Antihypertensives and Dementia: Which Class Offers Better Protection?

Key Insights on Blood Pressure Medications and Dementia

• Angiotensin II-stimulating blood pressure medications are associated with fewer changes in small brain vessels.
• The difference is most pronounced in patients on long-term medication for several years.
• Additionally, there is a reduction in phosphorylated tau levels in several brain regions.
• However, no significant differences were observed for amyloid-β42 and other classical Alzheimer’s markers.

What Was Investigated?

A study analyzed data from 756 elderly participants who had documented blood pressure readings and treatment regimens throughout their lives. Brain imaging was used for analysis, and post-mortem tissue samples were examined from 137 participants who passed away during the study period. On average, more than 22 years had elapsed from the first recorded treatment to the study’s conclusion. Researchers aimed to determine whether the two groups of medications were associated with differing brain changes, independently of blood pressure control.

The investigation focused not only on Alzheimer’s-related changes but also on vascular damage in the brain and other dementia-related findings, such as Lewy bodies. Additionally, key Alzheimer-related biomarkers such as amyloid-β42 and phosphorylated tau were quantitatively assessed in some samples.

Reduced Arteriolosclerosis with Sartans and Dihydropyridine CAs

The most significant difference between the two medication groups was observed in the arteriolosclerosis of small brain vessels. Angiotensin II-stimulating blood pressure medications were associated with a lower risk compared to other types:

• For every five additional years of use, the risk was reduced by 6%.
• The reduction was even more substantial with long-term use, showing a 24% lower risk after at least 15 years.

In terms of other types of vascular damage, such as larger and smaller brain infarcts and atherosclerotic changes in larger vessels, no clear differences were evident. Alzheimer-related changes in amyloid deposits, plaques, and neurofibrillary tangles also showed a tendency favoring the stimulating medications, although this was not statistically significant. Similar results were noted for other dementia-related findings, including Lewy bodies and LATE—a form of TDP-43 disease associated with aging.

Variations in Alzheimer Biomarkers

A further aspect of the study revealed differences between the two groups concerning phosphorylated tau levels. Those on angiotensin II-stimulating medications had lower levels of phosphorylated tau in several brain regions, including the temporal lobe, hippocampus, and transentorhinal cortex. No differences were found regarding amyloid-β42 levels between the two groups.

Conclusion

The findings suggest that Sartans and Dihydropyridine calcium antagonists may be associated with more favorable dementia-related brain changes compared to ACE inhibitors, beta-blockers, and non-dihydropyridine calcium antagonists. However, the current data is not sufficient to advocate for specific classes of drugs to be preferentially prescribed or avoided in clinical practice. Further research is necessary, as the study provides valuable insights but has notable limitations: it is an observational study, many participants used both medication groups over time, and corrections for multiple testing were not applied across numerous endpoints. Consequently, causal conclusions cannot be definitively drawn.