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The history is the most important part of the evaluation of a patient with possible cognitive impairment or dementia. Although it may be unreliable, eliciting the history first from the patient can be very informative and useful. Allowing patients to give their version of the history also enables assessment of recent and remote memory. Questions about their medical and surgical history as well as current medications may help to assess both recent and remote memory. For example, if a patient has denied any medical or surgical history, the discovery of a large abdominal surgical scar on examination is very informative.
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Because the history from a patient with cognitive impairment can be incomplete and incorrect, it is crucial to also obtain history from a family member, caregiver, or other source. The history should focus on how long the symptoms have been present, whether they began gradually or abruptly, and the rate and nature (stepwise vs. continual decline) of their progression. Specific areas on which to focus include the patient’s ability to learn new things (eg, use of a microwave or a remote control), language problems (eg, word-finding difficulties or absence of content), trouble with complex tasks (eg, balancing the checkbook, preparing a meal), spatial ability (eg, getting lost in familiar places), and personality changes, behavioral problems, or psychiatric symptoms (eg, delusions, hallucinations, paranoia). Obtaining a good functional assessment will help to determine the severity of impairment and the need for caregiver support or, in patients without caregivers, the need for more supervised placement. This should include an assessment of the activities of daily living (ADLs) and instrumental activities of daily living (IADLs; eg, cooking, cleaning, shopping, managing finances, using the telephone, managing medications, and driving or arranging transportation). In addition, the clinician should assess the patient’s family and social situation because information obtained may be instrumental in developing a treatment plan.
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It is important to obtain a detailed medication history and history of comorbid conditions, including symptoms of depression and alcohol and other substance use. Although potentially reversible causes of dementia account for <1% of cases, a large part of the work-up is directed toward identifying and treating these causes. Table 22–1 summarizes the key elements of the history and physical examination.
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Early signs and symptoms of dementia are often missed by both physicians and families, especially in AD, in which social graces are often retained until moderate stages of the disease. Subtle hints of early dementia or MCI may include frequent repetition of the same questions or stories, reduced participation in former hobbies, increased accidents, and missed appointments. Poorly controlled chronic conditions may suggest lack of adherence to medication prescriptions because of memory problems, especially if these conditions were previously well controlled. Self-neglect, difficulty handling money, and getting lost are more obvious signs.
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The classic triad of findings in AD is memory impairment manifested by difficulty learning and recalling information (especially new information), visuospatial problems, and language impairment, which, in combination, are severe enough to interfere with social or occupational functioning. Classically, AD patients have little or no insight into their deficits, which may be a result of their compromised executive functioning (planning, insight, and judgment). Early in the course of disease, patients with AD retain their social functioning and ability to accomplish overlearned, familiar tasks, but often have difficulty with more complicated tasks, such as balancing a checkbook or making complex decisions. Because symptoms are insidious and family members often dismiss the short-term memory loss as normal aging, several years may pass before the patient receives medical attention. Disorientation is common among patients with AD and typically begins with disorientation to time, then place, and ultimately to person. Patients develop a progressive language disorder that begins with subtle anomic aphasia and ultimately progresses to fluent aphasia and then to mutism at the end stages of the disease. They have difficulty with visuospatial tasks and may be prone to getting lost, even in familiar surroundings. The disease is slowly progressive, and patients show continual decline in their ability to remain independent.
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Behavioral changes are common in AD, as in all dementia subtypes, and no neuropsychiatric symptom or behavioral disturbance is pathognomonic. Early changes may be manifested by apathy and irritability (≤70% of patients) and depression (30% to 50% of patients). Agitation becomes more common as the disease progresses and may be especially notable regarding issues of grooming and dressing. Psychotic symptoms, such as delusions, hallucinations, and paranoia, are also common, affecting up to 50% of patients in moderate to advanced stages.
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Dementia with Lewy bodies—
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DLB is the second most common form of dementia after AD, affecting up to 20% to 30% of patients with dementia. The core features of DLB are parkinsonism, fluctuation in cognitive impairment, and visual hallucinations. The presence of 1 of these features suggests possible DLB, and the presence of 2–3 suggests probable DLB. Rapid eye movement (REM) sleep behavior disorder and severe sensitivity to antipsychotics are suggestive of DLB and autonomic insufficiency, syncope, and depression are supportive features. These symptoms should occur in the absence of other factors that could explain them. The parkinsonism in patients with DLB generally presents after, or concurrent with, the onset of the dementia. This is in contrast to the Parkinson disease (PD)-related dementia, which generally occurs late in the disease. Parkinsonism in DLB is manifested primarily by rigidity and bradykinesia; tremor is less common (<10% to 25% of patients in large series). The development of parkinsonism late in the stages of a dementia is not specific for DLB because many patients with advanced AD also develop increased tone, bradykinesia, and tremor.
