Objective: To investigate sex differences for regional Lewy body (LB) pathology burden, and regional LB pathology association with clinical diagnosis across people with a high likelihood for LB dementia (LBD) based on traditional pathology staging

Background: Higher levels of LB pathology based on traditional staging, increase the likelihood for LBD phenotype. However, regional burden is not captured in detail by the traditional staging schema. On the other hand, even when there is a high likelihood for LBD phenotype based on pathology, females are less likely than males to have dementia or LBD phenotype. It is unclear if this sex difference is associated with regional pathology burden.

Method: 131 females and 226 males with a high likelihood for LBD phenotype based on pathology, from the brain bank for neurodegenerative disorders at Mayo Clinic, Jacksonville, FL were included. Regional LB counts (middle frontal, superior temporal, inferior parietal, cingulate, entorhinal) were compared. Sex differences for the association between regional LB counts and clinical LBD diagnosis were assessed with linear models adjusting for age at death, Braak neurofibrillary tangle stage, Thal phase for amyloid β plaques. False discovery rate was used for multiple comparisons.

Results: Compared to males, females died older; had higher levels of pathology based on traditional staging for LB, neurofibrillary tangle, amyloid β plaques; had more regional LB in superior temporal, inferior parietal, entorhinal cortices. Compared to males, a lower percentage of females had a clinical LBD diagnosis. For females, more LB in the entorhinal cortex was associated with a higher likelihood for LBD phenotype. For males, more LB in the middle frontal, cingulate, entorhinal cortices was associated with a higher likelihood for LBD phenotype. The association between LBD phenotype and LB count in cingulate, entorhinal cortices was stronger in males than females.

Conclusion: In this cohort, although all had a high likelihood for LBD phenotype, regional LB burden differed by sex. In addition, despite more superior temporal, inferior parietal, entorhinal LB than males, females were less likely to have a clinical diagnosis of LBD. Regional LB burden in cingulate and entorhinal cortices was associated with a higher likelihood for LBD phenotype more so in males, supporting sex differences for clinicopathological correlations in LBD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/sex-differences-for-regional-lewy-body-pathology-in-pathologically-defined-lewy-body-dementia/