Association of Specific Leg Muscle Strength and Motor Features in Parkinson's Disease.

Background: Postural instability and gait difficulties (PIGD) are a significant cause of falls, mobility loss, and lower quality of life in Parkinson's disease (PD). The connection between PD progression and diminished strength in the lower limbs has been acknowledged. However, the identification of specific muscle groups linked to PIGD and non-PIGD motor features is still unknown. Objective: To explore the relationship between the strength of specific lower limb muscle groups, along with muscle mass, and their associations with PIGD, PIGD subtypes, and non-PIGD motor features in PD. Methods: 95 PD participants underwent detailed motor and non-motor test batteries, including lower limb isometric strength testing and whole-body lean mass assessments. Correlation analysis and univariate and multivariate linear/logistic forward stepwise regression were performed to test associations between PIGD and non-PIGD motor features with normalized value (z-score) of lower limb muscle strength and measures of lean mass. Results: Multivariate regression analysis, adjusted for age, gender, and levodopa equivalent dose, revealed that hip abductor strength was significantly associated with overall PIGD motor severity ratings (p < 0.001), impaired balance (p < 0.001), and non-PIGD Parkinsonian motor features (p < 0.001). Conversely, hip extensor strength was significantly associated with falls, slow walking, and FoG motor features (p=0.016; p=0.003; p=0.020, respectively). Conclusion: We found that lower hip abductor strength was associated with PIGD and non-PIGD motor features. The association between non-PIGD motor features may suggest specific vulnerability of the hip abductors as part of a proposed brain-muscle loop hypothesis in PD. Moreover, lower hip extensor strength correlated with falls, slow walking, and FoG.

Ketogenic-Mimicking Diet as a Therapeutic Modality for Bipolar Disorder: Biomechanistic Rationale and Protocol for a Pilot Clinical Trial.

There is growing interest in the investigation of ketogenic diets as a potential therapy for bipolar disorder. The overlapping pharmacotherapies utilized for both bipolar disorder and seizures suggest that a mechanistic overlap may exist between these conditions, with fasting and the ketogenic diet representing the most time-proven therapies for seizure control. Recently, preliminary evidence has begun to emerge supporting a potential role for ketogenic diets in treating bipolar disorder. Notably, some patients may struggle to initiate a strict diet in the midst of a mood episode or significant life stressors. The key question addressed by this pilot clinical trial protocol is if benefits can be achieved with a less restrictive diet, as this would allow such an intervention to be accessible for more patients. Recent development of so-called ketone esters, that once ingested is converted to natural ketone bodies, combined with low glycemic index dietary changes has the potential to mimic two foundational components of therapeutic ketosis: high levels of ketones and minimal spiking of glucose/insulin. This pilot clinical trial protocol thus aims to investigate the effect of a 'ketogenic-mimicking diet' (combining supplementation of ketone esters with a low glycemic index dietary intervention) on neural network stability, mood, and biomarker outcomes in the setting of bipolar disorder. Positive findings obtained via this pilot clinical trial protocol may support future target engagement studies of ketogenic-mimicking diets or related ketogenic interventions. A lack of positive findings, in contrast, may justify a focus on more strict dietary interventions for future research.

Cholinergic system correlates of postural control changes in Parkinson's disease freezers.

