Exposure to telmisartan reduced the incidence of Alzheimer disease (AD), specifically among older African American patients, according to findings published in Alzheimer’s & Dementia.
Telmisartan is an angiotensin II receptor blocker (ARB) used to treat hypertension. It is also the only ARB that is a partial agonist of peroxisome proliferative-activated receptor gamma (PPAR-γ), which has proven to inhibit cognitive decline in animal studies. PPAR-γ agonists demonstrate beneficial effects that inhibit onset of diabetes and improve renal function, mitigating risk for cognitive decline.
Researchers conducted race-conscious pharmacoepidemiologic studies, analyzing the correlation between exposure to telmisartan and onset of AD in 5.62 million people aged 60 years and older. Additionally, they used Mendelian randomization (MR) analysis to estimate causal relationships between telmisartan and AD in specific ethnic groups, especially among African American patients who demonstrate a higher prevalence of hypertension, type II diabetes, chronic kidney disease, and AD.
The researchers discovered that moderate to high levels of telmisartan exposure significantly reduced the incidence of AD among African American patients compared with low or no exposure to the drug (hazard ratio [HR], 0.77; 95% CI, 0.65-0.91; P =.0022).
In contrast, this beneficial effect of telmisartan exposure reducing onset of AD was not observed among non-Hispanic American adults of European ancestry (HR: 0.97, 95% CI, 0.89-1.05; P =.4110).
Duration of telmisartan exposure as calculated by the medication possession ratio (MPR) and the average hypertension daily dosage of telmisartan significantly correlated with increased reduction of AD and dementia among African American patients.
The MR analysis using ethnically diverse genetic data revealed that the PPAR-γ agonistic properties of telmisartan significantly correlated with the protective effect of the drug in African American patients with diabetes, hypertension, and/or chronic kidney disease compared with other ethnic groups.
“Using state-of-the-art retrospective cohort design analyses, we demonstrated that moderate/high telmisartan exposure was significantly associated with reduced risk of AD and dementia in [African American patients],” the researchers noted. “Our population-based discovery and MR analyses suggest that telmisartan offers a potential treatment for AD and dementia with uniquely specific efficacy in [African American] people.”
Study limitations included sole use of commercial insurers and Medicare Advantage beneficiaries for patient data, lack of assessment of education levels, socioeconomic status, brain imaging, and neurocognitive testing, which might influence study results. There was also a lack of assessment of actual medication usage/consumption. Additionally, despite the MR analysis, the researchers could not confirm cause and effect between telmisartan exposure and AD onset.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Zhang P, Hou Y, Tu W, et al. Population-based discovery and Mendelian randomization analysis identify telmisartan as a candidate medicine for Alzheimer’s disease in African Americans. Alzheimers Dement. Published online November 4, 2022. doi:10.1002/alz.12819