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.
Highlights
Cardiovascular health is well-established as a key determinant in the prevention of dementia, including Alzheimer disease [1,2], but the mechanisms by which vascular damage leads to cognitive decline remain largely unknown
The risk of dementia was increased in those with orthostatic hypotension (OH) who lacked a compensatory increase in heart rate
In this Swedish population, OH was associated with an increased risk of dementia at re-examination after 6 y, but the investigators were unable to adjust for cardiovascular risk factors aside from hypertension, and attrition was substantial, with 37.5% of participants lost to follow-up between examination rounds [14]
Summary
Cardiovascular health is well-established as a key determinant in the prevention of dementia, including Alzheimer disease [1,2], but the mechanisms by which vascular damage leads to cognitive decline remain largely unknown. OH is highly prevalent among patients with dementia and mild cognitive impairment, compared to healthy controls [10,11,12,13], but only one study has assessed the longitudinal relation between OH and the risk of dementia in initially healthy participants In this Swedish population, OH was associated with an increased risk of dementia at re-examination after 6 y, but the investigators were unable to adjust for cardiovascular risk factors aside from hypertension, and attrition was substantial, with 37.5% of participants lost to follow-up between examination rounds [14]. We aimed to determine the association between OH and the risk of developing dementia in the general population.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
