Differences in Symptomatic Presentation and Cognitive Performance Among Participants With LATE-NC Compared to FTLD-TDP
- 1 October 2021
- journal article
- research article
- Published by Oxford University Press (OUP) in Journal of Neuropathology and Experimental Neurology
- Vol. 80 (11), 1024-1032
- https://doi.org/10.1093/jnen/nlab098
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.Keywords
Funding Information
- NIA/NIH (U01 AG016976, R01 AG061111, RF1 NS118584, R56AG057191, R01AG057187, R21AG061551, R01AG054060)
- NIA (P30 AG019610, P30 AG013846, P50 AG008702, P50 AG025688, P50 AG047266, P30 AG010133, P50 AG005146, P50 AG005134, P50 AG016574, P50 AG005138, P30 AG008051, P30 AG013854, P30 AG008017, P30 AG010161, P50 AG047366, P30 AG010129, P50 AG016573, P50 AG005131, P50 AG023501, P30 AG035982, P30 AG028383, P30 AG053760, P30 AG010124, P50 AG005133, P50 AG005142, P30 AG012300, P30 AG049638, P50 AG005136, P50 AG033514, P50 AG005681, P50 AG047270)
- National Institute on Aging (UK-ADC P30AG028383)
- NIH
This publication has 31 references indexed in Scilit:
- Prevalence, characteristics, and survival of frontotemporal lobar degeneration syndromesNeurology, 2016
- Multisite assessment of NIA‐AA guidelines for the neuropathologic evaluation of Alzheimer's diseaseAlzheimer's & Dementia, 2015
- Hippocampal sclerosis of aging, a prevalent and high-morbidity brain diseaseActa Neuropathologica, 2013
- Appraisal of cognition in preclinical Alzheimer’s disease: a conceptual reviewNeurodegenerative Disease Management, 2012
- Modeling the Association between 43 Different Clinical and Pathological Variables and the Severity of Cognitive Impairment in a Large Autopsy Cohort of Elderly PersonsBrain Pathology, 2009
- The National Alzheimer's Coordinating Center (NACC) Database: The Uniform Data SetAlzheimer Disease & Associated Disorders, 2007
- Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar DegenerationActa Neuropathologica, 2007
- TDP‐43 immunoreactivity in hippocampal sclerosis and Alzheimer's diseaseAnnals of Neurology, 2007
- Ubiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral SclerosisScience, 2006
- The Uniform Data Set (UDS): Clinical and Cognitive Variables and Descriptive Data From Alzheimer Disease CentersAlzheimer Disease & Associated Disorders, 2006