Sexual and Gender Minorities More Likely to Have Adverse Brain Outcomes

People who identified as a sexual or gender minority (LGBTQ+) had a higher likelihood of adverse brain health outcomes, cross-sectional data showed.

Among nearly 400,000 participants in the All of Us research program, sexual and gender minority persons had higher odds of a composite outcome of stroke, dementia, and late-life depression than others (OR 1.15, 95% CI 1.08-1.22), reported Guido Falcone, MD, of Yale School of Medicine in New Haven, Connecticut, and co-authors in Neurology.

As a group, sexual and gender minority persons had significantly higher odds of late-life depression (OR 1.27, 95% CI 1.17-1.38).

The group trended toward higher odds of dementia (OR 1.14, 95% CI 1.00-1.29), which was significantly elevated among gender-diverse participants (assigned female at birth OR 1.94 95% CI 1.06-3.56; assigned male at birth OR 2.57, 95% CI 1.25-5.30).

Stroke risk was not higher for the overall group, but it was for transgender women (OR 1.68, 95% CI 1.04-2.70).

“This study highlights brain health disparities in sexual and gender minority populations, a group that has been historically underrepresented in neurological research,” co-author Shufan Huo, MD, PhD, also of Yale, told MedPage Today. “Understanding the unique risks that sexual and gender minority individuals face can help shape more inclusive care and interventions, ultimately improving outcomes for these communities.”

It’s “concerning how little is known about the health disparities faced by LGBTQ+ people,” Huo observed. Few studies have extensively examined neurologic health in sexual or gender minority communities.

“The findings of this study indicate higher odds of dementia among sexual and gender minorities, which is a significant public health concern,” said Jason Flatt, PhD, MPH, of the University of Nevada, Las Vegas, who wasn’t involved with the research.

“The increased odds of dementia among transgender and gender-diverse groups are particularly alarming,” Flatt pointed out.

“Many underrepresented sexual and gender minority groups face adverse social determinants of health, such as economic insecurity, discrimination, lower likelihood of having a caregiver, and reduced access to dementia care, including diagnosis and treatment,” he told MedPage Today.

Falcone and co-authors culled data from the NIH’s All of Us research program, a U.S. population-based study. Baseline questionnaires identified sexual minority (lesbian, gay, bisexual, or diverse sexual orientation) and gender minority (gender-diverse or transgender) participants. Data were collected from 2017 to 2022.

The primary outcome was a composite of stroke, dementia, and late-life depression — whichever occurred first — from electronic health record data and self-reports. Late-life depression was defined as a depressive episode first diagnosed at or after age 60.

“The bidirectional relationship between late-life depression and dementia, along with the well-described occurrences of post-stroke depression and post-stroke dementia, further complicates distinguishing between these conditions,” the researchers wrote. “Thus, including them under the umbrella of brain health reflects their interconnected nature.”

Overall, 393,041 people were included in the analysis. Of those, 39,632 people (10%) were categorized as sexual and gender minority participants.

Mean age in the study was 51 years, and about 62% of participants were assigned female sex at birth. The prevalence of cardiovascular risk factors was lower in the sexual and gender minority group, but the prevalence of smoking, substance use disorder, and HIV infection was higher.

The prevalence of the composite brain health outcome was 5.4% throughout the study, including 11,553 cases of late-life depression, 6,605 cases of stroke, and 2,933 cases of dementia.

The study had several limitations, the researchers acknowledged. It was cross-sectional and subject to unmeasured confounders. It did not assess variables like gender-affirming hormone therapy in transgender persons, which may have influenced some outcomes.

“We have no evidence that being a sexual or gender minority directly causes worse brain health,” Huo emphasized. “Based on what is known, there is no reason to believe that this is the case.”

“Research has shown the effect of external factors like stigma, discrimination, and lack of access to adequate healthcare on many health issues,” she continued. “These systemic challenges increase stress and other risk factors that can affect brain health outcomes — for example, through neuroinflammation — rather than the individual’s gender or sexuality being a direct cause.”