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Like AD, DLB is insidious in onset and progressive, although it classically has a fluctuating quality on a day-to-day basis. The fluctuation is seen in the level of alertness, cognitive functioning, and functional status. Early in the course, memory and language deficits are less prominent than in AD. In contrast, visuospatial abilities, problem solving, and processing speed are more significantly impaired than in AD at the same stage. Visual hallucinations occur in 60% to 85% of autopsy confirmed DLB patients compared with 11% to 28% of autopsy confirmed AD patients. They are classically very vivid and often are of animals, people, or mystical things. Unlike true psychosis, most patients with DLB can distinguish hallucinations from reality and, early on, tend not to be disturbed by them. Caution is advised in the use of antipsychotic medications because patients with DLB are exquisitely sensitive to neuroleptics, and a dramatic worsening of extrapyramidal symptoms may occur. Neuroleptics should not be given as a diagnostic test because deaths have been reported among those with DLB.
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In general, the diagnosis is based on the presence of clinical or radiographic evidence of cerebrovascular disease in a patient with dementia. Sudden onset of dementia after a stroke or stepwise, rather than continuous, decline is supportive of the diagnosis in the context of cortical strokes and focal neurologic findings on examination. However, because a considerable percentage of patients have subcortical vascular disease, the course may appear to be more gradual. In addition, many patients have mixed AD and VaD and mild, progressive, non-VaD may suddenly be unmasked by the occurrence of a stroke.
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Memory impairments in VaD are often less severe than in AD. Patients with VaD have impaired recall but tend to have better recognition and benefit from cueing in contrast to AD patients. On formal neuropsychiatric testing, “patchy” deficits may be found, often with difficulty on speeded tasks and tests of executive function. As in AD, behavioral and psychological symptoms are common. Depression may be more severe in patients with VaD.
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Frontotemporal dementia—
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FTD develops at a relatively young age (mean age of onset is in the 50s). It is estimated that FTD accounts for approximately 25% of presenile dementias. There is a behavioral variant (formerly known as Picks disease), and a language variant that includes primary progressive aphasia and semantic dementia.
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Behavioral variant FTD (bvFTD) is characterized by early changes in personality and behavior with relative sparing of memory and is often misdiagnosed as a psychiatric disorder. However, some symptoms are highly specific for bvFTD (97% to 100%; eg, hyperorality, early changes in personality and behavior, early loss of social awareness [disinhibition], compulsive or repetitive behaviors, progressive reduction in speech [early], and sparing of visuospatial abilities) and reliably distinguish it from AD. The hyperorality may be manifested by marked changes in food preference (often toward junk food and carbohydrates) or simply excessive eating. Another interesting phenomenon is that some patients with FTD develop new artistic talents without having had any prior interest.
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Cognitive testing in patients with FTD may reveal normal mini-mental state examination (MMSE) scores early in the disease. More formal neuropsychiatric testing reveals deficits in frontal systems tasks such as verbal fluency, abstraction, and executive functioning, and these deficits are seen earlier than in a typical patient with AD. In contrast to patients with AD, FTD patients tend to show preserved visuospatial abilities and relatively preserved memory, especially recognition memory.
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Many other diseases are associated with cognitive impairment and dementia, such as PD and its related disorders, Huntington disease (HD), HIV, and alcoholism. Approximately 30% of patients with PD develop dementia. This generally occurs late in the course of PD, and is characterized by slowing of mental processing, impaired recall (but usually preserved recognition memory), executive dysfunction, and visuospatial problems. HD is a rare autosomal dominant disorder characterized by motor (chorea, dystonia), behavioral, and cognitive impairments. With the advances in HIV care and the increasing numbers of long-term survivors, HIV-associated neurocognitive disorder (HAND) should be considered in the differential diagnosis of cognitive impairment. With the use of highly active antiretroviral therapy, the prevalence of HIV-associated dementia has declined, but up to 40% of HIV-infected persons may suffer from cognitive impairment. Although chronic alcohol abuse impairs cognitive functioning, there is controversy as to whether a true dementia syndrome related to alcohol exists (separate from thiamine deficiency and head trauma), partly because there have been no large-scale studies.
