Title | Characterizing Limbic-Predominant Age-Related TDP-43 Encephalopathy Without Alzheimer's Disease and Lewy Body Dementia in the Oldest Old: A Case Series. |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | Leiby, A-MC, Scambray, KA, Nguyen, HL, Basith, F, Fakhraee, S, Melikyan, ZA, Bukhari, SA, Montine, TJ, Corrada, MM, Kawas, CH, S Sajjadi, A |
Journal | J Alzheimers Dis |
Volume | 96 |
Issue | 1 |
Pagination | 113-124 |
Date Published | 2023 |
ISSN | 1875-8908 |
Keywords | Aged, Aged, 80 and over, Alzheimer Disease, DNA-Binding Proteins, Humans, Lewy Body Disease, Syncope, Tauopathies, TDP-43 Proteinopathies |
Abstract | BACKGROUND: Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is a clinicopathological construct proposed to facilitate studying TDP-43 pathology in older individuals. OBJECTIVE: Our aim was to describe clinical and cognitive characteristics of LATE-NC without Alzheimer's disease neuropathologic change (ADNC) and Lewy body (LB) and to compare this with ADNC and primary age related tauopathy (PART). METHODS: In 364 autopsies of the oldest old of The 90+ Study, we identified those with LATE-NC without ADNC and LB. Control groups were participants with ADNC and PART. RESULTS: Of 31% of participants who had LATE-NC, only 5 (1.4%) had LATE-NC without ADNC and LB, all of whom had tau. These participants had a gradual and progressive cognitive decline. Four (80%) had dementia at death, a rate that was higher than ADNC (50%) and PART (21.7%). Mean duration of cognitive impairment was twice as long in LATE-NC without ADNC and LB (6.2 years) compared to ADNC (2.9 years) and PART (3 years). LATE-NC without ADNC and LB group had a higher prevalence of syncope, depression, and extrapyramidal signs than the ADNC and PART groups. CONCLUSIONS: Despite the high prevalence of LATE-NC, LATE-NC without ADNC and LB was rare in this large oldest-old cohort, highlighting the very high prevalence of multiple pathologic changes in the oldest old. Slowly progressive cognitive decline, ubiquitous memory impairment, history of syncope and depression, and extrapyramidal signs were prominent features among our LATE-NC without ADNC and LB group. |
DOI | 10.3233/JAD-230238 |
Alternate Journal | J Alzheimers Dis |
PubMed ID | 37742640 |
PubMed Central ID | PMC10615772 |
Grant List | P30 AG066519 / AG / NIA NIH HHS / United States R01 AG021055 / AG / NIA NIH HHS / United States R01 AG062706 / AG / NIA NIH HHS / United States U24 AG021886 / AG / NIA NIH HHS / United States |