P3‐438: Associations Between Tdp‐43 Proteinopathy and Cognitive Test Scores in Non‐ftld Older Adults
Year: 2019
Type: article
Abstract: TAR-DNA binding protein 43 (TDP-43) is a key protein that – like tau, Ab, and a-synuclein – is frequently found to be misfolded in the brains of Alzheimer's disease (AD)-type dementia cases. TDP-43 deposition appears to develop in a sequential anatomic pattern . In this study, we examined the association between TDP-43 pathology in three brain regions (amygdala, hippocampus, and frontal neocortex) and cognition. Data were derived from 30 AD Centers (ADCs) with autopsies reported using the National Alzheimer's Coordinating Center Neuropathology (NACC NP) Form v10. FTLD and other rare neurological diseases were excluded. TDP-43 stage was defined as Stage 0 = no TDP-43 proteinopathy, Stage 1 = in amygdala only, Stage 2 = in hippocampus but not in frontal neocortex, and Stage 3 = in frontal neocortex. Cognitive data from at the last clinical visit (within 2 years of death) were obtained from the NACC Uniform Data Set (UDS) , including MMSE , Animal Naming Test , WMS-R Logical Memory IIA–delayed , WMS-R Digit Span forward (trials correct) , and CDR sum of boxes . Analysis of covariance (ANCOVA) with inverse-variance weights was used to examine the associations between TDP-43 pathology stages and the cognitive test scores, controlling for gender, age at death, years of education, APOE ε4 dosage, Braak NFT stage, and Thal Aβ phase. Adjusted mean differences in the test scores were compared between each of Stage 1 to 3 and Stage 0 (as a reference) with Bonferroni corrected p-value. A total of 730 autopsied participants (aged at death ≥ 65) were included in this study. There were 471 cases in Stage 0, 56 in Stage 1, 160 in Stage 2, and 43 in Stage 3. Cognitive test scores of MMSE, Animal Naming Test, and Logical Memory in the subjects with hippocampal TDP-43 pathology were significantly lower than in those without TDP-43 pathology (Table1).
Source: Alzheimer s & Dementia
Institution: University of Kentucky
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2980757490