Most people know that age is one of the biggest risk factors for neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. However, researchers have also discovered that biological sex plays an important role in determining who develops these conditions, how they progress, and which risk factors may have the greatest impact.

Women are more likely to develop Alzheimer’s disease, while men are diagnosed with Parkinson’s disease at higher rates. Scientists are still working to understand the reasons behind these differences, but emerging evidence points to a complex interplay between genetics, hormones, cardiovascular health, and the lifelong exposures and behaviors that shape brain health over time.

Understanding these sex-specific patterns may help researchers develop more personalized approaches to prevention and treatment. Dr. Kellyann Niotis, preventive neurologist and Director of Parkinson’s and Lewy Body Dementia Prevention Research at IND, explains what we currently know about the ways Alzheimer’s disease and Parkinson’s disease affect men and women differently.

Women and Alzheimer’s Disease: Understanding the Elevated Risk

When it comes to Alzheimer’s disease, women bear a significantly greater burden than men. As Dr. Niotis explains, “Women are at about a twofold higher increased risk compared to men, and that’s irrespective of their age.”

For many years, this disparity was largely attributed to the fact that women tend to live longer than men. However, longevity alone does not appear to fully explain the difference. According to Dr. Niotis, “there are probably a lot of factors that are at play.”

One of the leading areas of investigation involves the hormonal changes that occur during menopause. The decline in estrogen and other hormones may contribute directly to brain changes associated with Alzheimer’s disease. Yet menopause also coincides with a host of other health changes that may independently increase risk. Dr. Niotis points out that during this period, cholesterol levels often rise, body composition changes, sleep becomes more disrupted, and mood disturbances become more common. Women are also more likely to accumulate visceral adipose tissue, or fat stored around the abdominal organs, which is associated with inflammation, insulin resistance, and cardiovascular disease.

These overlapping changes can create a perfect storm for brain health, making midlife a particularly important period for prevention. Researchers have also identified important biological differences in how Alzheimer’s disease develops in men and women. Dr. Niotis explains that women appear to experience faster disease progression and accumulate more tau pathology, one of the hallmark proteins associated with Alzheimer’s disease. While men and women may have similar levels of amyloid, women tend to develop more tau at the same level of amyloid burden. This distinction is particularly important because tau is closely linked to cognitive decline. As Dr. Niotis notes, “women are accumulating more tau, and tau seems to be the biomarker that tracks more closely with Alzheimer’s disease and cognitive decline.”

Another major contributor to Alzheimer’s risk is the APOE4 gene, the strongest known genetic risk factor for late-onset Alzheimer’s disease. While the presence of APOE4 alleles is not related to sex, its impact appears to be greater in women. Dr. Niotis explains that “women who are APOE4 carriers are at about a four times higher risk than men between the ages of 65 and 75.” Some studies have even suggested that carrying one copy of APOE4 as a woman may confer a similar level of risk as carrying two copies in men. Although Dr. Niotis cautions that genetic risk is influenced by many other factors, including lifestyle, medical conditions, and additional genes, the evidence suggests that APOE4 may interact with female biology in unique ways.

Protecting Brain Health in Women

Many of the risk factors linked to Alzheimer’s disease are modifiable. Dr. Niotis highlights several areas women should prioritize, particularly during and after the menopausal transition. Cardiovascular health remains one of the most important. Monitoring cholesterol levels, blood pressure, and markers of insulin resistance can provide valuable insight into future brain health. She recommends paying close attention to measures such as hemoglobin A1C, fasting glucose, fasting insulin, and triglycerides. Blood pressure deserves special attention. Mild elevations are sometimes dismissed as “white coat hypertension,” but Dr. Niotis encourages individuals to monitor their readings at home to identify problems early. She advises, “if I were you, I would get your own blood pressure cuff and check your blood pressure at home, when you’re in your own comfortable environment.”

Mental health is another critical, and often overlooked, component of brain health. Depression affects women at higher rates and has been associated with increased Alzheimer’s risk. Dr. Niotis emphasizes that “getting your mental health in check is a part of brain health.” She encourages women to seek therapy, medication, or other evidence-based support when needed, adding that “there’s no shame in seeking therapy” and that mental health and brain health “really do go hand in hand.”

Men and Parkinson’s Disease: A Different Pattern

While women face a greater burden of Alzheimer’s disease, Parkinson’s disease tells a different story.

According to Dr. Niotis, “it’s actually men who are disproportionately affected by it, and they seem to be one and a half to two times more affected by it than women.” Unlike Alzheimer’s disease, researchers still do not fully understand why this sex difference exists. In fact, Dr. Niotis notes that Parkinson’s research remains behind Alzheimer’s research in many areas, including understanding sex-specific risk.

One theory focuses on environmental exposures. Historically, men have been more likely to work in occupations involving pesticides, industrial chemicals, and other toxic substances that have been linked to Parkinson’s disease. Growing evidence suggests that these exposures may contribute to the disease’s development. Another frequently cited hypothesis involves estrogen. Some studies suggest that estrogen may help protect the dopamine-producing neurons in the substantia nigra, the brain region most affected in Parkinson’s disease. However, Dr. Niotis points out that hormone-based explanations can sometimes oversimplify a much more complex biological reality.

Other theories have focused on uric acid, a naturally occurring compound in the blood that may have antioxidant properties. Some researchers have proposed that differences in uric acid levels could influence Parkinson’s risk, though the evidence remains inconclusive. As Dr. Niotis summarizes, “there’s a lot of explanations for why, but none of them really make a whole lot of sense. So it’s an area of active research.”

Body Composition and Brain Health

One emerging area of interest in men’s brain health involves body composition. Dr. Niotis points to research suggesting that men with sarcopenia, or age-related loss of muscle mass, may face a greater risk of future cognitive decline and dementia. Evidence also suggests that the combination of low muscle mass and excess body fat may be particularly harmful for men. Sarcopenia becomes increasingly common with age and can contribute to frailty, reduced mobility, metabolic dysfunction, and inflammation. Maintaining muscle mass through regular strength training, adequate protein intake, and physical activity may therefore support not only physical health, but brain health as well. These findings reinforce a growing body of research showing that physical health, metabolic health, and brain health are deeply interconnected.

Looking Ahead

Although Alzheimer’s disease and Parkinson’s disease affect men and women differently, one theme is becoming increasingly clear: sex matters in neurodegenerative disease. Biological differences, genetics, hormones, cardiovascular health, mental health, body composition, and the lifelong exposures and behaviors that shape overall health all contribute to risk in complex and interconnected ways.

As researchers continue to unravel these relationships, the goal is not simply to understand why men and women experience different outcomes, but to use that knowledge to develop more personalized prevention strategies. By recognizing these differences and addressing risk factors earlier, clinicians can help patients take a more proactive approach to protecting brain health across the lifespan.

For more insights on why women are disproportionately affected by Alzheimer’s, watch our full conversation with Dr. Niotis in the video above.

By Alicia Barber Minteer, PhD