Postural instability and freezing of gait are the most debilitating dopamine-refractory motor impairments in advanced stages of Parkinson's disease because of increased risk of falls and poorer quality of life. Recent findings suggest an inability to efficaciously utilize vestibular information during static posturography among people with Parkinson's disease who exhibit freezing of gait, with associated changes in cholinergic system integrity as assessed by vesicular acetylcholine transporter PET. There is a lack of adequate understanding of how postural control varies as a function of available sensory information in patients with Parkinson's disease with freezing of gait. The goal of this cross-sectional study was to examine cerebral cholinergic system changes that associate with inter-sensory postural control processing features as assessed by dynamic computerized posturography and acetylcholinesterase PET. Seventy-five participants with Parkinson's disease, 16 of whom exhibited freezing of gait, underwent computerized posturography on the NeuroCom© Equitest sensory organization test platform, striatal dopamine, and acetylcholinesterase PET scanning. Findings demonstrated that patients with Parkinson's disease with freezing of gait have greater difficulty maintaining balance in the absence of reliable proprioceptive cues as compared to those without freezing of gait [ß = 0.28 (0.021, 0.54), P = 0.034], an effect that was independent of disease severity [ß = 0.16 (0.062, 0.26), P < 0.01] and age [ß = 0.092 (-0.005, 0.19), P = 0.062]. Exploratory voxel-based analysis revealed an association between postural control and right hemispheric cholinergic network related to visual-vestibular integration and self-motion perception. High anti-cholinergic burden predicted postural control impairment in a manner dependent on right hemispheric cortical cholinergic integrity [ß = 0.34 (0.065, 0.61), P < 0.01]. Our findings advance the perspective that cortical cholinergic system might play a role in supporting postural control after nigro-striatal dopaminergic losses in Parkinson's disease. Failure of cortex-dependent visual-vestibular integration may impair detection of postural instability in absence of reliable proprioceptive cues. Better understanding of how the cholinergic system plays a role in this process may augur novel treatments and therapeutic interventions to ameliorate debilitating symptoms in patients with advanced Parkinson's disease.

Decreased vestibular efficacy contributes to abnormal balance in Parkinson's disease.

BACKGROUND AND PURPOSE: Abnormal balance is poorly responsive to dopaminergic therapy in Parkinson's disease (PD). Decreased vestibular efficacy may contribute to imbalance in PD. The purpose of this study was to investigate the relationship between vestibular measures of dynamic posturography and imbalance in PD while accounting for confounder variables. METHODS: 106 patients with PD underwent dynamic posturography for the 6 conditions of the sensory integration test (SOT) using the Neurocom Equitest device. All SOT measures, nigrostriatal dopaminergic denervation ((+)-[11C]DTBZ PET), brain acetylcholinesterase ([11C]PMP PET), age, duration of disease, cognitive and parkinsonian motor scores, and ankle vibration sensitivity were used as regressors in a stepwise logistic regression model comparing PD patients with versus without imbalance defined as Hoehn and Yahr (HY) stage 2.5 or higher. RESULTS: The presence of imbalance was significantly associated with vestibular ratio COP RMS (P = 0.002) independently from visual ratio COP velocity (P = 0.012), thalamic acetylcholinesterase activity (P = 0.0032), cognition (P = 0.006), motor severity (P = 0.0039), age (P = 0.001), ankle vibration sensitivity (P = 0.0008), and borderline findings for somatosensory ratio COP velocity (P = 0.074) and visual ratio COP RMS (P = 0.078). Nigrostriatal dopaminergic denervation did not achieve significance. CONCLUSIONS: The inability to efficaciously utilize vestibular information to retain upright stance is a determinant of imbalance in PD independent from visual and somatosensory processing changes and nigrostriatal dopaminergic losses. Thalamic, but not cortical, cholinergic denervation incrementally predicted balance abnormality. Further research is needed to investigate an intrinsic role of the cholinergic thalamus in multi-sensory, in particular vestibular, processing functions of postural control in PD.

Masking our risky behavior: how licensing and fear reduction reduce social distancing behavior.

Licensing and fear reduction can explain why people only partially adopt health precautions while still believing that they are remaining compliant with recommendations during the COVID-19 pandemic. We assessed individuals' attitudes regarding social distancing and personal protective practices, as well as concern about COVID-19 and behaviors in April of 2020. Concern about COVID-19 had dual, competing effects on social distancing behavior. Concern predicted increased social distancing behavior via more positive social distance policy attitudes. However, concern also predicted decreased social distancing behavior via more positive attitudes toward personal protective practices, such as mask wearing. Licensing and/or fear reduction allows individuals to view personal protective practices as substitutable rather than additive measures of safety that should complement social distancing, and this effect is not explained by partisanship or working from home. Policy makers should be cautious when advocating for multiple health precautions of varying effectiveness that are intended to be additive.