extent and in different brain locations.[60]
Biochemical characteristics
Alzheimer's disease has been identified as a protein misfolding disease, or proteopathy, due to the accumulation of abnormally folded A-beta and tau proteins in the brains of AD patients.[61] Plaques are made of a small peptide (39 to 43 amino acid residues) called beta-amyloid (also A-beta or Aβ), a protein fragment snipped from a larger protein called amyloid precursor protein (APP). APP is a transmembrane protein; which means that it sticks through the neuron's membrane; and is believed to help neurons grow, survive and repair themselves after injury.[62][63] In AD, something causes APP to be divided by enzymes through a mechanism called proteolysis.[64] One of these fragments is beta-amyloid. Beta-amyloid fragments (amyloid fibrils) outside the cell form clumps that deposit outside neurons in dense formations known as senile plaques.[65][10]
AD is also considered a tauopathy due to abnormal aggregation of the tau protein. Healthy neurons have an internal support structure, or cytoskeleton, partly made up of structures called microtubules. These microtubules act like tracks, guiding nutrients and molecules from the body of the cell down to the ends of the axon and back. A protein called tau makes the microtubules stable when phosphorylated, and is therefore called a microtubule-associated protein.[66] In AD, tau is changed chemically, becoming phosphate saturated (hyperphosphorylated).
Disease mechanism
If the production and aggregation of the amyloid beta peptide plays a key role in AD, the exact mechanism has not been elucidated.[67] The traditional formulation of the amyloid hypothesis points to the accumulation of beta-amyloid peptides as the central event triggering neurons degeneration. Accumulation of aggregated amyloid fibrils, which are believed to be the toxic form of the protein responsible for disrupting the cell's calcium ion homeostasis, induces apoptosis (programmed cell death).[68] It is also known that Aβ selectively builds up in the cells mitochondria of brains with AD and inhibits certain enzyme functions and the utilization of glucose by neurons. This process may also lead to the formation of damaging reactive oxygen species, calcium influx, and apoptosis.[69]
Various inflammatory processes and inflammatory cytokines may also have a role in the pathology of Alzheimer's disease. However, these are general markers of tissue damage in any disease, and may also be either secondary causes of tissue damage in AD, or else bystander "marker" effects.
Genetic
While earlier disease familial onset is mainly explained by three genes, later age of disease onset representing most cases of AD has yet to be explained by a purely genetic model. In the second case the APOE gene is the strongest genetic risk factor discovered but it is far from explaining all occurrences of the disease.[71]
Only 10% of AD cases occurring before 60 years of age are due to autosomal dominant (familial) mutations, which represents less than 0,01 of all patients.[71][72] These mutations have been discovered in three different genes: amyloid precursor protein or APP,[73] and presenilins 1,[74] and 2[75]. Most mutations in the APP and presenilin genes increase the production of a small protein called Abeta42, which is the main component of senile plaques in brains of AD patients.[76]
Most cases of Alzheimer's disease do not exhibit familial inheritance. In this case genes may act as risk factors. The best known genetic risk factor is the inheritance of the ε4 allele of the apolipoprotein E (APOE). This gene is regarded as a risk factor for development of up to 50% of late-onset sporadic Alzheimer's.[77] Genetic experts agree that there are other risk and protective factor genes that influence the development of late onset Alzheimer's disease.[71] Over 400 genes have been tested for association with late-onset sporadic AD.[78]
Diagnosis
Dementia is by definition a clinical condition but not an exact diagnosis. Alzheimer's disease is usually diagnosed clinically from the patient history, collateral history from relatives, and clinical observations, based on the presence of characteristic neurological and neuropsychological features and the absence of alternative conditions.[79][80] Advanced medical imaging with CT or MRI, and with SPECT or PET are generally used to help to diagnose the subtype of dementia and exclude other cerebral pathology.[81] Neuropsychological evaluation including memory testing and assessment of intellectual functioning can further characterize the dementia.[82] Medical organizations have created diagnostic criteria to ease and standardize the process for practicing physicians. Sometimes the diagnosis can be confirmed or made at postmortem when brain material is available and can be examined histologically and histochemically.[83]
Diagnostic criteria
The diagnostic criteria for Alzheimer of the NINCDS-ADRDA (NINCDS and the ADRDA) are among the most used.[84] These criteria require that the presence of cognitive impairment and a suspected dementia syndrome be confirmed by neuropsychological testing for a clinical diagnosis of possible or probable AD while they need histopathologic confirmation (microscopic examination of brain tissue) for the definitive diagnosis. They have shown good reliability and validity.[85] They specify as well eight cognitive domains that may be impaired in AD (i.e., memory, language, perceptual skills, attention, constructive abilities, orientation, problem solving and functional abilities). Similar to the NINCDS-ADRDA Alzheimer's Criteria are the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) criteria published by the American Psychiatric Association.[86][87]
Diagnostic tools
Neuropsychological screening tests can help in the diagnosis of AD. In them patients have to copy drawings similar to the one shown in the picture, remember words, read or sum.
