Pattern Formation in a Spatially Extended Model of Pacemaker Dynamics in Smooth Muscle Cells.

Spatiotemporal patterns are common in biological systems. For electrically coupled cells, previous studies of pattern formation have mainly used applied current as the primary bifurcation parameter. The purpose of this paper is to show that applied current is not needed to generate spatiotemporal patterns for smooth muscle cells. The patterns can be generated solely by external mechanical stimulation (transmural pressure). To do this we study a reaction-diffusion system involving the Morris-Lecar equations and observe a wide range of spatiotemporal patterns for different values of the model parameters. Some aspects of these patterns are explained via a bifurcation analysis of the system without coupling - in particular Type I and Type II excitability both occur. We show the patterns are not due to a Turing instability and that the spatially extended model exhibits spatiotemporal chaos. We also use travelling wave coordinates to analyse travelling waves.

Numerical Bifurcation Analysis of Pacemaker Dynamics in a Model of Smooth Muscle Cells.

Evidence from experimental studies shows that oscillations due to electro-mechanical coupling can be generated spontaneously in smooth muscle cells. Such cellular dynamics are known as pacemaker dynamics. In this article, we address pacemaker dynamics associated with the interaction of [Formula: see text] and [Formula: see text] fluxes in the cell membrane of a smooth muscle cell. First we reduce a pacemaker model to a two-dimensional system equivalent to the reduced Morris-Lecar model and then perform a detailed numerical bifurcation analysis of the reduced model. Existing bifurcation analyses of the Morris-Lecar model concentrate on external applied current, whereas we focus on parameters that model the response of the cell to changes in transmural pressure. We reveal a transition between Type I and Type II excitabilities with no external current required. We also compute a two-parameter bifurcation diagram and show how the transition is explained by the bifurcation structure.

Prospective observational study of vaginal microbiota pre- and post-rescue cervical cerclage.

OBJECTIVE: To investigate the relation between vaginal microbiota composition and outcome of rescue cervical cerclage. DESIGN: Prospective observational study. SETTING: Queen Charlotte's and Chelsea Hospital, London. POPULATION: Twenty singleton pregnancies undergoing a rescue cervical cerclage. METHODS: Vaginal microbiota composition was analysed in women presenting with a dilated cervix and exposed fetal membranes before and 10 days following rescue cervical cerclage and was correlated with clinical outcomes. MAIN OUTCOME MEASURES: Composition of vaginal bacteria was characterised by culture-independent next generation sequencing. Successful cerclage was defined as that resulting in the birth of a neonate discharged from hospital without morbidity. Unsuccessful cerclage was defined as procedures culminating in miscarriage, intrauterine death, neonatal death or significant neonatal morbidity. RESULTS: Reduced Lactobacillus spp. relative abundance was observed in 40% of cases prior to rescue cerclage compared with 10% of gestation age-matched controls (8/20, 40% versus 3/30, 10%, P = 0.017). Gardnerella vaginalis was over-represented in women presenting with symptoms (3/7, 43% versus 0/13, 0%, P = 0.03, linear discriminant analysis, LDA (log 10) and cases culminating in miscarriage (3/6, 50% versus 0/14, 0%, P = 0.017). In the majority of cases (10/14, 71%) bacterial composition was unchanged following cerclage insertion and perioperative interventions. CONCLUSIONS: Reduced relative abundance of Lactobacillus spp. is associated with premature cervical dilation, whereas high levels of G. vaginalis are associated with unsuccessful rescue cerclage cases. The insertion of a rescue cerclage does not affect the underlying bacterial composition in the majority of cases. TWEETABLE ABSTRACT: Preterm cervical dilatation associates with reduced Lactobacillus spp. Presence of Gardnerella vaginalis predicts rescue cerclage failure.

The role of nitric oxide in neurovascular coupling.

