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The relationship between cognitive decline and a genetic predictor of educational attainment.

ABSTRACT: Genetic and environmental factors both make substantial contributions to the heterogeneity in individuals' levels of cognitive ability. Many studies have examined the relationship between educational attainment and cognitive performance and its rate of change. Yet there remains a gap in knowledge regarding whether the effect of genetic predictors on individual differences in cognition becomes more or less prominent over the life course. In this analysis of over 5000 older adults from the Health and Retirement Study (HRS) in the U.S., we measured the change in performance on global cognition, episodic memory, attention & concentration, and mental status over 14 years. Growth curve models are used to evaluate the association between a polygenic risk score for education (education PGS) and cognitive change. Using the most recent education PGS, we find that individuals with higher scores perform better across all measures of cognition in later life. Education PGS is associated with a faster decline in episodic memory in old age. The relationships are robust even after controlling for phenotypic educational attainment, and are unlikely to be driven by mortality bias. Future research should consider genetic effects when examining non-genetic factors in cognitive decline. Our findings represent a need to understand the mechanisms between genetic endowment of educational attainment and cognitive decline from a biological angle.

SUBMITTER: Ding X

PROVIDER: S-EPMC6873779 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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The relationship between cognitive decline and a genetic predictor of educational attainment.

Ding Xuejie X Barban Nicola N Tropf Felix C FC Mills Melinda C MC

Social science & medicine (1982) 20190913

Genetic and environmental factors both make substantial contributions to the heterogeneity in individuals' levels of cognitive ability. Many studies have examined the relationship between educational attainment and cognitive performance and its rate of change. Yet there remains a gap in knowledge regarding whether the effect of genetic predictors on individual differences in cognition becomes more or less prominent over the life course. In this analysis of over 5000 older adults from the Health ...[more]

PMID: 31546143

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Project description:BackgroundThe potential association between level of education and age-related cognitive decline remains an open question, partly because of a lack of studies including large subsamples with low education and follow-up intervals covering a substantial part of the adult lifespan.ObjectivesTo examine cognitive decline assessed by a comprehensive clinical test of intelligence over a 35-year period of follow-up from ages 50 to 85 and to analyze the effect of education on trajectories of cognitive decline, including the effects of selective attrition.MethodsA longitudinal cohort study with a 35-year follow-up of community dwelling members of the Glostrup 1914 cohort. The study sample comprised 697 men and women at the 50-year baseline assessment and additional participants recruited at later follow-ups. Verbal, Performance, and Full Scale IQs were assessed using the Wechsler Adult Intelligence Scale at ages 50, 60, 70, 80, and 85. To be able to track cognitive changes between successive WAIS assessments, all IQs were based on the Danish 50-year norms. Information on school education was self-reported. The association between education and cognitive decline over time was examined in growth curve models. Selective attrition was investigated in subsamples of participants who dropped out at early or later follow-ups.ResultsThe trajectories for Verbal, Performance, and Full Scale IQ showed higher initial cognitive performance, but also revealed steeper decline among participants with a formal school exam compared to participants without a formal exam. Verbal IQ showed the largest difference in level between the two educational groups, whereas the interaction between education and age was stronger for Performance IQ than for Verbal IQ. In spite of the difference in trajectories, higher mean IQ was observed among participants with a formal school exam compared to those without across all ages, including the 85-year follow-up. Further analyses revealed that early dropout was associated with steeper decline, but that this effect was unrelated to education.ConclusionComprehensive cognitive assessment over a 35-year period suggests that higher education is associated with steeper decline in IQ, but also higher mean IQ at all follow-ups. These findings are unlikely to reflect regression towards the mean, other characteristics of the employed test battery or associations between educational level and study dropout.

Project description:This study aimed to investigate whether there is a causal relationship between educational attainment and delirium at the genetic level using the Mendelian randomization method, and provide new evidence for studies in this field. We found a causal relationship between educational attainment and delirium at the genetic level after excluding confounders using Mendelian randomization. The inverse variance weighting method of random effects was the main analysis method. The weighted median and Mendelian Randomization-Egger methods, as well as simple, and weighted modes were used as supplementary analysis methods. Additionally, horizontal pleiotropy tests were conducted, including the Mendelian Randomization-Egger intercept test and Mendelian Randomization Pleiotropy RESidual Sum and Outlier. Cochran's Q statistic was used to assess the size of heterogeneity. We retrieved all second single nucleotide polymorphism features and performed multivariate Mendelian randomization to adjust for the effect of potential confounders on our results. The inverse variance weighting suggested a negative correlation between genetically predicted educational attainment and delirium (0.67[0.49-0.92], p = 0.013); Mendelian Randomization Pleiotropy RESidual Sum and Outlier (0.67[0.49-0.92], p = 0.013) and multivariate Mendelian randomization (0.52[0.33-0.82], p = 0.005) results were generally consistent with the inverse variance weighting method. The Mendelian Randomization-Egger, simple, and weighted mode results were consistent with the inverse variance weighting results. Our results were not affected by pleiotropy or heterogeneity (p > 0.05, for both pleiotropy and heterogeneity). In addition, the "leave-one-out" analysis showed that the results of our Mendelian randomization analysis were not influenced by individual single nucleotide polymorphisms. Studies have found a causal relationship between educational attainment and delirium at the genetic level; higher educational attainment may be a protective factor against delirium. Clinically, more attention should be paid to patients at a high risk of delirium with low educational attainment.

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The relationship between cognitive decline and a genetic predictor of educational attainment.

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The relationship between cognitive decline and a genetic predictor of educational attainment.

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