Association between male gender and cortical Lewy body pathology in large autopsy series
Open accessAbstract
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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Only a few studies have directly investigated the association between sex and AD and other common neuropathologies, and these had small sample sizes (less than 200 brain autopsies) or did not examine pathologies other than AD.
“Yet, to date, only a few studies have directly investigated the association between sex and AD and other common neuropathologies. Further, these included only a small sample size (less than 200 brain autopsies) [41,53], or did not examine pathologies other than AD [41,43,53].”
From Sex differences in Alzheimer’s disease and common neuropathologies of aging (2018) · cites this paper as [43]
The paper contradicts the characterization attributed to it. Its Abstract reports 3,830 autopsied subjects, and the Introduction says it tested associations between sex and AD, neocortical Lewy body, and mixed pathologies—not AD alone. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredTwo studies that reported different sex-AD pathology association in different ages did not utilize statistical interaction modeling.
“Likewise, two studies that reported different sex-AD pathology association in different ages did not utilize statistical interaction modeling [34,43].”
From Sex differences in Alzheimer’s disease and common neuropathologies of aging (2018) · cites this paper as [43]
The Results (page not provided) report a different sex–AD pathology association before and after age 80, but they also state that an age-by-diagnosis interaction was assessed in a separate logistic model. That directly contradicts the claim that this study did not use statistical interaction modeling; the interaction was not significant. (LLM, conf=0.92)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredOne clinical-pathologic study reported that the odds of AD pathology was not different between women and men if they were younger than 80 years at death, but women older than 80 years had a higher odds of AD pathology compared to men.
“One clinical-pathologic study reported that the odds of AD pathology was not different between women and men if they were younger than 80 years at death, but women older than 80 years had a higher odds of AD pathology compared to men [43].”
From Sex differences in Alzheimer’s disease and common neuropathologies of aging (2018) · cites this paper as [43]
Few if any previous studies that investigated the association of sex with AD pathologies have examined menopausal factors.
“Few if any of the previous studies which investigated the association of sex with AD pathologies have examined menopausal factors [25,41,43,53].”
From Sex differences in Alzheimer’s disease and common neuropathologies of aging (2018) · cites this paper as [43]
The Introduction and Discussion discuss sex hormones as possible influences on neurodegenerative disease, but do not assess whether previous studies of sex and AD pathology examined menopausal factors. A search for menopause, postmenopausal status, and related factors found only a postmenopausal-estrogen study in the References, not a statement supporting the claimed assessment of prior studies. (LLM, conf=0.73)
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- Authors
- Nelson, P. T., Schmitt, F. A., Jicha, G. A., Kryscio, R. J., Abner, E. L., Smith, C. D., Van Eldik, L. J., & Markesbery, W. R.
- Affiliations
- University of Kentucky (US)
- Corresponding author
- Nelson, Peter T.
- ORCID
- Venue
- Journal of Neurology
- Published
- 2010-06-20
- Volume
- 257
- Issue
- 11
- Pages
- 1875-1881
- ISSN
- 0012-1037 (ISSN-L)
- 0340-5354
- 1432-1459
- PMC
- PMC3040648
- OpenAlex
- W2125396837
- Cited by
- 131
- References
- 31
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 7 · 2023: 10 · 2022: 13 · 2021: 6 · 2020: 35 · 2019: 6 · 2018: 5 · 2017: 7 · 2016: 7 · 2015: 4 · 2014: 5 · 2013: 4 · 2012: 5
- FWCI
- 2.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Kentucky
- National Institutes of Health
- National Institute on Aging (P30AG028383, R21AG036875, U01AG016976)
- National Institute of Neurological Disorders and Stroke (R01NS061933, K08NS050110)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- sex differences, cortical Lewy bodies, Alzheimer's disease, neurodegenerative diseases, neuropathology, autopsy findings, clinical trial design
- MeSH terms
- Age Factors, Aged, Aged, 80 and over, Autopsy, Brain, Female, Humans, Male, Risk Factors, Sex Characteristics, Lewy Body Disease
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