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Advanced & end-stage disease—
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The advanced symptoms of most dementias appear similar, and, in late stages, it is nearly impossible to distinguish between different types of dementia. In advanced dementia (typically with a score <10 on the MMSE), language skills are significantly impaired. There may be very little meaningful speech, and comprehension is very impaired. Some patients will progress to the point of mutism. Patients with advanced dementia have progressive difficulty with even the most basic ADLs, such as feeding themselves, and may progress to the point at which they are incontinent of bowel and bladder and are completely dependent in all ADLs. Symptoms of parkinsonism such as rigidity are common. Gait is impaired and, ultimately, patients may stop walking, leading to a bed-bound state. Seizures are occasionally seen in end-stage dementia patients. Patients who do not die of other comorbidities tend to develop concomitant complications (eg, malnutrition, pressure ulcers, recurrent infections). The most common cause of death in advanced dementia is pneumonia.
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Cardarelli
R, Kertesz
A, Knebl
JA Frontotemporal dementia: a review for primary care physicians.
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McKhann
GM, Knopman
DS, Chertkow
H
et al The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease.
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McKieth
IG, Dickson
DW, Lowe
J
et al Diagnosis and management of dementia with Lewy bodies. Third report of the DLB consortium.
Neurology. 2005;65(12):1863-–1872.
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Physical & Mental Status Examination
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The physical examination of a patient with cognitive impairment or dementia focuses on identifying clues to the cause of the dementia, comorbid conditions, conditions that may exacerbate the cognitive impairment (eg, sensory impairment or alcoholism), and signs of abuse or neglect. The neurologic examination should be directed at identifying evidence of prior strokes, such as focal signs, and of parkinsonism, such as rigidity, bradykinesia, or tremor, keeping in mind that late in the course of dementia increased tone and brisk reflexes are nonspecific. Gait and balance are an important part of the examination and should be assessed routinely. A careful cardiovascular evaluation, including measurement of blood pressure and examination for carotid disease and peripheral vascular disease, may help in supporting the diagnosis of VaD. Some patients without dementia who have significant hearing or visual impairments may demonstrate behavior that suggests dementia and have a low score on mental status testing. Therefore, it is important to identify and correct, if possible, sensory impairments before making a diagnosis of dementia.
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The effectiveness of screening asymptomatic patients for dementia is controversial. However, for patients with a high risk of dementia (eg, patients age 80 years and older) or for those who report memory impairment, screening with a standardized and validated tool is recommended.
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Mini-Mental State Examination—
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The MMSE, a 30-point tool that tests orientation, immediate recall, delayed recall, concentration/calculation, language, and visuospatial domains, has been the most widely used screening test of cognition. However, the MMSE is copyright protected and forms should be purchased from Psychological Assessment Resources. The MMSE, like many screening tests, is a culturally and language-biased test, and adjustments should be made for age and level of education. When scores are adjusted for age and education, the MMSE has a high sensitivity and specificity for detecting dementia (82% and 99%, respectively). Because it is administered verbally and patients are asked to write and draw, hearing, visual, or other physical impairments may make the scoring less valid. A patient with early cognitive impairment may score within normal limits for age and education; however, if the test is repeated every 6–12 months, the MMSE can detect cognitive decline and suggest a diagnosis of MCI or dementia. Among patients with AD, MMSE scores decline an average of 3 points per year, whereas for those with MCI, 1 point per year is more typical. In patients who are aging normally, MMSE scores should not decline much from year to year. As a general guideline, scores above 26 are normal, scores of 24–26 may indicate MCI, and a score <24 is consistent with dementia. However, it is best to compare each patient’s score with age and education adjusted median scores and to monitor for change in addition to assessing for functional decline.
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Montreal Cognitive Assessment—
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The Montreal Cognitive Assessment (MOCA) is gaining favor as a screening test for cognitive impairment. Similar to the MMSE, it is a 30-point screening test that assesses a variety of cognitive domains including memory (with a 5-word recall task), orientation, visuospatial function, concentration, calculation, attention, abstraction, language, and executive function (which is not represented on the MMSE). It is more sensitive than the MMSE, particularly for detecting MCI. The test and directions can be downloaded for free at www.mocatest.org in multiple languages, as well as for the blind. The form shows a cutoff score of 26 (25 and below indicating impairment), but this value is likely too high for most U.S. populations. For example, in a large, ethnically diverse sample of adults in the Dallas Heart Study, the mean score for a 70-year-old with high school education is about 20.5. Test scores are highly influenced by education level. Normative data is accumulating and providers should consult the literature for tables that provide age and education stratified means and standard deviations for populations similar to the patient being tested. Longitudinal data on the MOCA is needed.
