Abstract Body: Background Orthostatic hypotension (OH), a blood pressure (BP) dysregulatory condition, is associated with dementia, stroke, and all-cause mortality. OH develops from autonomic impairments, which may involve central control via the brain stem. Cognitive decline may indicate progressive neuropathological changes that could increase risk for developing OH.

Hypothesis We hypothesized that accelerated cognitive decline would be associated with a persistent change in orthostatic BP among older adults.

Methods The Atherosclerosis Risk in Communities (ARIC) Study measured participants’ global cognitive function, using memory, language, and executive function scores based on neuropsychological tests. We derived trajectories and categories of cognitive changes of visit 9 participants using data from visit 5 (2011-13) to visit 9 (2021-22). During visit 10 (2023), three supine and six standing BPs were measured. Supine BPs were measured after 5 minutes of rest at 30-second intervals, and standing BPs were timed at 0, 1, 2, 3, 4, and 5 minutes after standing. OH was determined if a drop in BP of systolic ≥20 or diastolic ≥10 mm Hg occurred after standing from the supine position. Patterns of OH were defined as transient (initial, early) and persistent (late, sustained) (see Table 1 legend for definitions). We determined the associations of cognitive change categories of visit 9 participants with OH patterns via multivariable logistic regression (see Table 2 legend for adjusted factors). We used inverse probability weighting to adjust for participants who attended visit 9 but not visit 10.

Results Of 696 participants (mean age 82.1±3.6 years, 58% female, 18% Black), 42% had initial OH, whereas 16% had sustained OH (Table 1). Half of the participants (50%) had mild decline in global cognition scores, whereas 44% and 6% had stable and accelerated decline, respectively (Figure 1). Similar patterns were observed across domain-specific scores. Participants with accelerated decline in global score had significantly higher odds of late and sustained OH compared to stable (Table 2). Similar but non-significant associations were identified across domain-specific scores.

Conclusion Very old adults with accelerated cognitive decline were more likely to have persistent impairments in orthostatic BP regulation. Future studies should explore the brain regions underlying cognitive decline to better understand how it might contribute to OH.