Predictors of Burden in Carers of Patients with Impulse Control Behaviors in Parkinson's Disease.

Background: Impulse control behaviors (ICBs) are problematic, reward-based behaviors, affecting 15% to 35% of patients with Parkinson's disease. Evidence exists of increased carer burden as a result of these behaviors; however, little is known about the variables mediating this effect and their management. Objective: To identify factors predictive of carer burden in a cohort of patients with Parkinson's disease with ICBs to enable the development of targeted therapeutic interventions for carers. Methods: Data were collected from 45 patients with clinically significant ICBs and their carers, including levodopa equivalent daily dosage, motor and neuropsychiatric symptoms, cognitive function, and ICB severity. Carer burden was quantified by Zarit Burden Interview (ZBI). Univariate analyses were performed using the Spearman rank correlation. Linear regression was used to create a multivariate model for predicting ZBI. Results: Univariate analysis identified significant correlations between ZBI and patient total Neuropsychiatric Inventory (NPI) (r s = 0.50), 4 NPI subscores (agitation/aggression, r s = 0.41; depression/dysphoria, r s = 0.47; apathy/indifference, r s = 0.49; and irritability/lability, r s = 0.38; all P < 0.02), and the carer 28-item General Health Questionnaire (GHQ-28) (r s = 0.52, P < 0.0005). Multivariate linear regression retained total NPI and GHQ-28 scores and were collectively predictive of 36.6% of the variance in the ZBI. Conclusions: Our study suggests that depressive symptoms and aspects of executive dysfunction (apathy and disinhibition) in the patient are potential drivers of carer burden in patients with ICBs. Such findings suggest the presence of executive difficulties and/or mood disturbance should point the clinician to inquire about burden in the caring role and encourage the carer to seek help for any of their own general health problems, which may compound carer burden.

Value of Clinical Signs in Identifying Patients with Scans without Evidence of Dopaminergic Deficit (SWEDD).

BACKGROUND: In clinical trials that recruited patients with early Parkinson's disease (PD), 4-15% of the participants with a clinical diagnosis of PD had normal dopamine transporter single photon emission computed tomography (DAT SPECT) scans, also called "scans without evidence of dopaminergic deficit" (SWEDD). OBJECTIVE: To investigate in patients with a clinical diagnosis of PD, if specific clinical features are useful to distinguish patients with nigrostriatal degeneration from those that have no nigrostriatal degeneration. METHODS: We performed a diagnostic test accuracy study. Patients that participated in the Levodopa in Early Parkinson's disease trial, a clinical trial in patients with early PD, were asked to participate if they had not undergone DAT SPECT imaging earlier. The index tests were specific clinical features that were videotaped. A panel of six neurologists in training (NT), six general neurologists (GN), and six movement disorders experts (MDE) received a batch of ten videos consisting of all SWEDD subjects and a random sample of patients with abnormal DAT SPECT scans. The raters analyzed the videos for presence of specific signs and if they suspected the patient to have SWEDD. The reference test was visually assessed DAT SPECT imaging. RESULTS: Of a total of 87 participants, three subjects were SWEDDs (3.4%). The overall intraclass correlation coefficient (ICC) of the Parkinsonian signs was poor to moderate with ICCs ranging from 0.14 to 0.67. NT correctly identified 50.0% of the SWEDD subjects, GN 33.3%, and MDE 66.7%. CONCLUSION: Our study suggests that the selected videotaped clinical features cannot reliably distinguish patients with a clinical diagnosis of PD and an abnormal DAT SPECT from patients with clinical PD and a SWEDD.

Barriers to reporting non-motor symptoms to health-care providers in people with Parkinson's.

BACKGROUND: Non-motor symptoms (NMS) are common in Parkinson's disease (PD) and cause significant distress. A high rate of non-declaration of NMS by patients to healthcare providers (HCP) means that many NMS remain untreated. Current understanding of the factors preventing disclosure of NMS to HCPs is limited. The present study aimed to i) further assess the prevalence of NMS and associated distress, ii) establish current rates of NMS reporting across a range of sources, and iii) explore overall and any symptom specific barriers to help-seeking for NMS. METHODS: 358 PD patients completed a cross-sectional survey of NMS severity, reporting and barriers to help-seeking. A series of Generalised Estimating Equations were used to determine whether barriers were symptom specific. RESULTS: A mean of 10.5 NMS were reported by each patient. Rates of non-reporting of NMS ranged from 15 to 72% of those experiencing distressing symptoms. The most commonly reported barriers to help-seeking were acceptance of symptoms; lack of awareness that a symptom was associated with PD, and belief that no effective treatments were available. Symptom specific barriers were found for sexual dysfunction (embarrassment), unexplained pain and urinary problems (belief about lack of treatment availability). CONCLUSION: A diverse range of barriers prevent PD patients reporting NMS to HCPs and these barriers differ between NMS. The study provides the foundations for developing interventions to increase reporting by targeting individual NMS. Increasing rates of help-seeking for NMS by patients to their Parkinson's healthcare providers will increase appropriate clinical care which may improve quality of life and well-being.

