PLOS : Orthostatic
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 Findings
Between
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.
Conclusions
In this population predominantly of European descent, OH was associated with an increase in long-term risk of dementia.
Author Summary
Why Was This Study Done?
- Orthostatic hypotension is a common cause of transient cerebral
hypoperfusion that is associated with subclinical brain disease, as well
as increased risk of stroke.
- Hypoperfusion has been implicated in the pathophysiology of
dementia, but whether orthostatic hypotension affects the risk of
dementia is uncertain.
What Did the Researchers Do and Find?
- Back in 1990, we measured orthostatic hypotension in 6,204
community-dwelling individuals participating in the Dutch
population-based Rotterdam Study, and we followed these people for
occurrence of dementia until 2014.
- Having orthostatic hypotension at start of the study increased the
risk of developing dementia over the next 25 years by 15%, with similar
results for all-cause dementia and Alzheimer disease.
- The risk of dementia was particularly increased when the orthostatic
blood pressure drops were not compensated for by a sufficient increase
in heart rate.
What Do These Findings Mean?
- These findings suggest that transient cerebral hypoperfusion plays a
role in the aetiology of dementia and that further studies are
warranted to investigate the effects of hypoperfusion and treatment of
orthostatic hypotension on markers of neurodegenerative disease and
cognition.
