Cognition at age 70 Life course predictors and associations with brain pathologies

Objective To investigate predictors of performance on a range of cognitive measures including the Preclinical Alzheimer Cognitive Composite (PACC) and test for associations between cognition and dementia biomarkers in Insight 46, a substudy of the Medical Research Council National Survey of Health and Development. Methods A total of 502 individuals born in the same week in 1946 underwent cognitive assessment at age 69-71 years, including an adapted version of the PACC and a test of nonverbal reasoning. Performance was characterized with respect to sex, childhood cognitive ability, education, and socioeconomic position (SEP). In a subsample of 406 cognitively normal participants, associations were investigated between cognition and beta-amyloid (A beta) positivity (determined from A beta-PET imaging), whole brain volumes, white matter hyperintensity volumes (WMHV), and APOE epsilon 4. Results Childhood cognitive ability was strongly associated with cognitive scores including the PACC more than 60 years later, and there were independent effects of education and SEP. Sex differences were observed on every PACC subtest. In cognitively normal participants, A beta positivity and WMHV were independently associated with lower PACC scores, and A beta positivity was associated with poorer nonverbal reasoning. A beta positivity and WMHV were not associated with sex, childhood cognitive ability, education, or SEP. Normative data for 339 cognitively normal A beta-negative participants are provided. Conclusions This study adds to emerging evidence that subtle cognitive differences associated with A beta deposition are detectable in older adults, at an age when dementia prevalence is very low. The independent associations of childhood cognitive ability, education, and SEP with cognitive performance at age 70 have implications for interpretation of cognitive data in later life.