Identifying barriers to help-seeking for non-motor symptoms in people with Parkinson's disease.

Non-motor symptoms of Parkinson's disease have a significant impact on quality of life. Despite this, many non-motor symptoms remain unreported by patients and consequently untreated. This study explored barriers to help-seeking using two theoretical frameworks, the Common Sense Model of illness perception and Theoretical Domains Framework. A total of 20 participants completed semi-structured interviews to explore symptom beliefs and help-seeking behaviour. Uncertainty about the relationship of non-motor symptoms to Parkinson's disease and lack of clarity around treatments were common. Embarrassment and communication difficulties were common for potentially sensitive symptoms such as sexual dysfunction. Symptom perceptions and beliefs about help-seeking acted as barriers to reporting non-motor symptoms.

Neuropsychological and Neuropsychiatric Concerns for Deep Brain Stimulation in Dystonia: Preoperative Profiles in a Deep Brain Stimulation Cohort and Postoperative Changes in Three Case Series Reports.

Cognitive deficits and psychiatric morbidities are commonly detected in dystonia. Psychiatric disturbances are of particular clinical concern as they not only contribute to poor quality of life and disease associated burden, but also exacerbate motor and cognitive symptoms. Bilateral deep brain stimulation of the globus pallidus internus improves motor symptoms in treatment-resistant dystonia, but its implications for non-motor manifestations are poorly understood. Improved prediction of cognitive and neuropsychiatric outcomes is important in deep brain stimulation (DBS) research and we aim to assess the latter through established assessment tools. We document the cognitive and neuropsychiatric profiles in 11 primary and 10 secondary dystonia patients attending our DBS clinic. We performed routine multidisciplinary assessments including a comprehensive battery of neuropsychometric tests and detailed neuropsychiatric evaluations. Post-operative assessment outcomes are reported for three patients in case series. The main cognitive deficit was on the Brixton test of spatial anticipation in primary dystonia. Background medical history included psychiatric illness in 38.1% of the patients with 76% of patients having mood abnormalities confirming elevated psychiatric morbidity in this population. Depressive illness was more prominent in primary, whereas clinically relevant histories in secondary dystonia were varied. Of the 21 patients three were able to perform on selected tests due to extensive limitations of their dystonia. No obvious alteration in intellectual functioning following DBS surgery relative to performance at the time of initial assessment was observed. The frequency of individual impairments suggests that difficulties associated with dystonia are likely to be of clinical relevance to cognitive functions in the majority of patients. In particular, current findings suggest that executive difficulties related to inductive processes and spatial learning may be a common in primary dystonias. Psychiatric disturbances demand recognition as a central aspect of dystonia as they contribute to overall disease burden, poor quality of life and exacerbated motor disabilities. The available evidence provides overwhelming suggestion that vulnerability to depression is inherent to the dystonia phenotype.

The effects of cognitive reserve and lifestyle on cognition and dementia in Parkinson's disease--a longitudinal cohort study.

OBJECTIVE: Cognitive reserve theory seeks to explain the observed mismatch between the degree of brain pathology and clinical manifestations. Early-life education, midlife social and occupational activities and later-life cognitive and social interactions are associated with a more favourable cognitive trajectory in older people. Previous studies of Parkinson's disease (PD) have suggested a possible role for the effects of cognitive reserve, but further research into different proxies for cognitive reserve and longitudinal studies is required. This study examined the effects of cognitive lifestyle on cross-sectional and longitudinal measures of cognition and dementia severity in people with PD. METHODS: Baseline assessments of cognition, and of clinical, social and demographic information, were completed by 525 participants with PD. Cognitive assessments were completed by 323 participants at 4-year follow-up. Cognition was assessed using the measures of global cognition dementia severity. Cross-sectional and longitudinal serial analyses of covariance for cognition and binomial regression for dementia were performed. RESULTS: Higher educational level, socio-economic status and recent social engagement were associated with better cross-sectional global cognition. In those with normal cognition at baseline, higher educational level was associated with better global cognition after 4 years. Increasing age and low levels of a measure of recent social engagement were associated with an increased risk of dementia. CONCLUSIONS: Higher cognitive reserve has a beneficial effect on performance on cognitive tests and a limited effect on cognitive decline and dementia risk in PD.

Thinking positively about chronic illness: An exploration of optimism, illness perceptions and well-being in patients with Parkinson's disease.

