Noradrenergic cardiac denervation is associated with gait velocity in Parkinson disease: a dual ligand PET study.

PURPOSE: Preliminary data suggest that gait abnormalities in Parkinson disease (PD) may be associated with sympathetic cardiac denervation. No kinematic gait studies were performed to confirm this observation. We aimed to correlate spatiotemporal kinematic gait parameters with cardiac sympathetic denervation as determined by cardiac [11C]HED PET in PD. METHODS: Retrospective database analysis of 27 PD patients with cardiac sympathetic denervation. All patients underwent spatiotemporal kinematic gait assessment (medication 'off' state), cardiac [11C]HED and dopaminergic brain [11C]DTBZ PET scans. We employed a hierarchical regression approach to examine associations between the extent of cardiac denervation, dopaminergic nigrostriatal neurodegeneration, and three gait parameters - velocity, step length and cadence. RESULTS: More extensive cardiac denervation was associated with slower velocity (estimate: -1.034, 95% CI [-1.65, -0.42], p = 0.002), shorter step length (estimate: -0.818, 95% CI [-1.43, -0.21], p = 0.011) and lower cadence (estimate: -0.752, 95% CI [-1.28, -0.23], p = 0.007) explaining alone 30% (Adjusted-R²: 0.297), 20% (Adjusted-R²: 0.202) and 23% (Adjusted-R²: 0.227) of the variability, respecivetly. These associations remained independent of striatal dopaminergic impairment and confounding factors such as age, Hoehn and Yahr (HY) stages, peripheral neuropathy, cognition, and autonomic symptoms. In contrast, striatal dopaminergic denervation was significantly associated with step length (estimate: 0.883, 95% CI [0.29, 1.48], p = 0.005), explaining about 24% of the variability but was dependent of HY stage. CONCLUSIONS: More severe cardiac noradrenergic denervation was associated with lower gait velocity, independent of striatal dopaminergic denervation and HY stage, impacting both step length and cadence. These results suggest independent contributions of the peripheral autonomic system degeneration on gait dynsfunction in PD.

Body Composition, Falls, and Freezing of Gait in Parkinson's Disease: Gender-Specific Effects.

BACKGROUND: Postural instability and gait difficulties (PIGD) are a significant cause of mobility loss and lower quality of life in Parkinson's disease (PD). When PD progresses, patients may experience falls and freezing of gait (FoG) resulting in fear of falling and increasing sedentariness. Sedentary behavior results in sarcopenia associated with other changes in body composition, especially in older patients becoming frail. Previous studies have shown gender-specific changes in body composition with aging as well as gender disparities in symptoms and progression of PD, yet the association between gender-specific body composition and PIGD symptoms such as FoG along with falls, remains unexplored. OBECTIVE: This study aimed to investigate the association between gender-specific changes in body composition, FoG and falls assessment. METHODS: 136 PD subjects underwent detailed clinical test batteries and had whole-body composition assessed using dual-energy X-ray absorptiometry (DXA). Multivariate logistic forward stepwise regression was performed to define body composition associations for FoG and falls. RESULTS: Multivariate regression analysis revealed that in males with PD, lower leg lean mass was significantly associated with the presence of FoG (OR, 0.429; 95% CI, 0.219-0.839; p=0.013) but not with falls. In females with PD, higher leg adipose mass was significantly associated with falls (OR, 4.780; 95% CI, 1.506-15.174; p=0.008) but not with FoG. CONCLUSION: These observations suggest gender specific associations between body composition and FoG vs. falls in PD. Future research should explore the impact of interventions on body composition in individuals with PD by paying specific attention to gender differences.

Cardiac sympathetic denervation and anxiety in Parkinson disease.

BACKGROUND: Anxiety in Parkinson disease (PD) negatively impacts quality of life. While research predominantly focuses on central nervous system changes, some evidence suggests a connection between peripheral autonomic dysfunctions and PD-related anxiety. The role of the peripheral autonomic nervous system in this context may be overlooked. OBJECTIVES: This study explores the link between anxiety symptoms and cardiac sympathetic denervation in PD using 11C-meta-hydroxyephedrine ([11C]HED) PET cardiac imaging. METHODS: We studied 34 non-demented PD subjects, assessing anxiety levels through the Spielberg Anxiety State-Trait test trait section (STAI-T). Patients underwent comprehensive assessments along with [11C]HED cardiac and [11C]DTBZ brain PET. To identify subdimensions of STAI-T, we employed principal components analysis (PCA). We examined associations between the anxiety subdimensions and two measures of cardiac sympathetic denervation from [11C]HED PET. We utilized correlation and linear regression models for these analyses. RESULTS: PCA revealed two STAI-T results components: anxiety-depressive and pure anxiety subcomponents. Only pure anxiety significantly correlated with measures of cardiac sympathetic denervation (rhos -0.40, p = 0.018; 0.35, p = 0.043). Regression models confirmed a significant association, with cardiac sympathetic denervation explaining ∼20 % of pure anxiety variance, independent of sex, dopaminergic impairment, and anxiolytic treatments. DISCUSSION: This study provides preliminary evidence of peripheral autonomic nervous system abnormalities contributing to PD-related anxiety, suggesting dysregulation in peripheral autonomic functions influencing anxiety perception.