F4-04-04: ASSOCIATION BETWEEN CEREBRAL AMYLOIDOSIS AND WORSE COGNITIVE PERFORMANCE IN PRECLINICAL AUTOSOMAL DOMINANT ALZHEIMER'S DISEASE: BASELINE FINDINGS FROM THE API COLOMBIA AUTOSOMAL DOMINANT AD TRIAL
We used baseline data from the Alzheimer's Prevention Initiative (API) Autosomal Dominant AD (ADAD) Colombia Trial to examine relationships between PET measurements of brain amyloid-b(Ab) burden and cognitive performance in cognitively unimpaired PSEN1 E280A mutation carriers and non-carriers from the world's largest ADAD kindred. Participants were 242 cognitively unimpaired 30–53 year-old prevention trial participants; 167 were positive for the AD-associated PSEN1 mutation and 75 were non-carrier family members. Baseline clinical ratings, neuropsychological test scores, and florbetapir cortical-to-pontine standard-uptake value ratios (SUVR) were used to characterize the relationships between fibrillar Aβ burden and cognitive performance in the carrier group, before and after adjustment for older age. Mutation carriers were slightly younger than non-carriers (37±5 versus 42±6 years, P<0.001). Carriers and non-carriers did not differ significantly in educational level, sex, APOE4 status, or global clinical dementia rating (CDR) scores. Mutation carriers had significantly lower Mini-Mental State Examination (MMSE), CERAD Word List delayed recall, and Free and Cued Selective Reminding Test (FCSRT) delayed recall scores (P<0.05) and significantly higher florbetapir SUVRs (P<0.0001). Florbetapir SUVRs in the carrier group were associated with worse performance on each of the above episodic memory tests (e.g. FCSRT recall: r= −0.34; P<0.0001), and these associations remained significant after adjustment for age. Cerebral amyloidosis is associated with lower episodic memory scores in cognitively unimpaired ADAD mutation carriers, even after adjustment for age. Additional analyses are needed to clarify the extent to which this association remains significant after adjustment for downstream AD biomarker measurements.