Urinary Incontinence in a Community-Based Autopsy Cohort Is Associated with Limbic Predominant Age-Related TDP-43 Encephalopathy Neuropathologic Changes

Article type: Research Article

Authors: Di, Jing^{a; 1} | Nelson, Ruth S.^{b; 1} | Jicha, Gregory A.^{c; d} | Moga, Daniela C.^{c; e} | Barber, Justin M.^c | Cykowski, Matthew D.^f | Fardo, David W.^{c; g} | Abner, Erin L.^{c; h} | Nelson, Peter T.^{a; c; *}

Affiliations: [a] Department of Pathology and Laboratory Medicine | [b] Emory University, Atlanta, GA, USA | [c] Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA | [d] Department of Neurology, University of Kentucky, Lexington, KY, USA | [e] Department of Pharmacy Practice and Science, College of Pharmacy, Sanders-Brown Center on Aging, and Department of Epidemiology, College of Public Health, University of Kentucky, Lexington, KY, USA | [f] Houston Methodist Hospital, Houston, TX, USA | [g] Department of Biostatistics, University of Kentucky, Lexington, KY, USA | [h] College of Public Health, University of Kentucky, Lexington, KY, USA

Correspondence: [*] Correspondence to: Peter T. Nelson, University of Kentucky, Rm 575 Todd Building, Lexington, KY 40536, USA. E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Background: Dementia and urinary incontinence (UI) are etiologically complex clinical syndromes. Dementia and UI often occur in the same individuals, but underlying factors connecting them are incompletely understood. Objective: Query data from a community-based autopsy series to assess pathologies that underlie UI. Methods: Included research subjects came to autopsy from the University of Kentucky Alzheimer’s Disease Research Center longitudinal cohort. A total of 368 research volunteers met inclusion criteria for this cross-sectional study. The average age at death was 85.3 years and the average number of annual clinic visits was 5.2 visits. Statistical models were run to evaluate which pathologies were associated with UI. Data included pathologies scored according to conventional stage-based systems, and these studies were complemented by quantitative digital neuropathology. Results: Dementia was diagnosed at the final clinical visit in 208 (56.7% of the sample) and UI was documented in 156 (42.7%). UI was associated with depression and dementia (both p < 0.001). More women than men had a history of UI (p < 0.04), and women with UI had had more biological children than those without UI (p < 0.005). Participants with limbic predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC) were more likely to have UI than those without LATE-NC (p < 0.001). The presence of LATE-NC (Stage > 1) was associated with UI with or without severe Alzheimer’s disease neuropathologic changes and/or Lewy body pathology. Conclusion: In this community-based autopsy cohort, multiple factors were associated with UI, but the neuropathologic change most robustly associated with UI was LATE-NC.

Keywords: ADNC, ARTAG, clinical dementia rating, obstetric, oldest-old, ScanScope, sex, synuclein, urology

DOI: 10.3233/JAD-230425

Journal: Journal of Alzheimer's Disease, vol. 94, no. 1, pp. 333-346, 2023