Some antihypertensive medications may lower dementia risk

Use of angiotensin II (ATII)-stimulating antihypertensive medication (AHM), angiotensin receptor blockers (ARBs), and dihydropyridine calcium channel blockers (CCBs) helps reduce the risk of dementia over a decade, but this beneficial effect decreases over time, according to a study.

“Possibly, significant associations observed in the short-term represented effects that were to some extent temporary or could not be replicated over the complete follow-up period because baseline AHM data were not fully representative of actual medication use over time,” the researchers said.

“However, even temporary effects, resulting in delayed manifestation of dementia, could be meaningful to both individuals and society,” they added.

Data from a dementia prevention trial (preDIVA and its observational extension), involving Dutch community-dwelling older adults without prior diagnosis of dementia, were analysed in this post hoc observational study. The researchers examined the differential associations between AHM classes and incident dementia after 7.0 and 10.4 years based on the median follow-up duration of dementia cases and all participants.

The risk of dementia after 7 years was lower among individuals who used ATII-stimulating antihypertensives (hazard ratio [HR], 0.68, 95 percent confidence interval [CI], 0.47‒1.00), ARBs (HR, 0.54, 95 percent CI, 0.31‒0.94), and dihydropyridine CCBs (HR, 0.52, 95 percent CI, 0.30‒0.91). [J Hypertens 2023;41:262-270]

Although this beneficial effect decreased after 10.4 years (ATII-stimulating antihypertensive: HR, 0.80, 95 percent CI, 0.61‒1.04; ARBs: HR, 0.75, 95 percent CI, 0.53‒1.07; dihydropyridine CCBs: HR, 0.73, 95 percent CI, 0.51‒1.04), dementia risk was still lower when compared with use of other AHM classes.

“Results could not be explained by competing risk of mortality,” the researchers said.

Earlier studies suggest that many risk factors for dementia are age-dependent, which is why the differential effects of AHM classes partly decrease with ageing. However, analyses stratified by age do not support this premise, according to the researchers. [Lancet Neurol 2005;4:487-499; Neurology 2005;64:1689-1695; J Alzheimers Dis 2015;43:739-755]

Another possible reason is that baseline data on medication use may have become less reliable indicators of actual medication use with increasing follow-up time.

“Nevertheless, sensitivity analyses in participants who used the same AHM class at baseline and during at least one follow-up visit did not substantially alter our results,” the researchers said.

In a recent meta-analysis, use of CCBs and ARBs correlated with a 12‒17 percent reduced dementia risk compared with angiotensin-converting enzyme inhibitors and beta blockers, but less so relative to diuretics (7‒11 percent). [J Am Med Dir Assoc 2021;22:1386.e15-1395.e15]

“However, all but one included studies had a follow-up period of less than approximately 7 years and most applied nonuse of AHM classes, including individuals who did not use any AHM at all, as reference groups, hindering accurate comparison with our results,” the researchers said. [Neurology 2016;87:601-608; Neurobiol Aging 2005;26:157-163; PLoS One 2015;10:e0140633]

“Further studies assessing the sustainability of class-specific associations in older adults should constitute detailed registration of AHM use over time, to account for intermediate class-changes and to assess potential dose–effect relationships,” they noted.