Difficulty performing more than one task at a time (dual tasking) is a common and disabling problem experienced by people with Parkinson disease (PD). If asked to perform another task when walking, people with PD often take shorter steps or walk more slowly. Currently there is uncertainty about whether clinicians should teach people with PD to avoid dual tasking or whether they should encourage them to practice dual tasking with the hope that practice will lead to enhanced performance. This study will address this issue by comparing single to dual task gait training.
Methods and design
A prospective randomised clinical trial is being conducted. Sixty participants with idiopathic PD will be recruited, provided they score I-IV on the modified Hoehn and Yahr (1967) scale, and fulfil other inclusion criteria. Participants will be randomly allocated to either a single or dual task gait training group. Both groups will receive 12 hours of walking training over 4 weeks. The single task group will undertake gait training with cueing strategies to increase step length. The dual task group will train to improve step length when walking and performing a variety of added tasks. Both groups will receive a tailored home program for 6 months. Blinded assessors will conduct four assessments: two baseline assessments, one post intervention and one at 6 months follow-up. The primary outcome measure will be step length when dual tasking over 8 m. Secondary outcome measures include: spatiotemporal gait parameters when walking under single and dual task conditions, measures of executive function, the timed up and go test, measures of community mobility, and quality of life. All analyses will be based on intention to treat principle.
This trial will examine the immediate and longer term effect of dual task walking training as compared to single task training in people with idiopathic PD, at the impairment, activity, and participation levels. It has the potential to identify a new intervention that may improve and maintain walking beyond the laboratory. The results of this trial will provide guidance for clinicians in the development of walking training programs for people with PD.
Palliative care is increasingly offered earlier in the cancer trajectory but rarely in Idiopathic Parkinson's Disease(IPD), Progressive Supranuclear Palsy(PSP) or Multiple System Atrophy(MSA). There is little longitudinal data of people with late stage disease to understand levels of need. We aimed to determine how symptoms and quality of life of these patients change over time; and what demographic and clinical factors predicted changes.
We recruited 82 patients into a longitudinal study, consenting patients with a diagnosis of IPD, MSA or PSP, stages 3–5 Hoehn and Yahr(H&Y). At baseline and then on up to 3 occasions over one year, we collected self-reported demographic, clinical, symptom, palliative and quality of life data, using Parkinson's specific and generic validated scales, including the Palliative care Outcome Scale (POS). We tested for predictors using multivariable analysis, adjusting for confounders.
Over two thirds of patients had severe disability, over one third being wheelchair-bound/bedridden. Symptoms were highly prevalent in all conditions - mean (SD) of 10.6(4.0) symptoms. More than 50% of the MSA and PSP patients died over the year. Over the year, half of the patients showed either an upward (worsening, 24/60) or fluctuant (8/60) trajectory for POS and symptoms. The strongest predictors of higher levels of symptoms at the end of follow-up were initial scores on POS (AOR 1.30; 95%CI:1.05–1.60) and being male (AOR 5.18; 95% CI 1.17 to 22.92), both were more predictive than initial H&Y scores.
The findings point to profound and complex mix of non-motor and motor symptoms in patients with late stage IPD, MSA and PSP. Symptoms are not resolved and half of the patients deteriorate. Palliative problems are predictive of future symptoms, suggesting that an early palliative assessment might help screen for those in need of earlier intervention.
Postural control was assessed on a tilting platform system in 20 patients with idiopathic Parkinson's disease and 20 age-matched controls. The amount of information provided by vision and lower limb proprioception was varied during the experiment to investigate the influence of changes in sensory cues on postural control. The patient group with clinical evidence of impaired postural control (Hoehn and Yahr III) had significantly higher sway scores over all sensory conditions than either the Hoehn and Yahr II group or controls. The pattern of sway scores indicated that no obvious deficit in the quality, or processing, of sensory information was responsible for the postural instability observed in this group. The patients in both Hoehn and Yahr groups were also able to respond appropriately to potentially destabilising sensory conflict situations and significantly improved their sway scores when provided with visual feedback of body sway. The results indicate that in Parkinson's disease, the main site of dysfunction in postural control is likely to be at a central motor level.
Parkinson's disease (PD) is the second most common neurodegenerative disorder in developed countries. There is an increasing interest in the use of mindfulness-related interventions in the management of patients with a chronic disease. In addition, interventions that promote personal control, stress-management and other lifestyle factors, such as diet and exercise, assist in reducing disability and improving quality of life in people with chronic illnesses. There has been little research in this area for people with PD.
