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The Influence of APOE ε4 on the Hippocampus and Hippocampus-Dependent Memory
Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

APOE ε4 is the major genetic risk factor for Alzheimer’s disease, a dementia characterized by memory impairment and hippocampal atrophy. While associated with episodic impairment and reduced hippocampal volume in healthy aging, APOE ε4 has been related to increased episodic memory performance in young adults. The effect of APOE ε4 on hippocampal volume in young age is uncertain, with studies showing comparable or smaller volumes in ε4 carriers. This thesis aims to further explore the effects of APOE ε4 on episodic memory and hippocampal volume in young adults. In addition to episodic memory, spatial memory will also be assessed, as both these memory types are hippocampus-dependent. Furthermore, potential modulating effects of sex are assessed, as sex differences has been found in relation to APOE-related pathology, episodic and spatial memory and hippocampal volume. Study I examined the effects of APOE ε4 on episodic and spatial memory and hippocampal volume in young adults. Hippocampal volume was assessed by manual tracing of the hippocampal head, body and tail. Study II considered whole-brain structural covariance patterns of the anterior and posterior hippocampus. Furthermore, the association between these patterns and episodic and spatial memory performance was assessed. Study III investigated the effects of APOE ε4 on episodic and spatial memory and hippocampal volume in three different age groups. This was done in order to further explore the different effects of APOE ε4 on cognition and hippocampal volume seen in young and older age. In summary, APOE ε4 was positively associated with spatial function and episodic memory in young adults. Although there were no effects of APOE ε4 on hippocampal volume, structural covariance patterns of the anterior and posterior hippocampus differed as a function of APOE ε4 and sex. Thus, structural covariance may provide an early measure of APOE ε4-related effects on brain structure. Moreover, sex was found to modulate the effects of APOE ε4 to the disadvantage of women. This was seen in both age-related hippocampal volume effects and in structural covariance patterns in young adults, as well as in spatial memory performance across age groups.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. , 85 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Social Sciences, ISSN 1652-9030 ; 130
Keyword [en]
APOE ε4, episodic memory, spatial memory, hippocampus
National Category
Psychology
Identifiers
URN: urn:nbn:se:uu:diva-302855ISBN: 978-91-554-9685-2 (print)OAI: oai:DiVA.org:uu-302855DiVA: diva2:968045
Public defence
2016-10-28, Auditorium Minus, Gustavianum, Akademigatan 3, Uppsala, 10:15 (English)
Opponent
Supervisors
Available from: 2016-10-06 Created: 2016-09-11 Last updated: 2016-10-11
List of papers
1. Apolipoprotein E ϵ4 is positively related to spatial performance but unrelated to hippocampal volume in healthy young adults
Open this publication in new window or tab >>Apolipoprotein E ϵ4 is positively related to spatial performance but unrelated to hippocampal volume in healthy young adults
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2016 (English)In: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 299, 11-18 p.Article in journal (Refereed) Published
Abstract [en]

The apolipoprotein E (APOE) ϵ4 allele is known to be a major genetic risk factor for Alzheimer's disease (AD). It has been linked to especially episodic memory decline and hippocampal atrophy in both healthy and demented elderly populations. In young adults, ϵ4 carriers have shown better performance in episodic memory compared to non-carriers. Spatial memory, however, has not been thoroughly assessed in relation to APOE in spite of its dependence on the hippocampus. In this study, we assessed the effect of APOE genotype on a variety of spatial and episodic memory tasks as well as hippocampal volume assessed through manual tracing in a sample of young adults (N=123). We also assessed whether potential effects were modulated by sex. The presence of one or more ϵ4 alleles had positive effects on spatial function and memory and object location memory, but no effect on word recognition. Men were superior to women in spatial function and memory but there were no sex differences in the other tasks. In spite of APOE ϵ4 carriers having superior performance in several memory tasks, no difference was found as a function of APOE genotype in hippocampal volume. To our knowledge, this study is the first to show that APOE ϵ4 has a positive effect on spatial ability in young adults.

Keyword
APOE epsilon 4; Spatial memory; Episodic memory; Hippocampus; Manual tracing; Young adults
National Category
Psychology
Identifiers
urn:nbn:se:uu:diva-269688 (URN)10.1016/j.bbr.2015.11.006 (DOI)000368565000003 ()26581118 (PubMedID)
External cooperation:
Funder
Swedish Research Council, 2009-2035
Available from: 2015-12-17 Created: 2015-12-17 Last updated: 2017-12-01
2. Specific patterns of whole-brain structural covariance of the anterior and posterior hippocampus in young APOE ε4 carriers
Open this publication in new window or tab >>Specific patterns of whole-brain structural covariance of the anterior and posterior hippocampus in young APOE ε4 carriers
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(English)Manuscript (preprint) (Other academic)
Keyword
APOE ε4, hippocampus, structural covariance, young adults, partial least squares, memory
National Category
Psychology (excluding Applied Psychology)
Research subject
Psychology
Identifiers
urn:nbn:se:uu:diva-302851 (URN)
External cooperation:
Available from: 2016-09-11 Created: 2016-09-11 Last updated: 2016-09-11
3. Age effects on hippocampal volume and episodic and spatial memory vary as a function of APOE status and sex
Open this publication in new window or tab >>Age effects on hippocampal volume and episodic and spatial memory vary as a function of APOE status and sex
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(English)Manuscript (preprint) (Other academic)
Keyword
APOE ε4, episodic memory, spatial memory, sex differences, hippocampal volume, aging
National Category
Psychology (excluding Applied Psychology)
Identifiers
urn:nbn:se:uu:diva-302853 (URN)
External cooperation:
Available from: 2016-09-11 Created: 2016-09-11 Last updated: 2016-09-11

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