Polygenic Risk Score for Alzheimer's Disease: Implications for Memory Performance and Hippocampal Volumes in Early Life

The American Journal of Psychiatry
Luiza K AxelrudGiovanni A Salum

Abstract

Alzheimer's disease is a heritable neurodegenerative disorder in which early-life precursors may manifest in cognition and brain structure. The authors evaluate this possibility by examining, in youths, associations among polygenic risk score for Alzheimer's disease, cognitive abilities, and hippocampal volume. Participants were children 6-14 years of age in two Brazilian cities, constituting the discovery (N=364) and replication samples (N=352). As an additional replication, data from a Canadian sample (N=1,029), with distinct tasks, MRI protocol, and genetic risk, were included. Cognitive tests quantified memory and executive function. Reading and writing abilities were assessed by standardized tests. Hippocampal volumes were derived from the Multiple Automatically Generated Templates (MAGeT) multi-atlas segmentation brain algorithm. Genetic risk for Alzheimer's disease was quantified using summary statistics from the International Genomics of Alzheimer's Project. Analyses showed that for the Brazilian discovery sample, each one-unit increase in z-score for Alzheimer's polygenic risk score significantly predicted a 0.185 decrement in z-score for immediate recall and a 0.282 decrement for delayed recall. Findings were similar ...Continue Reading

Citations

Jan 3, 2020·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Hannah L ChandlerThomas M Lancaster
May 14, 2019·Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring·Thomas M Lancaster
Sep 25, 2019·Cold Spring Harbor Perspectives in Medicine·Jill S Goldman
May 10, 2020·Genes, Brain, and Behavior·María Fernanda Vinueza-VelozChris I De Zeeuw
Apr 6, 2019·Frontiers in Aging Neuroscience·Qinqin WangJing Chen
Jun 11, 2020·Revista brasileira de psiquiatria : orgão oficial da Associação Brasileira de Psiquiatria, Asociación Psiquiátrica de la América Latina·Geraldo Busatto FilhoFabio L Duran
Apr 7, 2020·Journal of Alzheimer's Disease : JAD·Judith R HarrisonValentina Escott-Price
Mar 1, 2020·Nature Neuroscience·Rebecca SimsJulie Williams
Nov 24, 2020·Neurobiology of Aging·Amy N MurrayThomas M Lancaster
Apr 16, 2021·Frontiers in Neuroscience·Xiaopu ZhouNancy Y Ip
Apr 23, 2021·Cerebral Cortex·Yanhui DingUNKNOWN Alzheimer’s Disease Neuroimaging Initiative
Oct 8, 2020·Current Alzheimer Research·Matteo De Marco Alzheimer's Disease Neuroimaging Initiative
Aug 6, 2021·Therapeutic Advances in Neurological Disorders·Zhen-Yu ShuXiang-Yang Gong

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Methods Mentioned

BETA
genotyping
chips

Software Mentioned

FreeSurfer
MAGMA
Reactome
MAGeT
PRSice
Quantitative Scoring System

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