Association between cardiac autonomic dysfunction, cognitive impairment, and survival in patients with amyotrophic lateral sclerosis

PURPOSE: The aim of this study was to investigate the relationship between cardiac autonomic dysfunction, cognitive impairment, and survival in patients with amyotrophic lateral sclerosis (ALS). METHODS: The heart activity of 65 patients with ALS (28 with normal cognition [ALS-CN]; 37 with impaired cognition [ALS-CI]) and 38 healthy controls (HCs) was measured by 24-h Holter monitoring. Heart rate (HR) measures and heart rate variability (HRV) parameters were compared between the three study groups and, additionally, correlated with five Edinburgh Cognitive and Behavioral ALS Screen (ECAS) domains in the ALS subgroups. Age, gender, and educational level were adjusted. Factors associated with cognitive status were assessed using logistic regression. Survival predictors in patients with ALS were analyzed using the Kaplan-Meier estimator and Cox regression. RESULTS: Compared to the HCs, patients with ALS-CI exhibited lower RRI (R-R-interval; P = 0.017), SDNN (standard deviation of all normal RR intervals; P = 0.013), SDNN Index (P = 0.044), and VLF power (very low-frequency power; P = 0.012). Total power was reduced in the ALS-CI group compared to the HCs (P = 0.036) and ALS-CN group (P = 0.048). In patients with ALS-CN, language negatively correlated with mean HR (P = 0.001) and positively with the RRI (P = 0.003), SDNN (P = 0.001), SDANN (standard deviation of the average NN intervals; P = 0.005), total power (P = 0.006), VLF power (P = 0.011), and low-frequency power (P = 0.026). Visuospatial function correlated positively with the SDNN Index (P = 0.041). In patients with ALS-CI, executive function (P = 0.015) and ECAS total score (P = 0.009) negatively correlated with the RMSSD (square root of mean sum-of-squares of differences between adjacent NN intervals), while visuospatial function correlated positively with normalized LF value (LFnu; P = 0.049). No associations were observed between the other cognitive domains and any of the 14 HRV/HR measures in patients with either ALS-CI or ALS-CN. SDNN ≤ 100 ms was linked to cognitive impairment (P = 0.039) and also showed a borderline association (P = 0.066) with poorer survival, while cognitive impairment (P = 0.010) was significantly linked to worse outcomes. CONCLUSIONS: Patients with ALS with cognitive impairment demonstrated reduced cardiac autonomic modulations and altered cognitive autonomic associations. Cognitive impairment was linked to reduced survival, with baseline SDNN ≤ 100 ms identified as a potential marker.