A prospective mixed-method randomised clinical trial involving community living adults with PD aged <76 years and with moderate disease severity (Hoehn and Yahr stage 2) PD. Participants will be randomised into the ESSENCE 6-week programme or a matched wait list control group. ESSENCE is a multifaceted, healthy lifestyle and mindfulness programme designed to improve quality of life. We aim to determine whether participation in a mindfulness and lifestyle programme could improve PD-related function and explore self-management related experiences and changing attitudes towards self-management. The outcome measures will include 5 self-administered questionnaires: PD function and well-being questionnaire (PDQ39), Health Behaviours, Mental health, Multidimensional locus of control, and Freiburg mindfulness inventory. An embedded qualitative protocol will include in-depth interviews with 12 participants before and after participation in the 6-week programme and a researcher will observe the programme and take notes.
Repeated measures of Analysis of Variance (ANOVA) will examine the outcome measures for any significant effects from the group allocation, age, sex, adherence score and attendance. Qualitative data will be analysed thematically. We will outline the benefits of, and barriers to, the uptake of the intervention.
This protocol has received ethics approval from the Monash University Human Research Ethics Committee project number CF11/2662–2011001553.
This is the first research of its kind in Australia involving a comprehensive, lifestyle-based programme for people with PD and has the potential to involve a broader range of providers than standard care. The findings will be disseminated through peer reviewed journals, primary care conferences in Australia as well as abroad and through the Parkinson's community.
Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12612000440820.
PRIMARY CARE; COMPLEMENTARY MEDICINE
To obtain preliminary data on the effects of high-intensity exercise on functional performance in people with Parkinson's disease (PD) relative to exercise at low and no intensity; and to determine whether improved performance is accompanied by alterations in corticomotor excitability as measured through transcranial magnetic stimulation (TMS).
Cohort (prospective), randomized controlled trial.
University-based clinical and research facilities.
Thirty people with PD, 3 years or more since diagnosis, with Hoehn and Yahr stage 1 or 2.
Subjects were randomized to high-intensity exercise using body weight–supported treadmill training, low-intensity exercise, or a zero-intensity education group. Subjects completed 24 exercise sessions over 8 weeks and had 5 education classes over 8 weeks.
Main Outcome Measures
Unified Parkinson's Disease Rating Scales (UPDRS), biomechanic analysis of self-selected, fast walking, and sit-to-stand tasks; corticomotor excitability was assessed with cortical silent period durations (CSP) in response to single-pulse TMS.
A small improvement in total and motor UPDRS was observed in all groups. High-intensity group subjects demonstrated postexercise increases in gait speed, step and stride length, and hip and ankle joint excursion during self-selected and fast gait and improved weight distribution during sit-to-stand. Improvements in gait and sit-to-stand measures were not consistently observed in low- and zero-intensity groups. Importantly, the high-intensity group demonstrated lengthening in CSP.
The findings suggest the dose-dependent benefits of exercise and that high-intensity exercise can normalize corticomotor excitability in early PD.
Basal ganglia; Central nervous system; Neuronal plasticity; Rehabilitation; Walking
Objective To evaluate whether a multifaceted behavioural change programme increases physical activities in patients with Parkinson’s disease.
Design Multicentre randomised controlled trial.
Setting 32 community hospitals in the Netherlands, collaborating in a nationwide network (ParkinsonNet).
Participants 586 sedentary patients with idiopathic Parkinson’s disease aged between 40 and 75 years with mild to moderate disease severity (Hoehn and Yahr stage ≤3).
Intervention Patients were randomly assigned to the ParkFit programme or a matched general physiotherapy intervention. ParkFit is a multifaceted behavioural change programme, designed specifically to achieve an enduring increase in the level of physical activity (coaches using motivational strategies; ambulatory feedback).
Main outcome measures The primary endpoint was the level of physical activity, measured every six months with a standardised seven day recall (LASA physical activity questionnaire—LAPAQ). Secondary endpoints included two other measures of physical activity (activity diary and ambulatory activity monitor), quality of life (Parkinson’s disease questionnaire—PDQ-39), and fitness (six minute walk test).
Results 540 (92.2%) patients completed the primary outcome. During follow-up, overall time spent on physical activities (LAPAQ) was comparable between the groups (adjusted group difference 7%, 95% confidence interval −3 to 17%; P=0.19). Analyses of three secondary outcomes indicated increased physical activity in ParkFit patients, as suggested by the activity diary (difference 30%; P<0.001), the activity monitor (difference 12%; P<0.001), and the six minute walk test (difference 4.8 m; P=0.05). PDQ-39 did not differ between ParkFit patients and controls (difference −0.9 points; P=0.14). The number of fallers was comparable between ParkFit patients (184/299; 62%) and controls (191/287; 67%).
Conclusions The ParkFit behavioural change programme did not increase overall physical activity, as measured with the LAPAQ. The analysis of the secondary endpoints justifies further work into the possible merits of behavioural change programmes to increase physical activities in daily life in Parkinson’s disease.
Trial registration Clinical trials NCT00748488.
