Understanding the association between cognitive decline and motor dysfunction in ALS: Insights from patient assessments

Background Amyotrophic lateral sclerosis (ALS) is a multisystem disorder with cognitive involvement that heavily impacts quality of life and survival. Despite its importance, cognitive screening is rarely integrated into standard care. To address this gap, this study evaluated correlations between specific cognitive domains and the rate of functional decline in ALS patients. Methods In this cross-sectional study, 104 ALS patients underwent functional evaluation using the ALS Functional Rating Scale-Revised (ALSFRS-R) and cognitive assessment via the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). Results Participants (28 females, 76 males; mean age 57.7 years) predominantly presented with sporadic, limb-onset ALS. Initial analyses revealed significant associations between functional decline and ECAS memory (r = -0.33, p = 0.018) and executive scores (r = 0.29, p = 0.040). However, after adjusting for demographic and clinical confounders via multiple linear regression models using the functional decline rate (points per month) as the outcome, poorer memory performance remained a significant independent predictor of a faster decline rate (B = -0.072, 95% CI: -0.127 to -0.016, p = 0.012). The executive domain lost statistical significance in the adjusted model (B = 0.022, 95% CI: -0.014 to 0.059, p = 0.223). Notably, total ECAS scores significantly differed across disease onset sites (p = 0.021). Conclusions Cognitive performance in ALS is heterogeneous and inextricably linked to functional status and disease onset site. These findings emphasize the necessity of systematic cognitive screening to capture early cognitive-motor interactions, particularly memory deficits, to improve prognostic accuracy and guide care planning.