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Attempts have been made to create brief, focused, screening tools that are less time-consuming than the MMSE and are freely available. Two commonly used tests are the Clock Draw Test (CDT) and the 3-Item Recall; when used together, this is called the “Mini-Cog.” In the Mini-Cog, the patient is asked to draw a clock face with the hands set at a designated time. Several CDTs are available, each with a different scoring system. However, evidence suggests that a simple dichotomy between normal and abnormal clocks has a relatively good sensitivity (approximately 80%) for detecting dementia, even for inexperienced raters. Normal clocks have all the numbers in the correct position and the hands correctly placed to display the requested time. Using the Mini-Cog is quick and easy, and if both are normal, it essentially rules out dementia. The Mini-Cog may be particularly useful in poorly educated or non–English-speaking patients for whom the MMSE is not so helpful.
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The cognitive assessment of a patient with cognitive impairment or dementia should be paired with the physical examination. Patients are less likely to be threatened or offended by questions about cognitive abilities if the questions are framed as part of the physical examination. In addition to administering a standardized assessment tool such as the MMSE or MOCA, providers should also assess domains of cognitive functioning that are not well represented in the MMSE or MOCA, such as judgment and insight. The diagnosis of dementia requires that there be impairment in 2 or more cognitive functions such as memory, language, visuospatial function, and executive functioning. Language can be assessed by simply listening for a lack of content in the patient’s dialogue or the use of vague terms to replace nouns, such as “thing” or “it.” Asking the patient to name common things in the room may be helpful if the language seems normal. Evidence of impaired executive functioning is often discovered in the history and can be assessed during the examination as well. For example, if the patient is not able to describe a complex function that the patient may normally do (or used to do) in fine detail, there may be a problem with executive functioning.
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Borson
S, Scanlan
J, Brush
M, Vitaliano
P, Dokmak
A The mini-cog: a cognitive “vital signs” measure for dementia screening the multilingual elderly.
Int J Geriatr Psychiatry. 2000;15(11): 1021-–1027.
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Nasreddine
ZS, Phillips
NA, Bédirian
V
et al The Montreal Cognitive Assessment, MoCA: a brief tool for mild cognitive impairment.
J Am Geriatr Soc. 2005;53(4):695-–699.
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Rossetti
HC, Lacritz
LH, Cullum
CM, Weiner
MF Normative data for the Montreal Cognitive Assessment (MoCA) in a population-based sample.
Neurology. 2011;77(13):1272-–1275.
CrossRef
[PubMed: 21917776]
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In the evaluation of a patient with cognitive impairment or newly diagnosed dementia, laboratory studies are generally used to rule out potentially treatable causes of dementia (Table 22–2). Vitamin B12 deficiency and hypothyroidism are common in older adults and can affect cognitive functioning. Treatment of these conditions is warranted, although few cases of dementia are actually caused by (or improved with treatment of) vitamin B12 deficiency or hypothyroidism. Most clinicians will also perform complete blood count, electrolytes, creatinine, glucose, calcium, and liver function tests. One should screen for latent syphilis and HIV if there is a high index of suspicion of these conditions.
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Routine CT or MRI scanning in the evaluation of patients with dementia remains controversial, but it is generally recommended that 1 noncontrast CT or noncontrast MRI be obtained in the evaluation of cognitive impairment to rule out treatable causes of dementias, such as subdural hematoma, normal pressure hydrocephalus, and tumor. In addition to looking for structural lesions, imaging may be helpful in the diagnosis of the particular type of non-AD dementia. MRI is more sensitive for vascular changes and measures of hippocampal volume. Neuroimaging is likely to be of low yield in patients with a typical clinical appearance of AD and symptoms that have been present for more than 1–2 years. Advantages and disadvantages of neuroimaging can be discussed with patients and families.
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Imaging studies for VaD are also nonspecific. This is because many older patients will have some degree of small vessel ischemic disease on CT or MRI. In fact, by age 85 years, nearly 100% of patients will have white matter hyperintensities on imaging studies. Therefore, simply seeing evidence of vascular disease does not warrant diagnosis of VaD. If, however, there is extensive disease, multiple infarcts, or infarcts in key anatomical locations (eg, thalamus) in a patient with a history or neuropsychological findings consistent with VaD, it is probable that the imaging findings are clinically relevant. In FTD, there is classically asymmetric volume loss of the frontal or anterior temporal lobes in comparison to the overall atrophy seen in AD.
