Clinical diagnosis is made by identifying progressive decline in memory both with clinical examinations and neuropsychologic tests and has been historically based on the NINCDS-ADRA criteria, which divides patients according to the certainty of the diagnosis into:
1. definite: clinical diagnosis and histologic confirmation
2. probable: typical clinical syndrome without histologic confirmation
- 81% sensitive, 73% specific
-. possible: atypical clinical features without histologic confirmation but no alternative diagnosis
Although using longitudinal clinical criteria is highly sensitive in diagnosing a dementia of any type (>9'0%), they are relatively inaccurate (<70%) in diagnosing Alzheimer disease specifically.
Importantly the NINCDS-ADRA criteria only include imaging and laboratory examination or blood and CSF in excluding other causes.
The only definitive diagnostic test is brain biopsy which in practice is rarely obtained. As such the combination of clinical features and neuroimaging are usually considered sufficient although especially with the recognition of variants, this approach undoubtedly misdiagnoses a significant number of cases.
A number of CSF biomarkers are being used which may further help diagnosis. They include beta-amyloid, total tau, and hyperphosphorylated tau.