Summary: Black people are almost twice as likely to develop Alzheimer’s disease later in life than white people. Researchers report Telmisartan, a drug used to treat high blood pressure by blocking angiotensin II, appears to be helpful in preventing or treating Alzheimer’s disease in Black individuals. The drug did not show the same potential in white people.
Source: Cleveland Clinic
Considering how patients from different ethnic groups respond to the same drug could be crucial to finding new Alzheimer’s disease treatments – a disorder the Alzheimer’s Association previously deemed a “silent epidemic” among Black adults.
A Cleveland Clinic-led study published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association showed that telmisartan, a drug currently prescribed for people with high blood pressure, is associated with a lower risk of Alzheimer’s specifically in Black patients over age 60. Insurance data from millions of adults over age 60 did not show the same potential effect in white patients.
The findings suggest that future clinical trials should prioritize including patients from minority populations to find or reinforce these associations, says Feixiong Cheng, Ph.D., Cleveland Clinic Genomic Medicine Institute.
More than 6 million people in the U.S. suffer from Alzheimer’s disease, the most common form of dementia. Black adults over age 60 are 1.5 to twice as likely to develop Alzheimer’s than white patients. So far there is only one drug approved to treat a potential underlying cause for Alzheimer’s directly in the brain, though there are other options for addressing symptoms.
“Considering race-specific drug responses holds potential for drastically improving patient care,” Dr. Cheng says. “Identifying these candidate drugs can also reveal more information about the disease itself through referencing the medicine’s targets.”
Turning to data to find new treatments
Dr. Cheng’s team is applying innovative research techniques using artificial intelligence and de-identified data from Cleveland Clinic’s expansive electronic medical record systems to identify novel targets and repurposable medicines for Alzheimer’s treatment. Yuan Hou, Ph.D., a member of Dr. Cheng’s lab and Pengyue Zhang, Ph.D., Indiana University School of Medicine, are co-first authors on the study.
Dr. Cheng’s lab in Cleveland Clinic’s Lerner Research Institute utilizes human genome sequencing data from the Alzheimer’s Disease Sequencing Project, a nationwide network aiming at identifying the genetic underpinnings and effective drug targets for Alzheimer’s disease.
For this study, researchers used state-of-the-art retrospective cohort design analysis to examine data of more than 5 million patients in the Alzheimer’s Disease Sequencing Project. They found that telmisartan was significantly associated with a reduced incidence of Alzheimer’s in Black participants.
Telmisartan is part of a group of drugs that treat high blood pressure through blocking angiotensin II, a hormone that causes blood vessels to constrict. A blood pressure medication that treats high blood pressure differently, lisinopril, did not show the same potential benefits as telmisartan, indicating angiotensin II blockers might be helpful in preventing or treating Alzheimer’s in Black patients.
Designing more comprehensive clinical trials
Black patients are more likely to have the comorbidities already associated with Alzheimer’s, like hypertension, diabetes and chronic kidney diseases. Researchers are now working to determine how routine medical management of these conditions might also be associated with the reduced risk of developing Alzheimer’s when taking telmisartan.
Though Black patients are more likely to develop Alzheimer’s and suffer from associated comorbidities, they are chronically underrepresented in clinical trials. Keeping this in mind when recruiting for trials can help produce diverse population genetic data, critical to further investigation and drug discovery, Dr. Cheng says.
Funding: The study was supported by the National Institute on Aging of the National Institutes of Health (NIH), and the Translational Therapeutics Core of the Cleveland Alzheimer’s Disease Research Center.
Population-based discovery and Mendelian randomization analysis identify telmisartan as a candidate medicine for Alzheimer’s disease in African Americans
African Americans (AAs) and European Americans (EAs) differ in Alzheimer’s disease (AD) prevalence, risk factors, and symptomatic presentation and AAs are less likely to enroll in AD clinical trials.
We conducted race-conscious pharmacoepidemiologic studies of 5.62 million older individuals (age ≥60) to investigate the association of telmisartan exposure and AD outcome using Cox analysis, Kaplan–Meier analysis, and log-rank test. We performed Mendelian randomization (MR) analysis of large ethnically diverse genetic data to test likely causal relationships between telmisartan’s target and AD.
We identified that moderate/high telmisartan exposure was significantly associated with a reduced incidence of AD in the AAs compared to low/no telmisartan exposure (hazard ratio [HR] = 0.77, 95% CI: 0.65–0.91, p-value = 0.0022), but not in the non-Hispanic EAs (HR = 0.97, 95% CI: 0.89–1.05, p-value = 0.4110). Sensitivity and sex-/age-stratified patient subgroup analyses identified that telmisartan’s medication possession ratio (MPR) and average hypertension daily dosage were significantly associated with a stronger reduction in the incidence of both AD and dementia in AAs . Using MR analysis from large genome-wide association studies (GWAS) (over 2 million individuals) across AD, hypertension, and diabetes, we further identified AA-specific beneficial effects of telmisartan for AD.
Randomized controlled trials with ethnically diverse patient cohorts are warranted to establish causality and therapeutic outcomes of telmisartan and AD.