Adherence therapy for people with Parkinson's disease

Introduction: Medication non-adherence is prevalent in Parkinson’s disease (PD). However, factors associated with non-adherence are unknown. Despite interventions to improve medication adherence being investigated in long-term conditions, few studies have focused on PD. Adherence Therapy (AT) is a novel, patient-centred approach to maximising adherence that has shown benefit in other chronic conditions. Aim: To investigate the efficacy of AT for improving medication adherence and quality of Life (QoL) in people with PD. Methods: To achieve the above aim I conducted a systematic review to identify factors associated with medication non-adherence, followed by a Cochrane systematic review on interventions for improving medication adherence in PD. I then tested the efficacy of AT in PD in a randomised controlled trial (RCT). Semistructured interviews were used to explore patients’ experiences of receiving AT. Results: Mood disorders, cognition, poor symptom control/QoL, younger age/longer disease duration, regimen complexity/polypharmacy, risk taking behaviours, poor knowledge of PD/education, lack of spouse/partner, low income, desire to maintain employment and gender were identified as factors associated with non-adherence in PD. Only one study previously investigated an intervention (didactic educational material) for improving medication adherence in PD, according to my Cochrane systematic review. Seventy-six patients and 46 spouse/carers completed the RCT (CAAT-PARK). At week-12 follow-up the active treatment group significantly improved in adherence and QoL compared to the treatment as usual group. Thematic analysis of interviews from 10 patients and 3 spouse/carers suggested that positive effects and attributes of AT may be important for the success of AT. Furthermore, the findings suggested that the mechanism of AT may be bi-directional and associated with improved confidence and self-efficacy. Conclusions: Adherence Therapy improved medication adherence and QoL in PD. A larger pragmatic trial to test the efficacy and cost effectiveness of Adherence Therapy with a control group placebo intervention is required. ISRCTN0783095

Parkinson's disease subtypes in the Oxford Parkinson disease centre (OPDC) discovery cohort

Background: Within Parkinson’s there is a spectrum of clinical features at presentation which may represent sub-types of the disease. However there is no widely accepted consensus of how best to group patients. Objective: Use a data-driven approach to unravel any heterogeneity in the Parkinson’s phenotype in a well-characterised, population-based incidence cohort. Methods: 769 consecutive patients, with mean disease duration of 1.3 years, were assessed using a broad range of motor, cognitive and non-motor metrics. Multiple imputation was carried out using the chained equations approach to deal with missing data. We used an exploratory and then a confirmatory factor analysis to determine suitable domains to include within our cluster analysis. K-means cluster analysis of the factor scores and all the variables not loading into a factor was used to determine phenotypic subgroups. Results: Our factor analysis found three important factors that were characterised by: psychological well-being features; non-tremor motor features, such as posture and rigidity; and cognitive features. Our subsequent five cluster model identified groups characterised by (1) mild motor and non-motor disease (25.4%), (2) poor posture and cognition (23.3%), (3) severe tremor (20.8%), (4) poor psychological well-being, RBD and sleep (18.9%), and (5) severe motor and non-motor disease with poor psychological well-being (11.7%). Conclusion: Our approach identified several Parkinson’s phenotypic sub-groups driven by largely dopaminergic-resistant features (RBD, impaired cognition and posture, poor psychological well-being) that, in addition to dopaminergic-responsive motor features may be important for studying the aetiology, progression, and medication response of early Parkinson’s

The Effects of Yoga Versus Mindfulness on Anxiety in Individuals with Parkinson’s Disease

Parkinson’s disease is a progressive neurodegenerative disease that causes debilitating motor deficits in addition to many non-motor symptoms. Tremors, stiffness, and abnormal gait changes are easily recognized as disabling; however, effects from anxiety are more insidious to disease burden which negatively affect both motor and psychological capabilities. Anxiolytics or antidepressants are often prescribed but can cause adverse side effects, prompting the need for alternative treatments. Yoga and mindfulness therapies are favorable alternative treatments known to reduce anxiety. This two-arm, single-blinded randomized controlled trial compares effects of yoga and mindfulness therapies in the reduction of anxiety for patients with Parkinson’s disease. Yoga is hypothesized to have greater statistically significant effect in reducing anxiety compared to mindfulness due to its combined mental and physical benefits. However, if both interventions demonstrate positive outcomes, both may prove to be beneficial adjunctive treatments for patients with anxiety in Parkinson’s disease or other neurodegenerative movement disorders

Non-linear Analysis of Heart rate Variability Improves Differential Diagnosis Between Parkinson Diseases and Multiple System Atrophy

