Table 3.
Relevant aspects of the NINCDS-ADRDA and NIA-AA diagnostic criteria for Alzheimer’s disease
| NINCDS-ADRDA (1984) | NIA-AA (2011) | |
|---|---|---|
| Dementia criteria | Not provided | Provides criteria for all-cause dementia |
| Probable AD | ||
| Dementia diagnosis | Impairments in two cognitive domains based on clinical exam and documented by cognitive testing [1] | Impairments in two cognitive domains, and expands the definition on the nonmemory forms of AD (language, visuospatial, executive) [1] |
| Onset and progression | Progressive worsening of memory symptoms and other cognitive functions [1] | Insidious onset and clear-cut history of worsening of cognition by report or observation [1] |
| Comorbid systemic or neurological disorders | Absence of systemic or neurological disorders that in and of themselves could account for the cognitive deficits [1] | Absence of cerebrovascular disease or other neurological, nonneurological comorbidities or use of medication that could have substantial effect on cognition [1] |
| Age | Between ages 40 and 90 [1] | No age limitation |
| Behavioral and neurological symptoms | Altered pattern of behavior and mood-related disorders (e.g. depression), increased muscle tone, myoclonus, gait disorders | Mood-related and behavioral symptoms are considered a ‘domain’ in the definition of dementia |
| Level of consciousness | The diagnosis of AD cannot be made in patients with delirium, drowsiness, stupor/coma, or other abnormality that prevent adequate evaluation. | Symptoms cannot be explained by delirium or other major psychiatric disorder |
| Laboratory test | Normal lumbar puncture and blood tests. CT scan normal or with atrophy | Not stated |
| Biomarkers | Not available in 1984 | MRI, PET, and CSF studies. Any biomarker positive increases the certainty of AD in patients with probable AD. Recommended only for research purposes or clinical trials |
| Familial forms | Familial history of similar disorders, particularly if confirmed by autopsy supports the diagnosis of AD | Evidence of a causative gene (APP, PSEN1, and PSEN2) increases the likelihood of AD pathology. The APOE-4 allele is not sufficiently specific to be considered in this category |
| Possible AD | ||
| Comorbid conditions | Presence of systemic or neurological disorders that in and of themselves could account for the cognitive deficits, which is not considered to be the cause of the dementia | Meets clinical criteria for AD but there is cerebrovascular disease, or other neurological or non-neurological comorbidities, or use of medication that could have substantial effect on cognition |
| Atypical presentations | Presence of variations in the presentation, onset, or clinical course | Presence of atypical course, sudden onset, or there is insufficient historical detail or documentation of progressive decline |
| Single cognitive domain | Presence of a single cognitive deficit in the absence of other identifiable cause | Replaced by MCI |
| Non-AD phenotype | Not addressed | At least two biomarker categories positive (Aβ CSF, tau CSF, PET, or MRI) to support the presence of underlying AD pathology |
AD, Alzheimer’s disease; CSF, cerebrospinal fluid; MCI, mild cognitive impairment.