Cost of illness studies show that Parkinson disease (PD) is costly for individuals, the healthcare system and society. The costs of PD include both direct and indirect costs associated with falls and related injuries.
This protocol describes a prospective economic analysis conducted alongside a randomised controlled trial (RCT). It evaluates whether physical therapy is more cost effective than usual care from the perspective of the health care system. Cost effectiveness will be evaluated using a three-way comparison of the cost per fall averted and the cost per quality adjusted life year saved across two physical therapy interventions and a control group.
This study has the potential to determine whether targetted physical therapy as an adjunct to standard care can be cost effective in reducing falls in people with PD.
Objectives: To test the validity and feasibility of the generic 15D health related quality of life (HRQoL) instrument in Parkinson's disease (PD) and compare parkinsonian patients with the general population. Much effort has gone into developing disease specific HRQoL measures for PD, but only generic measures allow comparisons with the general population. New HRQoL tools are needed for PD because earlier ones have low feasibility in elderly patients.
Methods: The study comprised 260 patients with idiopathic PD and age and sex matched controls. HRQoL was evaluated using the disease specific questionnaire PDQ-39 and the 15D generic instrument. PD severity was assessed by Hoehn and Yahr staging, and the activities of daily living (ADL) and motor section of the Unified Parkinson's Disease Rating Scale (UPDRS).
Results: The mean 15D score (scale 0–1; overall HRQoL) was lower in PD (0.77) than in controls (0.86). Patients with PD had significantly lower scores than controls in 13 of the 15 dimensions of 15D. Scores of the corresponding dimensions of PDQ-39 and 15D correlated significantly, confirming the convergent validity of 15D. In multiple stepwise regression analysis, the UPDRS ADL score explained 55% of the variation in the 15D score.
Conclusions: 15D is a valid, feasible, and sensitive tool to assess quality of life in PD. PD has a major impact on HRQoL, which is related to disease progression. Mobility, eating, speech, and sexual functions are most affected. The ADL measure of the UPDRS and the 15D provide an easily assessable view of HRQoL in PD.
the factors that determine quality of life (QoL) in patients with
idiopathic Parkinson's disease in a population based sample. Quality
of life (QoL) is increasingly recognised as a critical measure in
health care as it incorporates the patients' own perspective of their health.
with Parkinson's disease seen in a
population based study on the prevalence of parkinsonism were asked to
complete a disease-specific QoL questionnaire (PDQ-39) and the Beck
depression inventory. A structured questionnaire interview and a
complete neurological examination, including the Hoehn and Yahr scale, the Schwab and England disability scale, the motor part of the unified
Parkinson's disease rating scale (UPDRS part III), and the mini mental
state examination were performed by a neurologist on the same day.
rate was 78%. The factor most closely associated with QoL was the
presence of depression, but disability, as measured by the Schwab and
England scale, postural instability, and cognitive impairment
additionally contributed to poor QoL. Although the UPDRS part III
correlated significantly with QoL scores, it did not contribute
substantially to predicting their variance once depression, disability,
and postural instability had been taken into account. In addition,
patients with akinetic rigid Parkinson's
disease had worse QoL scores than those with tremor dominant disease,
mainly due to impairment of axial features.
disability, postural instability, and cognitive impairment have the
greatest influence on QoL in Parkinson's
disease. The improvement of these features should therefore become an
important target in the treatment of the disease.
Parkinson's disease (PD) patients have an increased risk of under-nutrition, but we are unaware of any population based prevalence studies of under-nutrition in PD. The main objective of this study was to identify the prevalence, and nature, of under-nutrition in a representative population of people with PD.
People diagnosed with idiopathic PD from within two PD prevalence study sites in North-East England were asked to participate in this study. Those who participated (n = 136) were assessed using a number of standard rating scales including Hoehn & Yahr stage and Unified Parkinson's Disease Rating Scale (UPDRS). Body mass index (BMI), mid-arm circumference (MAC), triceps skin fold thickness (TSF) and grip strength were recorded together with social and demographic information.
BMI < 20 identified over 15% of the study group to have under-nutrition. The Malnutritional Universal Screening Tool (MUST) scoring system identified 23.5% of participants at medium or high risk of malnutrition. Low BMI, indicating under-nutrition, was associated with greater age and disease duration, lower MAC, TSF, mid-arm muscle circumference (MAMC), reduced grip strength and a report of unintentional weight loss. Problems increased with increasing age and disease duration and were greater in females.
Under-nutrition is a problem for around 15% of community dwelling people with PD. All PD patients should be screened for under-nutrition; the MUST score is a useful early screening tool.
