Longitudinal association between hippocampus atrophy and episodic-memory decline in non-demented ε4 carriers.

Introduction: The apolipoprotein E () 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 consortium.

Results: The change-change association for hippocampal volume and memory was significant only in ε4 carriers (N = 173, r = 0.21, = .007; non-carriers: N = 467, r = 0.073, = .117). The linear relationship was significantly steeper for the carriers [t(629) = 2.4, = .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.