ALS is usually considered a motor disorder, but cognitive or behavioral impairment occurs in up to half of the patients. The ALS Functional Rating Scale-revised (ALSFRS-r) is a patient-reported questionnaire and the most widely used scale for monitoring disease progression; it also serves as the primary outcome measure in clinical trials for ALS. However, cognitive and behavioral impairment may lead to impaired perception of disabilities confounding the reporting of disabilities in the ALSFRS-r.

Over an 8-month period, 26 ALS patients (13 male, mean age: 65.7, 51% University graduate, 4 with ALS-FTD) and their caregivers were enrolled in an ongoing cross-sectional study at University of California, Irvine ALS & Neuromuscular Center. Separate ALSFRS-r scales were independently completed with the patients and their caregivers. Patients’ cognitive and behavior were assessed using the ALS Cognitive Behavioral Screen scale (ALS-CBS).

The difference between ALSFRS-r scores obtained from the patients and their caregivers (P-CG FRS) ranged from -8 to 12. There was no significant association between P-CG FRS and age, education, onset region, and ALS-CBS total cognitive score; but attention sub-score was trending toward significant association (estimate:1.01, p=0.09). ALS-CBS behavior total score was also trending toward significant association with P-CG FRS (estimate: -0.13, p=0.1). Furthermore, P-CG FRS was significantly associated with the following behavioral sub-domains of ALS-CBS in the expected direction: apathy (F:2.9, p=0.04), lack of empathy (F:3.1, p=0.04), agitation (F:3.1, p=0.04), sweet tooth (F:5.1, p=0.008), lack of insight (F:3.1, p=0.04), and pseudobulbar affect (estimate:1.8, p=0.04).

Behavioral impairment can lead to misperception of ALS related motor disabilities. Therefore, accounting for the confounding effect of behavioral impairment is important in monitoring disease progression and interpretation of primary outcomes in ALS trials.