In a recent study published in Neurology, researchers investigated the effects of hypertension history, antihypertensive use, and baseline blood pressure (BP) on the risk of developing Alzheimer’s dementia (AD) and non-AD in late life.
Study: Blood Pressure, Antihypertensive Use, and Late-Life Alzheimer and Non-Alzheimer Dementia Risk. Image Credit: Orawan Pattarawimonchai/Shutterstock.com
Background
Hypertension, affecting 1.3 billion people globally, is the leading cause of strokes and cerebrovascular disease. Mid-life hypertension has been linked to a higher risk of vascular dementia (VaD) (Cognitive decline caused by reduced blood flow to the brain, often following strokes) and AD. However, studies on late-life hypertension show inconsistent results.
Antihypertensive use has been associated with reduced dementia risk, but its impact on AD remains unclear. Further research is needed to clarify the specific effects of BP and antihypertensive use on AD and non-AD risk, particularly considering variations by sex, age, and ethnicity.
About the study
The present analysis included data from 14 community-based longitudinal studies of aging, encompassing 31,250 participants from the Cohort Studies of Memory in an International Consortium (COSMIC) group.
This previously described consortium involves studies from 14 countries, examining cognitive changes and dementia diagnoses over time.
Participants were excluded if they were under 60 years old or had a dementia diagnosis at baseline. The studies varied in follow-up duration from 2 to 15 years. All participants provided consent, and each study obtained independent ethics approval.
BP measurements were taken at baseline, with up to three readings averaged. Hypertension history, antihypertensive medication use, and various covariates like age, education, sex, and health conditions were included in the analysis. Outliers in BP readings were excluded. Dementia outcomes were categorized as AD or non-AD based on diagnoses made within each study.
Statistical analyses were pre-specified, utilizing a one-step individual participant data approach, incorporating mixed-effects Cox proportional hazards survival models.
The main analysis focused on hypertension history and antihypertensive use, while additional analyses explored the effects of BP control, interaction with demographic factors, and specific risks for VaD. Data harmonization and analysis were conducted using R 4.3.1, with significance set at p < 0.05.
Study results
The study included 56,821 total participants from various community-based longitudinal studies. After excluding 2,884 participants with dementia at baseline, the analysis focused on 31,250 dementia-free individuals, representing 55% of the original cohort.
The mean baseline age of the participants was 72.1 years, with a standard deviation (SD) of 7.5 years, and 41% were male. The average follow-up period was 4.2 years (SD = 3.9), and the mean years of education was 8.3 years (SD = 5.3). The mean baseline systolic blood pressure (SBP) was 137.8 mm Hg (SD = 21), and the mean diastolic blood pressure (DBP) was 79.9 mm Hg (SD = 11.2).
Participants were categorized into different hypertension/antihypertensive groups, with 50.7% as having treated hypertension, 35.9% classified as “healthy controls,” and 9.4% as having untreated hypertension.
Those with untreated hypertension were more likely to have fewer years of education, be current smokers, be less likely to be Asian, and have lower baseline Mini-Mental State Examination (MMSE) scores compared to healthy controls.
The mean time to diagnosis of AD and non-AD dementia was 4.2 years (SD = 3.3) and 4.1 years (SD = 3.6), respectively, though these measures varied significantly by study.
Among the studies that included VaD diagnosis data, 35.6% of dementia cases were non-AD, and 45.2% of these non-AD cases were classified as VaD, representing 16.1% of all dementia cases.
In the primary analysis, participants with untreated hypertension had a significantly higher risk of developing AD (hazard ratio [HR] 1.363, 95% confidence interval [CI] 1.013–1.832, p = 0.0406) compared to healthy controls. However, those with treated hypertension did not show an increased risk of AD.
In contrast, both treated and untreated hypertension were associated with a higher risk of non-AD dementia compared to healthy controls. The untreated hypertension group also had a significantly higher risk of AD compared to those with treated hypertension (HR 1.418, 95% CI 1.075–1.872, p = 0.0135). However, the risk of non-AD did not differ significantly between these groups.
Further analysis, considering additional vascular covariates, showed that the association with AD remained significant, but the associations with non-AD did not. When the analysis was restricted to participants with more than five years of follow-up, none of the associations remained significant.
Heterogeneity across studies was generally low, except when comparing untreated hypertension to healthy controls or treated hypertension to healthy controls, where heterogeneity was higher.
The analysis of VaD risk yielded similar results to the non-AD analysis, with untreated hypertension showing a greater risk compared to treated hypertension. Additionally, baseline SBP was positively associated with VaD risk in participants with more than five years of follow-up.
Conclusions
To summarize, this study found that untreated hypertension in late life significantly increased the risk of AD compared to both healthy controls and those with treated hypertension. No difference in AD risk was observed between those with effectively controlled and uncontrolled hypertension.
Both treated and untreated hypertension were linked to higher non-AD risk, with untreated hypertension particularly increasing the risk of vascular dementia.
Baseline blood pressure did not predict AD risk, though diastolic blood pressure showed a U-shaped relationship with non-AD risk over time. The findings emphasize the importance of antihypertensive use in reducing AD risk.
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