APOE and aging-related cognitive change in a longitudinal cohort of men

Abstract

a b s t r a c tWe examined associations between APOE major isoforms, rs405509 promoter and rs440446 intron-1 polymorphisms, and nonpathologic cognitive aging. Men from the Helsinki Birth Cohort Study took the Finnish Defence Forces Basic Intellectual Ability Test twice, at age 20.1 (n ¼ 404) and 67.6 years (n ¼ 247). APOE major isoforms did not associate with cognitive ability. In the APOE major isoform-adjusted analyses, the number of rs405509 minor alleles was associated with a higher cognitive ability total and verbal, arithmetic, and visuospatial subtest scores at 67.6 years (p-values < 0.004). In the analyses of cognitive change, the visuospatial subtest score increased across time in rs440446 minor allele carriers but decreased in noncarriers (p ¼ 0.007). Associations in the APOE major isoformestratified analyses were significant in the APOE ε3/3 homozygotes only. The APOE locus harbors additional modifying alleles, independent of APOE major isoforms that are associated with better preserved general cognitive ability in nondemented elderly men and change in visuospatial ability across 5 decades. These results suggest that at least 2 distinct mechanisms link the APOE locus with cognitive ability.

The Contribution of Genetic Factors to Cognitive Impairment and Dementia: Apolipoprotein E Gene, Gene Interactions, and Polygenic Risk

“…The double homozygous genotype (rs405509 TT/ε4ε4) exhibited a significant reduction in general cognition, memory, and attention [68]. However, in a recent study that included elderly men from Finland, researchers found that the rs405509 TT genotype was significantly associated with improved general cognition, language, arithmetic, and visual spatial ability, independent of the APOE major isoforms [69]. This likely indicates that the effects of rs405509 are different among different ethnicities.…”

Cognitive ability in young adulthood predicts risk of early-onset dementia in Finnish men

“…12,15 Test scores have been associated with, for example, cardiovascular disease and stroke risk 16 and APOE polymorphisms. 17 For all analyses, the cognitive ability test scores were converted to IQ-type scores with mean 100 and SD 15.…”

Effects of an APOE Promoter Polymorphism on Fronto-Parietal Functional Connectivity During Nondemented Aging

“…APOE promoter polymorphisms are closely related to aging and may have independent mechanisms for normal aging and pathological aging (Rantalainen et al, 2016 , 2019 ). As we found in our study, the results of linear regression analysis showed that the interaction between the rs405509 genotype and age had a significant effect on general cognitive performance and execution function scores.…”