Moderating Role of Cognitive Reserve Markers Between Childhood Cognition and Cognitive Aging
Evidence From the 1946 British Birth Cohort
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Abstract
Background and Objectives As the population ages, differences in cognitive abilities become more evident. We investigated key genetic and life course influences on cognitive state at age 69 years, building on previous work using the longitudinal Medical Research Council National Survey of Health and Development (the British 1946 birth cohort).
Methods Multivariable regressions investigated the association between 4 factors: (1) childhood cognition at age 8 years; (2) a Cognitive Reserve Index (CRI) composed of 3 markers: (i) educational attainment by age 26 years, (ii) engagement in leisure activities at age 43 years, and (iii) occupation up to age 53 years; (3) reading ability assessed by the National Adult Reading Test (NART) at age 53 years; and (4) APOE genotype in relation to cognitive state measured at age 69 years with Addenbrooke's Cognitive Examination, third edition (ACE-III). We then investigated the modifying role of the CRI, NART, and APOE in the association between childhood cognition and the ACE-III.
Results The analytical sample comprised 1,184 participants. Higher scores in childhood cognition, CRI, and NART were associated with higher scores in the ACE-III. We found that the CRI and NART modified the association between childhood cognition and the ACE-III: for 30 additional points in the CRI or 20 additional points in the NART, the simple slope of childhood cognition decreased by approximately 0.10 points (CRI = 70: marginal effects (MEs) 0.22, 95% CI 0.12–0.32, p < 0.001 vs CRI = 100: MEs 0.12, 95% CI 0.06–0.17, p < 0.001; NART = 15: MEs 0.22, 95% CI 0.09–0.35, p = 0.001, vs NART = 35: MEs 0.11, 95% CI 0.05–0.17, p < 0.001). The association between childhood cognition and the ACE-III was nonsignificant at high levels of the CRI or NART. Furthermore, the e4 allele of the APOE gene was associated with lower scores in the ACE-III (β = −0.71, 95% CI −1.36 to −0.06, p = 0.03) but did not modify the association between childhood cognition and cognitive state in later life.
Discussion The CRI and NART are independent measures of cognitive reserve because both modify the association between childhood cognition and cognitive state.
Glossary
- ACE-III=
- Addenbrooke's Cognitive Examination III;
- AD=
- Alzheimer disease;
- CR=
- cognitive reserve;
- CRI=
- Cognitive Reserve Index;
- GHQ-28=
- General Health Questionnaire;
- LBC=
- Lothian birth cohort;
- MRC=
- Medical Research Council;
- NART=
- National Adult Reading Test;
- NSHD=
- National Survey of Health and Development;
- VIF=
- variance inflation factor
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Submitted and externally peer reviewed. The handling editor was Linda Hershey, MD, PhD, FAAN.
Editorial, page 497
- Received December 8, 2021.
- Accepted in final form May 19, 2022.
- © 2022 American Academy of Neurology
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