Editors' note: Association of orthostatic hypotension with incident dementia, stroke, and cognitive decline

Using the prospective observational Atherosclerosis Risk in Communities cohort, Rawlings et al. sought to determine an independent association between orthostasis and risk of stroke and dementia. After adjustment for known vascular risk factors and other medical history that are associated with stroke and dementia risk, the investigators found an independent association between orthostatic hypotension (OH) and stroke (hazard ratio [HR] 2.08, 95% confidence interval [CI] 1.65–2.62) and dementia (HR 1.54, 95% CI 1.20–1.97) throughout the 16-year follow-up period. Dr. Young disputes this independent association, suggesting that collinearity of OH with vascular risk factors may confound the results of this article. In response, Rawlings et al. performed a subgroup analysis of patients without diabetes or hypertension (25% of initial cohort) and found no statistically significant association between OH and incident dementia (HR 1.28, 95% CI 0.67–2.42). However, this analysis may be underpowered. OH may represent a clinical biomarker for morbidity and Dr. Young maintains that its proximate cause should be the target of aggressive intervention. In a second response to the article, Dr. Kawada elaborates on a potential mechanism to explain the association between OH and dementia—progressive subcortical ischemia—and suggests this relationship may be more pronounced among certain ethnic groups. Each of these questions warrant further scrutiny in future longitudinal cohort studies.