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

• DOI: 10.1176/appi.ajp.2017.17050529
• Publication Date: 2018-03-02T08:01:51Z
• Authors: Luiza K. Axelrud; Marcos L. Santoro; Daniel S. Pine; Fernanda Talarico; Ary Gadelha; Gisele G. Manfro; Pedro M. Pan; Andrea Jackowski; Felipe Picon; Elisa Brietzke; Rodrigo Grassi-Ol...; Rodrigo A. Bressan; Eurípedes C. Miguel; Luis A. Rohde; Hakon Hakonarson; Zdenka Pausova; Sintia Belangero; Tomas Paus; Giovanni A. Salum
• Keywords: Male; Canada; Multifactorial Inheritance; Adolescent; Organ Size; Neuropsychological Tests; Hippocampus; 3. Good health; Cognition; Alzheimer Disease; Memory; Risk Factors; Humans; Female; Child; Brazil

Objective: Alzheimer’s disease is a heritable neurodegenerative disorder in which early-life precursors may manifest cognition and brain structure. The authors evaluate this possibility by examining, youths, associations among polygenic risk score for disease, cognitive abilities, hippocampal volume. Method: Participants were children 6–14 years of age two Brazilian cities, constituting the discovery (N=364) replication samples (N=352). As an additional replication, data from Canadian sample (N=1,029), with distinct tasks, MRI protocol, genetic risk, included. Cognitive tests quantified memory executive function. Reading writing abilities assessed standardized tests. Hippocampal volumes derived Multiple Automatically Generated Templates (MAGeT) multi-atlas segmentation algorithm. Genetic was using summary statistics International Genomics Project. Results: Analyses showed that sample, each one-unit increase z-score significantly predicted 0.185 decrement immediate recall 0.282 delayed recall. Findings similar (immediate recall, β=−0.259 β=−0.232, both significant). Quantile regressions lower bilaterally individuals high scores. Associations fell short significance sample. Conclusions: affect volumes, as shown independent samples. These support previous evidence some forms late-life dementia represent developmental conditions roots childhood. This result vary depending on sample’s be specific to types tasks.