Aims: Parkinson's disease (PD) and multiple system atrophy (MSA) are neurodegenerative disorders characterized by motor "parkinsonian" symptoms and non-motor symptoms related to autonomic nervous system (ANS) dysfunction. The latter can be quantified with the analysis of Heart Rate Variability (HRVa) and of its complexity. In this study nonlinear (NL) HRV complexity parameters were calculated to assess their predictive accuracy as markers of “disease” useful for early differentiation between PD and MSA in parkinsonian syndromes of uncertain diagnosis. Study Design: Observational study. Place and Duration of Study: Clinical Physiology-Biomagnetism Center, Policlinico A. Gemelli, Rome Italy. Patients enrolled from January 2010 to October 2013. Methodology: 51 patients [25 with “certain” diagnosis of PD, 9 with a “highly probable” diagnosis of MSA and 17 with parkinsonian syndromes of uncertain neurological definition (6 with “undefined parkinsonism” and 11 with “suspected MSA”)] and 40 age-matched healthy control subjects were studied. Short-term NL HRVa was performed during daily activity and during REM/NREM sleep from 24 h ECG recordings. Discriminant analysis (DA) was used to identify which NL HRV parameters (or their combination) were efficient to differentiate between PD and MSA in cases of uncertain diagnosis. Results: Compared with healthy controls, most NL HRV parameters were significantly altered in patients (p<0.05), during both active and passive awakeness and during sleep. Most evident HRV abnormalities were found during active awakeness in MSA. DA of recurrence plot parameters provided the best predictive accuracy (76.5%) for the classification of parkinsonian patients with uncertain diagnosis. Conclusion: NL HRVa is efficient in differentiating MSA from PD and may improve earlier diagnosis in patients with parkinsonian symptoms of uncertain nature, useful to address second level diagnostic steps and to guide more individualized drug treatment

Integrated and patient-centred management of Parkinson’s disease:a network model for reshaping chronic neurological care

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Spectrum of impulse control behaviours in Parkinson's disease: pathophysiology and management.

Impulse control behaviours (ICBs) are a range of behaviours linked by their reward-based, repetitive natures. They can be precipitated in Parkinson's disease (PD) by dopamine replacement therapy, often with detrimental consequences for patients and caregivers. While now a well-recognised non-motor feature of treated PD, much remains unknown about the influence of risk factors, pathophysiological mechanisms, vulnerability factors for specific types of behaviour and the optimal management strategies. Imaging studies have identified structural and functional changes in striatal and prefrontal brain regions, among others. Gene association studies indicate a role for genetic predisposition to PD-ICB. Clinical observational studies have identified potential modifiable and non-modifiable risk factors. Psychological studies shed light on the neurocognitive domains implicated in PD-ICBs and identify psychosocial determinants that may perpetuate the cycle of impulsive and harm-avoidance behaviours. Based on these results, a range of pharmacological and non-pharmacological management strategies have been trialled in PD-ICBs with varying success. The purpose of this review is to update clinicians on the evidence around the pathophysiology of PD-ICB. We aim to translate our findings into an interpretable biopsychosocial model that can be applied to the clinical assessment and management of individual cases of PD-ICB

Cognitive impairment in Parkinson’s disease: Impact and identification of comorbid disease mechanisms

Cognitive impairment is a common and debilitating feature of Parkinson's disease (PD). While it is primarily caused by cerebral propagation of α-synuclein protein, evidence of comorbid diseases is frequently found in autopsy samples. This includes tau and amyloid-β pathologies – the hallmarks of Alzheimer's disease (AD) – and cerebrovascular damage. Comorbid diseases may influence cognition in PD over and above the effects of α-synuclein alone, and this influence may interfere with the results of clinical trials of next-generation medical treatments that target α-synuclein. The primary aims of this thesis were to define the extent and the effects of comorbid disease mechanisms in PD, and to identify viable clinical strategies for detecting coexistent disorders in vivo. Methods included a systematic review of autopsy studies; a factor analysis of the Montreal Cognitive Assessment (MoCA); a regression analysis of two genes; and a cross-sectional neuropsychological study of 45 patients. The systematic review found significant tau pathology in around one-third of PD patients at death. Significant amyloid-β pathology affected over half, and conferred a worse prognosis. Other pathologies (e.g. cerebrovascular disease) were less common, and did not contribute to dementia in PD. The factor analysis showed that the MoCA has limited value for distinguishing cognitive profiles in PD, suggesting that it should be used only for screening. The genetic project found that variation in the APOE gene influenced cognitive decline in early PD; the effect varied between men and women. Variation in MAPT did not affect cognitive decline. Finally, the neuropsychological study found that over half of cognitively impaired PD patients could be clinically diagnosed with a coexistent cognitive disorder, with AD being the most common. Collectively, the results of this thesis show that comorbid diseases, particularly AD, are common in PD, and these contribute to the cognitive phenotype. Consequently, a clinical assessment incorporating selected neuropsychological tests can be used to identify comorbid diseases in PD patients. It is important to consider the potentially confounding impact of multimorbidity in the design and analysis of clinical trials that aim to modulate neurodegeneration in PD by targeting α-synuclein