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Association between male gender and cortical Lewy body pathology in large autopsy series

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Abstract

Sex-linked factors may alter risk for neurodegenerative diseases. Definitive diagnoses are not established until autopsy, so neuropathological studies are critical. There have not been reported gender-related differences in neocortical Lewy bodies (LBs) using large multi-center autopsy series. We evaluated the associations between gender and pathologically characterized neurodegenerative diseases. Cases with Alzheimer’s disease (AD), neocortical LBs, AD + neocortical LBs, or neither pathology were evaluated as separate groups. Results were corrected for possible confounders including age at death, smoking history, and education. The settings were the University of Kentucky Alzheimer’s Disease Center and the National Alzheimer’s Coordinating Center (NACC) Registry autopsy series; 3,830 subjects met inclusion criteria. Patients with neocortical (“diffuse”) or intermediate (“limbic”) LB pathologies tended to be male (male:female odds ratios ~2.9 with 95% CI 2.02–4.18). The preponderance of males dying with neocortical LB pathology was seen consistently across age groups and was not due to the potential confounders evaluated. By contrast, individuals dying with AD pathology were more likely to be female if dying over 80 (male:female odds ratio 0.66, 95% CI 0.50–0.88), but that tendency was not seen in individuals dying with AD pathology prior to age 80. Increased understanding of the male predominance in neocortical LB pathology may help guide clinicians, because males are more likely to be “undercalled” for neocortical LBs clinically, and females are more likely to be “overcalled” (P < 0.05 for both). Males are far more likely than females to die with neocortical LB pathology. This phenomenon may help guide medical practice including clinical trial study design.

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Acknowledgments

We are deeply grateful to all of the study participants. We thank Ela Patel, Ann Tudor, Paula Thomason, Dr. Huaichen Liu and Sonya Anderson for technical support, Greg Cooper, MD, Nancy Stiles, MD and Allison Caban-Holt, PhD for the clinical evaluations, and Daron Davis MD for pathological evaluations. We also thank Leslie Phillips, MS for help with NACC data. Corresponding Author Dr. Nelson had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. This study was supported by NIH grants R01 NS061933, K08 NS050110, P30 AG028383, and U01 AG016976.

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Authors and Affiliations

  1. Division of Neuropathology, Department of Pathology, Sanders-Brown Center on Aging, University of Kentucky, Rm 311, Sanders-Brown Building, 800 S. Limestone, Lexington, KY, 40536-0230, USA

    Peter T. Nelson, Frederick A. Schmitt, Gregory A. Jicha, Richard J. Kryscio, Erin L. Abner, Charles D. Smith, Linda J. Van Eldik & William R. Markesbery

  2. Department of Neurology, Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, 40536, USA

    Frederick A. Schmitt, Gregory A. Jicha, Charles D. Smith & William R. Markesbery

  3. Department of Statistics, Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, 40536, USA

    Richard J. Kryscio

  4. Department of Anatomy and Neurobiology, Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, 40536, USA

    Linda J. Van Eldik

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  1. Peter T. Nelson
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Correspondence to Peter T. Nelson.

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Nelson, P.T., Schmitt, F.A., Jicha, G.A. et al. Association between male gender and cortical Lewy body pathology in large autopsy series. J Neurol 257, 1875–1881 (2010). https://doi.org/10.1007/s00415-010-5630-4

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  • DOI: https://doi.org/10.1007/s00415-010-5630-4

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