Effects of treadmill training on walking economy in Parkinson’s disease: a pilot study

Gait disturbances are frequent in Parkinson’s disease (PD) and are associated with increased energy expenditure during walking. This study evaluated whether the effects of treadmill training are associated with an improvement of walking economy. Ten patients with idiopathic PD underwent treadmill training (30 min, three times a week for 4 weeks). Walking performance (Τimed Up and Go, 6-min and 10-m walking tests) and metabolic function (oxygen uptake, heart and respiratory rate) were evaluated before training, at the end of treatment and after 30 days with two different graded exercises (treadmill and cycloergometer). Training significantly improved walking performance. Oxygen uptake, and heart and respiratory rates were significantly decreased only during graded exercise on the treadmill, but not on the cycloergometer. Treadmill training reduces energy expenditure during walking in PD, but the improvements of metabolic walking economy are associated with the specifically trained motor activity.     

Parkinson’s disease and the Stroop color word test: processing speed and interference algorithms

Objective: Processing speed alters the traditional Stroop calculations of interference. Consequently, alternative algorithms for calculating Stroop interference have been introduced to control for processing speed, and have done so in a multiple sclerosis sample. This study examined how these processing speed correction algorithms change interference scores for individuals with idiopathic Parkinson’s disease (PD, n = 58) and non-PD peers (n = 68). Method: Linear regressions controlling for demographics predicted group (PD vs. non-PD) differences for Jensen’s, Golden’s, relative, ratio, and residualized interference scores. To examine convergent and divergent validity, interference scores were correlated with standardized measures of processing speed and executive function. Results: PD–non-PD differences were found for Jensen’s interference score, but not Golden’s score, or the relative, ratio, and residualized interference scores. Jensen’s score correlated significantly with standardized processing speed but not executive function measures. Relative, ratio, and residualized scores correlated with executive function but not processing speed measures. Golden’s score did not correlate with any other standardized measures. Conclusions: The relative, ratio, and residualized scores were comparable for measuring Stroop interference in processing speed-impaired populations. Overall, the ratio interference score may be the most useful calculation method to control for processing speed in this population.     

Increased brain connectivity and activation after cognitive rehabilitation in Parkinson’s disease: a randomized controlled trial

Cognitive rehabilitation programs have demonstrated efficacy in improving cognitive functions in Parkinson’s disease (PD), but little is known about cerebral changes associated with an integrative cognitive rehabilitation in PD. To assess structural and functional cerebral changes in PD patients, after attending a three-month integrative cognitive rehabilitation program (REHACOP). Forty-four PD patients were randomly divided into REHACOP group (cognitive rehabilitation) and a control group (occupational therapy). T1-weighted, diffusion weighted and functional magnetic resonance images (fMRI) during resting-state and during a memory paradigm (with learning and recognition tasks) were acquired at pre-treatment and post-treatment. Cerebral changes were assessed with repeated measures ANOVA 2 × 2 for group x time interaction. During resting-state fMRI, the REHACOP group showed significantly increased brain connectivity between the left inferior temporal lobe and the bilateral dorsolateral prefrontal cortex compared to the control group. Moreover, during the recognition fMRI task, the REHACOP group showed significantly increased brain activation in the left middle temporal area compared to the control group. During the learning fMRI task, the REHACOP group showed increased brain activation in the left inferior frontal lobe at post-treatment compared to pre-treatment. No significant structural changes were found between pre- and post-treatment. Finally, the REHACOP group showed significant and positive correlations between the brain connectivity and activation and the cognitive performance at post-treatment. This randomized controlled trial suggests that an integrative cognitive rehabilitation program can produce significant functional cerebral changes in PD patients and adds evidence to the efficacy of cognitive rehabilitation programs in the therapeutic approach for PD.     

Comorbid disorders and hospitalisation in Parkinson’s disease: a prospective study

Abstract. Parkinsons disease (PD) is often associated with other disorders, typical of the disease or of the age of PD patients, that can lead to hospitalisation, sometimes as emergencies. In this one-year prospective, longitudinal study, we investigated the comorbid events prompting the hospitalisation, or occurring during the planned hospitalisation, of an unselected group of 180 PD patients, admitted to 9 general hospitals in the course of the study. The most frequent acute comorbid events were trauma (30.5%), mostly due to falls, and vascular disorders (29.3%). Comorbidities were closely related to PD in 50% of cases. More than 50% of patients did not require (in addition to PD therapy) specific treatment for the acute comorbid event. Older age was associated with increased risk of complications. The setting up of multidisciplinary networks covering entire territories could help to improve the way in which we tackle the clinical and social problems generated by PD and its comorbidities. *Members of the Parkinsons Disease Comorbidity Study Group D. Porazzi, F. Reverberi, Department of Neurology, Hospital of Busto Arsizio; G. Chiodelli, G. Guarneri, Department of Neurology, Hospital of Cremona; M. B. Zappacosta, Department of Neurology, Hospital of Gallarate; G. Mariani, R. Freschi, Department of Neurology, Hospital of Legnano; F. Sasanelli, G. Molini, Department of Neurology, Hospital of Melegnano; F. Schieroni, M. Di Costanzo, Department of Neurology, Hospital of Merate; G. Bargnani, E. Donati, Department of Neurology, Hospital of Rovato; G. Bono, Department of Neurology, Hospital of Varese; E. Magrotti, Department of Neurology, Hospital of Voghera.     

