High Rates Of Cognitive And Behavioral Impairment In A Large Prospective Als Study

OBJECTIVE: To investigate the cognitive and behavioral functioning of patients prospectively enrolled in the longitudinal ALS COSMOS study. BACKGROUND: Patients with ALS develop frontotemporal dementia (FTD), more subtle cognitive impairment (ALSci) and behavioral impairment (ALSbi). To recognize this extramotoneuronal involvement is essential to understand the pathogenesis of ALS. DESIGN/METHODS: 217 patients with confirmed ALS were administered three well-recognized screening cognitive-behavioral measures: the ALS-Cognitive Behavioral Screen (ALS-CBS), Frontal Behavioral Inventory-ALS version, and the Abrahams Written Fluency Test. Cognitive and behavioral impairment was defined using the ALS-CBS, based on Woolley et al. 2010 and the UCSF criteria. RESULTS: The sample was 42.9% female, with a mean age of 60.9 (SD=9.9), mean education of 15.0 years (SD=3.0), mean FVC of 79.7 (SD=22.1) and mean ALSFRS-R of 36.3 (SD=6.3). 9.8% of the sample met criteria for FTD with cognitive impairment, and 18.4% of the sample met criteria for FTD with behavioral impairment. An additional 64.4% and 13.4% met ALSci and ALSbi criteria, respectively. Increased levels of frontotemporal impairment were associated with more bulbar involvement, lower income, and lower education. Illness duration, age, and smoking history were uncorrelated with cognitive and behavioral performance, with the exception of advancing age correlating with cognitive impairment. ALS FRS-R was unassociated with cognitive performance but associated with behavioral changes. FVC was associated with verbal fluency score and ALS-CBS cognitive score. PBA levels correlated with behavioral impairment. Patients had greater negative symptoms such as apathy, and fewer symptoms of disinhibition. CONCLUSIONS: Approximately 10-15% of patients met FTD criteria, with larger proportions of patients meeting criteria for ALSci and ALSbi. Behavioral impairment correlated with more bulbar dysfunction, PBA, and lower socioeconomic status. Longitudinal data are being collected to determine if frontotemporal impairment is a continuum of extraneuronal involvement in ALS. Supported by: NIEHS R01ES016348 and MDA Wings. Disclosure: Dr. Murphy has nothing to disclose. Dr. Factor-Litvak has nothing to disclose. Dr. Goetz has nothing to disclose. Dr. Hupf has nothing to disclose. Dr. Woolley Levine has nothing to disclose. Dr. Lomen-Hoerth has nothing to disclose. Dr. Mitsumoto has received personal compensation for activities with Avanir, Knopp, Biogen Idec., Cytokinetics, Sanofi-Aventis, and Shionogi. Dr. Mitsumoto has received research support from Avanir, Knopp, Biogen Idec., Cytokinetics, Sanofi-Aventis, and Shionogi.