TY - JOUR
T1 - The long-term effects of a polygenetic predisposition to general cognition on healthy cognitive ageing
T2 - Evidence from the English Longitudinal Study of Ageing
AU - Ajnakina, Olesya
AU - Murray, Robin
AU - Steptoe, Andrew
AU - Cadar, Dorina
N1 - Funding Information:
The English Longitudinal Study of Ageing is funded by the National Institute on Aging (grant RO1AG7644) and by a consortium of UK government departments coordinated by the National Institute for Health Research (NIHR). OA is further funded by an NIHR Post-Doctoral Fellowship (PDF-2018-11-ST2-020). RM is supported by the NIHR Maudsley BRC. DC is funded by the National Institute on Aging (Grant R01AG017644) and Economic and Social Research Council (ESRC, Grant ES/T014091/1). The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health and Social Care.
Publisher Copyright:
Copyright © The Author(s), 2022. Published by Cambridge University Press.
PY - 2022/2/10
Y1 - 2022/2/10
N2 - Background As an accelerated cognitive decline frequently heralds onset of severe neuropathological disorders, understanding the source of individual differences in withstanding the onslaught of cognitive ageing may highlight how best cognitive abilities may be retained into advanced age. Methods Using a population representative sample of 5088 adults aged •50 years from the English Longitudinal Study of Ageing, we investigated relationships of polygenic predisposition to general cognition with a rate of change in cognition during a 10-year follow-up period. Polygenic predisposition was measured with polygenic scores for general cognition (GC-PGS). Cognition was measured employing tests for verbal memory and semantic fluency. Results The average baseline memory score was 11.1 (s.d. = 2.9) and executive function score was 21.5 (s.d. = 5.8). An increase in GC-PGS by one standard deviation (1-s.d.) was associated with a higher baseline verbal memory by an average 0.27 points (95% CI 0.19-0.34, p < 0.001). Similarly, 1-s.d. increase in GC-PGS was associated with a higher semantic fluency score at baseline in the entire sample (β = 0.45, 95% CI 0.27-0.64, p < 0.001). These associations were significant for women and men, and all age groups. Nonetheless, 1-s.d. increase in GC-PGS was not associated with decreases in verbal memory nor semantic fluency during follow-up in the entire sample, as well stratified models by sex and age. Conclusion Although common genetic variants associated with general cognition additively are associated with a stable surplus to cognition in adults, a polygenic predisposition to general cognition is not associated with age-related cognitive decline during a 10-year follow-up.
AB - Background As an accelerated cognitive decline frequently heralds onset of severe neuropathological disorders, understanding the source of individual differences in withstanding the onslaught of cognitive ageing may highlight how best cognitive abilities may be retained into advanced age. Methods Using a population representative sample of 5088 adults aged •50 years from the English Longitudinal Study of Ageing, we investigated relationships of polygenic predisposition to general cognition with a rate of change in cognition during a 10-year follow-up period. Polygenic predisposition was measured with polygenic scores for general cognition (GC-PGS). Cognition was measured employing tests for verbal memory and semantic fluency. Results The average baseline memory score was 11.1 (s.d. = 2.9) and executive function score was 21.5 (s.d. = 5.8). An increase in GC-PGS by one standard deviation (1-s.d.) was associated with a higher baseline verbal memory by an average 0.27 points (95% CI 0.19-0.34, p < 0.001). Similarly, 1-s.d. increase in GC-PGS was associated with a higher semantic fluency score at baseline in the entire sample (β = 0.45, 95% CI 0.27-0.64, p < 0.001). These associations were significant for women and men, and all age groups. Nonetheless, 1-s.d. increase in GC-PGS was not associated with decreases in verbal memory nor semantic fluency during follow-up in the entire sample, as well stratified models by sex and age. Conclusion Although common genetic variants associated with general cognition additively are associated with a stable surplus to cognition in adults, a polygenic predisposition to general cognition is not associated with age-related cognitive decline during a 10-year follow-up.
KW - APOE-ϵ4
KW - cognition
KW - genome-wide association studies
KW - healthy ageing
KW - polygenic score
UR - http://www.scopus.com/inward/record.url?scp=85124988494&partnerID=8YFLogxK
U2 - 10.1017/S0033291721004827
DO - 10.1017/S0033291721004827
M3 - Article
AN - SCOPUS:85124988494
SN - 0033-2917
JO - Psychological Medicine
JF - Psychological Medicine
ER -