Genetic effects on old-age cognitive functioning: A population-based study.

Abstract

Associations between genotypes and cognitive outcomes may provide clues as to which mechanisms cause individual differences in old-age cognitive performance. We investigated the effects of five polymorphisms on cognitive functioning in a population-based sample of 2,694 persons without dementia (60-102 years). A structural equation model (SEM) was fit to the cognitive data, yielding five specific latent factors (perceptual speed, episodic memory, semantic memory, category fluency, and letter fluency), as well as a global cognitive factor. These factors showed the expected associations with chronological age. Genotyping was performed for five single-nucleotide polymorphisms that have been associated with cognitive performance: APOE (rs429358), COMT (rs4680), BDNF (rs6265), KIBRA (rs17070145), and CLSTN2 (rs6439886). After controlling for age, gender, and education, as well as correcting for multiple comparisons, we observed negative effects of being an APOE ε4 carrier on episodic memory and perceptual speed. Furthermore, being a CLSTN2 TT carrier was associated with poorer semantic memory. For the global factor, the same pattern of results was observed. In addition, being a BDNF any A carrier was associated with better cognitive performance. Also, older age was associated with stronger genetic effects of APOE on global cognition. However, this interaction effect was partly driven by the presence of preclinical dementia cases in our sample. Similarly, excluding future dementia cases attenuated the effects of APOE on episodic memory and global cognition, suggesting that part of the effects of APOE on old-age cognitive performance may be driven by dementia-related processes.

The changing face of cognitive gender differences in Europe

“…As previously reported (25,26), differences were observed across regions and cognitive tasks, demonstrating both a birth cohort gradient, with later cohorts (younger age) performing at higher levels than earlier cohorts (older age), and a geographic skill gradient, indicating a northern advantage over central and southern regions (Fig. 1 A-I).…”

Investigating the influence of KIBRA and CLSTN2 genetic polymorphisms on cross-sectional and longitudinal measures of memory performance and hippocampal volume in older individuals

“…Subsequently this association has been replicated in two other independent studies in both adolescents and older adults (Jacobsen, Picciotto, Heath, Mencl, & Gelernter, 2009;Laukka et al, 2013). The mechanism/s by which these two polymorphisms (KIBRA rs17070145, CLSTN2 rs6439886) may influence episodic memory functioning is unclear.…”

Genetics and Functional Imaging: Effects of APOE, BDNF, COMT, and KIBRA in Aging

“…Similarly, in older adults aged 79 years, the ε4 allele was associated with more rapid decline in verbal memory and abstract reasoning across 8 years (Schiepers et al 2012). Importantly, one study showed that the relationship of APOE to episodic memory and global cognition was attenuated, after exclusion of future dementia cases (Laukka et al 2013). This suggests that dementia-related processes may contribute to the link between APOE and cognition in old age.…”