A computational study conducted on genetic data from 5.62 million ethnically diverse individuals over 60 years of age, found moderate or high use of temisartan, a drug currently prescribed for people with high blood pressure, is associated with lower risk of Alzheimer’s disease (AD) and dementia in African Americans but not European Americans.
Senior author of the paper, Feixiong Cheng, PhD, scientist at Cleveland Clinic’s Lerner Research Institute said, “The findings suggest that future clinical trials should prioritize including patients from minority populations to find or reinforce these associations.”
The study, published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, uncovers clues for potential treatments and prevention of AD. Yuan Hou, PhD, a postdoctoral fellow in Cheng’s lab and Pengyue Zhang, PhD, assistant research professor of biostatistics and health data science at the Indiana University School of Medicine, are co-lead authors of the study.
According to the U.S. Centers for Disease Prevention (CDC), AD affects 6.2 million Americans: 14% African Americans, 12% Hispanics, and 10% Whites. The prevalence, risk factors, and clinical presentation of AD, as well as responses to the same drugs, are different in African Americans and European Americans. Black adults over age 60 are 1.5 to 2 times as likely to develop AD than white patients. Moreover, black patients are more likely to have comorbidities such as hypertension, diabetes, and chronic kidney diseases.
Though black patients are more likely to develop AD and suffer from associated comorbidities, historical and socioeconomic issues make African Americans less likely to participate 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, said Cheng.
At present, there is only one drug approved to treat a potential underlying cause for AD directly in the brain, and a few other options for addressing related symptoms.
“Considering race-specific drug responses holds potential for drastically improving patient care,” said Cheng. “Identifying these candidate drugs can also reveal more information about the disease itself through referencing the medicine’s targets.”
Cheng’s team used artificial intelligence (AI) and de-identified data from Cleveland Clinic’s electronic medical record (EMR) systems to identify novel drug targets and drugs that could be repurposed for AD. The researchers used human genome sequencing data from the nationwide AD Sequencing Project network that aims to find effective drug targets for AD.
Telmisartan blocks the effects of angiotensin II at its receptors. Angiotensin II is a hormone secreted by various cell types that constricts blood vessels and increases blood pressure as part of the renin-angiotensin system. Angiotensin receptor blockers (ARBs) specifically appear to reduce the incidence of AD in African Americans, whereas other anti-hypertension drugs such as lisinopril act by preventing the conversion of angiotensin I to angiotensin II, did not show the same potential benefits as telmisartan in preventing or treating AD in African American patients.