Women with Parkinson’s disease may be more vulnerable to brain changes associated with Alzheimer’s disease than men, according to new research presented at the 2026 European Academy of Neurology (EAN) Congress.
Although Parkinson’s disease and Alzheimer’s disease frequently co-occur in older adults, sex differences in Alzheimer’s disease-related pathology in Parkinson’s disease patients remain unclear.
To address this knowledge gap, researchers at the Mayo Clinic in Arizona analyzed data from 230 autopsy-confirmed cases of Parkinson’s disease enrolled in the Arizona Aging and Neurodegenerative Disease Research and Brain and Body Donation Program. Participants underwent annual clinical evaluation before death and comprehensive neuropathological examination postmortem.
The study found that women with Parkinson’s disease have a significantly greater burden of amyloid plaques, a hallmark of Alzheimer’s disease, than men. Female participants had higher mean cortical total plaque scores (6.5/15 vs. 4.9/15; p=0.045) and higher neuritic plaque density (1.7/3 vs. 1.3/3; p=0.035) than men.
More than half of female participants (56.8%) had higher plaque burden compared to males (39.7%; p=0.015). Even after adjusting for age at death and APOE ε4, a major genetic risk factor for Alzheimer’s disease, women maintained amyloid plaque burden more than twice that of men (OR 2.18; 95% CI 1.17 – 4.06; p=0.014).
These findings suggest that women may be more susceptible to amyloid-driven pathology in the context of Parkinson’s disease, similar to the pattern observed in patients with clinically diagnosed and pathologically confirmed Alzheimer’s disease. ”
Dr. Erica Driver Dunkley, lead author, Mayo Clinic, Arizona
Despite observing a greater burden of amyloid plaques in women, the study found no significant differences between men and women in the incidence of Alzheimer’s disease or performance on cognitive tests.
Dr. Driver-Dunkley explained, “Men and women with Parkinson’s disease had similar rates of Alzheimer’s disease and similar cognitive function test results. However, women were shown to have a higher burden of amyloid plaques than men.”
This finding raises important questions about both the relationship between brain pathology and cognitive outcomes and the biological mechanisms underlying the observed sex differences.
“Higher severity of amyloid plaque pathology in women should influence the onset and severity of cognitive impairment, but we did not find this in our study,” Dr. Driver-Dunkley said. “Larger studies may reveal cognitive differences associated with increased plaque burden.”
Although the reasons for the observed gender differences remain unclear, previous studies have also reported more severe AD-related pathology and cognitive impairment in women with Alzheimer’s disease but not Parkinson’s disease, suggesting a possible biological susceptibility that warrants deeper investigation.
“Our findings highlight the need for further research into sex differences in Parkinson’s and Alzheimer’s disease-related pathology,” Dr. Driver-Dunkley concluded. “An important next step will be to confirm these findings in additional large-scale clinicopathological studies to better understand the biological mechanisms that may underlie these differences.”
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2026 European Academy of Neurology (EAN) Congress
