Key imaging markers for Alzheimer’s disease (AD) differ in older men and women who remain as yet unaffected the condition, researchers have discovered.
The findings, in JAMA Network Open, could help explain why lecanemab—a recently approved antibody treatment for early Alzheimer’s—appears to be more effective in women than men.
The study showed significant sex differences across the pathological constructs of Alzheimer’s disease among people in the seventh decade of life who did not yet have dementia.
Women had a greater brain burden of amyloid-β(Aβ) and tau in the middle to late Braak stages compared with men, yet their structural brain integrity was better preserved.
“In a diverse cohort, these findings support the notion that women have greater AD pathology, particularly APOE ε4–related tau burden, yet exhibit greater brain resilience cross-sectionally,” reported Müge Akinci, PhD, from Columbia University Irving Medical Center in New York, and co-workers.
Women represent two-thirds of patients with AD and have a higher risk of the disease than men, the researchers noted.
Furthermore, Hispanic and Black individuals are more likely than their White counterparts to develop the condition, possibly due to life experience, socioeconomic factors, and health conditions.
Akinci and team examined differences in AD pathology, neurodegeneration, and vascular injury, as well as potential moderators of these differences, among 503 ethnically diverse adults aged 60 to 69 years in New York who were not cognitively impaired.
Of note, non-Hispanic White participants were in the minority, at just 16% of the group. Even among 61% of Hispanic participants there was great diversity, with most of Dominican ethnicity, but several other Hispanic nationalities and cultures were present.
AD pathology was assessed from the aggregation of Aβ plaques and fibrillar tau tangles that eventually leads to neurodegeneration.
PET scans created a composite assessment of Aβ deposition in different parts of the brain, with another composite figure based on the Braak staging system, which characterizes the spread of tau pathology in AD.
The researchers used structural MRI scans to assess vascular brain injury from white matter hyperintensity volumes and examined neurodegeneration using a cortical thickness composite measure to reflect the characteristic pattern of cortical thinning in early AD.
Results showed that women had significantly higher brain amyloid burden and tau burden in Braak stages III through VI compared with men, with sex differences in regional tau burden more noticeable among APOE ε4 carriers across early to middle Braak stages.
Yet despite having greater AD pathology, women exhibited less neurodegeneration than men, with greater cortical thickness in regions affected early in AD.
“These results suggest that women have greater AD pathology yet demonstrate better preserved structural brain integrity compared with men aged in their 60s,” the researchers commented.
In an accompanying editorial, C. Elizabeth Shaaban, PhD, from the University of Pittsburgh, added: “These important study results from Akinci and colleagues suggest that a greater burden of core AD biomarkers in women and men could be a plausible explanation for gender and sex disparities in AD dementia in racially and ethnically diverse populations.”