OBJECTIVES: Holding positive beliefs about illness and having an optimistic outlook have been associated with increased well-being across a range of health conditions. However, research has indicated that being very optimistic may not actually be beneficial, and holding a realistic attitude is more adaptive in some forms of chronic illness, for example, Parkinson's disease (PD). This study aimed to explore the nature of relationships between illness perceptions, optimism and well-being: specifically, whether a linear or non-linear relationship best described the data. Additionally, the proposed moderating effect of optimism on the relationship between illness perceptions and well-being was tested. DESIGN: A total of 109 participants with idiopathic PD completed questionnaire measures of illness perception, optimism, mood and health-related quality of life (HRQoL). METHODS: Multiple regression analyses were used to explore relationships between illness perceptions, optimism, mood and HRQoL. The potential curvilinear effects of illness perceptions and optimism were modelled using squared variables and linear and quadratic curve estimation. RESULTS: Holding positive illness perceptions predicted better well-being. Some evidence for a non-linear relationship between optimism and mood was found. Optimism had a significant moderating effect on the relationship between specific illness perceptions and outcome. CONCLUSIONS: Optimism appears to provide protection against some negative perceptions of illness and was associated with better mood and HRQoL. The findings indicate that specific illness perceptions may be beneficial targets for therapy. Therapeutic interventions should focus on enhancing positive perceptions of PD but potentially more importantly general optimistic attitude to maximize well-being. STATEMENT OF CONTRIBUTION: What is already known on this subject? Positive illness perceptions and high optimism are associated with better well-being in a range of conditions, both chronic and acute. Preliminary studies suggest that in chronic degenerative diseases, marked positive optimism confers no additional benefit over medium levels of optimism for well-being and is associated with less use of adaptive coping. What does this study add? Optimism moderates the effects of specific negative illness perceptions on well-being in Parkinson's disease. No evidence was found that unrealistic positive illness perceptions are detrimental to well-being. Adaptive illness perceptions may be condition specific.

Cognition, coping, and outcome in Parkinson's disease.

BACKGROUND: Cognitive impairment and depression are common and disabling non-motor symptoms of Parkinson's disease (PD). Previous studies have shown associations between them but the nature of the relationship remains unclear. In chronic illness, problem- or task-oriented coping strategies are associated with better outcome but often require higher level cognitive functioning. The present study investigated, in a sample of patients with PD, the relationships between cognitive function, choice of coping strategies, and a broad index of outcome including depression, anxiety, and health-related quality of life (QoL). It was hypothesized that the coping strategy used could mediate the association between cognition and outcome. METHODS: 347 participants completed the Coping Inventory for Stressful Situations, the Hospital Anxiety and Depression Scale, the Parkinson's Disease Questionnaire-8, the Unified Parkinson's Disease Rating Scale, and the Addenbrooke's Cognitive Examination-Revised. Structural Equation Modeling was used to test the hypothesized model of cognition, coping, and outcome based on a direct association between cognition and outcome and an indirect association mediated by coping. RESULTS: Overall, poorer cognition predicted less use of task-oriented coping, which predicted worse outcome (a latent variable comprised of higher depression and anxiety and lower QoL). The analyses suggested a small indirect effect of cognition on outcome mediated by coping. CONCLUSIONS: The findings suggest that patients who fail to employ task-oriented coping strategies may be at greater risk of depression, anxiety, and poor health-related QoL. Even mild to moderate cognitive impairment may contribute to reduced use of task-oriented coping. Suitably adapted cognitive-behavioral approaches may be useful to enable the use of adaptive coping strategies in such patients.

Quetiapine in the treatment of psychosis in Parkinson's disease.

Psychosis (delusions and/or hallucinations) is a common nonmotor feature of Parkinson's disease (PD). Use of the older 'typical' antipsychotic drugs led to worsening of motor symptoms. The introduction of 'atypical' antipsychotics opened up a range of therapeutic options. These agents include clozapine, risperidone, olanzapine, aripiprazole and quetiapine. All have been used to treat psychosis in PD with varying success. Clozapine is the only drug with proven efficacy. We review the evidence for the efficacy of quetiapine. Eight open-label studies have assessed quetiapine use in 191 patients, with improvement in psychosis recorded in 152 (80%). In addition to the open-label studies, there have been two single-blind, randomized trials comparing quetiapine and clozapine. These studies suggest that quetiapine has similar efficacy to clozapine in controlling psychosis. Following the promising results of the open-label and clozapine comparison studies, five randomized, controlled trials (RCTs) have been performed to further establish the efficacy of quetiapine. Unfortunately, the results have been disappointing. The only positive placebo-controlled study excluded patients with delusions, which seem to be harder to treat than hallucinations. The four negative RCTs discussed seriously undermine the evidence from the open-label studies. The differences in design and interpretation of the RCTs emphasizes the need for further large, well-controlled trials, using strict inclusion criteria, appropriate psychosis rating scales, carer input and clinical significance. Currently, many physicians continue to cautiously offer a trial of low-dose quetiapine empirically. Clozapine should be considered in patients who can tolerate the required blood monitoring.