Despite having greater Alzheimer’s disease brain pathology on PET scans, cognitively unimpaired women between 60 and 69 years old show less neurodegeneration than men, according to a study published January 27 in JAMA Network Open.
The finding is from an analysis of a large, broadly representative group with racial and ethnic diversity, for which information on sex differences in Alzheimer’s disease neuropathology is limited, noted Muge Akinci, PhD, of Columbia University in New York City, and colleagues.
“These results suggest that women have greater [Alzheimer’s disease] pathology yet demonstrate better preserved structural brain integrity compared with men aged in their 60s,” the group wrote.
Alzheimer's disease affects approximately 7 million U.S. residents ages 65 and older, and women represent two-thirds of these patients. Previous studies have shown that this increase in prevalence may be driven by sex-specific biological factors, the authors explained. Studies have also shown that there are marked differences in risk and prevalence across racial and ethnic groups, they added.
In this article, the group aimed to expand on this earlier work by analyzing a larger diverse sample and incorporating biomarkers of neurodegeneration and vascular injury, alongside beta-amyloid plaque and tau, two proteins that drive the disease.
The researchers culled data from 503 cognitively unimpaired individuals who had participated in an earlier clinical trial. The mean age of the group was 64.6 years old. Of all participants, 321 (63.8%) were women and 182 (36.2%) were men. Overall, 305 participants (60.6%) were Hispanic, 120 (23.9%) were non-Hispanic Black, and 78 (15.5%) were non-Hispanic white.
The main outcomes were global amyloid burden measured by F-18 florbetaben PET, tau burden in Braak stages I to VI measured with F-18 MK-6240 PET, and MRI-derived Alzheimer’s disease signature cortical thickness and white-matter hyperintensity (WMH) volumes.
A regression analysis adjusted for demographics found that women had higher beta-amyloid standard uptake value (SUV) ratios (B = 0.05; p < 0.001) and tau SUV ratios in Braak stages III and IV (B = 0.05; p = 0.002) and V and VI (B = 0.09; p < 0.001) compared with men. Tau SUV ratios in Braak stages I to II did not differ significantly by sex.
In addition, MRI scans revealed that women showed greater Alzheimer’s disease signature thickness (B = 0.04; p < 0.001) and lower WMH (B = -0.03; p = 0.001) than men, the researchers reported.
“Overall, our findings suggest greater brain resilience to [Alzheimer’s disease] pathology in women. This notion is supported by previous research reporting better preservation of brain structure in women compared with men after exposure to [Alzheimer’s disease] pathology,” the group concluded.
In a related editorial, C. Elizabeth Shaaban, PhD, of the University of Pittsburgh, noted that the study’s findings that women without dementia have greater beta amyloid and tau yet thicker cortex are “intriguing” and consistent with greater brain resilience in women early in the disease.
Future studies on sex differences in tau burden in later stages are needed, however, to clarify whether women’s tau levels lead to greater neurodegeneration through simply greater levels, stronger tau-neurodegeneration associations, or both, she wrote.
“Understanding these gender and sex differences is crucial to identifying effective and equitable [Alzheimer’s disease] prevention and treatment for women and men,” Shaaban wrote.
The full study is available here.