Nitric oxide (NO) is a neurotransmitter known to act as a potent cerebral vasodilator. Its role in neurovascular coupling (NVC) is discussed controversially and one of the main unanswered questions is which cell type provides the governing source of NO for the regulation of vasodynamics. Mathematical modelling can be an appropriate tool to investigate the contribution of NO towards the key components of NVC and analyse underlying mechanisms. The lumped parameter model of a neurovascular unit, including neurons (NE), astrocytes (AC), smooth muscle cells (SMC) and endothelial cells (EC), was extended to model the NO signalling pathway. Results show that NO leads to a general shift of the resting regional blood flow by dilating the arteriolar radius. Furthermore, dilation during neuronal activation is enhanced. Simulations show that potassium release is responsible for the fast onset of vascular response, whereas NO-modulated mechanisms maintain dilation. Wall shear stress-activated NO release from the EC leads to a delayed return to the basal state of the arteriolar radius. The governing source of vasodilating NO that diffuses into the SMC, which determine the arteriolar radius, depends on neuronal activation. In the resting state the EC provides the major contribution towards vasorelaxation, whereas during neuronal stimulation NO produced by the NE dominates.

Anxiety and anxious-depression in Parkinson's disease over a 4-year period: a latent transition analysis.

BACKGROUND: Depression and anxiety in Parkinson's disease are common and frequently co-morbid, with significant impact on health outcome. Nevertheless, management is complex and often suboptimal. The existence of clinical subtypes would support stratified approaches in both research and treatment. METHOD: Five hundred and thirteen patients with Parkinson's disease were assessed annually for up to 4 years. Latent transition analysis (LTA) was used to identify classes that may conform to clinically meaningful subgroups, transitions between those classes over time, and baseline clinical and demographic features that predict common trajectories. RESULTS: In total, 64.1% of the sample remained in the study at year 4. LTA identified four classes, a 'Psychologically healthy' class (approximately 50%), and three classes associated with psychological distress: one with moderate anxiety alone (approximately 20%), and two with moderate levels of depression plus moderate or severe anxiety. Class membership tended to be stable across years, with only about 15% of individuals transitioning between the healthy class and one of the distress classes. Stable distress was predicted by higher baseline depression and psychiatric history and younger age of onset of Parkinson's disease. Those with younger age of onset were also more likely to become distressed over the course of the study. CONCLUSIONS: Psychopathology was characterized by relatively stable anxiety or anxious-depression over the 4-year period. Anxiety, with or without depression, appears to be the prominent psychopathological phenotype in Parkinson's disease suggesting a pressing need to understanding its mechanisms and improve management.

The burden of non-motor symptoms in Parkinson's disease using a self-completed non-motor questionnaire: a simple grading system.

BACKGROUND: Non-motor symptoms (NMS) of Parkinson's disease (PD) affect virtually every patient, yet they are under-recognized and under-treated. The NMS Questionnaire (NMSQuest) is a validated 30-item self-assessment instrument useful for NMS screening in clinic. OBJECTIVE: Development of a straight forward grading classification of the burden of non-motor symptoms in PD based on the number of NMS as assessed by the NMS Questionnaire. METHODS: In an observational, cross-sectional, international study of 383 consecutive patients distribution of the declared NMS as per NMSQuest was analyzed according to previously published levels based on the Non-Motor Symptoms Scale and also the median and interquartile range (IR, percentiles 25 and 75) of the total NMSQuest scores. After post hoc checking, these values were proposed as cut-off points for estimating NMS burden based only on the accumulation of symptoms. RESULTS: Burden and number of NMS correlate closely (r ≥ 0.80). On the basis of this finding, five levels (0 = No NMS to 4 = Very severe) of NMSQuest grading were proposed after identification of their cut-offs by ordinal logistic regression and median and interquartile range distribution. These values coincided almost completely with those obtained by median and interquartile range in an independent sample. Concordance between this classification and HY staging was weak (weighted kappa = 0.30), but was substantial (weighted kappa = 0.68) with the Non-Motor Symptoms Scale grading. CONCLUSION: Completion of NMSQuest and subsequent grading of the burden could allow the health care professional to approach the severity of NMS burden using the self completed NMSQuest in a primary care setting.

