From a recent study published in Neurology, researchers examined the effects of a history of hypertension, use of antihypertensive medications, and baseline blood pressure (BP) on the risk of developing Alzheimer’s disease (AD) and non-AD later in life.
Study: Blood pressure, use of antihypertensive medications and risk of Alzheimer’s and non-Alzheimer’s dementia later in life. Image credits: Orawan Pattarawimonchai/Shutterstock.com
Background
Hypertension, which affects 1.3 billion people worldwide, is the leading cause of stroke and cerebrovascular disease. Hypertension in mid-life has been associated with a higher risk of vascular dementia (VaD) (cognitive decline caused by reduced blood flow to the brain, often after strokes) and AD. However, research into hypertension in later life shows inconsistent results.
The use of antihypertensive medications has been associated with a reduced risk of dementia, but their impact on AD remains unclear. Further research is needed to clarify the specific effects of BP and antihypertensive drug use on AD and non-AD risk, especially given the variations by gender, age, and ethnicity.
About the study
The current analysis included data from 14 community-based longitudinal studies on aging, involving 31,250 participants from the Cohort Studies of Memory in an International Consortium (COSMIC) group.
This previously described consortium includes studies from 14 countries examining cognitive changes and dementia diagnoses over time.
Participants were excluded if they were younger than 60 years or had a diagnosis of dementia at baseline. The studies ranged in follow-up duration from 2 to 15 years. All participants gave consent and each study received independent ethical approval.
Blood pressure measurements were taken at baseline, with a maximum of three measurements being averaged. History of hypertension, use of antihypertensive medications and several covariates such as age, education, sex and health status were included in the analysis. Outliers in blood pressure measurements were excluded. Dementia outcomes were categorized as AD or non-AD based on the diagnoses made within each study.
Statistical analyzes were prespecified using a one-step approach to individual participant data using Cox proportional hazards mixed-effects survival models.
The main analysis focused on history of hypertension and use of antihypertensive medications, while additional analyzes examined the effects of blood pressure control, interaction with demographic factors, and specific risks for VaD. Data harmonization and analysis were performed using R 4.3.1, with significance set at p < 0.05.
Study results
The study included a total of 56,821 participants from several 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 participants was 72.1 years, with a standard deviation (SD) of 7.5 years, and 41% were male. The mean follow-up period was 4.2 years (SD = 3.9) and the mean years of education was 8.3 years (SD = 5.3). Mean baseline systolic blood pressure (SBP) was 137.8 mm Hg (SD = 21) and mean diastolic blood pressure (DBP) was 79.9 mm Hg (SD = 11.2).
Participants were classified into different hypertension/antihypertensive groups, with 50.7% treating hypertension, 35.9% classified as ‘healthy controls’ and 9.4% having untreated hypertension.
Those with untreated hypertension were more likely to have had fewer years of education, were current smokers, were less likely to be Asian, and had 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, although these measures varied significantly across studies.
Of 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 cases of dementia.
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 showed no increased risk of AD.
In contrast, both treated and untreated hypertension were associated with a higher risk of non-AD dementia compared with healthy controls. The untreated hypertension group also had a significantly higher risk of AD compared with 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, taking into account 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 between studies was generally low, except when comparing untreated hypertension with healthy controls or when comparing treated hypertension with 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. Furthermore, baseline SBP was positively associated with VaD risk in participants with more than five years of follow-up.
Conclusions
In summary, this study found that untreated hypertension in later life significantly increased the risk of AD compared to both healthy controls and people with treated hypertension. No difference in AD risk was observed between those with effectively controlled and uncontrolled hypertension.
Both treated and untreated hypertension were associated with higher non-AD risk, with untreated hypertension particularly increasing the risk of vascular dementia.
Baseline blood pressure did not predict AD risk, although diastolic blood pressure showed a U-shaped relationship with non-AD risk over time. The findings highlight the importance of using antihypertensive medications in reducing AD risk.