Sex differences for regional pathology in people with a high likelihood of Lewy body dementia phenotype based on underlying pathology

Abstract

Introduction: Clinicopathological correlations differ by sex in Lewy body dementia (LBD). However, previous studies have focused on pathological staging systems that place less emphasis on regional pathologies. Methods: We included 357 people (131 female, 226 male) with a high likelihood of LBD based on pathology from the Brain Bank for Neurodegenerative (Jacksonville, FL). Sex differences for regional Lewy body, senile plaque, and neurofibrillary tangle counts and their associations with clinical LBD diagnosis were assessed. Results: Females were less likely to have a clinical LBD diagnosis; they had more Lewy bodies, neurofibrillary tangles, and senile plaques in various regions than males (all p’s < 0.05). A higher likelihood of clinical LBD diagnosis was associated with more middle frontal, cingulate, and entorhinal Lewy body pathology, and more so for males than for females (all p’s < 0.045). Discussion: Sex differences for clinicopathological correlations in LBD also occur at the regional pathology level. Females have a higher frequency of clinical misdiagnosis than males. Highlights: Females have a higher risk of clinical underdiagnosis for Lewy body dementia (LBD) than males. Regional pathology counts differ by sex for people with a high likelihood of LBD. Regional pathology association with clinical LBD diagnosis differs by sex. Regional Lewy body counts have a stronger association with LBD phenotype for males.