A Network of Genetic Effects on Non-Demented Cognitive Aging: Alzheimer's Genetic Risk (CLU + CR1 + PICALM) Intensifies Cognitive Aging Genetic Risk (COMT + BDNF) Selectively for APOEɛ4 Carriers

Journal of Alzheimer's Disease : JAD
Shraddha Sapkota, Roger A Dixon

Abstract

Trajectories of complex neurocognitive phenotypes in preclinical aging may be produced differentially through selective and interactive combinations of genetic risk. We organize three possible combinations into a "network" of genetic risk indices derived from polymorphisms associated with normal and impaired cognitive aging, as well as Alzheimer's disease (AD). Specifically, we assemble and examine three genetic clusters relevant to non-demented cognitive trajectories: 1) Apolipoprotein E (APOE), 2) a Cognitive Aging Genetic Risk Score (CA-GRS; Catechol-O-methyltransferase + Brain-derived neurotrophic factor), and 3) an AD-Genetic Risk Score (AD-GRS; Clusterin + Complement receptor 1 + Phosphatidylinositol-binding clathrin assembly protein). We use an accelerated longitudinal design (n = 634; age range = 55-95 years) to test whether AD-GRS (low versus high) moderates the effect of increasing CA-GRS risk on executive function (EF) performance and change as stratified by APOE status (ɛ4+ versus ɛ4-). APOEɛ4 carriers with high AD-GRS had poorer EF performance at the centering age (75 years) and steeper 9-year decline with increasing CA-GRS but this association was not present in APOEɛ4 carriers with low AD-GRS. APOEɛ4 carriers wit...Continue Reading

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Citations

Jan 1, 2020·Brain : a Journal of Neurology·AmanPreet BadhwarPierre Bellec
Aug 11, 2020·Journal of the International Neuropsychological Society : JINS·H Sebastian CaballeroRoger A Dixon
Apr 7, 2020·Journal of Alzheimer's Disease : JAD·Judith R HarrisonValentina Escott-Price
Oct 5, 2021·Frontiers in Aging Neuroscience·Shraddha SapkotaRoger A Dixon

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