Blood pressure drug could reduce Alzheimer's risk in older black adults

Blood pressure drug could reduce Alzheimer’s risk in older black adults

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Scientists can find new treatments for dementia by ensuring that all races are represented in clinical trials. Visual Vic/Getty Images
  • 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 the blood pressure drug telmisartan may reduce the risk of Alzheimer’s disease in black people over 60. However, this benefit was not evident in older Caucasians.
  • Experts say exploring ethnicity-specific responses to drugs “has the potential to dramatically improve patient care.”

About 6.5 million Americans 65 and older live with Alzheimer’s disease, the fifth leading cause of death in this population.

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

A new study suggests that different ethnicities may respond differently to certain therapies. The survey, bringing together data from millions of individuals, found that the drug telmisartan is associated with a lower incidence of Alzheimer’s disease in older black adults, but not in older white adults.

Dr. Feixiong Cheng, who led this research in his lab at the Cleveland Clinic’s Genomic Medicine Institute, said:

“Considering race-specific drug responses offers potential to dramatically improve patient care. Identifying these drug candidates may also reveal more information about the disease itself by benchmarking drug targets.

The results appear in Alzheimer’s and dementia: the journal of the Alzheimer’s Association.

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

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

Given the higher prevalence of these diseases in black adults, researchers wondered if telmisartan might also help protect against Alzheimer’s disease. However, this population is underrepresented in most research, including dementia studies.

To find a link, scientists mined data on more than 5.6 million non-Hispanic and AA European Americans aged 60 and older.

Dr Cheng and his team applied artificial intelligence and a range of statistical analyzes to test the “causal relationships between the telmisartan target and AD”.

His laboratory has also used human genome sequencing data from Alzheimer’s Disease Sequencing Projecta national program set up to discover genetic determinants and effective therapies for AD.

The researchers examined 5.62 million people aged 60 or over from a database of insured persons. 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.

The research team found that over five years, older black adults with moderate or high exposure to telmisartan had a 2.5% incidence of AD or dementia. AA with little or no exposure to telmisartan had an AD incidence of 3.8%.

Additionally, moderate or high exposure to telmisartan was associated with a 6.3% incidence of dementia in black participants. AAs with little or no exposure to telmisartan during this period had an incidence of dementia of 8.6%.

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

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

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

Dr. Cheng said the drug has shown benefits for kidney dysfunction, which is associated with an increased risk of Alzheimer’s disease and dementia in black people. 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 cross the blood-brain barrier. This may allow the drug to reduce plaque buildup, which is thought to contribute to cognitive decline.

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

The researchers cautioned that the results of their study do not establish causation and may not extend to all older Americans.

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

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

Additionally, the telmisartan dosage information entered may not reflect actual drug usage. Experts pointed out that “the joint modeling of dosing frequency and dosing strength is an important future direction for the development of statistical methodology”.

Additionally, the authors said that small populations of black adults who participated in genetic studies of Alzheimer’s disease influenced the outcome of their analyses. They hope that future reviews will use larger samples.

Nonetheless, Dr. Scott Kaiser, geriatrician and director of geriatric cognitive health at the Pacific Neuroscience Institute at Providence Saint John’s Health Center in Santa Monica, Calif., who was not involved in the study, was very impressed with the scope of this research.

Talk with Medical News TodayDr. Kaiser commented:

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

Dr Kaiser said he was encouraged by the findings that identified the potential for a “multimodal orchestral approach” that could target AD markers.

Dr. Derek M. Griffith, 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 other ideas with DTM.

Dr. Griffith, who was not involved in this research, believed that black participants had been excluded from clinical research because health care providers did not invite them to participate.

He said providers “must think you are eligible and that you will actually do it. Very often we are not asked, or assumed that we will not […] follow the protocol […]”

However, Dr. Griffith said he has seen higher participation rates with studies specifically targeting black populations.

Be culturally sensitive

Dr. Griffith argued that ensuring black participation requires a more personalized and culturally sensitive approach.

In his experience, black participants react more favorably when researchers frame their discourse around a collective benefit: “We may be willing to participate if we know it is important for black people to be represented. […]”

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

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