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Impact and Risk Factors of Limbic Predominant Age-Related TDP-43 Encephalopathy Neuropathologic Change in an Oldest Old Cohort. Neurology Sajjadi, S. A., Bukhari, S., Scambray, K., Yan, R., Kawas, C., Montine, T. J., Corrada, M. M. 2022

Abstract

BACKGROUND AND OBJECTIVES: Limbic predominant age related TDP-43 encephalopathy neuropathologic change (LATE-NC) is a prevalent degenerative pathology in the oldest old who are the fastest growing segment of our population with the highest rates of dementia. We aimed to determine the relationship between LATE-NC and cognitive impairment and to identify its potential risk factors by studying its relationship with common past medical histories in an oldest old cohort.METHODS: Participants from The 90+ Study with longitudinal evaluations and autopsy data were included. Dementia status and impairment in 5 main cognitive domains were determined at postmortem conferences leveraging all clinical and neuropsychological data blind to neuropathological diagnosis. Medical history information was obtained from patients and their informants. LATE-NC and Alzheimer's disease neuropathologic change (ADNC) were considered present in those with TDP-43 pathology in hippocampus and/or neocortex and those with high likelihood of ADNC according to NIA-AA guidelines respectively. We examined the association of degenerative pathologies with cognitive outcomes and multiple comparisons adjusted relationship of medical history variables with LATE-NC and ADNC using logistic regressions adjusted for age at death, sex, and education.RESULTS: 328 participants were included in this study. LATE-NC was present in 32% of the participants. It had a significant association with the presence of dementia (OR: 2.8, 95% CI: 1.7-4.6) and impairment in memory (OR: 3.0, 95% CI: 1.8-5.1), language (OR: 2.6, 95% CI: 1.6-4.3), and orientation (OR: 3.5, 95% CI: 2.1-5.9). The association with impaired orientation was unique to LATE-NC and the strength and significance of the other associations were comparable to ADNC. Furthermore, we found history of osteoarthritis (OR: 0.37, adjusted 95% CI: 0.21-0.66) and hypertension (OR: 0.52, adjusted 95% CI: 0.28-0.98) were associated with a reduced likelihood of LATE-NC, but not ADNC.DISCUSSION: Our results suggest that LATE-NC is a prevalent degenerative pathology in the oldest old and has significant associations with dementia and impairment in cognitive domains with magnitudes that are comparable to ADNC. We also found that past medical histories of hypertension and osteoarthritis were associated with a lower likelihood of LATE-NC. This might help identify upstream mechanisms leading to this important pathology.

View details for DOI 10.1212/WNL.0000000000201345

View details for PubMedID 36302666