Patients with idiopathic Parkinson’s disease exhibit impairments in executive processes, including planning and set-shifting, even at the early stages of the disease. We have recently developed a new card-sorting task to study the specific role of the caudate nucleus in such executive processes and have shown, using functional magnetic resonance imaging (fMRI) in young healthy adults, that the caudate nucleus is specifically required when a set-shift must be planned. Here the same fMRI protocol was used to compare the patterns of activation in a group of early-stage Parkinson’s disease patients (seven right-handed patients at Hoehn and Yahr stages 1 and 2; mean age 62 years, range 56–70) and matched control subjects. Increased cortical activation was observed in the patients compared with the control group in the condition not specifically requiring the caudate nucleus. On the other hand, decreased cortical activation was observed in the patient group in the condition significantly involving the caudate nucleus. This event-related fMRI study showed a pattern of cortical activation in Parkinson’s disease characterized by either reduced or increased activation depending on whether the caudate nucleus was involved or not in the task. This activation pattern included not only the prefrontal regions but also posterior cortical areas in the parietal and prestriate cortex. These findings are not in agreement with the traditional model, which proposes that the nigrostriatal dopamine depletion results in decreased cortical activity. These observations provide further evidence in favour of the hypothesis that not only the nigrostriatal and but also the mesocortical dopaminergic substrate may play a significant role in the cognitive deficits observed in Parkinson’s disease.
PMID: 17121746 CAMSID: cams3203
executive functions; fMRI; Parkinson’s disease; set-shifting; striatum
Patients with Parkinson's disease have substantially impaired balance, leading to diminished functional ability and an increased risk of falling. Although exercise is routinely encouraged by health care providers, few programs have been proven effective.
We conducted a randomized, controlled trial to determine whether a tailored tai chi program could improve postural control in patients with idiopathic Parkinson's disease. We randomly assigned 195 patients with stage 1 to 4 disease on the Hoehn and Yahr staging scale (which ranges from 1 to 5, with higher stages indicating more severe disease) to one of three groups: tai chi, resistance training, or stretching. The patients participated in 60-minute exercise sessions twice weekly for 24 weeks. The primary outcomes were changes from baseline in the limits-of-stability test (maximum excursion and directional control; range, 0 to 100%). Secondary outcomes included measures of gait and strength, scores on functional-reach and timed up-and-go tests, motor scores on the Unified Parkinson's Disease Rating Scale, and number of falls.
The tai chi group performed consistently better than the resistance-training and stretching groups in maximum excursion (between-group difference in the change from baseline, 5.55 percentage points; 95% confidence interval [CI], 1.12 to 9.97; and 11.98 percentage points; 95% CI, 7.21 to 16.74, respectively) and in directional control (10.45 percentage points; 95% CI, 3.89 to 17.00; and 11.38 percentage points; 95% CI, 5.50 to 17.27, respectively). The tai chi group also performed better than the stretching group in all secondary outcomes and outperformed the resistance-training group in stride length and functional reach. Tai chi lowered the incidence of falls as compared with stretching but not as compared with resistance training. The effects of tai chi training were maintained at 3 months after the intervention. No serious adverse events were observed.
Tai chi training appears to reduce balance impairments in patients with mild-to-moderate Parkinson's disease, with additional benefits of improved functional capacity and reduced falls. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00611481.)
Parkinson’s disease (PD) and osteoporosis are two conditions that affect a considerable proportion of the elderly population and have a significant socio-economic impact, which is linked partly to increases in hospital admissions following fractures and partly to increased consumption of drugs.
Reduced walking speed, difficulty walking in tandem, reduced visual acuity and reduced thigh circumference are independent risk factors for fall-related hip fractures. Falls are a major fracture risk factor in elderly people and are the leading cause of emergency department admissions in parkinsonian patients. Falls are a much more frequent occurrence in PD patients than in their healthy peers and the factors that contribute most to this increased risk are older age, longer disease duration, more severe disease (as measured using the Hoehn & Yahr scale), bradykinesia, rigidity, gait disorders, postural instability, the presence of dementia and the presence of atypical parkinsonism. Fractures, obviously correlated with the frequency of falls, are also more common in individuals with PD compared with the age-matched healthy population, and the femur is the most frequent fracture site. A reduced bone mass density (BMD) appears to be a factor correlated with increased fracture risk in parkinsonian subjects. Individuals with PD have lower BMD values than healthy, age-matched controls and this reduction seems to be related to their bodyweight (a low body mass index, BMI), reduced physical activity, disease duration, disease severity (Hoehn and Yahr stage), calcium intake and exposure to sunlight. From a pathophysiological point of view, various factors are implicated in osteoporosis in PD:
- immobilisation: this is known to be a factor in bone loss, even though, at present, the precise pathophysiological mechanism by which it might induce osteopenia remains unclear; one hypothesis suggests an increase in osteoclast activity and a suppression of osteoblast activity.- endocrine factors: in addition to reduced levels of GH, ACTH and cortisol in PD patients versus age-matched controls, there also seems to be a vitamin D deficiency. Vitamin D acts not only on bone metabolism but also on various other tissues, including the nervous system.- nutritional factors: weight loss is a factor often present in patients with PD, even early in the disease; however, it is much more marked in the advanced stages of PD, when the cognitive problems, dysphagia and delayed gastric emptying appear. BMD is even lower in PD patients with low bodyweight compared with the overall population of PD patients who, per se, already have a low BMD compared with that of the general population. Low bodyweight and low physical activity are risk factors for low BMD in PD. Fracture risk may be reduced by dietary supplementation of calcium and vitamin D.- iatrogenic factors: a recent study showed that high daily doses of levodopa are associated with an increased fracture risk and this is probably linked to the fact that levodopa increases hyperhomocysteinaemia in subjects with PD.
