Cognitive Status, Gray Matter Atrophy, and Lower Orthostatic Blood Pressure in Older Adults

Background: Associations between orthostatic blood pressure and cognitive status ( CS) have been described with conflicting results. Objective: We hypothesize that long-term exposure to lower orthostatic blood pressure is related to having worse CS later in life and that atrophy of regions involved in central regulation of autonomic function mediate these associations. Methods: Three-to-four measures of orthostatic blood pressure were obtained from 1997-2003 in a longitudinal cohort of aging, and average systolic orthostatic blood pressure response ( ASOBPR) was computed as % change in systolic blood pressure from sit-to-stand measured at one minute post stand. CS was determined in 2010-2012 by clinician-adjudication ( n = 240; age = 87.1 +/- 2.6; 59% women; 37% black) with a subsample also undergoing concurrent structural neuroimaging ( n = 129). Gray matter volume of regions related to autonomic function was measured. Multinomial regression was used to compare ASOBPR in those who were cognitively intact versus those with a diagnosis of mild cognitive impairment or dementia, controlling for demographics, trajectories of seated blood pressure, incident cardiovascular risk/events and medications measured from 1997 to 2012. Models were repeated in the subsample with neuroimaging, before and after adjustment for regional gray matter volume. Results: There was an inverse association between ASOBPR and probability of dementia diagnosis ( 9% lower probability for each % point higher ASOBPR: OR 0.91, CI95% = 0.85-0.98; p = 0.01). Associations were similar in the subgroup with neuroimaging before and after adjustment for regional gray matter volume. Conclusion: ASOBPR may be an early marker of risk of dementia in older adults living in the community.