title: TDP-43 pathology and memory impairment in elders without pathologic diagnoses of AD or FTLD.
abstract: OBJECTIVE
  To investigate the association of TAR DNA-binding protein 43 (TDP-43) pathology with memory, other cognitive domains, and dementia in community-dwelling elders without pathologic diagnoses of Alzheimer disease (AD) or frontotemporal lobar degeneration (FTLD).
  
  
  METHODS
  Of 1,058 autopsied participants, 343 (32.4%) did not have pathologic diagnoses of AD or FTLD. Diagnosis of dementia was based on clinical evaluation and cognitive performance tests, which were used to create summary measures of global cognition and of 5 cognitive domains. TDP-43 pathology evaluated in 6 brain regions by immunohistochemistry was converted into a summary measure of TDP-43 severity.
  
  
  RESULTS
  Of 343 participants, 135 (39.4%) had TDP-43 pathology with a mean TDP-43 severity score of 0.394 (SD 0.490). TDP-43 inclusions were confined to the amygdala (stage 1) in 43.7% of participants, 40% showed additional involvement of the hippocampus or entorhinal cortex (stages 2), while fewer (16.3%) showed additional TDP-43 pathology in the temporal and frontal cortices (stage 3). Severity of TDP-43 pathology was independently related to lower function in global cognition and episodic and semantic memory while increased odds of dementia was only a trend. When participants with hippocampal sclerosis (HS) were excluded from the models, TDP-43 pathology remained associated with lower episodic memory but relationships with global cognition, semantic memory, and dementia were attenuated.
  
  
  CONCLUSIONS
  TDP-43 pathology in elders, without pathologic diagnoses of AD or FTLD, is common and independently associated with lower function in episodic memory, while its associations with global cognitive impairment and dementia are difficult to separate from HS.
authors.affiliation: From the Rush Alzheimer's Disease Center (S.N., L.Y., R.S.W., E.-Y.C., D.A.B., J.A.S.) and Departments of Neurological Sciences (L.Y., R.S.W., D.A.B., J.A.S.), Behavioral Sciences (R.S.W.), and Pathology (Neuropathology) (S.N., J.A.S.), Rush University Medical Center, Chicago, IL. Sukriti_Nag@rush.edu.
authors.forename: Sukriti
authors.initials: S
authors.lastname: Nag
authors.affiliation: From the Rush Alzheimer's Disease Center (S.N., L.Y., R.S.W., E.-Y.C., D.A.B., J.A.S.) and Departments of Neurological Sciences (L.Y., R.S.W., D.A.B., J.A.S.), Behavioral Sciences (R.S.W.), and Pathology (Neuropathology) (S.N., J.A.S.), Rush University Medical Center, Chicago, IL.
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
authors.affiliation: From the Rush Alzheimer's Disease Center (S.N., L.Y., R.S.W., E.-Y.C., D.A.B., J.A.S.) and Departments of Neurological Sciences (L.Y., R.S.W., D.A.B., J.A.S.), Behavioral Sciences (R.S.W.), and Pathology (Neuropathology) (S.N., J.A.S.), Rush University Medical Center, Chicago, IL.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Wilson
authors.affiliation: From the Rush Alzheimer's Disease Center (S.N., L.Y., R.S.W., E.-Y.C., D.A.B., J.A.S.) and Departments of Neurological Sciences (L.Y., R.S.W., D.A.B., J.A.S.), Behavioral Sciences (R.S.W.), and Pathology (Neuropathology) (S.N., J.A.S.), Rush University Medical Center, Chicago, IL.
authors.forename: Er-Yun
authors.initials: EY
authors.lastname: Chen
authors.affiliation: From the Rush Alzheimer's Disease Center (S.N., L.Y., R.S.W., E.-Y.C., D.A.B., J.A.S.) and Departments of Neurological Sciences (L.Y., R.S.W., D.A.B., J.A.S.), Behavioral Sciences (R.S.W.), and Pathology (Neuropathology) (S.N., J.A.S.), Rush University Medical Center, Chicago, IL.
authors.forename: David A
authors.initials: DA
authors.lastname: Bennett
authors.affiliation: From the Rush Alzheimer's Disease Center (S.N., L.Y., R.S.W., E.-Y.C., D.A.B., J.A.S.) and Departments of Neurological Sciences (L.Y., R.S.W., D.A.B., J.A.S.), Behavioral Sciences (R.S.W.), and Pathology (Neuropathology) (S.N., J.A.S.), Rush University Medical Center, Chicago, IL.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Schneider
mesh_terms: D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology*; D003071:Cognition; D003704:Dementia / Q000150:complications / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D008569:Memory Disorders / Q000150:complications / Q000473:pathology*; D008609:Mental Status Schedule; D009483:Neuropsychological Tests; D012720:Severity of Illness Index; D057177:TDP-43 Proteinopathies / Q000150:complications / Q000473:pathology* / Q000523:psychology; D014402:Tuberous Sclerosis / Q000150:complications / Q000473:pathology / Q000523:psychology