Predictors of anxiety in Parkinson's disease: results from a 3-year longitudinal cohort study.

INTRODUCTION: Anxiety symptoms are the most common neuropsychiatric manifestation of Parkinson's disease (PD), contributing to decreased quality of life. Few longitudinal studies in PD samples have examined correlates of anxiety symptoms over time. Understanding predictor variables may help to identify novel targets for reducing anxiety in PD. The aim of this study was to identify predictors of anxiety symptoms over 3 years in a clinic-based PD cohort. METHODS: Our cohort included patients with PD at an academic medical center in the Southeastern United States (n = 105). Visits included assessment of motor, psychiatric, and cognitive features, including neuropsychological testing. For our multivariate model, we selected 11 predictor variables with the most existing evidence or theoretical support for an association with anxiety symptoms in PD. Multivariate linear mixed model regression was performed to determine which variables were significantly associated with anxiety symptoms over time. RESULTS: Over half of participants (57%) met the screening threshold for an anxiety disorder at some point during the study. Independent predictors of anxiety symptoms over time included symptoms of REM sleep behavior disorder (RBD) and dysautonomia. DISCUSSION: In this PD sample, RBD and dysautonomia symptoms were significantly associated with anxiety symptoms over time. Each of these relationships has been reported in one of two prior longitudinal studies. Unlike prior studies, cognitive impairment was not a significant predictor of anxiety symptoms in our sample. Future research should confirm the direction and mechanisms underlying these relationships, including the potential for anxiety symptom reduction through treatment for RBD and dysautonomia.

Psychiatric predictors of quality of life in Parkinson's disease: A three-year longitudinal study.

INTRODUCTION: Parkinson's disease (PD) is associated with worsened quality of life (QOL) over time. Few longitudinal studies exist investigating the relationship of psychiatric comorbidities with QOL in people with PD (PwP). We sought to determine specific psychiatric symptoms associated with decreasing QOL in PwP over time. METHODS: We recruited PwP without dementia from a movement disorders clinic at an academic medical center. Participants were evaluated annually with motor and neuropsychological assessments at each visit. QOL was measured using the Parkinson's Disease Questionnaire-39 (PDQ-39). We assessed psychiatric symptoms, including depression (Beck Depression Inventory II, BDI-II), anxiety (Beck Anxiety Index, BAI), and apathy (Apathy Scale). Psychosis and impulse control disorders (ICDs) were recorded as present or absent. Using random coefficient regression, we analyzed psychiatric features associated with worsened QOL in PwP over three years. RESULTS: From the 105 participants enrolled at baseline, 67 completed three years of follow up. Mean PDQ-39 scores increased from 16.0 at baseline to 19.8 at year three. In multivariate analysis, higher BDI-II scores, BAI scores, and apathy scores were uniquely associated with worsened QOL over time (p < 0.001 for all measures), while presence of ICDs (p = 0.18) or psychosis (p = 0.10) were not. Changes in the BAI score and the BDI-II score exerted similar effects on the overall PDQ-39 score. CONCLUSION: Depression, anxiety, and apathy are all associated with worsening quality of life over time in PwP, while presence of ICDs and psychosis are not. Treatment of these symptoms may lead to improved QOL in PwP.

Primary Palliative Care in Huntington's Disease.

Background: Palliative care practices, including communication about patient-centered goals of care and advance care planning (ACP), have the potential to enhance care throughout the course of Huntington's disease (HD) and related disorders. The goal of our project was to develop a pilot program that integrates primary palliative care practices with interdisciplinary care for HD. Objectives: (1) To train HD team members to facilitate goals of care and ACP conversations at all stages of HD; (2) To create materials for care planning in HD focused on patient-centered goals of care and health-related quality of life; and (3) To modify clinic workflow to include goals of care and ACP discussions. Methods: We defined planning domains to expand care planning beyond end-of-life concerns. We created a patient and family guide to advance care planning in HD. We conducted VitalTalk communications training with the HD team. We modified the interdisciplinary clinic workflow to include ACP and developed an EMR template for documentation. Results: After communication training, more team members felt well prepared to discuss serious news (12.5% to 50%) and manage difficult conversations (25% to 62.5%). The proportion of clinic visits including advance care planning discussions increased from 12.5% to 30.6% during the pilot phase. Conclusions: Provision of primary palliative care for HD in an interdisciplinary clinic is feasible. Integration of palliative care practices into HD specialty care requires additional training and modification of clinic operations.

Cholinergic nucleus 4 atrophy and gait impairment in Parkinson's disease.

