Faculty Collaboration Database

Interactive effects of physical activity and APOE-ε4 on white matter tract diffusivity in healthy elders. Neuroimage 2016 May 01;131:102-12

Date

08/13/2015

Pubmed ID

26265157

Pubmed Central ID

PMC4746115

DOI

10.1016/j.neuroimage.2015.08.007

Scopus ID

2-s2.0-84941695218 (requires institutional sign-in at Scopus site)   43 Citations

Abstract

Older adult apolipoprotein-E epsilon 4 (APOE-ε4) allele carriers vary considerably in the expression of clinical symptoms of Alzheimer's disease (AD), suggesting that lifestyle or other factors may offer protection from AD-related neurodegeneration. We recently reported that physically active APOE-ε4 allele carriers exhibit a stable cognitive trajectory and protection from hippocampal atrophy over 18months compared to sedentary ε4 allele carriers. The aim of this study was to examine the interactions between genetic risk for AD and physical activity (PA) on white matter (WM) tract integrity, using diffusion tensor imaging (DTI) MRI, in this cohort of healthy older adults (ages of 65 to 89). Four groups were compared based on the presence or absence of an APOE-ε4 allele (High Risk; Low Risk) and self-reported frequency and intensity of leisure time physical activity (PA) (High PA; Low PA). As predicted, greater levels of PA were associated with greater fractional anisotropy (FA) and lower radial diffusivity in healthy older adults who did not possess the APOE-ε4 allele. However, the effects of PA were reversed in older adults who were at increased genetic risk for AD, resulting in significant interactions between PA and genetic risk in several WM tracts. In the High Risk-Low PA participants, who had exhibited episodic memory decline over the previous 18-months, radial diffusivity was lower and fractional anisotropy was higher, compared to the High Risk-High PA participants. In WM tracts that subserve learning and memory processes, radial diffusivity (DR) was negatively correlated with episodic memory performance in physically inactive APOE-ε4 carriers, whereas DR was positively correlated with episodic memory performance in physically active APOE-ε4 carriers and the two Low Risk groups. The common model of demyelination-induced increase in radial diffusivity cannot directly explain these results. Rather, we hypothesize that PA may protect APOE-ε4 allele carriers from selective neurodegeneration of individual fiber populations at locations of crossing fibers within projection and association WM fiber tracts.

Author List

Smith JC, Lancaster MA, Nielson KA, Woodard JL, Seidenberg M, Durgerian S, Sakaie K, Rao SM

Authors

Melissa A. Lancaster PhD Assistant Professor in the Neurology department at Medical College of Wisconsin
Kristy Nielson PhD Professor in the Psychology department at Marquette University

MESH terms used to index this publication - Major topics in bold

Aged
Aging
Anisotropy
Apolipoprotein E4
Body Water
Brain
Connectome
Diffusion
Diffusion Tensor Imaging
Exercise
Female
Heterozygote
Humans
Male
Nerve Net
Neuronal Plasticity
Reference Values
White Matter