Cued memory decline in biomarker-defined preclinical Alzheimer disease

To determine whether a decline in cued recall is observable in the preclinical stage of Alzheimer disease (AD) in clinically normal older adults with elevated β-amyloid (Aβ) burden on PET imaging.

Clinically normal older adults underwent baseline neuroimaging (PET to assess Aβ^+/- status and MRI) and annual neuropsychological testing. Cox proportional hazards models were used to assess the relative risk of cued memory decline (drop of 1, 2, 3, or 4 points on the total score of the Free and Cued Selective Reminding Test) in relation to neuroimaging measures, functional status, age, sex, and education.

A total of 276 older adults (Clinical Dementia Rating = 0, mean Mini-Mental State Examination score = 29 ± 1.06) were followed up for a mean of 3.6 ± 1.2 years. Despite the infrequency of cued memory decline (only 19% of participants scored ≤46/48 in total recall by year 3), Aβ⁺ participants were 3.55 times (95% confidence interval = 1.77-7.12) more likely to exhibit decline in total recall (≤46/48) compared with their Aβ^- peers. Furthermore, Aβ⁺ participants who scored ≤46/48 had smaller hippocampal volumes (t = 3.37, p = 0.001) and evidence of early functional decline, i.e., greater risk of progression to global Clinical Dementia Rating of 0.5 (χ² = 14.30, p < 0.001), compared with their Aβ⁺ peers with intact total recall.

Cued memory decline in healthy older adults may be particularly indicative of Aβ-related decline during the preclinical stage of AD and useful for identifying Aβ⁺ clinically normal individuals at greatest risk of short-term clinical progression.