Orthostatic Hypotension and the Long-Term Risk of Dementia: A Population-Based Study

Abstract

BackgroundOrthostatic hypotension (OH) is a common cause of transient cerebral hypoperfusion in the population. Cerebral hypoperfusion is widely implicated in cognitive impairment, but whether OH contributes to cognitive decline and dementia is uncertain. We aimed to determine the association between OH and the risk of developing dementia in the general population.Methods and FindingsBetween 4 October 1989 and 17 June 1993, we assessed OH in non-demented, stroke-free participants of the population-based Rotterdam Study. OH was defined as a ≥20 mm Hg drop in systolic blood pressure (SBP) or ≥10 mm Hg drop in diastolic blood pressure (DBP) within 3 min from postural change. We furthermore calculated within participant variability in SBP related to postural change, expressed as coefficient of variation. Follow-up for dementia was conducted until 1 January 2014. We determined the risk of dementia in relation to OH and SBP variability, using a Cox regression model, adjusted for age; sex; smoking status; alcohol intake; SBP; DBP; cholesterol:high-density lipoprotein ratio; diabetes; body mass index; use of antihypertensive, lipid-lowering, or anticholinergic medication; and apolipoprotein E genotype. Finally, we explored whether associations varied according to compensatory increase in heart rate. Among 6,204 participants (mean ± standard deviation [SD] age 68.5 ± 8.6 y, 59.7% female) with a median follow-up of 15.3 y, 1,176 developed dementia, of whom 935 (79.5%) had Alzheimer disease and 95 (8.1%) had vascular dementia. OH was associated with an increased risk of dementia (adjusted hazard ratio [aHR] 1.15, 95% CI 1.00–1.34, p = 0.05), which was similar for Alzheimer disease and vascular dementia. Similarly, greater SBP variability with postural change was associated with an increased risk of dementia (aHR per SD increase 1.08, 95% CI 1.01–1.16, p = 0.02), which was similar when excluding those who fulfilled the formal criteria for OH (aHR 1.08, 95% CI 1.00–1.17, p = 0.06). The risk of dementia was particularly increased in those with OH who lacked a compensatory increase in heart rate (within lowest quartile of heart rate response: aHR 1.39, 95% CI 1.04–1.85, p-interaction = 0.05). Limitations of this study include potential residual confounding despite rigorous adjustments, and potentially limited generalisability to populations not of European descent.ConclusionsIn this population predominantly of European descent, OH was associated with an increase in long-term risk of dementia.

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

“…Discrepancies may reflect the longer duration of longitudinal follow-up in the current study, our use of longitudinal OBP measurements and investigation of a clinically adjudicated cognitive outcome rather than cognitive scores. However both lower and elevated OBP may reflect increased OBP variability, which has also been linked to poorer CS but which requires additional standing OBP measures to calculate [3]. Therefore, the impact of elevated OBP may have been underestimated in the current study.…”

“…Thus, ASOBPR may be a more sensitive indicator of hemodynamic homeostasis than the simple presence or absence of consensus OH, or absolute change in OBP, as it takes into account relative baseline SBP. Conceptualized as a measure of hemodynamic homeostasis these findings investigating ASOBPR are perhaps akin to the stronger relationship reported in the Rotterdam cohort between a baseline measure of systolic OBP variability and later dementia than with consensus OH [3]. …”

“…A larger OBP drop would be expected from the supine position and may account for a lack of association with traditional OBP indices and the low prevalence of consensus OH. Optimal timing of the standing BP measurement is contested, however [42], and measurements of standing BP beyond one minute at each annual visit would have allowed investigation of systolic OBP variability [3]. However, a single measurement of standing OBP at one minute is a limitation common to other studies [11, 32].…”

“…Three other prospective population-based studies, however, found no longitudinal association [7–9]. Furthermore the associations described in the Atherosclerosis Risk in Communities study did not survive correction for demographic factors or conventional cardiovascular risk [1] and the most comprehensive cohort study to date did not investigate MCI [3]. The majority of prior studies have investigated screening tests of cognition rather than clinician-directed adjudicated diagnosis, and measured OBP at a single time point [10–12].…”

“…The majority of prior studies have investigated screening tests of cognition rather than clinician-directed adjudicated diagnosis, and measured OBP at a single time point [10–12]. Moreover, measurement protocols and definitions of OBP investigated have varied across studies [1, 3, 6, 10]. …”