Hypertension and Stroke as Mediators of Air Pollution Exposure and Incident Dementia

Abstract

ImportanceFine particulate matter air pollution (PM2.5) has been consistently associated with cardiovascular disease, which, in turn, is associated with an increased risk of dementia. As such, vascular dysfunction might be a mechanism by which PM2.5 mediates dementia risk, yet few prior epidemiological studies have examined this potential mechanism.ObjectiveTo investigate whether hypertension and stroke serve as mediators and modifiers of the association of PM2.5 with incident dementia.Design, Setting, and ParticipantsAs part of the Environmental Predictors of Cognitive Health and Aging (EPOCH) Project, this cohort study used biennial survey data collected between 1998 and 2016 from respondents of the Health and Retirement Study (HRS), a nationally representative, population-based, cohort in the US. Eligible participants were those over 50 years of age who were free of dementia at baseline and had complete exposure, mediator, outcome, and demographic data from the HRS. Data analysis was conducted from August to November 2022.ExposuresExposure to PM2.5, calculated for the 10 years preceding each person’s baseline examination according to residential histories and spatiotemporal models.Main Outcomes and MeasuresIncident dementia was identified using a validated algorithm based on cognitive testing and informant reports. The 4-way decomposition causal mediation analysis method was used to quantify the degree to which hypertension and stroke mediated or modified the association of PM2.5 with incident dementia after adjustment for individual-level and area-level covariates.ResultsAmong 27 857 participants (mean [SD] age at baseline, 61 [10] years; 15 747 female participants [56.5%]; 19 249 non-Hispanic White participants [69.1%]), 4105 (14.7%) developed dementia during the follow-up period (mean [SD], 10.2 [5.6] years). Among participants with dementia, 2204 (53.7%) had a history of hypertension at baseline and 386 (9.4%) received a diagnosis of hypertension during the follow up. A total of 378 participants (9.2%) had a history of stroke at baseline and 673 (16.4%) developed stroke over the follow-up period. The IQR of baseline PM2.5 concentrations was 10.9 to 14.9 μg/m3. In fully adjusted models, higher levels of PM2.5 (per IQR) were not associated with increased risk of incident dementia (HR, 1.04; 95% CI, 0.98 to 1.11). Although there were positive associations of prevalent stroke (HR, 1.67; 95% CI, 1.48 to 1.88) and hypertension (HR, 1.15; 95% CI, 1.08 to 1.23) with incident dementia compared with those free of stroke and hypertension during follow-up, there was no statistically significant association of PM2.5 with stroke (odds ratio per IQR increment in PM2.5, 1.08; 95%CI, 0.91 to 1.29) and no evidence of an association of PM2.5 with hypertension (odds ratio per IQR increment in PM2.5, 0.99; 95%CI, 0.92 to 1.07). Concordantly, there was no evidence that hypertension or stroke acted as mediators or modifiers of the association of PM2.5 with incident dementia. Although the nonmediated interaction between PM2.5 and hypertension accounted for 39.2% of the total excess association (95% CI, −138.5% to 216.9%), the findings were not statistically significant.Conclusions and RelevanceThese findings suggest that although hypertension may enhance the susceptibility of individuals to air pollution, hypertension and stroke do not significantly mediate or modify the association of PM2.5 with dementia, indicating the need to investigate other pathways and potential mediators of risk.

An assessment of the mediating role of hypertension in the effect of long-term air pollution exposure on dementia

“…57 The present study expands upon recent work examining the mediating role of hypertension by using a more objective measure of hypertension (based on BP measurements and medical record review), rather than self-or proxy-report. 25 Additional strengths of the present study include a well-characterized clinical trial population with detailed information on potential confounders and comprehensive prospective assessment for dementia, the primary endpoint of the trial. Regular screening visits enhanced the precision of diagnosis dates, and the use of brain MRI and an expert adjudication panel to determine subtypes ensured highly accurate dementia classification.…”

“…These findings are consistent with a recent study that evaluated whether hypertension mediated the effect of PM 2.5 on dementia using survey data from a population-based cohort of US retirees. 25 Pathways other than hypertension (such as inflammation, oxidative stress, or disruption of the blood-brain barrier) may explain the effect of air pollution on dementia. Several recent studies have aimed to quantify the potential mediating role of diabetes, stroke, and cardiovascular disease.…”

“…Few studies have quantified the mediating role of cardiovascular disease events, 22 , 23 stroke, 22 and diabetes 24 in the association between air pollution and dementia, and only one has evaluated the role of hypertension, 25 despite previously established mechanistic links. Identifying modifiable intermediaries, such as BP, can help target public health resources to control hypertension and possibly dementia outcomes.…”