Alzheimer's disease diagnostic criteria

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kiran Singh, M.D. [2] Akshun Kalia M.B.B.S.[3]

Overview

The diagnosis of Alzheimer's disease (AD) is made on the basis of clinical criteria described by either the National Institute on Aging and the Alzheimer's Association (NIA-AA) or DSM-V (Diagnostic and Statistical Manual of Mental Disorders, fifth edition). Histopathologic examination for diagnosis of Alzheimer's disease is rarely done. Elderly patients presenting with progressive decline in memory and other cognitive impairments such as aphasia, agnosia or apraxia should be suspected for Alzheimer's disease. In these patients, mental status examination (MSE) and neuropsychological testing should be performed to further evaluate the status of cognitive abilities. Laboratory investigation are not required to diagnose Alzheimer's and are done to exclude other conditions which may present with similar symptoms as seen in Alzheimer's disease (such as vit B12 deficiency, syphilis, or tuberculosis). Patients with atypical clinical presentation may also be tested for biomarkers such as Aβ and total and phosphorylated tau protein.

Diagnostic Criteria

The diagnosis of Alzheimer's disease (AD) can be made either on the basis of:

• National Institute on Aging and the Alzheimer's Association (NIA-AA); most recently updated in 2011, or
• DSM-V (Diagnostic and Statistical Manual of Mental Disorders, fifth edition) diagnostic criteria for major or mild neurocognitive disorder due to Alzheimer’s disease

National Institute on Aging and the Alzheimer's Association (NIA-AA)

National Institute on Aging and the Alzheimer's Association (NIA-AA) describes Alzheimer's disease as either probable Alzheimer's disease or possible Alzheimer's disease.

• Probable Alzheimer's disease includes all of the following criteria:
  • A decline from a previous level of functioning with inability or interference in carrying out usual daily activities.
  • Loss of two or more cognitive abilities such as anterograde amnesia, aphasia, apraxia, agnosia, or other disturbance in executive functioning.
  • Cognitive loss documented by mental status examination (MSE) or neuropsychological tests.
  • Symptoms not consistent with other cerebrovascular disease, psychiatric disorders or delirium.
  • Insidious onset and gradual progression of symptoms.
  • Intact consciousness

• Possible Alzheimer's disease (AD): The possible Alzheimer's disease differs from probable Alzheimer's disease in terms of onset, course over time and underlying disorder. Possible Alzheimer's disease is diagnosed in the presence of either one of the following:
  • In possible AD cognitive impairment is sudden in onset with insufficient history or documentation of progressive decline in cognitive abilities.
  • The patient has insidious onset of cognitive impairment with gradual progression over time but in the presence of neurologic, medical condition or medications that may have notable effect on the cognitive abilities of the patient.

The The NIA-AA criteria differ from prior DSM criteria in the following way:

• NIA-AA recommends patients with positive biomarkers (such as Aβ and total and phosphorylated Tau protein) be diagnosed with Alzheimer's disease even in the absence of symptoms.
• NIA-AA defines three distinct stages of Alzheimer's disease:
  • Preclinical Alzheimer's disease: No symptoms but measurable biologic evidence of Alzheimer's disease pathology.
  • Mild cognitive impairment (MCI): Mild memory loss but no functional impairment.
  • Alzheimer's disease leading to dementia.

DSM V (Diagnostic and Statistical Manual of Mental Disorders, fifth edition) criteria

Alzheimer's disease is the most common cause of dementia. In DSM V, dementia has been renamed as major neurocognitive disorder and minor neurocognitive disorder. The DSM-V diagnostic criteria for major or mild neurocognitive disorder due to Alzheimer’s disease includes the following:

• Insidious onset with gradual decline in one or more cognitive abilities (for major neurocognitive disorder, at least two domains must be impaired).
• Criteria are met for major or mild neurocognitive disorder due to probable or possible Alzheimer’s disease as follows:

For major neurocognitive disorder:

Probable Alzheimer’s disease is diagnosed if either of the following is present; otherwise, possible Alzheimer’s disease should be diagnosed.

• Evidence of a causative Alzheimer’s disease genetic mutation from family history or genetic testing.
• All three of the following are present:
  • Clear evidence of decline in memory and learning and at least one other cognitive domain (based on detailed history or serial neuropsychological testing).
  • Steadily progressive, gradual decline in cognition, without extended plateaus.
  • No evidence of mixed etiology (i.e., absence of other neurodegenerative or cerebrovascular disease, or another neurological, mental, or systemic disease or condition likely contributing to cognitive decline).

For mild neurocognitive disorder:

• Probable Alzheimer’s disease is diagnosed if there is evidence of a causative Alzheimer’s disease genetic mutation from either genetic testing or family history.
• Possible Alzheimer’s disease is diagnosed if there is no evidence of a causative Alzheimer’s disease genetic mutation from either genetic testing or family history, and all three of the following are present:
  • Clear evidence of decline in memory and learning.
  • Steadily progressive, gradual decline in cognition, without extended plateaus.
  • No evidence of mixed etiology (i.e., absence of other neurodegenerative or cerebrovascular disease, or another neurological or systemic disease or condition likely contributing to cognitive decline).