Women in their 60s exhibit a paradoxical pattern of greater Alzheimer pathology alongside markers of relative structural brain resilience, according to a cross-sectional neuroimaging study published in JAMA Network Open.
Researchers reported that women show higher amyloid and tau burden than men, with sex differences in tau influenced by apolipoprotein E epsilon 4 carrier status. In a racially and ethnically diverse, community-based cohort of adults without cognitive impairment, women also demonstrated greater cortical thickness in regions affected early in Alzheimer disease, independent of age, educational level, race and ethnicity, and vascular health-related factors.
The study, led by Merve Akinci, MD, of Columbia University Irving Medical Center, and colleagues, included 503 adults aged 60 to 69 years recruited from communities surrounding Columbia University Irving Medical Center in New York City between March 2016 and September 2022. Women accounted for 64% of the cohort, which included 61% Hispanic participants, 24% non-Hispanic Black participants, and 16% non-Hispanic White participants. All participants completed amyloid positron emission tomography and magnetic resonance imaging, and a subset of 355 participants also underwent tau positron emission tomography (PET).
Amyloid burden was assessed using florbetaben PET, with standardized uptake value ratios derived from composite Thal phase regions. Tau pathology was measured using 18F-MK-6240 PET with partial volume correction, with regional standardized uptake value ratios calculated for Braak stages I through VI. Neurodegeneration was evaluated using an Alzheimer disease signature cortical thickness composite derived from magnetic resonance imaging, while vascular brain injury was assessed using total white matter hyperintensity volumes normalized to total cranial volume.
In multivariable linear regression analyses adjusted for demographic factors, women had higher global amyloid burden than men and greater tau burden in Braak stages III and IV and Braak stages V and VI. Women also showed greater Alzheimer disease signature cortical thickness and lower white matter hyperintensity burden than men. However, this association was attenuated after adjustment for vascular health-related variables.
A significant interaction between sex and apolipoprotein E epsilon 4 status indicated that sex differences in tau burden were more pronounced among epsilon 4 carriers, particularly across early to middle Braak stages. No significant interactions were observed between sex and age or race and ethnicity.
The researchers acknowledged several limitations. Because the analysis was cross-sectional, the findings do not establish causal relationships between sex and Alzheimer disease pathology. Sex was determined by self-report rather than biological measures, and gender-related sociocultural factors were not assessed, which may have introduced misclassification or residual confounding. In addition, the sample was unevenly distributed by sex and racial and ethnic subgroups, and larger, more balanced cohorts are needed to further evaluate how sex, race, and ethnicity intersect in Alzheimer disease–related outcomes.
Disclosures can be found in the study.
Source: JAMA Network Open