Neurovascular coupling and the influence of luminal agonists via the endothelium.

A numerical model of neurovascular coupling (NVC) is presented based on neuronal activity coupled to vasodilation/contraction models via the astrocytic mediated perivascular K(+) and the smooth muscle cell Ca(2+) pathway. Luminal agonists acting on P2Y receptors on the endothelial cell surface provide a flux of IP3 into the endothelial cytosol. This concentration of IP3 is transported via gap junctions between endothelial and smooth muscle cells providing a source of sacroplasmic derived Ca(2+) in the smooth muscle cell. The model is able to relate a neuronal input signal to the corresponding vessel reaction. Results indicate that blood flow mediated IP3 production via the agonist ATP has a substantial effect on the contraction/dilation dynamics of the SMC. The resulting variation in cytosolic Ca(2+) can enhance and inhibit the flow of blood to the cortical tissue. IP3 coupling between endothelial and smooth muscle cells seems to be important in the dynamics of the smooth muscle cell. The VOCC channels are, due to the hyperpolarisation from K(+) SMC efflux, almost entirely closed and do not seem to play a significant role during neuronal activity. The current model shows that astrocytic Ca(2+) is not necessary for neurovascular coupling to occur in contrast to a number of experiments outlining the importance of astrocytic Ca(2+) in NVC, however this Ca(2+) pathway is not the only one mediating NVC. Importantly agonists in flowing blood have a significant influence on the endothelial and smooth muscle cell dynamics.

Frequency, prevalence, incidence and risk factors associated with visual hallucinations in a sample of patients with Parkinson's disease: a longitudinal 4-year study.

OBJECTIVE: To examine the prevalence, incidence and risk factors associated with visual hallucinations (VHs) amongst people suffering from Parkinson's disease (PD). METHODS: We recruited 513 patients with PD from movement disorder and PD clinics within three sites in the UK. Patients were interviewed using a series of standardised clinical rating scales at baseline, 12, 24 and 36 months. Data relating to VHs were collected using the North-East Visual Hallucinations Interview. Prevalence rates for VHs at each assessment were recorded. Associations were determined using multiple regression analysis. RESULTS: Cross-sectional prevalence rates for VHs at baseline, 12, 24 and 36 months indicated VHs in approximately 50% of patients. A cumulative frequency of 82.7% of cases at the end of the study period exhibited VHs. The incidence rate for VHs was 457 cases per 1000 population. Longer disease duration, greater impairment in activities of daily living and higher rates of anxiety were most commonly associated with VHs. No factors predictive of VHs could be ascertained. CONCLUSIONS: When examined longitudinally, VHs affect more patients than is commonly assumed in cross-sectional prevalence studies. Clinicians should routinely screen for VHs throughout the disease course. Disease duration, impairment in activities of daily living and anxiety presented as co-morbidities associated with VHs in PD, and therefore those presenting with VHs should be screened for anxiety disorder and vice versa.

Habitat fragmentation: simple models for local persistence and the spread of invasive species.

Understanding the persistence and growth of natural populations in environments subject to random localised change is relevant both to the conservation of threatened species and to the control of invasive species. By developing and analysing simple strategic growth models in environments subject to random fragmentation events, we show that simple approximations can be used to predict invasion speeds and extinction probabilities. The rate and size of fragmentation events interact in a nonlinear way, a finding with important consequences for the efficient control of invasive species. Infrequent, large-scale fragmentation events provide more effective means of control than more frequent, smaller scale efforts.

Impulse control disorders and dopamine dysregulation in Parkinson's disease: a broader conceptual framework.

