Locke, Dona E.C.

AbstractBackgroundIt is not known whether preclinical cognitive decline is associated with fibrillar β‐amyloid (Aβ) deposition irrespective of apolipoprotein E (APOE) ε4 status.MethodsFrom a prospective observational study of 623 cognitively normal individuals, we identified all subjects who showed preclinical decline of at least 2 standard deviations beyond the decline of the entire group in memory or executive function. Fourteen decliners were matched by APOE ε4 gene dose, age, sex, and education with 14 nondecliners. Dynamic Pittsburgh compound B (PiB) positron emission tomography (PET) scans, the Logan method, statistical parametric mapping, and automatically labeled regions of interest were used to characterize and compare cerebral‐to‐cerebellar PiB distribution volume ratios (DVRs), reflecting fibrillar Aβ burden.ResultsAt P < .005 (uncorrected), decliners had significantly greater DVRs in comparison to nondecliners.ConclusionsAsymptomatic longitudinal neuropsychological decline is associated with subsequent increased fibrillar amyloid deposition, even when controlling for APOE ε4 genotype.

AbstractBackgroundIt is unclear whether self‐ or informant‐based subjective cognition better distinguishes emotional factors from early‐stage Alzheimer's disease (AD).MethodsHealthy members (n = 447) of the Arizona apolipoprotein E (APOE) cohort and their informants completed the self and informant paired Multidimensional Assessment of Neurodegenerative Symptoms questionnaire (MANS).ResultsDecline on the MANS was endorsed by 30.6% of members and 26.2% of informants. Self‐ and informant‐based decliners had higher scores of psychological distress and slightly lower cognitive scores than nondecliners. Over the next 6.7 years, 20 developed mild cognitive impairment (MCI). Converters were older at entry than nonconverters (63.8 [7.0] vs 58.8 [7.3] years, P = .003), 85% were APOE ε4 carriers (P < .0001), and they self‐endorsed decline earlier than informants (58.9 [39.2] vs 28.0 [40.4] months before MCI; P = .002).ConclusionsSelf‐ and informant‐based subjective decline correlated with greater psychological distress and slightly lower cognitive performance. Those with incident MCI generally self‐endorsed decline earlier than informants.

AbstractObjectiveA National Institute on Aging–sponsored work group on preclinical Alzheimer's disease (AD) articulated the need to characterize cognitive differences between normal aging and preclinical AD.MethodsSeventy‐one apolipoprotein E (APOE) ε4 homozygotes, 194 ε3/ε4 heterozygotes, and 356 ε4 noncarriers age 21 to 87 years who were cognitively healthy underwent neuropsychological testing every 2 years. Longitudinal trajectories of test scores were compared between APOE subgroups.ResultsThere was a significant effect of age on all cognitive domains in both APOE ε4 carriers and noncarriers. A significant effect of APOE ε4 gene dose was confined to the memory domain and the Dementia Rating Scale. Cross‐sectional comparisons did not discriminate the groups.ConclusionsAlthough cognitive aging patterns are similar in APOE ε4 carriers and noncarriers, preclinical AD is characterized by a significant ε4 gene dose effect that impacts memory and is detectable longitudinally. Preclinical neuropsychological testing strategies should emphasize memory‐sensitive measures and longitudinal design.