BACKGROUND: There is evidence that cortical cholinergic denervation contributes to gait and balance impairment in Parkinson's Disease (PD), especially reduced gait speed. OBJECTIVES: The objective of this study was to determine the relationship between cholinergic basal forebrain gray matter density (GMD) and gait in PD patients. METHODS: We investigated 66 PD patients who underwent a pre-surgical evaluation for a neurosurgical procedure to treat motor symptoms of PD. As part of this evaluation patients had a brain MRI and formal gait assessments. By applying probabilistic maps of the cholinergic basal forebrain to voxel-based morphometry of brain MRI, we calculated gray matter density (GMD) for cholinergic nucleus 4 (Ch4), cholinergic nucleus 1, 2, and 3 (Ch123), and the entire cortex. RESULTS: Reduced Ch4 GMD was associated with reduced Fast Walking Speed in the "on" medication state (FWSON, p = 0.004). Bilateral cortical GMD was also associated with FWSON (p = 0.009), but Ch123 GMD was not (p = 0.1). Bilateral cortical GMD was not associated with FWSON after adjusting for Ch4 GMD (p = 0.44). While Ch4 GMD was not associated with improvement in Timed Up and Go (TUG) or Cognitive TUG in the "on" medication state, reduced Ch4 GMD was associated with greater percent worsening based on dual tasks (p = 0.021). CONCLUSIONS: Reduced Ch4 GMD is associated with slower gait speed in PD and greater percent worsening in TUG during dual tasks in patients with PD. These findings have implications for planning of future clinical trials investigating cholinergic therapies to improve gait impairment in PD.

Olfaction, cholinergic basal forebrain degeneration, and cognition in early Parkinson disease.

INTRODUCTION: Impaired olfaction and reduced cholinergic nucleus 4 (Ch4) volume both predict greater cognitive decline in Parkinson's disease (PD). We examined the relationship between olfaction, longitudinal change in cholinergic basal forebrain nuclei and their target regions, and cognition in early PD. METHODS: We analyzed a cohort of 97 PD participants from the Parkinson's Progression Markers Initiative with brain MRIs at baseline, 1 year, 2 years, and 4 years. Using probabilistic maps, regional grey matter density (GMD) was calculated for Ch4, cholinergic nuclei 1, 2, and 3 (Ch123), and their target regions. RESULTS: Baseline University of Pennsylvania Smell Identification Test score correlated with change in GMD of all regions of interest (all p < 0.05). Rate of change of Ch4 GMD was correlated with rate of change of Ch123 (p = 0.034), cortex (p = 0.001), and amygdala GMD (p < 0.001), but not hippocampus GMD (p = 0.38). Rate of change of Ch123 GMD was correlated with rate of change of cortex (p = 0.001) and hippocampus (p < 0.001), but not amygdala GMD (p = 0.133). In a linear regression model including change in GMD of all regions of interest and age as predictors, change in cortex GMD (߈slope= 38.2; 95 % CI: [0.47, 75.9]) and change in hippocampus GMD (߈slope= 24.8; 95 % CI: [0.80, 48.8]) were significant predictors of Montreal Cognitive Assessment score change over time. CONCLUSION: Impaired olfaction is associated with degeneration of the cholinergic basal forebrain and bilateral cortex, amygdala, and hippocampus in PD. The relationship between impaired olfaction and cognitive decline may be mediated by greater atrophy of the cortex and hippocampus.

Comparison of Parkinson's Disease Patients' Characteristics by Indication for Deep Brain Stimulation: Men Are More Likely to Have DBS for Tremor.

Background: We investigated whether the characteristics of Parkinson's disease (PD) patients differ based on the primary indication for deep brain stimulation (DBS). Methods: We reviewed data for 149 consecutive PD patients who underwent DBS at the University of Virginia. Patients were categorized based on primary surgical indication, and clinical characteristics were compared between groups. Results: Twenty-nine (93.5%) of 31 PD patients who underwent DBS for medication refractory tremor were men, and 66 (62.3%) of 106 PD patients who underwent DBS for motor fluctuations were men (p = 0.001). Other primary indications for DBS were tremor and fluctuations (n = 5), medication intolerance (n = 5), and dystonia (n = 2). Discussion: Patients who underwent DBS for medication refractory tremor were predominantly men, while patients who had DBS for motor fluctuations approximated the gender distribution of PD. Possible explanations are that men with PD are more likely to develop medication refractory tremor or undergo surgery for medication refractory tremor in PD compared to women.