Blood–brain barrier crossing antihypertensives linked to lower dementia and mortality risk
核心洞察
A prospective analysis of 66,610 propensity-matched hypertensive adults found BBB-crossing antihypertensives were associated with a 16% lower risk of new-onset dementia (搜索) (HR 0.84; 95% CI 0.80–0.88).
Use of BBB-crossing antihypertensives was also linked to reduced all-cause mortality (HR 0.83) and dementia (搜索)-related mortality (HR 0.85) over a mean follow-up of 11.9 years.
Among drug classes, only angiotensin II receptor blockers (HR 0.89) and β-blockers (搜索) (HR 0.76) significantly reduced dementia (搜索) risk, with no significant sex interaction (p = 0.067).
A prospective cohort study using the 45 and Up Study has found that use of blood–brain barrier (BBB)-crossing antihypertensive medications (AHMs) is associated with a significantly lower risk of new-onset dementia (搜索), all-cause mortality, and dementia-related mortality compared with non-BBB-crossing antihypertensives. The analysis, which included 66,610 propensity-matched participants with hypertension (搜索), positions BBB crossing as a potentially relevant pharmacokinetic property influencing dementia prevention.
The study included participants aged 45 years and older with hypertension (搜索) who initiated either BBB-crossing or non-crossing AHMs between January 2004 and June 2022. Participants were followed from the index date until dementia (搜索) diagnosis, death, or 30 June 2023. BBB-crossing AHM users were propensity matched (1:1) with non-crossing AHM users by age, sex, smoking status, and follow-up duration.
After matching, the cohort comprised 66,610 participants with a mean age of 66.9 years (standard deviation 9.3), of whom 53.2% were women, and a mean follow-up of 11.9 years (standard deviation 5.3). Cox proportional hazards models, adjusted for covariates including diet and physical activity, were used to estimate hazard ratios (HRs) for incident dementia (搜索), all-cause mortality, and dementia-related mortality.
Compared with non-BBB-crossing AHMs, use of BBB-crossing AHMs was associated with a lower risk of new-onset dementia (搜索) (HR, 0.84; 95% CI 0.80–0.88), all-cause mortality (HR, 0.83; 95% CI 0.82–0.86), and dementia-related mortality (HR, 0.85; 95% CI 0.79–0.92).
Subgroup analyses revealed a significant reduction in dementia (搜索) risk for both females and males, with no significant sex interaction (p = 0.067). When examined by AHM class, only angiotensin II receptor blockers (HR, 0.89; 95% CI 0.80–0.99) and β-blockers (搜索) (HR, 0.76; 95% CI 0.63–0.93) were found to significantly reduce the risk of dementia.
The dementia (搜索)-protective effect of BBB-crossing AHMs remained significant in sensitivity analyses, both after excluding individuals with hypertension (搜索) identified solely by AHM use (HR, 0.84; 95% CI 0.79–0.89) and when accounting for competing mortality risk (HR, 0.84; 95% CI 0.80–0.89).
The authors conclude that use of BBB-crossing AHMs was associated with a reduced risk of dementia (搜索) and mortality, and that the findings highlight BBB crossing as a potentially relevant pharmacokinetic property of AHMs influencing dementia prevention, warranting further investigation in randomised controlled trials.