Cognitive capacity in amyotrophic lateral sclerosis: The value of diagnostic markers in cerebrospinal fluid and the influence of nutrition and pulmonary function#

Authors#

Sabrina M. Wölfel, Catherine Widmann, Sergio Castro-Gomez, Patrick Weydt, Pawel Tacik, Michael Heneka

Abstract#

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease that is fatal with a median of 3-4 years. It is characterized by degeneration of the first and second motor neurons. In addition to physical limitations, neuropsychological abnormalities occur in more than 50% of cases. This leads to a rapid loss of autonomy and increases the need for care. An individual prognosis for the course of the disease is currently not possible. As part of our investigations, we focused on cognitive performance and behavioral abnormalities measured by the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) in patients with ALS (pALS) and investigated possible prognostic biomarkers in cerebrospinal fluid as well as modifiable factors such as nutrition and lung function. Retrospective data analysis of 99 pALS cases, examined between 2018 and 2021 at the Department for Neurodegenerative Diseases and Gerontopsychiatry at the University Hospital of Bonn, using ECAS found that increased levels of total tau (tTau) and phospho-Tau181 (pTau) correlates with a poorer performance of pALS on the ECAS. Weight loss during the disease also negatively affects cognitive performance. We also showed a correlation between abnormalities in the ECAS and low-normal serum thiamine levels. Previous findings of a negative effect of reduced lung function on cognitive performance were not replicated. Whether the onset of ALS is bulbar or spinal does not appear to have an effect on cognition and behavior. We also confirmed that the ECAS is useful in identifying a behavioral variant of frontotemporal dementia in ALS patients. Our findings provide insight into the prognosis of pALS in terms of their cognitive performance and behavioral abnormalities as the disease progresses, as well as possible therapeutic approaches to stabilize and support neuropsychological abnormalities. In addition, interesting new avenues of research are emerging, particularly regarding the role of thiamine in ALS.