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 sub-study of the MRC National Survey of Health and Development.

Methods: 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 non-verbal reasoning. Performance was characterised with respect to sex, childhood cognitive ability, education and socioeconomic position (SEP). In a sub-sample of 406 cognitively-normal participants, associations were investigated between cognition and β-amyloid (Aβ) positivity (determined from Aβ-PET imaging), whole brain volumes, white matter hyperintensity volumes (WMHV), and APOE-ε4.

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 sub-test. In cognitively-normal participants, Aβ-positivity and WMHV were independently associated with lower PACC scores, and Aβ-positivity was associated with poorer non-verbal reasoning. Aβ-positivity and WMHV were not associated with sex, childhood cognitive ability, education or SEP. Normative data for 339 cognitively-normal Aβ-negative participants are provided.

Conclusions: This study adds to emerging evidence that subtle cognitive differences associated with Aβ 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 aged 70 have implications for interpretation of cognitive data in later life.