Given the mortality and morbidity of fractures in the elderly population, and particularly in subjects with PD, it is reasonable to suggest that these patients should be submitted to measurement of vitamin levels (vitamins D, B12 and folate), BMD measurement and assessment of fall risk, and also that preventive measures should be implemented in order to reduce their fracture risk. In the absence of specific guidelines and recommendations on the treatment and prevention of osteoporosis in PD, it currently seems reasonable to follow the existing indications for post-menopausal treatment of osteoporosis, given that the fracture risk profile in PD subjects may differ from that of the general population on account of their increased fall risk, low level of physical activity, reduced vitamin D intake and swallowing difficulties.
The ability to maintain a steady gait rhythm is impaired in patients with Parkinson's disease (PD). This aspect of locomotor dyscontrol, which likely reflects impaired automaticity in PD, can be quantified by measuring the stride-to-stride variability of gait timing. Previous work has shown an increase in both the variability of the stride time and swing time in PD, but the origins of these changes are not fully understood. Patients with PD also generally walk with a reduced gait speed, a potential confounder of the observed changes in variability. The purpose of the present study was to examine the relationship between walking speed and gait variability.
Stride time variability and swing time variability were measured in 36 patients with PD (Hoehn and Yahr stage 2–2.5) and 30 healthy controls who walked on a treadmill at four different speeds: 1) Comfortable walking speed (CWS), 2) 80% of CWS 3) 90% of CWS, and 4) 110% of CWS. In addition, we studied the effects of walking slowly on level ground, both with and without a walker.
Consistent with previous findings, increased variability of stride time and swing time was observed in the patients with PD in CWS, compared to controls. In both groups, there was a small but significant association between treadmill gait speed and stride time variability such that higher speeds were associated with lower (better) values of stride time variability (p = 0.0002). In contrast, swing time variability did not change in response to changes in gait speed. Similar results were observed with walking on level ground.
The present results demonstrate that swing time variability is independent of gait speed, at least over the range studied, and therefore, that it may be used as a speed-independent marker of rhythmicity and gait steadiness. Since walking speed did not affect stride time variability and swing time variability in the same way, it appears that these two aspects of gait rhythmicity are not entirely controlled by the same mechanisms. The present findings also suggest that the increased gait variability in PD is disease-related, and not simply a consequence of bradykinesia.
gait; speed; Parkinson's disease; treadmill; stride variability
Research evidence from observational studies suggests that cognitive activity reduces the risk of cognitive impairment in later life as well as the rate of cognitive decline of people with dementia. The Promoting Healthy Ageing with Cognitive Exercise (PACE) study has been designed to determine whether a cognitive activity intervention decreases the rate of cognitive decline amongst older adults with mild cognitive impairment (MCI).
The study will recruit 160 community-dwelling men and women aged 65 years of age or over with mild cognitive impairment (MCI). Participants will be randomly allocated to two treatment groups: non-specific education and cognitive activity. The intervention will consist of ten 90-minute sessions delivered twice per week over a period of five weeks. The primary outcome measure of the study is the change from baseline in the total score on the Cambridge Cognitive Score (CAMCOG). Secondary outcomes of interest include changes in memory, attention, executive functions, mood and quality of life. Primary endpoints will be collected 12, 52 and 104 weeks after the baseline assessment.
The proposed project will produce the best available evidence on the merits of increased cognitive activity as a strategy to prevent cognitive decline among older adults with MCI. We anticipate that the results of this study will have implications for the development of evidence-based preventive strategies to reduce the rate of cognitive decline amongst older people at risk of dementia.
Parkinson disease (PD) is characterized by the degeneration of nigrostriatal dopaminergic neurons. However, postmortem evidence indicates that the pathology of lower brainstem regions, such as the pons and medulla, precedes nigral involvement. Consistently, pontomedullary damage was implicated by structural and PET imaging in early PD. Neurochemical correlates of this early pathological involvement in PD are unknown.
