Decline of cognitive and behavioral functions in amyotrophic lateral sclerosis: a longitudinal study

Abstract

Background: A cognitive impairment, ranging from frontotemporal dementia (FTD) to milder forms of dysexecutive or behavioral dysfunction, is detected in 30–50% of patients affected by amyotrophic lateral sclerosis (ALS) at diagnosis. Such condition considerably influences the prognosis, and possibly impacts on the decision-making process with regards to end-of-life choices. The aim of our study is to examine the changes of cognitive and behavioral impairment in a large population of ALS from the time of diagnosis to a 6-month follow-up (IQR 5.5–9.0 months), and to examine to what extent the progression of cognitive impairment affects survival time and rate of disease progression.

Methods: We recruited 146 ALS patients classified according to revised criteria of ALS and FTD spectrum disorder. In a multidisciplinary setting, during two subsequent visits we examined clinical features with ALSFRS-r score, FVC% and BMI, and cognitive status with an extensive neuropsychological evaluation.

Results: At second examination, one-third of patients showed a worsening of cognitive impairment, namely 88% of ALSbi, 27% of ALSci, 40% of ALScbi, and, interestingly, also 24% of cognitive normal ALS developed a significant cognitive dysfunction. We find that those who changed their cognitive status presented a lower ALSFRS-r score at t1 and a shorter survival time compared to those who did not change, regardless of the type of cognitive impairment.

Conclusion: We show how cognitive disorders in ALS patients can not only be present at diagnosis, but also manifest during disease and influence the progression of motor deficit and the prognosis.

Keywords:

• Amyotrophic Lateral Sclerosis
• cognitive impairment
• fronto-temporal dementia
• longitudinal study

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Declaration of interest

Adriano Chiò serves on scientific advisory boards for Mitsubishi Tanabe, Roche, Biogen, and Cytokinetics and has received a research grant from Italfarmaco. Andrea Calvo has received research grant from Cytokinetics.

Enrica Bersano, Maria Francesca Sarnelli, Valentina Solara, Barbara Iazzolino, Laura Peotta, Fabiola De Marchi, Alessio Facchin, Cristina Moglia, Antonio Canosa, and Letizia Mazzini report no conflicts of interest.

The sponsor organizations had no role in data collections and analysis and did not participate to writing and approving the manuscript. The information reported in the manuscript has never been reported elsewhere.

Additional information

Funding

This work was in part supported by the Italian Ministry of Health [Ministero della Salute, Ricerca Sanatoria Finalizzata, grants RF-2010-2309849, RF-2011-02351193, RF-2016-02362405, and GR-2011-02351217], the European Commission’s Health Seventh Framework Program [FP7/2007-2013 under grant agreement 259867], and the Joint Program - Neurodegenerative Disease Research (Strength, ALS-Care and Brain-Mend projects), granted by Italian Ministry of Education, University and Research, and the Progetti di Ricerca di Rilevante Interesse Nazionale (PRIN) [grant 2017SNW5MB], granted by the Italian Ministry of Education, University and Research. This paper was written under the Department of Excellence grant of the Italian Ministry of Education, University and Research to the ‘Rita Levi Montalcini’ Department of Neuroscience, University of Torino, Italy, and to the Department of Translational Medicine, University of Eastern Piedmont.