Association of LATE-NC With Neuropathologic Lesions and Cognitive Abilities: A Population-Based Autopsy Study.

Abstract (English)

BACKGROUND AND OBJECTIVES: Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is a common finding in aging brains. However, most previous studies were limited to ethnoracially homogeneous cohorts from high-income countries. The objective of this study was to investigate the associations between LATE-NC, cognitive performance, and coexisting neuropathologic lesions in a large, ethnoracially and socioeconomically diverse sample from Brazil. METHODS: This cross-sectional study analyzed data from the Biobank for Aging Studies, a Brazilian population-based autopsy study based at the University of S&#xe3;o Paulo. The study included a consecutive series of autopsies performed between 2004 and 2024. Inclusion criteria required participants to be at least 18 years old with a knowledgeable informant. LATE-NC, Alzheimer disease neuropathologic change (ADNC), Lewy body pathology (LBP), lacunar infarcts, small vessel disease, cerebral amyloid angiopathy, and hippocampal sclerosis were assessed following international criteria. Cognitive abilities were evaluated with the Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB). Logistic and linear regression models were applied to examine associations of LATE-NC with comorbid neuropathologies and cognitive outcomes, with adjustments for sociodemographic, clinical, and neuropathologic covariates. RESULTS: The sample comprised 1,860 participants (mean age = 72.6 &#xb1; 14.2 years; 49.1% female; 62.2% White; 35.4% Black). LATE-NC was present in 7.4% of participants (stage 1: 3.0%; stage 2: 4.0%; stage 3: 0.4%). After adjustment for sociodemographic, clinical, and other neuropathologic covariates, LATE-NC (stages 2-3) was associated with hippocampal sclerosis (OR = 14.95; 95% CI 7.42-30.27; <i>p</i> < 0.001), advanced Braak NFT stages (OR = 2.23; 95% CI 1.32-3.83; <i>p</i> = 0.003), and LBP (OR = 1.89; 95% CI 1.02-3.37; <i>p</i> = 0.036). Factoring in other pathologies, LATE-NC was associated with the CDR-SOB score (&#x3b2; = 4.06; 95% CI 2.95-5.18; <i>p</i> < 0.001), demonstrating a consistent association with cognition, similar to the one observed for moderate/severe ADNC (&#x3b2; = 3.78; 95% CI 3.14-4.42; <i>p</i> < 0.001) in the same sample. DISCUSSION: LATE-NC was prevalent and associated with cognitive impairment in this ethnoracially and socioeconomically diverse sample. The cross-sectional design limits causal inference, and some estimates had wide confidence intervals due to the small number of advanced-stage cases.