BACKGROUND: Impulse control disorders (ICDs) and dopamine dysregulation syndrome (DDS) in Parkinson's disease are motivation-based behaviours that involve repetitive occurrences of impulsive and uncontrolled activity. Psychiatric classification is currently inconsistent and unclear. An accurate conceptualisation of these problems is important to guide research and treatment. METHODS AND RESULTS: The review considers conceptual and methodological problems underlying the diagnosis of ICDs and the assessment of their severity. Whilst having features of obsessive-compulsive spectrum model, ICD-5 may bring them together for the first time into a single category of behavioural addictions. Whilst matching clinical and biological evidence, any such psychiatric classification in Parkinson's disease will remain complicated by the interactions of pathophysiology and medication and fail to capture the range of subthreshold but still clinically significant symptomatology. CONCLUSIONS: A non-diagnostic, dimensional construct of disinhibitory psychopathology may be a useful tool to guide research and inform treatment. The role of dysphoria is suggested as a further important factor in driving some of these problem behaviours. This opens the opportunity for adjunctive psychological approaches in management.

Coping in Parkinson's disease: an examination of the coping inventory for stressful situations.

BACKGROUND: Parkinson's disease (PD) brings with it a range of stresses and challenges with which a patient must cope. The type of coping strategies employed can impact upon well-being, although findings from coping studies in PD remain inconsistent. The variety of coping scales used without validation in PD has been cited as a possible cause of this inconsistency. The present study sought to examine the validity of the coping inventory for stressful situations (CISS) in a sample of patients with PD. METHODS: Five hundred and twenty-five patients with PD were recruited as part of a longitudinal investigation of mood states in PD. Four hundred and seventy-one participants completed the CISS. Confirmatory factor analysis was used to explore the structural validity of the scale. Internal reliability, test-retest reliability, convergent validity and discriminant validity were assessed using Cronbach's alpha, intraclass correlations and Pearson's correlations. RESULTS: Both three and four factor solutions were examined. The four factor model was found to provide a better fit of the data than the three factor model. The internal reliability, discriminant validity, convergent validity, and test-retest reliability of the CISS scales were shown to be good. Use of emotion-focused coping was associated with greater depression and anxiety whilst, task-oriented coping was associated with better psychological well-being. CONCLUSION: The results provide support for the validity and reliability of the CISS as a measure of coping in patients with PD. Further research into the relationship between coping and well-being is warranted. The identification of helpful and unhelpful coping strategies may guide the development of evidence-based therapies to improve well-being in patients with PD.

Midlife Neuroticism and the age of onset of Alzheimer's disease.

BACKGROUND: There may be important public health implications of increasing our knowledge of factors associated with age of dementia onset. The pre-morbid personality domain of Neuroticism constituted an interesting and theoretically plausible, yet uninvestigated, candidate for such an association. We aimed to examine whether midlife Neuroticism was associated with earlier age of onset of Alzheimer's disease (AD). METHOD: This was a case-comparison study of 213 patients with probable AD. Detailed clinical information was collected for all patients including age of onset of dementia symptoms. One or two knowledgeable informants rated each patient's midlife personality retrospectively using the Neuroticism, Extraversion, Openness Five-Factor Inventory (NEO-FFI) questionnaire. The relationship between midlife Neuroticism and age of dementia onset was evaluated using both correlational analysis and backward linear regression analysis. RESULTS: Midlife Neuroticism predicted younger age of dementia onset in females but not in males. The association found in females was independent of pre-morbid history of affective disorder. CONCLUSIONS: This finding and its potential mechanism warrant further investigation.

A randomized controlled trial with 4-month follow-up of adjunctive repetitive transcranial magnetic stimulation of the left prefrontal cortex for depression.

