Determinants of Cognitive Trajectories in Normal Aging: A Longitudinal PET-MRI Study in a Community-based Cohort.

Abstract

BACKGROUND\nThe determinants of the progressive decrement of cognition in normal aging are still a matter of debate. Alzheimer disease (AD)-signature markers and vascular lesions, but also psychological variables such as personality factors, are thought to have an impact on the longitudinal trajectories of neuropsychological performances in healthy elderly individuals.\n\n\nOBJECTIVE\nThe current research aimed to identify the main determinants associated with cognitive trajectories in normal aging.\n\n\nMETHODS\nWe performed a 4.5-year longitudinal study in 90 older community-dwellers coupling two neuropsychological assessments, medial temporal atrophy (MTA), number of cerebral mi- crobleeds (CMB), and white matter hyperintensities (WMH) at inclusion, visual rating of amyloid and FDG PET at follow-up, and APOE genotyping. Personality factors were assessed at baseline using the NEO-PI-R. Univariate and backward stepwise regression models were built to explore the association between the continuous cognitive score (CCS) and both imaging and personality variables.\n\n\nRESULTS\nThe number of strictly lobar CMB at baseline (4 or more) was related to a significant in- crease in the risk of cognitive decrement. In multivariable models, amyloid positivity was associat- ed with a 1.73 unit decrease of the CCS at follow-up. MTA, WMH and abnormal FDG PET were not related to the cognitive outcome. Among personality factors, only higher agreeableness was re- lated to better preservation of neuropsychological performances.\n\n\nCONCLUSION\nCMB and amyloid positivity are the only imaging determinants of cognitive trajecto- ries in this highly selected series of healthy controls. Among personality factors, higher agreeable- ness confers a modest but significant protection against the decline of cognitive performances.