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Fluorodeoxyglucose positron emission tomography (FDG-PET) scans measure glucose metabolism in specific areas of the brain and may be helpful in distinguishing early AD from FTD or DLB. Although FDG-PET has been shown to improve diagnostic accuracy of pathologically confirmed AD, it is not considered standard in the work up of AD and is generally not needed to make a diagnosis. In addition, Medicare currently only pays for FDG-PET when used to distinguish AD from FTD. Amyloid-binding PET tracers (such as AV-45) have recently become clinically available. However, as of the writing of this chapter, amyloid PET imaging is not covered by Medicare and the role of its use in the clinical diagnosis of AD is yet to be determined. It is not recommended as a screening test for asymptomatic individuals in part because up to 30% of cognitively “normal” older adults test positive for brain amyloid, and because there is currently no treatment that will delay or prevent onset of symptoms.
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Hort
J, O’Brien
JT, Gainotti
G
et al EFNS guidelines for the diagnosis and management of Alzheimer’s disease.
Eur J Neurol. 2010;17(10):1236–1248.
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Knopman
DS, DeKosky
ST, Cummings
JL
et al Practice parameter: diagnosis of dementia (an evidence-based review). Report of the quality standards subcommittee of the American Academy of Neurology.
Neurology. 2001;56(9):1143-–1153.
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Special Tests/Examinations
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Neuropsychological testing—
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Neuropsychological testing is generally performed by neuropsychologists and consists of an in-depth battery of standardized examinations that test multiple cognitive domains, including intelligence, memory, language, visuospatial abilities, attention, reasoning, and problem solving, as well as other measures of executive function. The diagnosis of dementia can generally be made by obtaining a detailed history and physical examination (including a brief cognitive evaluation) and does not require neuropsychological testing. However, there are instances in which referral for formal neuropsychological testing can be particularly helpful (eg, when patients have early or mild symptoms, especially if they have high premorbid intelligence and are performing “normally” on tools such as the MMSE). Neuropsychological testing can also be helpful in patients with low intelligence or education and in those with depression, schizophrenia, or other psychiatric illness in which it may be hard to determine how much the condition is contributing to the apparent cognitive deficits. Likewise, in patients with atypical features, such as early language impairment, neuropsychological testing may be helpful in the differential diagnosis of an unusual type of dementia. In addition, a more thorough cognitive battery can identify relative strengths that may be important to patients and their caregivers and may be useful for establishing a baseline from which to reassess.
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Kohlman Evaluation of Living Skills—
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A Kohlman Evaluation of Living Skills (KELS), generally performed by occupational therapists, assesses a patient’s ability to perform tasks required for safe independent living. For example, a patient is asked to write a check for a mock bill, use the telephone, or identify dangerous situations in pictures and state what he or she would do. This evaluation may be helpful when a patient with known or suspected dementia is living alone and there is concern about whether the patient needs to be moved to a more supervised setting such as assisted living.
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Tremendous advances have been made in elucidating the genetics of AD. Two categories of genetic defects have been defined: those that cause early onset AD and those involved in late-onset AD. Early onset familial AD is rare and accounts for approximately 5% of all AD cases. Patients with early onset AD usually develop dementia in their 40s to 50s and almost always before age 65 years. Because early onset AD is often familial, it is important to obtain a detailed family history of dementia. It is inherited in an autosomal dominant fashion. Mutations that cause early onset AD have been identified in 3 genes thus far: presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid precursor protein (APP) on chromosomes 14, 1, and 21, respectively. A mutation in PSEN1 is the most common. Testing for genetic mutations in a patient with early onset AD is not clinically useful for that patient because it will not alter the management of the disease. However, if the patient has children who wish to know whether they have inherited the gene, the family should be referred for genetic counseling. In addition, genetic testing of patients with early onset AD may be valuable for research.
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In contrast to early onset AD, late-onset AD (age >60–65 years) is associated with genes that increase the risk of AD but not in an autosomal dominant fashion. Physicians may be asked by patients or family members for the “Alzheimer blood test,” most likely referring to apolipoprotein E (APOE) genotyping. The association between APOE and risk of AD is well established. The presence of one ε4 allele increases the risk of AD by about 2–3 times, whereas the ε2 allele may be protective. It is important to keep in mind that APOE–ε4 is only a genetic risk factor for AD; therefore, the absence of an ε4 allele does not rule out the diagnosis nor does the presence of homozygous ε4/ε4 rule it in. In fact, most patients with AD do not carry the ε4 allele. There is broad consensus that APOE testing be reserved for research purposes only.
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Pinsky
LE, Burke
W, Bird
TD Why should primary care physicians know about the genetics of dementia?
West J Med. 2001;175(6):412-–416.
CrossRef
[PubMed: 11733436]