Analyzing data from more than 5 million patients revealed telmisartan is associated with lower Alzheimer’s disease incidence in Black patients, providing clues for potential treatment and prevention.
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, PhD, Associate Staff at the Cleveland Clinic Genomic Medicine Institute.
More than 6.5 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.”
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, PhD, a member of Dr. Cheng’s lab and Pengyue Zhang, PhD, 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.
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.
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.
Dr. Cheng’s team developed an endophenotype-based drug repurposing methodology that identified the FDA-approved drug sildenafil as a candidate for the prevention and treatment of Alzheimer’s disease.
Dr. Cheng will develop and implement computational tools to identify and test novel repurposable drugs and drug combinations for Alzheimer’s disease.
With this award, Dr. Cheng’s team will develop artificial intelligence and machine learning tools capable of identifying novel endophenotypes and actionable targets for drug repurposing in Alzheimer’s disease.
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