BACKGROUND: Effectiveness of repetitive transcranial magnetic stimulation (rTMS) for major depression is unclear. The authors performed a randomized controlled trial comparing real and sham adjunctive rTMS with 4-month follow-up. METHOD: Fifty-nine patients with major depression were randomly assigned to a 10-day course of either real (n=29) or sham (n=30) rTMS of the left dorsolateral prefrontal cortex (DLPFC). Primary outcome measures were the 17-item Hamilton Depression Rating Scale (HAMD) and proportions of patients meeting criteria for response (50% reduction in HAMD) and remission (HAMD8) after treatment. Secondary outcomes included mood self-ratings on Beck Depression Inventory-II and visual analogue mood scales, Brief Psychiatric Rating Scale (BPRS) score, and both self-reported and observer-rated cognitive changes. Patients had 6-week and 4-month follow-ups. RESULTS: Overall, Hamilton Depression Rating Scale (HAMD) scores were modestly reduced in both groups but with no significant groupxtime interaction (p=0.09) or group main effect (p=0.85); the mean difference in HAMD change scores was -0.3 (95% CI -3.4 to 2.8). At end-of-treatment time-point, 32% of the real group were responders compared with 10% of the sham group (p=0.06); 25% of the real group met the remission criterion compared with 10% of the sham group (p=0.2); the mean difference in HAMD change scores was 2.9 (95% CI -0.7 to 6.5). There were no significant differences between the two groups on any secondary outcome measures. Blinding was difficult to maintain for both patients and raters. CONCLUSIONS: Adjunctive rTMS of the left DLPFC could not be shown to be more effective than sham rTMS for treating depression.

The effects of commonly prescribed drugs in patients with Alzheimer's disease on the rate of deterioration.

BACKGROUND: Prescribed drugs in patients with Alzheimer's disease may affect the symptomatic progression of their disease, both positively and negatively. AIM: To examine the effects of drugs on the progression of disease in a representative group of patients with Alzheimer's disease. METHODS: Patients with the diagnosis of probable Alzheimer's disease were recruited from the community. The prescribed drugs taken by 224 patients (mean age 82.3 years) were recorded at initial assessment and then correlated in logistic regression analysis with progression of the disease, defined as an increase of one point or more in the Global Deterioration Scale over the next 12-month period. RESULTS: Patients who were taking antipsychotic drugs and sedatives had a significantly higher risk of deterioration than those who were taking none (odds ratios (ORs) 2.74 (95% confidence interval (CI) 1.17 to 6.41) and 2.77 (95% CI 1.14 to 6.73), respectively). Higher risk of deterioration was observed in those who were taking both antipsychotic and sedative drugs together (OR 3.86 (95% CI 1.28 to 11.7). Patients taking drugs licensed for dementia, drugs affecting the renin-angiotensin system and statins had a significantly lower risk of deterioration than those who were not taking any of these drugs (ORs 0.49 (95% CI 0.25 to 0.97), 0.31 (95% CI 0.11 to 0.85) and 0.12 (95% CI 0.03 to 0.52), respectively). CONCLUSION: Our findings have implications for both clinicians and trialists. Most importantly, clinicians should carefully weigh any potential benefits of antipsychotics and benzodiazepines, especially in combination, against the risk of increased decline. Researchers need to be aware of the potential of not only licensed drugs for dementia but also drugs affecting the renin-angiotensin system and statins in reducing progression in clinical trials.

Measuring brain stem and cerebellar damage in parkinsonian syndromes using diffusion tensor MRI.

