The neuropsychology of normal aging and preclinical Alzheimer's disease

Abstract

Background An NIA-sponsored workgroup on preclinical Alzheimer’s disease (AD) articulated the need to characterize cognitive differences between normal aging and preclinical AD. Methods 71 apolipoprotein E (APOE) e4 homozygotes (HMZ), 194 e3/4 heterozygotes (HTZ), and 356 e4 noncarriers (NC) aged 21–87 years who were cognitively healthy underwent neuropsychological testing every two years. Longitudinal trajectories of test scores were compared between APOE subgroups. Results There was a significant effect of age on all cognitive domains in both APOE e4 carriers and NC. A significant effect of APOE e4 gene dose was confined to the memory domain and the Dementia Rating Scale. Cross sectional comparisons did not discriminate the groups. Conclusions While cognitive aging patterns are similar in APOE e4 carriers and NC, preclinical AD is characterized by a significant e4 gene dose effect that impacts memory and is detectable longitudinally. Preclinical neuropsychological testing strategies should emphasize memory sensitive measures and longitudinal design.

APOE ε4 moderates amyloid-related memory decline in preclinical Alzheimer's disease

“…Therefore, when taken together, the data suggest that in early or preclinical AD, 34 carriage increases the rate of Ab-related cognitive decline, although this decline may be clearer and consistently observed in the domain of memory. This finding is consistent with neuropsychological models of preclinical AD, which emphasize that the earliest and most substantial cognitive changes in cognitively normal older adults occur primarily in the domain of memory (Caselli et al, 2014;Lim et al, 2014), with decline in other aspects of cognition more subtle, or becoming clearer with increased disease progression . The finding that 34 carrier status increased the rate of Ab-related memory decline over 54 months in healthy older adults is consistent with the observation of Mormino et al (2014) that 34 carriage increased Abþ related memory decline in healthy adults, despite this previous study being conducted over a shorter time period and in samples aggregated across studies with different inclusion and/or exclusion criteria.…”

Early neuropsychological detection of Alzheimer's disease

“…Other studies have also investigated the issue of cognitive markers of AD in other at-risk people, such as carriers of the APOE ε4 allele (see Caselli et al 22 for a review). The current review will, however, focus on longitudinal studies in large cohorts from the population and in MCI patients.…”

Predictive Testing for Alzheimer’s Disease

“…Members of the Arizona APOE Cohort are cognitively normal residents of Maricopa County age 21 years and older recruited through local media ads, genotyped for APOE, and who undergo longitudinal neuropsychological assessment every two years 7 . The participants agreed to have the results of the APOE test withheld from them as a precondition to their participation in this study.…”

“…With the advent of presymptomatic clinical trials, recruitment strategies include mass screening of individuals harboring genetic or biomarker evidence of high risk for Alzheimer’s disease (AD) 4–6 . The present study explores possible demographic, cognitive, psychological, and personality characteristics that might identify a potential research participant as one at high risk of suicidal ideation by administering the same questionnaire to our longstanding research cohort, the Arizona APOE Cohort 7 .…”