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

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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.

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Most cited references 31

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Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families.

E H Corder, A M Saunders, W J Strittmatter … (1993)

The apolipoprotein E type 4 allele (APOE-epsilon 4) is genetically associated with the common late onset familial and sporadic forms of Alzheimer's disease (AD). Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with increasing number of APOE-epsilon 4 alleles in 42 families with late onset AD. Thus APOE-epsilon 4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE-epsilon 4 was virtually sufficient to cause AD by age 80.

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Shared memories reveal shared structure in neural activity across individuals

J. Chen, Y.C. Leong, C.J. Honey … (2016)

Our lives revolve around sharing experiences and memories with others. When different people recount the same events, how similar are their underlying neural representations? Participants viewed a fifty-minute movie, then verbally described the events during functional MRI, producing unguided detailed descriptions lasting up to forty minutes. As each person spoke, event-specific spatial patterns were reinstated in default-network, medial-temporal, and high-level visual areas. Individual event patterns were both highly discriminable from one another and similar between people, suggesting consistent spatial organization. In many high-order areas, patterns were more similar between people recalling the same event than between recall and perception, indicating systematic reshaping of percept into memory. These results reveal the existence of a common spatial organization for memories in high-level cortical areas, where encoded information is largely abstracted beyond sensory constraints; and that neural patterns during perception are altered systematically across people into shared memory representations for real-life events.

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Is Open Access

Developmental cognitive neuroscience using latent change score models: A tutorial and applications

Rogier A. Kievit, Andreas Brandmaier, Gabriel Ziegler … (2017)

Assessing and analysing individual differences in change over time is of central scientific importance to developmental neuroscience. However, the literature is based largely on cross-sectional comparisons, which reflect a variety of influences and cannot directly represent change. We advocate using latent change score (LCS) models in longitudinal samples as a statistical framework to tease apart the complex processes underlying lifespan development in brain and behaviour using longitudinal data. LCS models provide a flexible framework that naturally accommodates key developmental questions as model parameters and can even be used, with some limitations, in cases with only two measurement occasions. We illustrate the use of LCS models with two empirical examples. In a lifespan cognitive training study (COGITO, N = 204 (N = 32 imaging) on two waves) we observe correlated change in brain and behaviour in the context of a high-intensity training intervention. In an adolescent development cohort (NSPN, N = 176, two waves) we find greater variability in cortical thinning in males than in females. To facilitate the adoption of LCS by the developmental community, we provide analysis code that can be adapted by other researchers and basic primers in two freely available SEM software packages (lavaan and Ωnyx).

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Author and article information

Contributors

Lars Nyberg: lars.nyberg@umu.se

Journal

Journal ID (nlm-ta): Alzheimers Dement (Amst)

Journal ID (iso-abbrev): Alzheimers Dement (Amst)

Journal ID (doi): 10.1002/(ISSN)2352-8729

Journal ID (publisher-id): DAD2

Title: Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring

Publisher: John Wiley and Sons Inc. (Hoboken )

ISSN (Electronic): 2352-8729

Publication date (Electronic): 28 September 2020

Publication date Collection: 2020

Volume: 12

Issue: 1 ( doiID: 10.1002/dad2.v12.1 )

Electronic Location Identifier: e12110

Affiliations

[ ¹ ] Department of Integrative Medical Biology Umeå University Umeå Sweden

[ ² ] Umeå Center for Functional Brain Imaging Umeå University Umeå Sweden

[ ³ ] Department of Medicine, Faculty of Medicine and Health Sciences University of Barcelona Barcelona Spain

[ ⁴ ] Center for Lifespan Psychology Max Planck Institute for Human Development Berlin Germany

[ ⁵ ] Max Planck UCL Centre for Computational Psychiatry and Ageing Research Berlin Germany

[ ⁶ ] MRC Cognition and Brain Sciences Unit University of Cambridge, Cambridge UK

[ ⁷ ] Oslo Delirium Research Group, Department of Geriatric Medicine University of Oslo, Oslo Norway

[ ⁸ ] Center for Lifespan Changes in Brain and Cognition University of Oslo, Oslo Norway

[ ⁹ ] Department of Radiology and Nuclear Medicine Oslo University Hospital, Oslo Norway

[ ¹⁰ ] Department of Radiation Sciences Umeå University Umeå Sweden

Author notes

[*] [* ] Correspondence

Lars Nyberg, Umeå Center for Functional Brain Imaging, 90187, Umeå, Sweden.

Email: lars.nyberg@ 123456umu.se

Article

Publisher ID: DAD212110

DOI: 10.1002/dad2.12110

PMC ID: 7521596

PubMed ID: 33015312

SO-VID: 42094409-fe26-4196-a186-6a8a41eb2468

License:

This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

History

Date received : 20 August 2020

Date accepted : 26 August 2020

Page count

Figures: 2, Tables: 4, Pages: 9, Words: 5717

Funding

Funded by: EU Horizon 2020 Grant: “Healthy minds 0‐100 years: Optimising the use of European brain imaging cohorts (‘Lifebrain’).”

Award ID: 732592

Funded by: The European Research Council's Starting/Consolidator Grant

Award ID: 283634

Award ID: 725025

Award ID: 313440

Funded by: Norwegian Research Council , open-funder-registry 10.13039/501100005416;

Funded by: The National Association for Public Health's dementia research program, Norway

Funded by: Medical Student Research Program at the University of Oslo

Funded by: Partially supported by a Spanish Ministry of Economy and Competitiveness (MINECO)

Award ID: PSI2015‐64227‐R

Funded by: Walnuts and Healthy Aging study

Award ID: NCT01634841

Funded by: California Walnut Commission, Sacramento, California

Funded by: German Federal Ministry of Education and Research

Award ID: 16SV5537/16SV5837/16SV5538/16SV5536K/01UW0808/01UW0706/01GL1716A/01GL1716B

Funded by: BMBF funded EnergI consortium

Award ID: 01GQ1421B

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cover-date 2020

details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.1 mode:remove_FC converted:28.09.2020

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

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Abstract

Introduction

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Results

Discussion

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Embodied Memory

Most cited references 31

Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families.

Shared memories reveal shared structure in neural activity across individuals

Developmental cognitive neuroscience using latent change score models: A tutorial and applications

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