Medial temporal lobe dysfunction during encoding and retrieval of episodic memory in non-demented APOE ε4 carriers

• Published in: Neuroscience Vol. 168; no. 2; pp. 487 - 497
• Main Authors: Kukolja, J, Thiel, C.M, Eggermann, T, Zerres, K, Fink, G.R
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 01.06.2010
• Subjects: Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Fundamental and applied biological sciences. Psychology; Medical sciences; Neurology; Vertebrates: nervous system and sense organs; item not encoded; CERAD; scR; blood oxygen level dependent; Mehrfachwahl–Wortschatz test (multiple choice vocabulary test); GLM; iR; ANCOVA; SPM; BOLD; Alzheimer's disease; VBM; scNR; AD; regions of interest; spatial context not encoded; echo planar images; ROI; general linear model; fMRI; scNE; apolipoprotein E; analysis of covariance; functional magnetic resonance imaging; PCR; standard deviation; statistical parametric mapping; BDI; HAWIE-R; MNI; spatial context retrieved; item recognized; spatial context not retrieved; hemodynamic response function; SD; analysis of variance; ANOVA; MMSE; APOE; polymerase chain reaction; iNE; MAC-Q; item not recognized; voxel-based morphometry; iNR; episodic memory; item encoded; Montreal Neurological Institute; MCI; spatial context encoded; scE; revised Hamburg Wechsler intelligence exam; mild cognitive impairment; MWT-B; iE; mini-mental state examination; HRF; memory assessment clinics questionnaire; Beck Depression Inventory; consortium to establish a registry of AD; EPI; Temporal lobe; Memory retrieval; Nervous system diseases; Alzheimer disease; Memory; Nuclear magnetic resonance imaging; Cerebral disorder; Apolipoprotein E; Central nervous system disease; Degenerative disease; Functional imaging
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2010.03.044

Abstract Presence of the apolipoprotein E (APOE) ε4 allele is linked to an increased risk to develop Alzheimer's dementia (AD). However, there are controversial data concerning the impact of the APOE genotype on cognitive functioning and brain activity in healthy subjects. We used event-related functional magnetic resonance imaging (fMRI) to investigate the effects of APOE genotype on spatial contextual memory encoding and retrieval success in healthy older adults. Eighteen subjects (eight APOE4 heterozygotes (ε4+) and 10 non-carriers (ε4−), mean age 60.0±5.0 years) were included in the present analysis. Behaviorally, ε4+ subjects performed significantly worse than ε4− subjects in item memory and spatial context retrieval. fMRI data revealed that ε4+ subjects, compared to ε4-subjects, predominantly showed an increase of neural activity specific to encoding of items and their spatial context in prefrontal, temporal and parietal regions. In contrast, ε4+ subjects showed activity decreases in the right amygdala during successful item recognition and in the prefrontal cortex bilaterally during spatial context retrieval when compared to ε4− subjects. While the activity increases during encoding may reflect compensatory activity in the attempt to maintain normal performance, the decreases during retrieval indicate incipient neural decline in ε4+ subjects. These data highlight that preclinical ApoE-related changes in neural activity are not unidirectional but dissociate depending on the memory phase, i.e., encoding or retrieval.