Objective: To assess sex differences in prodromal Lewy body dementia (LBD) compared to Alzheimer’s disease (AD)

Background: Identifying LBD at the prodromal stage can provide insights into the pathogenesis and guide clinical trials. However, LBD often gets misdiagnosed as AD, with higher misdiagnosis rates for females than males. Autopsy-confirmed cohorts help better define the clinical profile. Sex differences occur at the time of diagnosis for autopsy-confirmed LBD, and potential sex differences in the prodromal stage and progression also need to be investigated.

Method: Data were obtained from the National Alzheimer’s Coordinating Center for visits between September 2005 and December 2023. We included individuals (a) with dementia diagnosis during follow-up, (b) with at least two visits prior to the first visit with dementia, (c) with Lewy body (low to high LBD likelihood; LBD group) or AD pathology (intermediate/high AD likelihood; AD group), (d) without other neuropathologic diagnoses associated with cognitive decline. Effects of sex and pathology (LBD, n=196 vs AD groups, n=308) for clinical symptom prevalence were assessed with linear mixed models adjusting for age and education.

Results: Within the LBD group, overall prevalence of females with parkinsonism, judgment and language deficits were lower than males in the prodromal stage (p<.040 for all). While prevalence of females with judgment, language, visuospatial deficits were lower than males in the prodromal stage, prevalence was higher for females than males at time of diagnosis (p<.026 for all). Compared to females in the AD group, prevalence of females with affective symptoms in the LBD group were higher in the prodromal stage but increased at a slower rate (p=.027). Compared to males in the AD group, overall prevalence of males with attention deficits and parkinsonism in the LBD group were higher in the prodromal stage (p<.036 for all). While prevalence of males with attention deficits were higher in the prodromal stage for LBD than AD, it increased at a slower rate (p=.023).

Conclusion: Despite slight differences by sex and pathology in the prodromal stage, differentiation of LBD and AD with individual clinical symptoms may be challenging. Utilizing a combination of different symptoms and biomarkers can be more useful for identification of the underlying pathology and clinical differentiation.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/sex-differences-for-autopsy-confirmed-prodromal-lewy-body-dementia/