Symptomatic Profile and Cognitive Performance in Autopsy-Confirmed Limbic-Predominant Age-Related TDP-43 Encephalopathy With Comorbid Alzheimer Disease
Year: 2022
Type: article
Abstract: Transactive response DNA-binding protein 43 kDa (TDP-43) proteinopathy is the hallmark of limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). LATE-NC is a common copathology with Alzheimer disease neuropathologic change (ADNC). Data from the National Alzheimer's Coordinating Center were analyzed to compare clinical features and copathologies of autopsy-confirmed ADNC with versus without comorbid LATE-NC. A total of 735 participants with ADNC alone and 365 with ADNC with LATE-NC were included. Consistent with prior work, brains with LATE-NC had more severe ADNC, more hippocampal sclerosis, and more brain arteriolosclerosis copathologies. Behavioral symptoms and cognitive performance on neuropsychological tests were compared, stratified by ADNC severity (low/intermediate vs high). Participants with ADNC and LATE-NC were older, had higher ADNC burden, and had worse cognitive performance than participants with ADNC alone. In the low/intermediate ADNC strata, participants with comorbid LATE-NC had higher prevalence of behavioral symptoms (apathy, disinhibition, agitation, personality change). They also had worsened performance in episodic memory and language/semantic memory. Differences narrowed in the high ADNC strata, with worsened performance in only episodic memory in the comorbid LATE-NC group. The co-occurrence of LATE-NC with ADNC is associated with a different pattern of behavioral and cognitive performance than ADNC alone, particularly in people with low/intermediate ADNC burden.
DOI: 10.1093/jnen/nlac093
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1017046091, G1053905225, G117713310, G1224480130, G1228824270, Michigan Alzheimer's Disease Core Center, G1343836163, UC Davis Alzheimer's Disease Core Center, Indiana Alzheimer Disease Center, G1417337112, G1480831932, G1602633198, G2190936067, G219693323, G2234397790, G2515091901, Neurobiology of Alzheimer's Disease and Aging, G2622865600, G2742075923, G2984989008, G343469054, Alzheimer's Disease Research Center, Pleiotropy GWAS of Alzheimer's Disease, G384347443, G3919444319, G40706755, G4076092645, G413369726, G415047313, G4186766937, Nevada Exploratory Alzheimer's Disease Research Center (NVEADRC), G423967958, Alzheimer's Disease Core Center, The Alzheimer's Disease Research Center at the University of California, Irvine, G4417220376, Genomic Architecture of a Key Alzheimer's Disease Mimic: CARTS, Oregon Alzheimer's Disease Center, UAB Alzheimer's Disease Research Center, G556672640, G5977822913, G603598372, G611802359, Wisconsin Alzheimer's Disease Research Center, University of Kansas Alzheimer's Disease Core Centers, New Mexico Alzheimer's Disease Research Center, Alzheimer's Disease Research Center, Alzheimer Disease Research Center, Yale Alzheimer Disease Research Center, Arizona Alzheimer's Disease Core Center, Johns Hopkins Alzheimer's Disease Research Center, Boston University Alzheimer's Disease Center, Vanderbilt Alzheimer's Disease Research Center, Alzheimer's Disease Core Center, Emory Alzheimer's Disease Center, University of Florida - Mt. Sinai Medical Center AD Research Center, G816726602, G828200374, Novel misfolded proteins in ADRD: proteomics, genetics, and clinical-pathological correlations, University of Washington Alzheimer's Disease Research Center, Wisconsin Alzheimer's Disease Research Center, University of Kentucky Alzheimer's Disease Research Center, Mayo Alzheimer's Disease Research Center
OpenAlex ID: W4306898448