Neuropsychological screening tests can help in the diagnosis of AD. In them patients have to copy drawings similar to the one shown in the picture, remember words, read or sum.
Neuropsychological screening tests such as the Mini mental state examination (MMSE) are widely used to evaluate the cognitive impairments needed for diagnosis, but more comprehensive tests arrays are necessary for high reliability by this method, especially in the earliest stages of the disease.[88][89] Neurological examination in early AD will usually be normal, independent of cognitive impairment; but for many of the other dementing disorders is key for diagnosis. Therefore, neurological examination is crucial in the differential diagnosis of Alzheimer and other diseases.[82] In addition, interviews with family members are also utilized in the assessment of the disease. Caregivers can supply important information on the daily living abilities, as well as on the decrease over time of the patient's mental function.[90] This is especially important since a patient with AD is commonly unaware of his or her own deficits (anosognosia).[91] Many times families also have difficulties in the detection of initial dementia symptoms and in adequately communicating them to a physician.[92] Finally, supplemental testing provides extra information on some features of the disease or are used to rule out other diagnoses. Examples are blood tests, which can identify other causes for dementia different than AD,[82] which rarely may even be reversible;[93] or psychological tests for depression, as depression can both co-occur with AD or, on the contrary, be at the origin of the patient's cognitive impairment.[94][95]
Increasingly, the functional neuroimaging modalities of single photon emission computed tomography (SPECT) and positron emission tomography (PET) are being used to diagnose Alzheimer's, as they have shown similar ability to diagnose Alzheimer's disease as methods involving mental status examination.[96] Furthermore, the ability of SPECT to differentiate Alzheimer's disease from other possible causes, in a patient already known to be suffering from dementia, appears to be superior to attempts to differentiate the cause of dementia cause by mental testing and history.[97] A new technique known as "PiB PET" has been developed for directly and clearly imaging beta-amyloid deposits in vivo using a contrasting tracer that binds selectively to the Abeta deposits.[98][99][100] Another recent objective marker of the disease is the analysis of cerebrospinal fluid for amyloid beta or tau proteins.[101] Both advances (neuroimaging and cerebrospinal fluid analysis) have led to the proposal of new diagnostic criteria.[84][82]
Prevention
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.
Intellectual activities such as playing chess or regular social interaction have been linked to a reduced risk of AD in epidemiological studies, although no causal relationship has been found.
At present contradictory results in global studies, incapacity to prove causal relationships between risk factors and the disease, and possible secondary effects indicate a lack of specific measures to prevent or delay the onset of AD.[102] Different 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, in fact, these factors can help to prevent AD.[103]
The components of a Mediterranean diet, which include fruit and vegetables, bread, wheat and other cereals, olive oil, fish, and red wine, may all individually or together reduce the risk and course of Alzheimer's disease. Vitamins B and C, or folic acid have appeared to be related to a reduced risk of AD, but other studies indicate that they do not have any significant effect on the onset or course of the disease and may have important secondary effects.[106] Curcumin in curry has shown some effectiveness in preventing brain damage in mouse models.
Although cardiovascular risk factors, such as hypercholesterolemia, hypertension, diabetes, and smoking, are associated with a higher risk of onset and course of AD,[108][109] statins, which are cholesterol lowering drugs, have not been effective in preventing or improving the course of the disease.[110][111] However long-term usage of non-steroidal anti-inflammatory drug (NSAIDs), is associated with a reduced likelihood of developing AD in some individuals.[112] Other pharmaceutical therapies such as female hormone replacement therapy are no longer thought to prevent dementia,[113][114] and a 2007 systematic review concluded that there was inconsistent and unconvincing evidence that ginkgo has any positive effect on dementia or cognitive impairment.[115]
Intellectual activities such as playing chess, completing crossword puzzles or regular social interaction, may also delay the onset or reduce the severity of Alzheimer's disease.[116][117] Bilingualism is also related to a later onset of Alzheimer.[118]
Some studies have shown a positive relationship between risk of developing AD and different occupational exposures such as magnetic field exposure,[119][120], metals intake and specifically aluminium,[121][122] or solvents.[123] The quality of some of these studies has been criticized,[124] and other research does not confirm this link.[125][126] [127][128]
[edit] Management
There is no known 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.
