Objective: To determine sex-specific clinical correlations of different Lewy body (LB), Alzheimer’s disease (AD) pathology staging and nigral neuron loss levels in people with LB pathology.

Background: Levels of LB, AD pathologies and nigral neuron loss are associated with different levels of likelihood for a typical Lewy body dementia (LBD) phenotype [1,2]. Sex impacts the prevalence, level and clinical associations of LB and AD pathologies. Neocortical LB is more common in men, co-pathologies are more common in women [3,4]. Women are less likely to have a LBD phenotype compared to men with limbic and neocortical LB [5–7]. However, sex differences across all LB pathology stages with different levels of AD pathology and nigral neuron loss are unclear.

Method: Data was obtained from the National Alzheimer’s Coordinating Center Uniform Data Set (UDS) and Neuropathology Data Set for UDS visits conducted between September 2005 and August 2019 [8,9]. Analysis included 267 women and 370 men from 31 AD Research Centers with LB pathology, available nigral neuron loss and AD pathology data, excluding those with other neuropathologic diagnoses. Clinical profile at first visit with dementia and at last visit before death was included. Linear models were used to determine sex-specific clinicopathological correlations controlling for age. For significant sex-specific associations from these initial models including all pathology variables, sex interaction was assessed for significant pathology variable controlling for age and other pathologies.

Results: At first visit with dementia, women had more severe dementia and were older than men. At last visit, women were older than men, but had similar dementia severity. Women died at an older age, had higher AD and lower LB pathology staging, and were less likely to have a clinical LBD diagnosis. Higher AD pathology stage was associated with worse dementia, moreso for women. Higher LB pathology stage and more nigral neuron loss were associated with higher likelihood for a clinical LBD diagnosis, moreso for men.

Conclusion: Clinicopathological correlations differ based on sex for people with LB pathology. AD pathology may impact cognition more in women; LB pathology and nigral neuron loss may be associated with LBD phenotype more in men. These sex differences can impact the diagnostic accuracy as well as potential treatment targets and efficacy.

References: [1] McKeith IG, Boeve BF, Dickson DW, Halliday G, Taylor J-P, Weintraub D, et al. Diagnosis and management of dementia with Lewy bodies. Neurology 2017;89:88–100. doi:10.1212/WNL.0000000000004058.
[2] Coughlin DG, Hurtig HI, Irwin DJ. Pathological Influences on Clinical Heterogeneity in Lewy Body Diseases. Mov Disord 2019;35:5–19. doi:10.1002/mds.27867.
[3] Nelson PT, Schmitt FA, Jicha GA, Kryscio RJ, Abner EL, Smith CD, et al. Association between male gender and cortical Lewy body pathology in large autopsy series. J Neurol 2010;257:1875–81. doi:10.1007/s00415-010-5630-4.
[4] Barnes LL, Lamar M, Schneider JA. Sex differences in mixed neuropathologies in community-dwelling older adults. Brain Res 2019;1719:11–6. doi:10.1016/j.brainres.2019.05.028.
[5] Bayram E, Coughlin DG, Banks SJ, Litvan I. Sex differences for phenotype in pathologically defined dementia with Lewy bodies. J Neurol Neurosurg Psychiatry 2021;92:745–50. doi:10.1136/jnnp-2020-325668.
[6] Bayram E, Coughlin DG, Litvan I. Sex Differences for Clinical Correlates of Alzheimer’s Pathology in People with Lewy Body Pathology. Mov Disord 2022;37:1505–15. doi:10.1002/mds.29044.
[7] Chiu SY, Wyman-Chick KA, Ferman TJ, Bayram E, Holden SK, Choudhury P, et al. Sex differences in dementia with Lewy bodies: Focused review of available evidence and future directions. Parkinsonism Relat Disord 2023:105285. doi:10.1016/j.parkreldis.2023.105285.
[8] Besser L, Kukull W, Knopman DS, Chui H, Galasko D, Weintraub S, et al. Version 3 of the national Alzheimer’s coordinating center’s uniform data set. Alzheimer Dis Assoc Disord 2018;32:351–8. doi:10.1097/WAD.0000000000000279.
[9] Besser LM, Kukull WA, Teylan MA, Bigio EH, Cairns NJ, Kofler JK, et al. The revised national Alzheimer’s coordinating center’s neuropathology form-available data and new analyses. J Neuropathol Exp Neurol 2018;77:717–26. doi:10.1093/jnen/nly049.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/sex-differences-for-clinicopathological-correlations-in-people-with-lewy-body-pathology/