Longitudinal association between hippocampus atrophy and episodic‐memory decline in non‐demented APOE ε4 carriers

Gorbach T., Pudas S., Bartrés‐Faz, D., Brandmaier AM., Düzel S., Henson RN., Idland AV., Lindenberger U., Macià Bros D., Athanasia MM., Solé‐Padullés C., Sørensen Ø., Walhovd KB., Watne LO., Westerhausen R., Fjell AM., Nyberg L. 

Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring (DADM), September, 2020

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Abstract

Introduction

The apolipoprotein E (APOE) ε4 allele is the main genetic risk factor for Alzheimer's disease (AD), accelerated cognitive aging, and hippocampal atrophy, but its influence on the association between hippocampus atrophy and episodic‐memory decline in non‐demented individuals remains unclear.

Methods

We analyzed longitudinal (two to six observations) magnetic resonance imaging (MRI)–derived hippocampal volumes and episodic memory from 748 individuals (55 to 90 years at baseline, 50% female) from the European Lifebrain consortium.

Results

The change‐change association for hippocampal volume and memory was significant only in ε4 carriers (N = 173, r = 0.21, P = .007; non‐carriers: N = 467, r = 0.073, P = .117). The linear relationship was significantly steeper for the carriers [t(629) = 2.4, P = .013]. A similar trend toward a stronger change‐change relation for carriers was seen in a subsample with more than two assessments.

Discussion

These findings provide evidence for a difference in hippocampus‐memory association between ε4 carriers and non‐carriers, thus highlighting how genetic factors modulate the translation of the AD‐related pathophysiological cascade into cognitive deficits.

Published Jan. 19, 2021 12:11 PM - Last modified Feb. 1, 2021 9:45 AM