Abstract

We examined associations of single nucleotide polymorphisms (SNP) in the vitamin D receptor (VDR; CdX‐2, BsmI, ApaI, TaqI) and Megalin (rs2075252, rs4668123, rs3755166) regions with longitudinal annual rates of cognitive change (LARCC) using data from 702 Non‐Hispanic White participants in the Baltimore Longitudinal Study of Aging. LARCC were predicted with linear mixed models using all time points (Prediction I) or time points before dementia onset (Prediction II). In regression models of three SNP latent classes (SNPLC) per region, there were significant changes in cognitive decline on a number of tests, including Trails A (Prediction I) and B (Predictions I and II) in men when contrasting VDR2:CdX‐2[‐‐]/BsmI[AA]/ApaI[‐‐]/TaqI[GG] with VDR1:CdX‐2[‐‐]/BsmI[AG]/ApaI[‐‐]/TaqI[GA] SNPLC; and California verbal learning Task‐Delayed Recall (CVLT‐DR) in men (Predictions I and II) when comparing VDR3:CdX‐2[‐‐]/BsmI[GG]/ApaI[‐‐]/TaqI[AA] to VDR1. Megalin2:rs3755166[‐‐]/rs2075252[TT]/rs4668123[T‐](vs.Megalin1:rs3755166[‐‐]/rs2075252[CC]/rs4668123[‐‐]) was associated with accelerated decline on CVLT‐DR in men and overall (Prediction II) and CVLT‐List A in men (Prediction II). Variations in VDR and Megalin genes may influence cognitive decline among US adults in a sex‐specific fashion.

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