To map biochemical alterations in the brains of individuals with mild-moderate PD we quantified neurochemical profiles of the pons, putamen and substantia nigra by 7 tesla (T) proton magnetic resonance spectroscopy. Thirteen individuals with idiopathic PD (Hoehn & Yahr stage 2) and 12 age- and gender-matched healthy volunteers participated in the study. γ-Aminobutyric acid (GABA) concentrations in the pons and putamen were significantly higher in patients (N = 11, off medications) than controls (N = 11, p<0.001 for pons and p<0.05 for putamen). The GABA elevation was more pronounced in the pons (64%) than in the putamen (32%). No other neurochemical differences were observed between patients and controls.
The GABA elevation in the putamen is consistent with prior postmortem findings in patients with PD, as well as with in vivo observations in a rodent model of PD, while the GABA finding in the pons is novel. The more significant GABA elevation in the pons relative to the putamen is consistent with earlier pathological involvement of the lower brainstem. This study provides in vivo evidence for an alteration in the GABAergic tone in the lower brainstem and striatum in early-moderate PD, which may underlie disease pathogenesis and may provide a biomarker for disease staging.
Objective: To investigate the heterogeneity of idiopathic Parkinson's disease (PD) in a data driven manner among a cohort of patients in the early clinical stages of the disease meeting established diagnostic criteria.
Methods: Data on demographic, motor, mood, and cognitive measures were collected from 120 consecutive patients in the early stages of PD (Hoehn and Yahr I–III) attending a specialist PD research clinic. Statistical cluster analysis of the data allowed the existence of the patient subgroups generated to be explored.
Results: The analysis revealed four main subgroups: (a) patients with a younger disease onset; (b) a tremor dominant subgroup of patients; (c) a non-tremor dominant subgroup with significant levels of cognitive impairment and mild depression; and (d) a subgroup with rapid disease progression but no cognitive impairment.
Conclusions: This study complements and extends previous research by using a data driven approach to define the clinical heterogeneity of early PD. The approach adopted in this study for the identification of subgroups of patients within Parkinson's disease has important implications for generating testable hypotheses on defining the heterogeneity of this common condition and its aetiopathological basis and thus its treatment.
Chronic kidney disease (CKD) affects up to 16% of the adult population and is associated with significant morbidity and mortality. People at highest risk from progressive CKD are defined by a sustained decline in estimated glomerular filtration rate (eGFR) and/or the presence of significant albuminuria/proteinuria and/or more advanced CKD. Accurate mapping of the bio-clinical determinants of this group will enable improved risk stratification and direct the development of better targeted management for people with CKD.
The Renal Impairment In Secondary Care study is a prospective, observational cohort study, patients with CKD 4 and 5 or CKD 3 and either accelerated progression and/or proteinuria who are managed in secondary care are eligible to participate. Participants undergo a detailed bio-clinical assessment that includes measures of vascular health, periodontal health, quality of life and socio-economic status, clinical assessment and collection of samples for biomarker analysis. The assessments take place at baseline, and at six, 18, 36, 60 and 120 months; the outcomes of interest include cardiovascular events, progression to end stage kidney disease and death.
The determinants of progression of chronic kidney disease are not fully understood though there are a number of proposed risk factors for progression (both traditional and novel). This study will provide a detailed bio-clinical phenotype of patients with high-risk chronic kidney disease (high risk of both progression and cardiovascular events) and will repeatedly assess them over a prolonged follow up period. Recruitment commenced in Autumn 2010 and will provide many outputs that will add to the evidence base for progressive chronic kidney disease.
CKD progression; Observational cohort study; Inflammation; Arterial stiffness; Periodontitis
Neuropsychological and motor deficits in Parkinson’s disease that may contribute to driving impairment were examined in a cohort study comparing patients with Parkinson’s disease (PD) to patients with Alzheimer’s disease (AD) and to healthy elderly controls. Nondemented individuals with Parkinson’s disease [Hoehn & Yahr (H&Y) stage I–III], patients with Alzheimer’s disease [Clinical Demetia Rating scale (CDR) range 0–1], and elderly controls, who were actively driving, completed a neuropsychological battery and a standardized road test administered by a professional driving instructor. On-road driving ability was rated on number of driving errors and a global rating of safe, marginal, or unsafe. Overall, Alzheimer’s patients were more impaired drivers than Parkinson’s patients. Parkinson’s patients distinguished themselves from other drivers by a head-turning deficiency. Drivers with neuropsychological impairment were more likely to be unsafe drivers in both disease groups compared to controls. Compared to controls, unsafe drivers with Alzheimer’s disease were impaired across all neuropsychological measures except finger tapping. Driving performance in Parkinson’s patients was related to disease severity (H&Y), neuropsychological measures [Rey Osterreith Complex Figure (ROCF), Trails B, Hopkins Verbal List Learning Test (HVLT)-delay], and specific motor symptoms (axial rigidity, postural instability), but not to the Unified Parkinson Disease Rating Scale (UPDRS) motor score. Multifactorial measures (ROCF, Trails B) were useful in distinguishing safe from unsafe drivers in both patient groups.
