Associative memory and in vivo brain pathology in asymptomatic presenilin-1 E280A carriers.

Objective: To determine whether performance on the Free and Cued Selective Reminding Test (FSCRT) is associated with PET in vivo markers of brain pathology, and whether it can distinguish those who will develop dementia later in life due to autosomal-dominant AD from age-matched controls. Methods: Twenty-four cognitively-unimpaired Presenilin-1 E280A carriers (mean age: 36 years) and twenty-eight non-carriers (mean age: 37) underwent PiB-PET (amyloid), Flortaucipir-PET (tau), and cognitive testing, including the FCSRT (immediate and delayed free and cued recall scores). Linear regressions were used to examine the relationships among FCSRT scores, age, mean cortical amyloid and regional tau burden. Results: Free and total recall scores did not differ between cognitively-unimpaired mutation carriers and non-carriers. Greater age predicted lower free recall, and delayed free and total recall scores in carriers. In cognitively-impaired carriers, delayed free recall predicted greater amyloid burden and entorhinal tau, while worse immediate free recall scores predicted greater tau in the inferior temporal and entorhinal cortices. In turn, in all carriers, lower free and total recall scores predicted greater amyloid and regional tau pathology. Conclusions: FCSRT scores were associated with in vivo markers of AD-related pathology in cognitively-unimpaired individuals genetically determined to develop dementia. Difficulties on free recall, particularly delayed recall, were evident earlier in the disease trajectory, while difficulties on cued recall were only seen as carriers neared the onset of dementia, consistent with the pathological progression of the disease. Findings suggest that the FCSRT can be a useful measure to track disease progression in AD.