Pharmaceutical
3d molecular spacefill of donepezil, an acetylcholinesterase inhibitor used in the treatment of AD symptoms
3d molecular spacefill of donepezil, an acetylcholinesterase inhibitor used in the treatment of AD symptoms
Molecular structure of memantine, a medication approved for advanced AD symptoms
Molecular structure of memantine, a medication approved for advanced AD symptoms
Four medications, to treat the cognitive manifestations of AD, are currently approved by regulatory agencies, including the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMEA). Three are acetylcholinesterase inhibitors and the other is memantine, an NMDA receptor antagonist. No drug has an indication for delaying or halting the progression of the disease.
Because reduction in the activity of the cholinergic neurons in the disease is well known, acetylcholinesterase inhibitors are employed to reduce the rate at which acetylcholine (ACh) is broken down and so to increase the concentration of ACh in the brain, thereby combatting the loss of ACh caused by the death of the cholinergin neurons.[130] Cholinesterase inhibitors currently approved include donepezil (brand name Aricept),[131] galantamine (Razadyne),[132] and rivastigmine (branded as Exelon,[133] and Exelon Patch[134]). There is also evidence for the efficacy of these medications in mild to moderate Alzheimer’s disease,[135] and some evidence for their use in the advanced stage. Only donepezil is approved for treatment of advanced AD dementia.[136] The use of these drugs in mild cognitive impairment has not shown any effect in a delay of the onset of AD.[137] Most common side effects include nausea and vomiting, both of which are linked to cholinergic excess. These side effects arise in approximately ten to twenty percent of users and are mild to moderate in severity. Less common secondary effects include muscle cramps; decreased heart rate (bradycardia), decreased appetite and weight, and increased gastric acid.[138][139][140][141]
Glutamate is a useful excitatory neurotransmitter of the nervous system, although excessive amounts in the brain can lead to cell death through a process called excitotoxicity which consists of the overstimulation of glutamate receptors. Excitotoxicity occurs not only in Alzheimer's disease, but also in other neurological diseases such as Parkinson's disease and multiple sclerosis.[142] Memantine (brand names Akatinol, Axura, Ebixa/Abixa, Memox and Namenda),[143] is a noncompetitive NMDA receptor antagonist first used as an anti-influenza agent. It acts on the glutamatergic system by blocking NMDA glutamate receptors and inhibits their overstimulation by glutamate.[142] Memantine has been shown to be moderately efficacious in the treatment of moderate to severe Alzheimer’s disease. Its effects in the initial stages are unknown.[144] Reported adverse events with memantine are infrequent and mild, including hallucinations, confusion, dizziness, headache and fatigue.[145] Memantine used in combination with donepezil has been shown to be "of statistically significant but clinically marginal effectiveness".[146]
Neuroleptic anti-psychotic drugs commonly given to Alzheimer's patients with behavioural problems are modestly useful in reducing aggression and psychosis, but are associated with serious adverse effects, such as cerebrovascular events, movement difficulties or cognitive decline, that do not permit their routine use.[147][148][149]
Psychosocial intervention
A specifically designed room for sensory integration therapy, or snoezelen; an emotion-oriented psychosocial intervention for people with dementia
A specifically designed room for sensory integration therapy, or snoezelen; an emotion-oriented psychosocial intervention for people with dementia
Psychosocial interventions are used as an adjunct to pharmaceutical treatment and can be classified within behavior, emotion, cognition or stimulation oriented approaches. Research on efficacy is unavailable and rarely specific to the disease, focusing instead on dementia.[150]
Behavioral interventions attempt to identify and reduce the antecedents and consequences of problem behaviors. This approach has not shown success in the overall functioning of patients,[151] but can help to reduce some specific problem behaviors, such as incontinence.[152] There is still a lack of high quality data on the effectiveness of these techniques in other behavior problems such as wandering.[153][154]
Emotion-oriented interventions include reminiscence therapy, validation therapy, supportive psychotherapy, sensory integration or snoezelen, and simulated presence therapy. Supportive psychotherapy has received little or no formal scientific study, but some clinicians find it useful in helping mildly impaired patients adjust to their illness.[150] Reminiscence therapy (RT) involves the discussion of past experiences individually or in group, many times with the aid of photographs, household items, music and sound recordings, or other familiar items from the past. Although there are few quality studies on the effectiveness of RT it may be beneficial for cognition and mood.[155] Simulated presence therapy (SPT) is based on attachment theories and is normally carried out playing a recording with voices of the closest relatives of the patient. There is preliminary evidence indicating that SPT may reduce anxiety and challenging behaviors.[156][157] 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 little evidence to support the usefulness of these therapies.[158][159]