Dementia; Motor vehicles; Cognition; Memory; Neurodegenerative diseases; Basal ganglia
Parkinson disease (PD) reduces health-related quality of life (HRQoL), but exercise may improve HRQoL. This pilot study compared the effects of Tango, Waltz/Foxtrot, Tai Chi and No Intervention on HRQoL in individuals with PD. Seventy-five persons with PD (Hoehn and Yahr I-III) were assigned to twenty lessons of Tango, Waltz/Foxtrot, Tai Chi, or an untreated No Intervention group. Participants completed the PDQ-39 before and after participation in 20 classes or within thirteen weeks in the case of the No Intervention group. Two-way repeated measures ANOVAs determined differences between interventions. Tango significantly improved on Mobility (p = 0.03), Social Support (p = 0.05) and the PDQ-39 SI (p < 0.01) at post-testing. No significant changes in HRQoL were noted in the Waltz/Foxtrot, Tai Chi or No Intervention. Tango may be helpful for improving HRQoL in PD because it addresses balance and gait deficits in the context of a social interaction that requires working closely with a partner.
Parkinson disease; quality of life; PDQ-39; exercise; dance
high frequency electrostimulation of the globus pallidus internus
mimics pallidotomy and improves clinical symptoms in Parkinson's
disease. The aim of this study was to investigate the cognitive
consequences of unilateral deep brain stimulation.
non-demented patients with Parkinson's disease (age range 38-70
years) were neuropsychologically assessed 2 months before and 3 months
after unilateral pallidal stimulation. The cognitive assessment
included measures of memory, spatial behaviour, and executive and
psychomotor function. In addition to group analysis of cognitive
change, a cognitive impairment index (CII) was calculated for each
individual patient representing the percentage of cognitive measures
that fell more than 1 SD below the mean of a corresponding normative sample.
assessment with the Hoehn and Yahr scale and the unified Parkinson's
disease rating scale disclosed a significant postoperative reduction in
average clinical Parkinson's disease symptomatology (p<0.001).
Repeated measures multivariate analysis of variance (using right/left
side of stimulation as a between subjects factor) showed no significant
postoperative change in cognitive performance for the total patient
group (main effect of operation). The side of stimulation did not show
a significant differential effect on cognitive performance (main effect
of lateralisation). There was no significant operation by
lateralisation interaction effect. Although the patients experienced
significant motor symptom relief after pallidal stimulation, they
remained mildly depressed after surgery. Analysis of the individual CII
changes showed a postoperative cognitive decline in 30% of the
patients. These patients were significantly older and took higher
preoperative doses of levodopa than patients showing no change or a
postoperative cognitive improvement.
right pallidal stimulation for the relief of motor symptoms in
Parkinson's disease seems relatively safe, although older patients and
patients needing high preoperative doses of levodopa seem to be more
vulnerable for cognitive decline after deep brain stimulation.
Gait performance is widely evaluated to assess health status in older adult populations. While several investigators have presented normative values for spatiotemporal gait parameters drawn from older adult populations, the literature has been void of large-scale cohort studies, which are needed in order to provide quantitative, normative gait data in persons with Parkinson’s disease. The aim of this investigation was to provide reference values for clinically important gait characteristics in a large sample of ambulatory persons with Parkinson’s disease to aid both clinicians and researchers in their evaluations and treatments of gait impairment.
Gait performance was collected in 310 individuals with idiopathic Parkinson’s disease as they walked across a pressure sensitive walkway. Fourteen quantitative gait parameters were measured and evaluated with respect to Hoehn and Yahr disease staging and gender. Disease duration and age were controlled for in all analyses. Individuals with the greatest Parkinson’s disability walked significantly slower with shorter steps and stride lengths than the mild and moderately affected groups. Further, the most affected patients spent more time with both feet on the ground, and walked with a wider base of support than the moderately disabled patients. No differences were detected between the mild and moderate disability groups on any of the gait parameters evaluated.
Reference values for 14 gait parameters in a large cohort of ambulatory patients with Parkinson’s disease are provided and these may be highly useful for assessing and interpreting an individual’s gait dysfunction. It is important for clinicians and researchers to appreciate the lack of change in quantitative parameters as PD patients move from mild to moderate gait impairment.
To investigate the incidence of and risk factors for cognitive impairment in a large, well-defined clinical trial cohort of patients with early Parkinson disease (PD).
The Mini-Mental State Examination (MMSE) was administered periodically over a median follow-up period of 6.5 years to participants in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism trial and its extension studies. Cognitive impairment was defined as scoring 2 standard deviations below age- and education-adjusted MMSE norms.
