Abstract Body: We previously reported an increased risk of cognitive decline and dementia with high visit-to-visit long-term blood pressure variability (BPV) in the ASPREE randomized trial of low-dose aspirin, conducted in 19,114 community-dwelling older adults in Australia and the USA who were initially free of significant cognitive impairment and diagnosed dementia at enrollment. Upon completion of the randomized trial phase, ASPREE participants were invited into the ASPREE-eXTension (ASPREE-XT) observational study. In this analysis, we re-examined the risks of cognitive decline and dementia using extended follow-up from ASPREE-XT, and including recently available APOe genotype as an additional covariate. Long-term BPV was estimated in each participant using standard deviation (SD) of the means of three within-visit systolic BPs obtained with a validated automated oscillometric BP monitor from the baseline and first two annual ASPREE visits. During ASPREE and continued into ASPREE-XT, participants underwent annual/biennial standardized cognitive testing (4-test battery). Incident cognitive decline was defined as >1.5 SD decline from baseline score on any cognitive test; incident dementia was a pre-specified secondary endpoint of ASPREE/ASPREE-XT and adjudicated by expert panel using DSM-IV criteria and clinical records. Participants reaching cognitive decline or dementia endpoints during the BPV estimation period were excluded from the analysis. Multivariable Cox proportional hazards regression showed the highest SD tertile of BPV, compared to the lowest SD tertile, remained associated with highest risk of cognitive decline (HR=1.16, 95% CI=1.04-1.30) and dementia (HR=1.27 (95% CI=1.02-1.59) in men, and cognitive decline (HR=1.12, 95% CI=1.01-1.24) in women (see accompanying Table), over a median follow-up of 5.8 years (for cognitive decline) and 6.5 years (for dementia). When APOe genotype was included as an additional covariate in an available subset of the cohort (81%), the presence of APOe4 allele partially attenuated the associations in both sexes, although cognitive decline remained significant in men. Our findings suggest the relationship between high long-term BPV and cognitive decline and dementia is stronger in men than women, but also modified by underlying APOe genotype.