OBJECTIVE: To use diffusion tensor MRI to quantify and compare degeneration of the pons and cerebellar peduncles in multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and Parkinson disease (PD) and to relate changes in diffusion measures to clinical features and localized atrophy. METHODS: We used a region-of-interest approach to measure changes in fractional anisotropy and mean diffusivity in the middle cerebellar peduncles, decussation of the superior cerebellar peduncles, and pons in 17 patients with MSA, 17 with PSP, 12 with PD, and 12 healthy volunteers. We also evaluated atrophy of the cerebellar peduncles and pons on T2-weighted magnetic resonance images in patients with MSA and PSP. RESULTS: In MSA, fractional anisotropy was markedly reduced in the middle cerebellar peduncles, and mean diffusivity increased both here and in the pons compared with other groups, whereas in PSP, mean diffusivity was strikingly increased in the decussation of superior cerebellar peduncles. Cerebellar ataxia was related to mean diffusivity in the middle cerebellar peduncles (r = 0.71, p = 0.001) and pons (r = 0.60, p = 0.01) in MSA. Diffusion measures were related to localized atrophy in both MSA and PSP. CONCLUSIONS: Diffusion tensor MRI can be used to quantify neurodegenerative processes in different brain stem and cerebellar structures in multiple system atrophy and progressive supranuclear palsy during life, and may have diagnostic value. Larger studies of early, undifferentiated parkinsonian syndromes are indicated to provide estimates of the relative diagnostic value of diffusion measures, atrophy measures, and visual assessment of scans.

Longitudinal predictors of psychological distress and self-esteem in people with ALS.

OBJECTIVE: To identify predictors of psychological distress (measured by anxiety and depression) and low self-esteem and to determine whether these change over time in people with ALS. METHOD: We interviewed 50 patients with ALS living with a spouse/partner; further interviews were held at median intervals of 6 and then 5 months. Although carers were interviewed, we report the patients' data. Patients completed measures about their social support and marital relationship; the functional impact of ALS; everyday cognitive, emotional, and behavioral changes; symptoms of anxiety and depression; and self-esteem. The ALS Severity Scale was also completed. RESULTS: From the initial sample of 50, 26 patients were interviewed on all three occasions. At the first interview, negative social support and bulbar impairment were most predictive of psychological distress; pre-illness marital intimacy was the best predictor of patients' self-esteem. Over time, negative social support and pre-illness marital intimacy retained an ability to predict patients' affective state and self-esteem. CONCLUSIONS: Social factors are important in determining longer-term psychological well-being in people with ALS who are in the relatively early stages of the disease.

Proteome-based plasma biomarkers for Alzheimer's disease.

Alzheimer's disease is a common and devastating disease for which there is no readily available biomarker to aid diagnosis or to monitor disease progression. Biomarkers have been sought in CSF but no previous study has used two-dimensional gel electrophoresis coupled with mass spectrometry to seek biomarkers in peripheral tissue. We performed a case-control study of plasma using this proteomics approach to identify proteins that differ in the disease state relative to aged controls. For discovery-phase proteomics analysis, 50 people with Alzheimer's dementia were recruited through secondary services and 50 normal elderly controls through primary care. For validation purposes a total of 511 subjects with Alzheimer's disease and other neurodegenerative diseases and normal elderly controls were examined. Image analysis of the protein distribution of the gels alone identifies disease cases with 56% sensitivity and 80% specificity. Mass spectrometric analysis of the changes observed in two-dimensional electrophoresis identified a number of proteins previously implicated in the disease pathology, including complement factor H (CFH) precursor and alpha-2-macroglobulin (alpha-2M). Using semi-quantitative immunoblotting, the elevation of CFH and alpha-2M was shown to be specific for Alzheimer's disease and to correlate with disease severity although alternative assays would be necessary to improve sensitivity and specificity. These findings suggest that blood may be a rich source for biomarkers of Alzheimer's disease and that CFH, together with other proteins such as alpha-2M may be a specific markers of this illness.

Brain mechanisms of successful compensation during learning in Alzheimer disease.

