Why women bear the burden of dementia: Unraveling the sex gap

Almost two-thirds of Americans diagnosed with Alzheimer’s are women, and in many cases experience faster cognitive decline than men. The reasons behind this sex gap have remained a mystery until now.

A study led by Dr. Farida Sorabuji, professor and director of the Women’s Health in the Neuroscience Program at Texas A&M University, observed that biological sex significantly increases the risk of stroke. Elderly womana condition that accelerates the onset and progression of dementia.

“Every ten years from 50 years onwards, women are more likely to experience strokes than men, especially those with severe strokes. Cognitive impairment And it is ultimately dementia, the basis of future drug development and personalized medicine. ”

A new approach to treatment

The Sohrabji findings support the ever-growing number of research in Precision Medicine. This is an approach that coordinates medical care to individual characteristics such as biological sex.

“Similar drugs don’t always work effectively or in the same way on gender. The illness and condition may be the same, but the effects of treatment on the brains of men and women may not,” Sohrabji said.

This insight is urgent for Alzheimer’s disease care, where women make up the majority of patients. For women over the age of 60, the risk of developing Alzheimer’s disease can be nearly twice as likely as breast cancer.

“We’re already customizing and personalizing treatments for certain cancers,” Sorabuji said. “It’s fundamental that we do the same for stroke and dementia, and I think it’s overall better results.”

Sohrabji’s lab set out to understand why women are disproportionately affected by dementia and Alzheimer’s disease.

One important finding points to changes in hormones during menopause. When estrogen levels drop, the female brain becomes more vulnerable to inflammation, damage and ultimately stroke. This is a known contributor to dementia and Alzheimer’s disease.

“We found that estrogen appears to protect against stroke,” she said. “In fact, in a model where the ovaries are removed, the outcome of the stroke was worse, but estrogen treatment reversed it.”

However, the evidence is complicated and the relationship is not easy.

“We repeated the same study and used estrogen substitutions to see if it protects the elderly female model population. To our surprise, it wasn’t,” explained Sohrabji. “Estrogen was actually toxic. The loss of brain tissue was more severe, the damage became more severe, and the damage was followed for a long period of time, and clear signs of neurodegeneration were shown.”

Promise of sex-specific therapy

Based on these complex results, Sohrabji and her team investigated whether a small peptide called IGF-1 (insulin-like growth factor) in combination with estrogen therapy could improve outcomes in middle-aged female models, and investigated whether the findings were groundbreaking.

This combination not only reversed the normal toxic effects of estrogen on this older group, but it was shown that IGF-1 treatment alone was sufficient to improve. stroke result.

“If you give a subject estrogen And IGF-1, you have a clear view of the neuroprotective effect, Sohrabji said.

In other studies, researchers tested small-scale non-coding RNA molecules, and once again the results were noticeable.

Drug administration significantly reduced both the protection of brain tissue and long-term signs of Cognitive decline.

“Our findings suggest that agents played a protective role in the process, and were most effective in older female subjects compared to age-matched men,” Sorabuji said.

Gender differences are important in brain research

Sohrabji’s research represents the transition from treatments that fit all sizes to tailored treatments, adding to the increasing appeal of neuroscience and medicine to recognize the importance of gender differences.

“These differences are not minor, they are profound, and that’s why we see women burdened with chronic diseases like dementia and Alzheimer’s,” Sorabji said.

By furthering sex-specific research, Sorabuji defends a promising future in which Alzheimer’s burden is no longer the most intense on women and treatments improve overall human health.

“As a basic scientist and on my personal journey, we follow our passion for improving human health and solving these truly important problems,” Sorabuji said.

Sohrabji’s research is Journal of Neuroscience, Brain behavior and immunity, Neurobiology of aging. she Latest work Available at biorxiv Preprint server.