Late-life, visit-to-visit blood pressure variability and its association with sex-specific long-term cognitive outcomes

In 19 114 community-dwelling older adults enrolled in the ASPREE trial, high late-life visit-to-visit blood pressure variability (BPV) was associated with increased risks of incident dementia and cognitive decline during the median 4.7 year trial period. Whether sex or apolipoprotein E (ApoE) affect these associations over longer-term follow-up is unknown. We investigated the association between BPV and long term risks of dementia and cognitive decline using data from the ASPREE-eXTension (ASPREE-XT) study (median 8.3 year follow-up for dementia, 7.3 years for cognitive decline, after BPV estimation). Long-term BPV was estimated using standard deviation (SD) of the mean systolic BPs measured at ASPREE baseline, year 1 and 2 visits. Incident dementia was an adjudicated secondary endpoint and cognitive decline was defined as ≥1.5 SD decline in score from baseline sustained on the same of one, or more, standardized cognitive tests administered annually/biennially throughout ASPREE/ASPREE-XT. Analyses were stratified a priori by sex, using sex-specific SD tertiles of systolic BPV. Multivariable Cox proportional hazards regression comparing the highest BPV tertile to the lowest showed increased risk of dementia (HR = 1.33, 1.10-1.61) and cognitive decline (HR = 1.17, 1.06-1.30) in males, and cognitive decline in females (HR = 1.17, 1.07-1.28). In ApoE genotyped participants (81%), females in the highest BPV tertile lacking the ɛ4 allele had increased risk of dementia (HR = 1.39; 1.04-1.84), while risk of cognitive decline was increased in both sexes lacking the ɛ4 allele (males HR = 1.25; 1.09-1.43; females HR = 1.14; 1.01-1.29). These findings suggest both sex and ApoE impact the association of high BPV with long-term cognitive changes.