Diminished Learning Over Repeated Exposures (LORE) in preclinical Alzheimer's disease.

Introduction We determine whether diminished Learning Over Repeated Exposures (LORE) identifies subtle memory decrements in cognitively unimpaired (CU) older adults with Alzheimer's disease (AD) biomarker burden. Methods Ninety-four CU participants (mean age = 77.6 ± 5.02) completed a challenging associative memory test, at home, monthly, for up to 1 year (mean = 9.97 months) on a study-issued iPad. Learning curves for face-name memory were computed for two versions completed monthly: same face-name pairs (A-A-A) and alternate face-name pairs (B-C-D). Positron emission tomography (PET) imaging characterized global amyloid (Pittsburgh Compound-B (PiB); amyloid beta (Aβ)+/-) and regional tau burden (flortaucipir). Results Diminished LORE for same (but not alternate) face-name pairs was associated with greater amyloid and tau burden. Aβ+/- group differences for same face-name pairs emerged by the fourth exposure and was of medium-to-large magnitude (Cohen's d = 0.66; 95% confidence interval [CI] = 0.25-1.08). Discussion Subtle decrements in learning related to AD pathological burden in CU are detectable over short time-intervals (ie, months). Implications for prevention trial design are discussed.