Abstract

Objective
~35% of amyotrophic lateral sclerosis (ALS) patients exhibit mild cognitive deficits in, executive functions, language and fluency, without dementia. The precise pathology of these extra-motor symptoms has remained unknown. This study aimed to determine the pathological correlate of cognitive impairment in non-demented ALS patients.

Methods
In-depth neuropathological analysis of 27 non-demented ALS patients who had undergone cognitive testing (ECAS) during life. Analysis involved assessing TDP-43 accumulation in brain regions specifically involved in executive functions, language functions and verbal fluency to ascertain whether functional deficits would relate to a specific regional distribution of pathology.

Results
All patients with cognitive impairment had TDP-43 pathology in extra-motor brain regions (positive predictive value of 100%). The ECAS also predicted TDP-43 pathology with 100% specificity in brain regions associated with executive, language and fluency domains. We also detected a subgroup with no cognitive dysfunction, despite having substantial TDP-43 pathology, so called mismatch cases.

Conclusions
Cognitive impairment as detected by the ECAS is a valid predictor of TDP-43 pathology in non-demented ALS. The profile of mild cognitive deficits specifically predicts regional cerebral involvement. These findings highlight the utility of the ECAS, in accurately assessing the pathological burden of disease.
Original languageEnglish
Pages (from-to)149-157
JournalJournal of Neurology, Neurosurgery & Psychiatry
Volume91
Issue number2
Early online date12 Sep 2019
DOIs
Publication statusPublished - Feb 2020

Keywords

  • ECAS
  • TDP-43
  • cognition
  • ALS
  • neuropathology

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