P68 Divergent associations between life course cognitive trajectories and brain pathologies: findings from the 1946 british birth cohort

BackgroundCognitive function may serve as an early indicator of prodromal Alzheimer’s disease (AD). We examined how cognitive measures over the life course are associated with the AD-related biomarkers of amyloid (Aβ) status and whole brain volume in a population-based sample free of dementia and other major neurological disorders.MethodsData were from 458 (49% female) dementia-free participants from Insight 46, a sub-study of the National Survey of Health and Development (1946 British birth cohort). At age 70–72, participants underwent 18F-Florbetapir amyloid-PET and multi-modal MRI imaging. Regression analyses and multilevel modelling examined patterns between cognitive measures (spanning age 8–69) and the neuroimaging outcomes of Aβ status (±) and whole brain volume.ResultsOf a range of cognitive tests, word-list learning (WLT) at age 69 was specifically associated with Aβ status at the 5% level (OR 0.75 (0.57, 0.96)). Aβ+ individuals additionally showed faster WLT decline in the 26 years preceding imaging (M1: β=-0.06 (-0.09,-0.01)). Measures of reaction time (M1: b=-0.17 (95% CI -0.27,-0.08) and search speed (M1: b=0.12 (95% CI 0.03, 0.22)) at age 60, and decline in search speed over 26 years (M1: β=0.01 (0.00,0.01)), were associated with smaller whole brain volume. These patterns remained similar after adjusting for childhood cognition, sex, education, child and adult SEP, affective problems and concurrent pathology. APOE-e4 status attenuated the association between verbal memory and Aβ.ConclusionAssociations between cognitive function and neuropathology at age 70–72 appear to manifest between ages 60–69 in a population-based sample without dementia or other major neurological problems. In particular, decline in WLT is associated with Aβ+ and is partially attributed to the effects of APOE-ε4; whereas level of reaction time and rate of decline of search speed are associated with smaller brain volume and are APOE-ε4-independent. Our findings are consistent with evidence of cognitive changes as part of an AD prodromal syndrome in early older-age; and provide evidence that cognitive domains can differentiate underlying pathophysiology associated with AD.