The aim of cognition-oriented treatments, which include reality orientation and cognitive retraining is the restoration of cognitive deficits. Reality orientation consists in the presentation of information about time, place or person in order to ease the understanding of the person about its surroundings and his 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,[160][161] although in some works these effects were transient and negative effects, such as frustration, have also been reported.[150]
Stimulation-oriented treatments include art, music and pet therapies, exercise, and any other kind of recreational activities for patients. 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 improvement in the patient daily life routine they suppose.[150]
Caregiving
Further information: Caregiving and dementia
Since there is no cure for Alzheimer's, caregiving is an essential part of the treatment. Due to the eventual inability for the sufferer to self-care, Alzheimer's has to be carefully care-managed. Home care in the familiar surroundings of home may delay onset of some symptoms and delay or eliminate the need for more professional and costly levels of care.[162] Many family members choose to look after their relatives,[12] but two-thirds of nursing home residents have dementias.[163]
Modifications to the living environment and lifestyle of the Alzheimer's patient can improve functional performance and ease caretaker burden. Assessment by an occupational therapist is often indicated. Adherence to simplified routines and labeling of household items to cue the patient can aid with activities of daily living, while placing safety locks on cabinets, doors, and gates and securing hazardous chemicals can prevent accidents and wandering. Changes in routine or environment can trigger or exacerbate agitation, whereas well-lit rooms, adequate rest, and avoidance of excess stimulation all help prevent such episodes.[164][165] Appropriate social and visual stimulation can improve function by increasing awareness and orientation. For instance, boldly colored tableware aids those with severe AD, helping people overcome a diminished sensitivity to visual contrast to increase food and beverage intake.[166]
Prognosis
As the disease progresses, the patient will advance from mild cognitive impairment, when the suspected underlying pathology may or may not yet have been diagnosed, to mild and advanced stages of dementia, finally reaching a severe stage of dementia.[27] Once Alzheimer's has been diagnosed, the average life expectancy is approximately seven years, while less than three percent of the patients live more than fourteen years.
History
Auguste D, first described patient with AD by Alöis Alzheimer in 1901
Although the concept of dementia goes as far back as the ancient Greek and Roman philosophers and physicians,[179] it was in 1901 when Alöis Alzheimer, a German psychiatrist, identified the first case of what became known as Alzheimer's disease in a fifty-year-old woman he called Auguste D. Alöis Alzheimer followed her until she died in 1906, when he first reported the case publicly.[180] In the following five years, eleven similar cases were reported in the medical literature, some of them already using the term Alzheimer's disease.[179] The official consideration of the disease as a distinctive entity is attributed to Emil Kraepelin, who included Alzheimer’s disease or presenile dementia as a subtype of senile dementia in the eighth edition of his Textbook of Psychiatry, published in 1910.[181]
For most of the twentieth century, the diagnosis of Alzheimer's disease was reserved for individuals between the ages of 45 and 65 who developed symptoms of dementia. The terminology changed after 1977 when a conference concluded that the clinical and pathological manifestations of presenile and senile dementia were almost identical, although the authors also added that this did not rule out the possibility of different etiologies.[182] This eventually led to the use of Alzheimer's disease independently of onset age of the disease.[183] The term senile dementia of the Alzheimer type (SDAT) was used for a time to describe the condition in those over 65, with classical Alzheimer's disease being used for those younger. Eventually, the term Alzheimer's disease was formally adopted in medical nomenclature to describe individuals of all ages with a characteristic common symptom pattern, disease course, and neuropathology.[184]
Society and culture
Social costs
Because the median age of the industrialised world's population is gradually increasing, AD is a public health challenge. The World Health Organization estimates that globally the total disability adjusted life years (DALYs) for AD and other dementias exceeded eleven million in 2005, with a projected 3.4% annual increase.[185] The DALYs are a measure for the overall disease burden that quantifies the impact of premature death and disability on a population by combining them into a single measure.
The solvency of governmental social safety nets will be impacted by the increased aged population which may develop Alzheimer's in the same proportions as earlier generations
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