Characterizing Limbic-Predominant Age-Related TDP-43 Encephalopathy Without Alzheimer’s Disease and Lewy Body Dementia in the Oldest Old: A Case Series

Article type: Research Article

Authors: Leiby, Anne-Marie C.^{a; 1} | Scambray, Kiana A.^{a; 1} | Nguyen, Hannah L.^a | Basith, Farheen^a | Fakhraee, Shahrzad^a | Melikyan, Zarui A.^b | Bukhari, Syed A.^c | Montine, Thomas J.^c | Corrada, María M.^{a; b; d} | Kawas, Claudia H.^{a; b; e} | Sajjadi, S. Ahmad^{a; b; f; *}

Affiliations: [a] Department of Neurology, University of California, Irvine, CA, USA | [b] Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA | [c] Department of Pathology, Stanford University, Palo Alto, CA, USA | [d] Department of Epidemiology and Biostatistics, University of California, Irvine, CA, USA | [e] Department of Pathology, University of California, Irvine, CA, USA | [f] Department of Neurobiology and Behavior, University of California, Irvine, CA, USA

Correspondence: [*] Correspondence to: S. Ahmad Sajjadi, MD, PhD, Office 364, Medical Surge Building 2, Irvine, CA 92697, USA. Tel.: +1 949 824 1485; E-mail: ssajjadi@hs.uci.edu.

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

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.

Keywords: Alzheimer’s disease, case studies, dementia, oldest old, TDP-43 protein

DOI: 10.3233/JAD-230238

Journal: Journal of Alzheimer's Disease, vol. 96, no. 1, pp. 113-124, 2023