Prostate drugs like terazosin may help lower dementia with Lewy bodies risk

Medical News Today Article Written by Corrie Pelc on June 20, 2024 — Fact checked by Jill Seladi-Schulman, Ph.D.

Dementia with Lewy bodies — also known as Lewy body dementia — is the second most common neurodegenerative dementia affecting older adults, accounting for between 15–20% of all dementia cases.

Dementia with Lewy bodies is most likely caused by deposits of a protein called alpha-synuclein in the brain. There is currently no cure for dementia with Lewy bodies, though some medications, physical therapy, and other interventions are available to help manage the disease’s symptoms.

“Right now, we [only] have therapies for symptoms of neurodegenerative diseases like dementia with Lewy bodies,” explained Jacob E. Simmering, PhD, assistant professor of internal medicine — pulmonary, critical care, and occupational medicine at the University of Iowa, and lead author of a new study recently published in Neurology, the medical journal of the American Academy of Neurology.

“They can help reduce the severity of the symptoms but can’t stop the disease from progressing,“ he explained. “This is similar to how taking a Tylenol can help with the pain associated with an injury but doesn’t cause the injury to heal any faster.“

“We need to find a way to slow the progression — or prevent the development — of dementia with Lewy bodies,” Simmering told Medical News Today.

In their new study, Simmering and his team found that males taking three commonly prescribed prostate medications may lower their risk of developing dementia with Lewy bodies.

Why prostate drugs for brain health?

For this study, researchers analyzed health information data for almost 643,000 males taking medication to treat urinary issues caused by an enlarged prostate.

About 126,000 participants were taking the prostate medications terazosin, doxazosin, or alfuzosin.

“We became interested in these medications — terazosin, doxazosin, and alfuzosin — a bit over 5 years ago,” Simmering explained to MNT. “It was realized [then] that the medications have a secondary effect where they activate an enzyme called PGK1.”

“PGK1 is important because it is the first enzyme that produces ATP — the chemical cells use for energy,” he continued.

“We then demonstrated in bench work with animal models — flies, rodents — that these medications seemed to increase ATP molecules in cells and slow or stop the development of neurodegeneration in these models.”

– Jacob E. Simmering, PhD

How terazosin, doxazosin, alfuzosin compare to other prostate drugs

Researchers compared the findings from the participants taking terazosin, doxazosin, or alfuzosin to participants taking other prostate medications — about 437,000 taking tamsulosin and about 80,000 on 5ARIs.

“Terazosin, doxazosin, alfuzosin — our three medications that we think increased energy in the cell — and tamsulosin are all of the same class of medications,” Simmering explained. “All are commonly used to treat this prostate disorder — benign prostatic hyperplasia (BPH) — and work with similar levels of effectiveness. These medications reduce the symptoms of BPH almost immediately once started.”

However, he noted, “[t]he 5ARIs are of a different medication class and work differently.”

“While terazosin, doxazosin, alfuzosin, and tamsulosin help relax muscles around the bladder allowing easier urination, 5ARIs act to reduce the size of the enlarged prostate. 5ARIs work through a hormonal process and take much longer to kick in — a couple [of] months,” Simmering pointed out.

Men on terazosin 40% less likely to develop dementia with Lewy bodies

All study participants were followed for an average of 3 years to see who developed dementia with Lewy bodies.

Upon analysis, the scientists reported that 195 participants taking terazosin, doxazosin, or alfuzosin developed dementia with Lewy bodies for a rate of 5.21 cases per 10,000 people per year.

In comparison, 1,286 participants taking tamsulosin developed dementia with Lewy bodies for a rate of 10.76 cases per 10,000 people per year, and 193 participants in the 5ARIs group developed dementia with Lewy bodies for a rate of 7.78 cases per 10,000 people per year.

After factoring in age and other health conditions, Simmering and his team discovered that male participants taking terazosin, doxazosin, or alfuzosin were 40% less likely to develop dementia with Lewy bodies than participants taking tamsulosin, and 37% less likely than those taking the 5ARIs.

“I am excited about these results for many reasons,” Simmering told us. “[Dementia with Lewy bodies] is a progressive disease in dire need of an effective neuroprotective therapy. We have decades of clinical experience and safety data on these medications, often in elderly patients — the population at the most risk of neurodegenerative diseases.“

“The theorized mechanism — activation of PGK1 creates more energy for the cell to slow or stop the neurodegeneration associated with these diseases — suggests a broad potential benefit,” he continued.

“This association between these prostate medications and risk of [dementia with Lewy bodies] doesn’t provide proof of an effect but it is an exciting development and, hopefully, will someday lead to a treatment demonstrated in a randomized controlled trial,” added Simmering.

New ways to lower dementia with Lewy bodies risk needed

After reviewing this study, Verna Porter, MD, a board-certified neurologist and director of the Dementia, Alzheimer’s Disease and Neurocognitive Disorders at Pacific Neuroscience Institute in Santa Monica, CA, not involved in this research, told MNT she was cautiously optimistic about the findings.

“The findings are promising, suggesting that certain commonly used prostate drugs could potentially offer a protective effect against [dementia with Lewy bodies],“ Porter told us. “Given the significant impact [dementia with Lewy bodies] has on patients’ quality of life and the current lack of effective preventive treatments, this study opens a potential new avenue for reducing the risk of this debilitating disease.”

“However,“ she cautioned, “I am also aware that the study establishes an association rather than causation, so further research is necessary to confirm these findings and understand the underlying mechanisms.”

Porter said there are several reasons why researchers need to continue exploring new ways to reduce dementia with Lewy bodies risk, including the fact that dementia with Lewy bodies is the second most common neurodegenerative dementia after Alzheimer’s disease.

“Currently, there are no drugs specifically approved to prevent or treat [dementia with Lewy bodies] effectively,” she emphasized. “Finding new methods or repurposing existing drugs could help to address this significant therapeutic gap.”

“In addition, neurodegenerative diseases, including [dementia with Lewy bodies], pose a substantial economic burden on healthcare systems due to the need for long-term care and management,” Porter added.

“Preventive strategies could potentially reduce these costs. Identifying ways to reduce the risk of [dementia with Lewy bodies] can greatly enhance the quality of life for at-risk populations, preserving cognitive function and independence for a longer period,” explained the specialist.

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