Psychological Medicine

Original Articles

Interaction effects of subjective memory impairment and ApoE4 genotype on episodic memory and hippocampal volume

N. Striepensa1, L. Scheefa2, A. Winda1, D. Meibertha1, J. Poppa1, A. Spottkea1a3, H. Kölscha1, M. Wagnera1 and F. Jessena1 c1

a1 Department of Psychiatry, University of Bonn, Bonn, Germany

a2 Department of Radiology, University of Bonn, Bonn, Germany

a3 Department of Neurology, University of Bonn, Bonn, Germany


Background The apolipoprotein E4 allele (ApoE4) is an established genetic risk factor for Alzheimer's disease (AD). However, its effects on cognitive performance and brain structure in healthy individuals are complex. We investigated the effect of ApoE4 on cognitive performance and medial temporal lobe volumetric measures in cognitively unimpaired young elderly with and without subjective memory impairment (SMI), which is an at-risk condition for dementia.

Method Altogether, 40 individuals with SMI and 62 without were tested on episodic memory and on tasks of speed and executive function. All participants were ApoE genotyped. 21 subjects with SMI and 47 without received additional structural magnetic resonance imaging. Volumetric measures of the hippocampus, the entorhinal cortex and the amygdala were obtained manually.

Results In the SMI group, ApoE4 carriers performed worse on the episodic memory (p=0.049) and showed smaller left hippocampal volumes (p=0.030). In the individuals without SMI, the ApoE4 carriers performed better on episodic memory (p=0.018) and had larger right hippocampal volumes (p=0.039). The interaction of group (SMI/no SMI) and ApoE genotype was significant for episodic memory (p=0.005) and right and left hippocampal volumes (p=0.042; p=0.035). There were no within-group differences or interaction effects on speed and executive function composite measures or other volumetric measures.

Conclusions The negative effect of ApoE4 on episodic memory and hippocampal volume in SMI supports SMI as a prodromal condition of AD. The positive effects of ApoE4 in subjects without SMI adds to a number of reports on positive ApoE4 effects in young and very old individuals.

(Received August 03 2010)

(Revised December 10 2010)

(Accepted December 15 2010)

(Online publication February 02 2011)


c1 Address for correspondence: Prof. Dr. med. F. Jessen, Department of Psychiatry, University of Bonn, Bonn, Germany. (Email: