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Sortilin receptor 1 predicts longitudinal cognitive change

Journal article
Authors C. A. Reynolds
C. Zavala
M. Gatz
L. Vie
Boo Johansson
B. Malmberg
E. Ingelsson
J. A. Prince
N. L. Pedersen
Published in Neurobiology of Aging
Volume 34
Issue 6
Pages 1710.e11–1710.e18
ISSN 0197-4580
Publication year 2013
Published at Department of Psychology
Pages 1710.e11–1710.e18
Language en
Keywords Cognitive decline, SORL1 association, Sortilin receptor 1, SNP set risk scores, Sex differences, Aging, nucleotide polymorphism arrays, genome-wide association, swedish twin, registry, alzheimer-disease, sequence variation, sorl1 variants, high-fidelity, gene, abilities, risk
Subject categories Neurology, Geriatrics


The gene encoding sortilin receptor 1 (SORL1) has been associated with Alzheimer's disease risk. We examined 15 SORL1 variants and single nucleotide polymorphism (SNP) set risk scores in relation to longitudinal verbal, spatial, memory, and perceptual speed performance, testing for age trends and sex-specific effects. Altogether, 1609 individuals from 3 population-based Swedish twin studies were assessed up to 5 times across 16 years. Controlling for apolipoprotein E genotype (APOE), multiple simple and sex-moderated associations were observed for spatial, episodic memory, and verbal trajectories (p = 1.25E-03 to p = 4.83E-02). Five variants (rs11600875, rs753780, rs7105365, rs11820794, rs2070045) were associated across domains. Notably, in those homozygous for the rs2070045 risk allele, men demonstrated initially favorable performance but accelerating declines, and women showed overall lower performance. SNP set risk scores predicted spatial (Card Rotations, p = 5.92E-03) and episodic memory trajectories (Thurstone Picture Memory, p = 3.34E-02), where higher risk scores benefited men's versus women's performance up to age 75 but with accelerating declines. SORL1 is associated with cognitive aging, and might contribute differentially to change in men and women.

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