Differences in Symptomatic Presentation and Cognitive Performance Among Participants With LATE-NC Compared to FTLD-TDP
Year: 2021
Type: article
Abstract: Transactive response DNA-binding protein 43 kDa (TDP-43) is aberrantly aggregated and phosphorylated in frontotemporal lobar degeneration of the TDP-43 type (FTLD-TDP), and in limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). We examined data from the National Alzheimer's Coordinating Center to compare clinical features of autopsy-confirmed LATE-NC and FTLD-TDP. A total of 265 LATE-NC and 92 FTLD-TDP participants were included. Cognitive and behavioral symptoms were compared, stratified by level of impairment based on global clinical dementia rating (CDR) score. LATE-NC participants were older at death, more likely to carry APOE ε4, more likely to have Alzheimer disease neuropathology, and had lower (i.e. less severe) final CDR global scores than those with FTLD-TDP. Participants with FTLD-TDP were more likely to present with primary progressive aphasia, or behavior problems such as apathy, disinhibition, and personality changes. Among participants with final CDR score of 2-3, those with LATE-NC were more likely to have visuospatial impairment, delusions, and/or visual hallucinations. These differences were robust after sensitivity analyses excluding older (≥80 years at death), LATE-NC stage 3, or severe Alzheimer cases. Overall, FTLD-TDP was more globally severe, and affected younger participants, whereas psychoses were more common in LATE-NC.
DOI: 10.1093/jnen/nlab098
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G1017046091, G1053905225, G1173778324, G1228824270, Michigan Alzheimer's Disease Core Center, G1343836163, UC Davis Alzheimer's Disease Core Center, Indiana Alzheimer Disease Center, G1417337112, G1602633198, G2190936067, G219693323, G2515091901, Neurobiology of Alzheimer's Disease and Aging, Age-related TDP-43 neuropathology: using disease-driving mechanisms to guide classification, G2984989008, Alzheimer's Disease Research Center, G3582452738, Pleiotropy GWAS of Alzheimer's Disease, G36881302, G384347443, G3919444319, G3946457848, G40706755, G4076092645, G413369726, 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, G556672640, G5977822913, G603598372, G611802359, Wisconsin Alzheimer's Disease Research Center, University of Kansas Alzheimer's Disease Core Centers, G6750444795, 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, Alzheimer's Disease Core Center, Emory Alzheimer's Disease Center, University of Florida - Mt. Sinai Medical Center AD Research Center, G828200374, Novel misfolded proteins in ADRD: proteomics, genetics, and clinical-pathological correlations, G9000003466, G9000010277, G9000030076, G9000035486, G9000132673, G9000246517, G9000252716, G9000354213, Safety and modulation of ABCC9 pathways by nicorandil for the treatment of hippocampal sclerosis of aging (SMArTâHS), Mayo Alzheimer's Disease Research Center
OpenAlex ID: W3202710185