Cognitive Dysfunction Is Associated With an Underestimation of Respiratory Function in ALS

INTRODUCTION/AIMS: The association between low forced vital capacity (FVC) and cognitive impairment in ALS is ambiguous; it could be due to respiratory dysfunction and/or poor effort from cognitive deficits. We used the objective, non-volitional phrenic nerve motor response amplitude (PAmp) to clarify how cognitive status affects the relationship between diaphragmatic strength and FVC. METHODS: This retrospective study included 73 patients with ALS followed in our clinic. FVC and PAmp were measured, and cognitive status was assessed with the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). Regression models tested for associations between FVC and distinct ECAS domains and whether these domains influenced the PAmp-FVC relationship. RESULTS: PAmp (β = 0.58, p = 0.001) and its interaction with an abnormal ECAS's Executive score (β = -0.20, p < 0.045) were significant predictors of FVC. The latter indicated that patients with abnormal executive function had lower FVC than cognitively normal patients at similar PAmp values. Moreover, in patients with abnormal executive function, a reduction in PAmp was associated with a shallower decline in FVC. Severe bulbar dysfunction was also negatively associated with FVC (β = -0.22, p = 0.024). DISCUSSION: FVC may underestimate respiratory capacity in cognitively impaired patients; therefore, we recommend non-volitional measures when evaluating ALS patients with executive dysfunction.