Increased markers of cardiac vagal activity in leucine-rich repeat kinase 2-associated Parkinson's disease.

PurposeCardiac autonomic dysfunction manifests as reduced heart rate variability (HRV) in idiopathic Parkinson's disease (PD), but no significant reduction has been found in PD patients who carry the LRRK2 mutation. Novel HRV features have not been investigated in these individuals. We aimed to assess cardiac autonomic modulation through standard and novel approaches to HRV analysis in individuals who carry the LRRK2 G2019S mutation.MethodsShort-term electrocardiograms were recorded in 14 LRRK2-associated PD patients, 25 LRRK2-non-manifesting carriers, 32 related non-carriers, 20 idiopathic PD patients, and 27 healthy controls. HRV measures were compared using regression modeling, controlling for age, sex, mean heart rate, and disease duration. Discriminant analysis highlighted the feature combination that best distinguished LRRK2-associated PD from controls.ResultsBeat-to-beat and global HRV measures were significantly increased in LRRK2-associated PD patients compared with controls (e.g., deceleration capacity of heart rate: p = 0.006) and idiopathic PD patients (e.g., 8th standardized moment of the interbeat interval distribution: p = 0.0003), respectively. LRRK2-associated PD patients also showed significantly increased irregularity of heart rate dynamics, as quantified by Rényi entropy, when compared with controls (p = 0.002) and idiopathic PD patients (p = 0.0004). Ordinal pattern statistics permitted the identification of LRRK2-associated PD individuals with 93% sensitivity and 93% specificity. Consistent results were found in a subgroup of LRRK2-non-manifesting carriers when compared with controls.ConclusionsIncreased beat-to-beat HRV in LRRK2 G2019S mutation carriers compared with controls and idiopathic PD patients may indicate augmented cardiac autonomic cholinergic activity, suggesting early impairment of central vagal feedback loops in LRRK2-associated PD

Beyond shallow feelings of complex affect: Non-motor correlates of subjective emotional experience in Parkinson's disease.

Affective disorders in Parkinson's disease (PD) concern several components of emotion. However, research on subjective feeling in PD is scarce and has produced overall varying results. Therefore, in this study, we aimed to evaluate the subjective emotional experience and its relationship with autonomic symptoms and other non-motor features in PD patients. We used a battery of film excerpts to elicit Amusement, Anger, Disgust, Fear, Sadness, Tenderness, and Neutral State, in 28 PD patients and 17 healthy controls. Self-report scores of emotion category, intensity, and valence were analyzed. In the PD group, we explored the association between emotional self-reported scores and clinical scales assessing autonomic dysregulation, depression, REM sleep behavior disorder, and cognitive impairment. Patient clustering was assessed by considering relevant associations. Tenderness occurrence and intensity of Tenderness and Amusement were reduced in the PD patients. Tenderness occurrence was mainly associated with the overall cognitive status and the prevalence of gastrointestinal symptoms. In contrast, the intensity and valence reported for the experience of Amusement correlated with the prevalence of urinary symptoms. We identified five patient clusters, which differed significantly in their profile of non-motor symptoms and subjective feeling. Our findings further suggest the possible existence of a PD phenotype with more significant changes in subjective emotional experience. We concluded that the subjective experience of complex emotions is impaired in PD. Non-motor feature grouping suggests the existence of disease phenotypes profiled according to specific deficits in subjective emotional experience, with potential clinical implications for the adoption of precision medicine in PD. Further research on larger sample sizes, combining subjective and physiological measures of emotion with additional clinical features, is needed to extend our findings

Increased markers of cardiac vagal activity in leucine-rich repeat kinase 2-associated Parkinson's disease.

PurposeCardiac autonomic dysfunction manifests as reduced heart rate variability (HRV) in idiopathic Parkinson's disease (PD), but no significant reduction has been found in PD patients who carry the LRRK2 mutation. Novel HRV features have not been investigated in these individuals. We aimed to assess cardiac autonomic modulation through standard and novel approaches to HRV analysis in individuals who carry the LRRK2 G2019S mutation.MethodsShort-term electrocardiograms were recorded in 14 LRRK2-associated PD patients, 25 LRRK2-non-manifesting carriers, 32 related non-carriers, 20 idiopathic PD patients, and 27 healthy controls. HRV measures were compared using regression modeling, controlling for age, sex, mean heart rate, and disease duration. Discriminant analysis highlighted the feature combination that best distinguished LRRK2-associated PD from controls.ResultsBeat-to-beat and global HRV measures were significantly increased in LRRK2-associated PD patients compared with controls (e.g., deceleration capacity of heart rate: p = 0.006) and idiopathic PD patients (e.g., 8th standardized moment of the interbeat interval distribution: p = 0.0003), respectively. LRRK2-associated PD patients also showed significantly increased irregularity of heart rate dynamics, as quantified by Rényi entropy, when compared with controls (p = 0.002) and idiopathic PD patients (p = 0.0004). Ordinal pattern statistics permitted the identification of LRRK2-associated PD individuals with 93% sensitivity and 93% specificity. Consistent results were found in a subgroup of LRRK2-non-manifesting carriers when compared with controls.ConclusionsIncreased beat-to-beat HRV in LRRK2 G2019S mutation carriers compared with controls and idiopathic PD patients may indicate augmented cardiac autonomic cholinergic activity, suggesting early impairment of central vagal feedback loops in LRRK2-associated PD