Blood pressure drug may reduce Alzheimer's risk in older Black adults

• The Alzheimer’s Association has called Alzheimer’s disease (AD) a “silent epidemic” among African American adults.
• Historically, however, African Americans have been less likely to participate in AD clinical studies.
• Researchers recently found that telmisartan, a hypertension drug, may lower the risk of AD in Black people over age 60. However, this benefit was not evident among white seniors.
• The experts say that exploring ethnicity-specific responses to medications “holds potential for drastically improving patient care.”

About 6.5 million Americans ages 65 and over are living with Alzheimer’s disease, the fifth-leading cause of death among this population.

Ethnic groups have different AD rates of prevalence, risk factors, and symptoms. Black adults over the age of 60 are up to twice as likely to develop AD than white adults.

A new study suggests that different ethnicities may respond differently to certain therapies. The investigation, culling data from millions of individuals, found that the drug telmisartan is associated with a lower incidence of AD in older Black adults but not older white adults.

Dr. Feixiong Cheng, who spearheaded this research at his laboratory at Cleveland Clinic’s Genomic Medicine Institute, said:

“Considering race-specific drug responses holds potential for drastically improving patient care. Identifying these candidate drugs can also reveal more information about the disease itself through referencing the medicine’s targets.”

The results appear in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

Repurposing Telmisartan

Telmisartan is a strong but generally well-tolerated prescription medication for regulating blood pressure. It is an angiotensin II receptor blocker (ARB), which works by blocking an enzyme that narrows blood vessels.

Telmisartan shows more advantages than other ARBs for people with diabetes (T2D) and chronic kidney disease (CKD) as well as hypertension. Further, animal studies indicate that this drug may help reduce cognitive decline.

Considering the higher prevalence of these diseases among Black adults, researchers wondered if telmisartan might help protect against AD as well. However, this population is underrepresented in most research, including dementia studies.

To find a link, the scientists explored data on over 5.6 million AA and non-Hispanic European Americans ages 60 years and older.

AI and genome sequencing

Dr. Cheng and his team applied artificial intelligence and a range of statistical analyses to test for “causal relationships between telmisartan’s target and AD.”

His lab also harnessed human genome sequencing data from the Alzheimer’s Disease Sequencing Project, a nationwide program set up to uncover genetic determinants and effective therapies for AD.

The researchers screened 5.62 million individuals ages 60 or older from a database of insured people. Subjects included 115,394 Black ARB users and 583,941 non-Hispanic European American ARB users enrolled in their insurance plans for three or more years.

Lowered dementia risk

The research team found that, over five years, older Black adults with moderate or high telmisartan exposure had a 2.5% incidence of AD or dementia. The AAs with low or no telmisartan exposure had a 3.8% incidence of AD.

Moreover, moderate or high telmisartan exposure over was associated with a 6.3% incidence of dementia for Black participants. AAs with low or no telmisartan exposure during this time had 8.6% dementia incidences.

Among non-Hispanic European American participants in the study, the level of telmisartan exposure did not affect the incidence of AD and dementia.

Telmisartan’s possible protective mechanisms

Dr. Cheng’s team pointed out that telmisartan’s AA-specific benefits for AD may be due to its multi-targeted effects on hypertension, diabetes, and the kidneys.

Telmisartan’s effect on peroxisome proliferator-activated receptors (PPAR-y) promotes carbohydrate and lipid metabolism, lessening the severity of inflammation and diabetes.

Dr. Cheng said that the drug has demonstrated benefits for kidney dysfunction, which is associated with an increased AD and dementia risk in Blacks. A 2021 JAMA Neurology study reported that the renal system is “an important new pathway impacted by AD risk loci in the AA population.”

Crossing the blood-brain barrier

Even at low doses, telmisartan can penetrate the blood-brain barrier. This may enable the medication to reduce plaque accumulation, which has been thought to contribute to cognitive decline.

In animal studies, the drug also suppressed neuroinflammation, oxidative stress, and neuronal cell death.

The study’s limitations

The researchers cautioned that their study’s results do not establish causality and may not extend to all older Americans.

The patient data included people enrolled in commercial insurance plans and Medicare Advantage. As of 2022, 48% of Medicare beneficiaries have Medicare Advantage, which provides additional benefits not covered by traditional Medicare.

The data sources did not include socioeconomic status, education level, blood pressure records, or results from neurological exams, brain imaging studies, or genotypes.

Additionally, the telmisartan dosage information captured may not have reflected actual medication usage. The experts stressed that “joint modeling of dosing frequency and dosage strength is an important future direction for the development of statistical methodology.”

Further, the authors stated that small populations of Black adults who participated in AD genetic studies influenced the outcome of their analyses. They hope that future examinations will use larger samples.

“Exciting” potential

Nevertheless, Dr. Scott Kaiser, a geriatrician and director of Geriatric Cognitive Health for the Pacific Neuroscience Institute at Providence Saint John’s Health Center in Santa Monica, CA, who was not involved in the study, was greatly impressed with the magnitude of this research.

Speaking with Medical News Today, Dr. Kaiser commented:

“The ‘take homes’ for me were that it’s exciting to see this kind of work that looks at things at a population level like this, […] being able to look at the big picture and then focus in on control trials that can be better targeted so that we can [find] effective treatment and preventive strategies of AD and related dementias.”

Dr. Kaiser said he was encouraged by the findings which identified potential for an “orchestral, multimodal approach” that might target AD markers.

Fixing the lack of racial mix

Dr. Derek M. Griffith, the founding co-director of the Racial Justice Institute, founder and director of the Center for Men’s Health Equity, and professor of health systems administration and oncology at Georgetown University in Washington, DC, shared further insights with MNT.

Dr. Griffith, who was not involved in this research, believed that Black participants have been left out of clinical research because healthcare providers are not inviting them to participate.

He said that providers “have to think that you’re eligible and that you’ll actually do it. So often, we are not asked, or the assumption is that we won’t […] keep up with the protocol […]”

However, Dr. Griffith said he has observed higher participation rates with studies that specifically target Black populations.

Being culturally sensitive

Dr. Griffith argued that securing Black participation requires a more personalized, culturally sensitive approach.

In his experience, Black participants respond more favorably when researchers frame their pitch around a collective benefit: “We may be willing to participate if we know that it’s important for Black people to be represented […]”

Further, he recommended appealing to the prospective subjects’ inner motivation. In his research, he said: “One of the ways that we ask or frame the way that we want them to engage is, what’s your ‘why’?”

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