Criteria

The National Institute on Aging and the Alzheimer's Association workgroup on diagnostic guidelines for Alzheimer's disease criteria[87]

Probable AD dementia. The patient meets criteria for dementia and has the following characteristics:

  • Insidious onset

  • Clear-cut history of worsening of cognition by report or observation, and

  • The initial and most prominent cognitive deficits are evident on history and examination (amnestic versus nonamnestic presentation).

    The diagnosis of probable AD dementia should not be applied when there is evidence of (a) substantial concomitant cerebrovascular disease; or (b) core features of dementia with Lewy bodies; or (c) prominent features of behavioral variant frontotemporal dementia; or (d) prominent features of semantic variant primary progressive aphasia or nonfluent/agrammatic variant progressive aphasia; or (e) evidence for another concurrent, active neurological disease, or a non-neurological medical comorbidity, or use of medication that could have a substantial effect on cognition.

Possible AD dementia. If any of the following circumstances exist:

  • Atypical course. Meets the core criteria in terms of the nature of the cognitive deficits for AD dementia, but either has a sudden onset of cognitive impairment or demonstrates insufficient historical detail or objective cognitive documentation of progressive decline.

  • Etiologically mixed representation. Meets the core criteria for AD dementia but has evidence of (a) concomitant cerebrovascular disease; or (b) features of dementia with Lewy bodies other than dementia itself; or (c) evidence for another neurological disease or a non-neurological medical comorbidity or medication used that could have a substantial effect on cognition.

Diagnostic and statistical manual of mental disorders, 5th ed., text revision (DSM-5-TR) criteria for major or mild neurocognitive disorder due to Alzheimer’s disease[3][4]

For a diagnosis of major or mild neurocognitive disorder due to Alzheimer disease, the following criteria must be met.

  1. The criteria are met for a major or mild neurocognitive disorder.

    1. Major neurocognitive disorder: evidence of significant cognitive decline from a previous level of performance in one or more cognitive domains that interferes with independence in everyday activities. The cognitive deficits do not occur exclusively in the context of a delirium and are not better explained by another mental disorder.

      1. Specify severity:

        1. Mild: difficulties with instrumental activities of daily living (e.g., housework, managing money)

        2. Moderate: difficulties with basic activities of daily living (e.g., feeding, dressing)

        3. Severe: fully dependent.

      2. Specify:

        1. With agitation: if the cognitive disturbance is accompanied by clinically significant agitation

        2. With anxiety: if the cognitive disturbance is accompanied by clinically significant anxiety

        3. With mood symptoms: if the cognitive disturbance is accompanied by clinically significant mood symptoms (e.g., dysphoria, irritability, euphoria)

        4. With psychotic disturbance: if the cognitive disturbance is accompanied by delusions or hallucinations

        5. With other behavioral or psychological disturbance: if the cognitive disturbance is accompanied by other clinically significant behavioral or psychological disturbance (e.g., apathy, aggression, disinhibition, disruptive behaviors or vocalizations, sleep or appetite/eating disturbance)

        6. Without accompanying behavioral or psychological disturbance: if the cognitive disturbance is not accompanied by any clinically significant behavioral or psychological disturbance.

    2. Mild neurocognitive disorder: evidence of modest cognitive decline from a previous level of performance in one or more cognitive domains that does not interfere with independence in everyday activities. Greater effort, compensatory strategies, or accommodation may be required to preserve independence in complex instrumental activities of daily living (e.g., paying bills, managing medications). The cognitive deficits do not occur exclusively in the context of a delirium and are not better explained by another mental disorder.

      1. Specify:

        1. Without behavioral disturbance: if the cognitive disturbance is not accompanied by any clinically significant behavioral disturbance

        2. With behavioral disturbance (specify disturbance): if the cognitive disturbance is accompanied by a clinically significant behavioral disturbance (e.g., apathy, agitation, anxiety, mood symptoms, psychotic disturbance, or other behavioral symptoms).

  2. There is insidious onset and gradual progression of impairment in one or more cognitive domains (for major neurocognitive disorder, at least two domains must be impaired).

  3. Criteria are met for either probable or possible Alzheimer disease. For major neurocognitive disorder, probable Alzheimer disease is diagnosed if either of the following is present; otherwise, possible Alzheimer disease should be diagnosed.

    1. Evidence of a causative Alzheimer disease genetic mutation from family history or genetic testing.

    2. All three of the following are present:

      1. Clear evidence of decline in memory and learning and at least one other cognitive domain (based on detailed history or serial neuropsychological testing).

      2. Steadily progressive, gradual decline in cognition, without extended plateaus.

      3. 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 disease is diagnosed if there is evidence of a causative Alzheimer disease genetic mutation from either genetic testing or family history. Possible Alzheimer disease is diagnosed if there is no evidence of a causative Alzheimer disease genetic mutation from either genetic testing or family history, and all three of the following are present:

    1. Clear evidence of decline in memory and learning.

    2. Steadily progressive, gradual decline in cognition, without extended plateaus.

    3. 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).

  4. The disturbance is not better explained by cerebrovascular disease, another neurodegenerative disease, the effects of a substance, or another mental, neurological, or systemic disorder.

The National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorder Association criteria for Alzheimer's disease[97]

Definite AD: meets the criteria for probable AD and has histopathologic evidence of AD on autopsy or brain biopsy.

Probable AD: dementia established by clinical and neuropsychological examination and involves:

  • Progressive deficits in two or more areas of cognition, including memory

  • Onset between the ages of 40-90 years

  • Absence of systemic or other brain diseases capable of producing a dementia syndrome, including delirium.

Possible AD: a dementia syndrome with an atypical onset, presentation, or progression and without a known etiology. Any comorbid diseases capable of producing dementia are not believed to be the cause.

Unlikely AD: a dementia syndrome with any of the following: sudden onset, focal neurologic signs, seizures, or gait disturbance early in the course of the illness.

Proposed biomarker classification[98]

A descriptive classification scheme that categorizes cerebrospinal fluid and imaging biomarker findings at the individual level.

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