Association of caregiver strain with the trajectory of quality of life in Parkinson's disease.

We aimed to identify caregiver characteristics associated with the trajectory of quality of life (QoL) in Parkinson's disease (PD). We fit a growth mixture model to longitudinal data from the Parkinson Foundation Parkinson's Outcomes Project (POP) to identify the heterogeneity of QOL trajectories in PD. We then used multinomial logistic regression to model baseline factors that predicted class membership. Baseline growth models were fit to QOL scores measured over 4 disease duration time points. A random intercept and slope model was determined to best fit the data. Next, growth mixture models (1, 2, 3, 4, and 5-class) were fit with covariates (Hoehn & Yahr, sex, and depression) and a three-class model was found to provide the best fit. Class 1 (problematic class (10.0%)) represented individuals with poor QOL at baseline and minor improvement over time. Class 2 (moderate class (32.6%)) represented individuals with moderate QOL at baseline with slight worsening over time. Class 3 (favorable class (56.9%)) represented individuals with good QOL at baseline and slight worsening over time. Multinomial regression revealed that lower caregiver strain, better mobility, and better verbal fluency at baseline predicted membership in the favorable compared to the moderate class. Worse mobility and younger age predicted membership in the problematic compared to the moderate class. While previous studies have reported on the association between mobility and cognition, the novel finding of an association between caregiver strain and PD QOL trajectory suggests caregiver strain is important to measure and address in future research and practice.

'Anxious fluctuators' a subgroup of Parkinson's disease with high anxiety and problematic on-off fluctuations.

Anxiety that occurs in association with on-off dopamine medication fluctuations is a major cause of distress, dysfunction, and lower quality of life in people with Parkinson's disease (PD). However, the association between anxiety and on-off fluctuations is poorly understood and it is difficult to predict which patients will suffer from this atypical form of anxiety. To understand whether fluctuating anxiety in PD exists as part of an endophenotype that is associated with other signs or symptoms, we prospectively assessed the change in anxiety and a battery of clinical variables when transitioning from the off-dopamine medication state to the on state in 200 people with PD. We performed latent profile analysis with observed variables as latent profile indicators measuring the on-off-state difference in anxiety, depression, motor function, daily functioning, and the wearing off questionnaire 19 item scale (WOQ-19) in order to model unobserved (i.e., latent) profiles. A two-class model produced the best fit. The majority of participants, 69%, were categorized as having a 'typical on-off response' compared to a second profile constituting 31% of the sample who experienced a worsening in anxiety in the off state that was three times that of other participants. This profile referred to as "anxious fluctuators" had a Hamilton Anxiety Rating Scale change between the off and on medication state of 10.22(32.85) compared to 3.27 (7.62), higher depression scores, greater disability and was less likely to improve on select WOQ-19 items when in the on-state. Anxious fluctuators were more likely to be male and have a family history of anxiety disorder. Given the adverse impact of this profile we believe it may be important to distinguish patients with a typical on-off response from those with this more problematic course of fluctuations.

Effect of STN DBS on vesicular monoamine transporter 2 and glucose metabolism in Parkinson's disease.

INTRODUCTION: Deep brain stimulation (DBS) is an established treatment for Parkinson's Disease (PD). Despite the improvement of motor symptoms in most patients by sub-thalamic nucleus (STN) DBS and its widespread use, the neurobiological mechanisms are not completely understood. The objective of the present study was to elucidate the effects of subthalamic nucleus (STN) DBS in PD on the dopamine system and neural circuitry, employing high-resolution positron emission tomography (PET) imaging. The hypotheses tested were that STN DBS would decrease the striatal vesicular monoamine transporter (VMAT2), secondary to an increase in dopamine concentrations, and would decrease striatal cerebral metabolism and increase cortical cerebral metabolism. METHODS: PET imaging of the vesicular monoamine transporter (VMAT2) and cerebral glucose metabolism was performed prior to DBS surgery and after 4-6 months of STN stimulation in seven PD patients (mean age 67 ±â€¯7). RESULTS: The patients demonstrated significant improvement in motor and neuropsychiatric symptoms after STN DBS. Decreased VMAT2 was observed in the caudate, putamen and associative striatum and in extra-striatal, cortical and limbic regions. Cerebral glucose metabolism was decreased in striatal sub-regions and increased in temporal and parietal cortices and the cerebellum. Decreased striatal VMAT2 was correlated with decreased striatal and increased cortical and limbic metabolism. Improvement of depressive symptoms was correlated with decreased VMAT2 in striatal and extra-striatal regions and with striatal decreases and cortical increases in metabolism. CONCLUSIONS: The present results support further investigation of the role of VMAT2, and associated changes in neural circuitry in the improvement of motor and non-motor symptoms with STN DBS in PD.