OBJECTIVE: To determine whether patients with Alzheimer disease (AD) compensate for neuropathologic changes when performing a mnemonic task by recruiting 1) the same brain regions as age-matched, healthy controls, but to a greater extent; 2) additional brain regions not activated by controls; or 3) both. METHODS: Twelve patients with mild probable AD and 12 healthy age- and education-matched controls participated in an fMRI study of successful encoding and retrieval of visuospatial paired associates. To ensure successful performance in both groups, participants were given multiple attempts to learn associations between two and three object locations. RESULTS: The pattern of brain activity in patients with AD performing an easy version of the task was indistinguishable from that of controls performing a harder version of the task. Increased activation in left medial and right lateral prefrontal cortices was found in patients with AD compared to controls during encoding of two object locations, but not when this level of encoding in patients was compared with encoding of three object locations in controls. CONCLUSIONS: There was no evidence of neural plasticity in the form of recruitment of novel brain regions in patients with Alzheimer disease. Data supported greater recruitment of the same brain regions as age-matched controls as a means of compensating for neuropathology and associated cognitive impairment in Alzheimer disease.

Parkinsonism following bilateral lesions of the globus pallidus: performance on a variety of motor tasks shows similarities with Parkinson's disease.

OBJECTIVES: The authors report the results of detailed investigations into the motor function of a patient who, after a heavy drinking binge and subsequent unconsciousness, respiratory acidosis, and initial recovery, developed parkinsonism characterised by hypophonic speech and palilalia, "fast micrographia", impaired postural reflexes, and brady/akinesia in proximal (but not distal) alternating upper limb movements. METHODS: In addition to brain magnetic resonance imaging (MRI), different aspects of motor function were investigated using reaction time (RT) tasks, pegboard and finger tapping tasks, flex and squeeze tasks, movement related cortical potentials (MRCPs), and contingent negative variation (CNV). Cognitive function was also assessed. The results were compared to those previously reported in patients with Parkinson's disease (PD). RESULTS: Brain MRI showed isolated and bilateral globus pallidus (GP) lesions covering mainly the external parts (GPe). These lesions were most probably secondary to respiratory acidosis, as other investigations failed to reveal an alternative cause. The results of the RT tasks showed that the patient had difficulties in preparing and maintaining preparation for a forthcoming movement. MRCP and CNV studies were in line with this, as the early component of the MRCP and CNV were absent prior to movement. The patient's performance on pegboard and finger tapping, and flex and squeeze tasks was normal when performed with one hand, but clearly deteriorated when using both hands simultaneously or sequentially. CONCLUSIONS: In general, the present results were similar to those reported previously in patients with PD. This provides further indirect evidence that the output of globus pallidus is of major importance in abnormal motor function in PD. The possible similarities of the functional status of GP in PD and our case are discussed.

Cognitive behavioural therapy (CBT) for carers of patients with Parkinson's disease: a preliminary randomised controlled trial.

OBJECTIVE: Most individuals with Parkinson's disease live in their own homes cared for by a family member. Providing such long term care can be a source of significant stress, with many carers experiencing sleep difficulty, depression, anxiety, loneliness, and other symptoms of psychological strain. Cognitive behavioural therapy (CBT) is one of the most widely used psychological treatments in clinical use today, with applications across the full range of clinical conditions. It has been previously used in the management of other carer groups. The present study sought to evaluate the efficacy of CBT in treating psychological distress in a group of Parkinson's disease carers. METHOD: A total of 30 carers scoring at caseness level on the 28 item General Health Questionnaire (GHQ-28) were randomised to receive either a course of 12-14 sessions of CBT or to a no-treatment control group. RESULTS: Although some change was observed in both groups, significantly greater improvement on the GHQ-28 was observed after three months in the CBT treated group. Similar findings were observed in measures of caregiver strain and subjective burden, with the benefits being maintained over a subsequent three month follow up period. CONCLUSIONS: These results offer preliminary support to the value of a CBT approach in the management of psychological morbidity in Parkinson's disease carers. Further larger scale research is needed in the future to examine the generalisability of the findings to a broader range of carers, assess the longer term impact on outcome in carers and those with Parkinson's disease, and explore how CBT can be best delivered in the most cost effective manner.