Genetic Risk for Alzheimer Disease Predicts Hippocampal Volume Through the Human Lifespan

Overview

Journal Neurol Genet

Date 2020 Nov 2

PMID 33134508

Citations 28

Authors

Kristine B Walhovd

Anders M Fjell

Oystein Sorensen

Athanasia Monika Mowinckel

Celine Sonja Reinbold

Ane-Victoria Idland

Leiv Otto Watne

Andre Franke

Valerija Dobricic

Fabian Kilpert

Lars Bertram

Yunpeng Wang

Affiliations

Soon will be listed here.

Abstract

Objective: To test the hypothesis that genetic risk for Alzheimer disease (AD) may represent a stable influence on the brain from early in life, rather than being primarily age dependent, we investigated in a lifespan sample of 1,181 persons with a total of 2,690 brain scans, whether higher polygenic risk score (PGS) for AD and presence of ε4 was associated with lower hippocampal volumes to begin with, as an offset effect, or possibly faster decline in older age.

Methods: Using general additive mixed models, we assessed the relations of PGS for AD, including variants in with hippocampal volume and its change in a cognitively healthy longitudinal lifespan sample (age range: 4-95 years, mean visit age 39.7 years, SD 26.9 years), followed for up to 11 years.

Results: AD-PGS and ε4 in isolation showed a significant negative effect on hippocampal volume. The effect of a 1 sample SD increase in AD-PGS on hippocampal volume was estimated to -36.4 mm (confidence interval [CI]: -71.8, -1.04) and the effect of carrying ε4 allele(s) -107.0 mm (CI: -182.0, -31.5). Offset effects of AD-PGS and ε4 were present in hippocampal development, and interactions between age and genetic risk on volume change were not consistently observed.

Conclusions: Endophenotypic manifestation of polygenic risk for AD may be seen across the lifespan in cognitively healthy persons, not being confined to clinical populations or older age. This emphasizes that a broader population and age range may be relevant targets for attempts to prevent AD.

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