Association of hippocampal volume polygenic predictor score with baseline and change in brain volumes and cognition among cognitively healthy older adults

• Published in: Neurobiology of aging 2020-10, Vol.94, p.81-88
• Main Authors: Armstrong, Nicole M., Dumitrescu, Logan, Huang, Chiung-Wei, An, Yang, Tanaka, Toshiko, Hernandez, Dena, Doshi, Jimit, Erus, Guray, Davatzikos, Christos, Ferrucci, Luigi, Resnick, Susan M., Hohman, Timothy J.
• Format: Article
• Language: English
• Subjects: Age Factors; Aged; Aged, 80 and over; APOE; Atrophy; Brain - pathology; Cognition; Cognitive function; Executive Function; Female; Genetic Predisposition to Disease; Genetics; Genome-Wide Association Study; Healthy Aging - genetics; Healthy Aging - pathology; Healthy Aging - psychology; Hippocampus; Hippocampus - pathology; Humans; Male; Middle Aged; Organ Size - genetics; Polygenic predictor score
• ISSN: 0197-4580; 1558-1497; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2020.05.007

A high hippocampal volume polygenic predictor score (HV-PPS), computed based on GWAS summary statistics (n = 33,536), could be protective against declines in brain volume and cognition in older adults. Linear mixed-effects models with random intercepts and slopes were used to estimate associations of HV-PPS with baseline and annual rate of change in both brain volumes (n = 508) and cognitive performance (n = 1041) in Caucasian Baltimore Longitudinal Study of Aging participants. Higher HV-PPS was associated with greater baseline volumes of the hippocampus and parahippocampal gyrus, and slower rates of ventricular enlargement and volume loss in frontal and parietal white matter, all adjusted for intracranial volume. In addition, higher HV-PPS was associated with better executive function performance and slower rates of decline in verbal fluency scores over time. Individuals with a genetic predisposition toward larger hippocampal volumes show better baseline executive function, slower decline in verbal fluency performance, and slower rates of longitudinal brain atrophy. •Higher hippocampal volume polygenic predictor score (HV-PPS) predicts larger hippocampal and parahippocampal gyrus volumes.•Higher HV-PPS predicts slower declines in white matter and verbal fluency.•Higher HV-PPS predicts slower rates of ventricular enlargement.•Higher HV-PPS predicts higher baseline executive function.•Associations of HV-PPS with white matter and ventricular enlargement change were independent of hippocampal volume.