Cumulative incidence of cognitive impairment in the 740 participants with clinically confirmed PD (baseline age 61.0 ± 9.6 years, Hoehn-Yahr stage 1–2.5) was 2.4% (95% confidence interval: 1.2%–3.5%) at 2 years and 5.8% (3.7%–7.7%) at 5 years. Subjects who developed cognitive impairment (n = 46) showed significant progressive decline on neuropsychological tests measuring verbal learning and memory, visuospatial working memory, visuomotor speed, and attention, while the performance of the nonimpaired subjects (n = 694) stayed stable. Cognitive impairment was associated with older age, hallucinations, male gender, increased symmetry of parkinsonism, increased severity of motor impairment (except for tremor), speech and swallowing impairments, dexterity loss, and presence of gastroenterologic/urologic disorders at baseline.
The relatively low incidence of cognitive impairment in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism study may reflect recruitment bias inherent to clinical trial volunteers (e.g., younger age) or limitations of the Mini-Mental State Examination–based criterion. Besides confirming known risk factors for cognitive impairment, we identified potentially novel predictors such as bulbar dysfunction and gastroenterologic/urologic disorders (suggestive of autonomic dysfunction) early in the course of the disease.
= confidence interval;
= Controlled Word Association task;
= Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism;
= dementia with Lewy bodies;
= Digit Span Test;
= Mini-Mental State Examination;
= New Dot Task;
= Odd Man Out test;
= Parkinson disease;
= dementia in Parkinson disease;
= postural instability and gait difficulty;
= Symbol Digit Modalities Test;
= Selective Reminding Test;
= Unified Parkinson's Disease Rating Scale.
People with idiopathic Parkinson’s disease (PD) frequently have low activity levels, poor mobility and reduced quality of life. Although increased physical activity may improve mobility, balance and wellbeing, adherence to exercises and activity programs over the longer term can be challenging, particularly for older people with progressive neurological conditions such as PD. Physical activities that are engaging and enjoyable, such as dancing, might enhance adherence over the long term. The objective of this study was to evaluate the feasibility of a randomized controlled trial of Irish set dancing compared with routine physiotherapy for people with mild to moderately severe PD.
Twenty-four people with idiopathic PD referred for movement rehabilitation were randomized to receive standard physiotherapy exercises or Irish set dancing classes once per week plus a weekly home program for 6 months (12 in each group). The feasibility and safety of the proposed RCT protocol was the main focus of this evaluation. The primary outcome was motor disability measured by the motor component of the UPDRS, which was assessed prior to and after therapy by trained assessors blinded to group assignment. The Timed Up and Go, the Berg Balance Scale and the modified Freezing of Gait Questionnaire were secondary measures. Quality of life of the people with PD was evaluated using the PDQ-39.
Both the Irish set dancing and physiotherapy exercise program were shown to be feasible and safe. There were no differences between groups in the rate of adverse events such as falls, serious injuries, death or rates of admission to hospital. The physiotherapists who provided usual care remained blind to group allocation, with no change in their standard clinical practice. Compliance and adherence to both the exercise and dance programs were very high and attrition rates were low over the 6 months of therapy. Although improvements were made in both groups, the dance group showed superior results to standard physiotherapy in relation to freezing of gait, balance and motor disability.
Irish dancing and physiotherapy were both safe and feasible in this sample from Venice, with good adherence over a comparatively long time period of 6 months. A larger multi-centre trial is now warranted to establish whether Irish set dancing is more effective than routine physiotherapy for enhancing mobility, balance and quality of life in people living with idiopathic PD.
EudraCT number 2012-005769-11
Parkinson’s disease; Dancing; Rehabilitation; Exercise therapy; Balance; Randomized controlled trial; Geriatrics
Alterations in blood–brain barrier permeability have been proposed to represent a relevant factor contributing to Parkinson’s disease progression. However, few studies have addressed this issue in patients at different stages of disease.
Albumin was measured in cerebrospinal fluid and serum samples obtained from 73 non-demented subjects with idiopathic Parkinson’s disease and 47 age-matched control subjects. The albumin ratio (AR) was calculated to assess blood-cerebrospinal fluid and blood–brain barrier function. The group of patients with Parkinson’s disease included 46 subjects with Hoehn-Yahr staging between 1 and 2 and 27, with a score ranging from 2.5 to 4.
Statistically significant differences in albumin ratio were found between patients with advanced disease, and both early-stage and unaffected groups. Conversely, early-phase patients did not differ from healthy subjects. Additionally, dopaminergic treatment seems to exert a possible effect on AR values.
Our study demonstrates that possible dysfunction of the blood-cerebrospinal fluid barrier, blood–brain barrier, or both, characterize Parkinson’s disease progression. The associations between clinical scores, treatments and biochemical findings suggest a progressive impairment of barrier integrity during the course of the disease.
Albumin ratio; Blood–brain barrier; Blood-cerebrospinal fluid barrier; Cerebrospinal fluid; Parkinson’s disease