Summary: Blacks are twice as likely to develop Alzheimer’s later in life as whites. Researchers report that telmisartan, a drug used to treat high blood pressure by blocking angiotensin II, appears to be useful 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 of different ethnicities respond to the same drug could be critical to finding new treatments for Alzheimer’s disease — which the Alzheimer’s Association previously considered a “silent epidemic” among black adults.

A study led by the Cleveland Clinic has been published Alzheimer’s and Dementia: Journal of the Alzheimer’s Association Telmisartan, a drug currently prescribed for high blood pressure, has been shown to reduce the risk of Alzheimer’s disease, particularly in black patients over 60. .

The findings suggest that future clinical trials should prioritize including patients from minority populations to find or strengthen these associations, said Feixiong Cheng, PhD, Cleveland Clinic Genomic Medicine Institute.

More than 6 million people in the US suffer from Alzheimer’s disease, the most common form of dementia. Black adults over age 60 are 1.5 to two times more likely to develop Alzheimer’s disease than white patients. So far, there is only one drug approved to treat the underlying cause of Alzheimer’s in the brain, although there are other options for addressing symptoms.

“Considering race-specific drug responses has the potential to greatly improve patient care,” said Dr. Cheng. “Identifying these candidate drugs will reveal more information about the disease with reference to the drug’s targets.”

Turning to data to find new treatments

Dr. Cheng’s team is applying new research methods using artificial intelligence from Cleveland Clinic’s extensive electronic medical record systems to identify new targets and repurposed drugs for Alzheimer’s treatment. Yuan Hu, PhD, a member of Dr. Cheng’s lab, and Pengyu Zhang, PhD, Indiana University School of Medicine, are co-first authors on the study.

Dr. Cheng’s lab at the Cleveland Clinic’s Lerner Research Institute uses human genome sequencing data from the Alzheimer’s Disease Sequencing Project.

For this study, researchers used a state-of-the-art retrospective cohort design analysis to examine data from more than 5 million patients in the Alzheimer’s Disease Sequencing Project. They found that telmisartan was significantly associated with a reduced risk of Alzheimer’s disease in black participants.

Telmisartan is part of a group of medicines that treat high blood pressure by blocking the hormone angiotensin II, which causes blood vessels to constrict. The antihypertensive drug lisinopril, which treats high blood pressure differently, did not show the same benefit as telmisartan, an angiotensin II blocker that may be useful in preventing or treating Alzheimer’s in black patients.

Designing more comprehensive clinical trials

Black patients are more likely to develop Alzheimer’s-related diseases, such as high blood pressure, diabetes, and chronic kidney disease. Researchers are working to determine how regular medical management of these conditions is associated with a reduced risk of developing Alzheimer’s while taking telmisartan.

Although black patients are more likely to develop Alzheimer’s and suffer from comorbidities, they are chronically underrepresented in clinical trials. Keeping this in mind when recruiting for trials can help generate diverse population genetic information that is important for further testing and drug discovery, says Dr. Cheng.

Financial support The research was supported by the National Institute on Aging (NIH) and the Cleveland Alzheimer’s Disease Research Center’s Translational Therapeutics Core.

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So Neuropharmacology and Alzheimer’s Disease Research News

Author: Alicia Royal
Source: Cleveland Clinic
Contact: Alicia Real – Cleveland Clinic
Image: The image is in the public domain.

Preliminary study: Open Access.
“A population-based discovery and Mendelian randomization analysis identified telmisartan as a candidate drug for Alzheimer’s disease in African Americans.” by Feixiong Cheng et al. Alzheimer’s and dementia

Draft

A population-based discovery and Mendelian randomization analysis identified telmisartan as a candidate drug for Alzheimer’s disease in African Americans.

Introduction

African Americans (AAAs) and European Americans (EAs) differ in Alzheimer’s disease (AD) prevalence, risk factors, and symptom presentation, and AAs are less likely to be enrolled in AD clinical trials.

Methods

Using Cox analysis, Kaplan-Meier analysis, and log-rank test, telmisartan exposure and AD were compared. To test results, we conducted a pharmacoepidemiological study of 5.62 million elderly (age ≥60) stratified by ethnicity. To test the causal relationship between telmisartan targeting and AD, we performed a Mendelian randomization (MR) analysis of genetic data with large genetic variation.

Results

We identified that moderate/high telmisartan exposure was significantly associated with ADA incidence compared with low/no telmisartan exposure (hazard ratio) in AAs. [HR] = 0.77, 95% CI: 0.65–0.91; Page-value = 0.0022), but not in non-Hispanic EAs (HR = 0.97, 95% CI: 0.89–1.05; Page-value = 0.4110). Sensitivity and sex-/age-stratified patient subgroup analyzes of telmisartan drug-property ratio (MPR) and mean blood pressure daily rate in patients with AD. and dementia in AAA. Using MR analysis from large genome-wide association studies (GWAS) (over 2 million individuals) in AD, hypertension, and diabetes, we identified AA-specific beneficial effects of telmisartan for AD.

Discussion

Randomized controlled trials with ethnically diverse patient groups to establish the causal and therapeutic effects of telmisartan and AD.