Neuropsychological measures that detect early impairment and decline in preclinical Alzheimer disease

Abstract Identifying which neuropsychological measures detect early cognitive changes associated with Alzheimer disease (AD) brain pathology would be helpful clinically for the diagnosis of early AD and for the design of clinical trials. We evaluated which neuropsychological measures in our cognitive battery are most strongly associated with cerebrospinal fluid (CSF) biomarkers of AD brain pathology. We studied a large cohort (n=233) of middle- to older-aged community-dwelling individuals (mean age 61 years) who had no clinical symptoms of dementia and underwent baseline CSF collection at baseline. Participants completed a battery of nine neuropsychological measures at baseline and then every one to three years. CSF tau/Aβ42 was associated with baseline performance on 5/9 neuropsychological measures, especially measures of episodic memory, and longitudinal performance on 7/9 neuropsychological measures, especially measures of global cognition. The free recall portion of the Free and Cued Selective Reminding Task (FCSRT-free) detected declining cognition in the high CSF tau/Aβ42 group the earliest, followed by another measure of episodic memory and a sequencing task.