Sleep attacks in Parkinson’s disease: a clinical and polysomnographic study

Abstract. The objective of the study was to evaluate daytime sleepiness, (the features of episodes of sudden sleep onset), i. e., so-called sleep attacks (SAs), in three male Parkinsons disease (PD) patients (mean age 66 years) on chronic therapy with ropirinole or pramipexole. A structured clinical interview, the Epworth Sleepiness Scale, and continuous 24-h ambulatory polysomnography were used to assess the features of SAs occurring in the patients in their normal home environments. The polysomnographic patterns characterizing SAs (sleep occurring against a background of wakefulness, and not preceded by a feeling of sleepiness or by other heralding symptoms) were analyzed. The results showed that SAs can be clearly documented through polysomnographic monitoring and really, but rarely, occur in PD. SAs seem to represent the extreme of the continuum of daytime sleepiness observed in PD patients.     

Profiling cognitive and neuropsychiatric heterogeneity in Parkinson’s disease

BackgroundParkinson’s disease (PD) is a highly heterogeneous disease, in which motor symptom subtypes are often-described. While it is recognized that motor, cognitive and affective neuropsychiatric symptoms negatively influence the patients’ quality of life, it is currently unknown how these symptoms contribute to phenotypic subtypes. The objective of this study was to assess subtypes of motor, cognitive and affective symptoms in PD.MethodsA hierarchical cluster analysis was conducted on clinical data of 226 PD patients screened at the VU University Medical Center using comprehensive assessment of cognitive, affective and motor symptoms. Subsequent linear discriminant analyses were conducted to investigate discriminating constructs between clusters.ResultsThe cluster analysis yielded four clusters: (1) a young-age (59.9 years), mildly affected cluster (N = 86), (2) an old-age (72.3 years) cluster with severe motor and non-motor symptoms (N = 15), (3) a cluster (age 64.7 years) with mild motor symptoms, below-average executive functioning and affective symptoms (N = 46) and (4) a cluster (age 64.8 years) with severe motor symptoms, affective symptoms and below-average verbal memory (N = 79).ConclusionsCluster 1 and 2 seem to represent opposite ends of the PD disease stages. Patients in clusters 3 and 4 had similar age, educational level and disease duration but different symptom profiles – we therefore suggest that these clusters represent different pathways of disease progression, presumably with distinct underlying pathology localization. Future research on the neuropathophysiological characteristics of these two clusters and monitoring of disease progression is required.     

Continuous apomorphine infusion and neuropsychiatric disorders: a controlled study in patients with advanced Parkinson’s disease

Abstract. The aim of this study was to asses whether patients with Parkinsons disease (PD) develop cognitive and psychiatric complications more frequently during prolonged therapy with continuous apomorphine infusion compared with standard oral treatment. Thirty consecutive PD patients with severe motor fluctuations were included in the study. Twelve patients accepted the treatment with subcutaneous continuous apomorphine infusion, while the remaining 18 preferred to continue with oral dopaminergic therapy. The two groups were evaluated with neuropsychological, psychiatric, and motor tests at baseline and after 1 year. The off daily duration and the levodopa dosage were significantly reduced in infused patients. The neuropsychiatric assessment did not change in both groups compared with baseline, except for a significant improvement of mood in the apomorphine group.     

Long-term duodenal levodopa infusion in Parkinson’s disease: a 3-year motor and cognitive follow-up study

Duodenal infusion of levodopa/carbidopa gel (Duodopa) is an effective treatment option for advanced Parkinson’s disease (PD). Long-term clinical experience up to 16 years suggests that the safety of this procedure is acceptable, while several observational studies showed that Duodopa reduces motor fluctuations and dyskinesias improving patients’ quality of life (QoL). The aim of this study is to investigate the long-term motor and cognitive outcome of Duodopa treatment in advanced PD patients and its’ impact on the QoL. Twenty-five consecutive PD patients were assessed using the Unified PD rating scale (UPDRS), a battery of neuropsychological tests, and the PD questionnaire (PDQ-39) at baseline and after a mean period of three years of Duodopa treatment. Seventeen out of 25 patients reached the follow-up evaluation; five patients discontinued Duodopa and three patients died of causes unrelated to drug infusion. Duodopa improved motor complications (UPDRS-IV) and quality of life (PDQ-39). A sub-group of subjects (41 %) developed a significant deterioration of cognitive functions over time. The most common adverse events were dislocation and the kinking of the intestinal tube. In conclusion, Duodopa therapy is effective in the long-term treatment of advanced PD patients. Continuous enteral levodopa infusion achieves a reduction of motor fluctuations and dyskinesias improving patients’ QoL, despite the progression of PD motor symptoms and a significant decline in cognitive functions in a sub-group of patients.     

Timed tests of motor function in Parkinson’s disease

IntroductionTimed tests of motor function in Parkinson’s disease (PD) may be useful for the diagnosis of bradykinesia or to monitor disease progression or treatment response. However, normal ranges have not been established.AimTo define normal ranges of hand-tapping and timed walking tests in non-parkinsonian controls and compare with PD patients’ performance.MethodsWe recruited PD patients and age- and gender-matched controls for a prospective community-based incidence study of parkinsonian disorders in North-East Scotland. We counted the times participants tapped between two counters in 30 s. We also timed a 6m get-up-and-go test. We assessed age and gender effects and calculated 95% reference ranges for controls. We compared PD patients with controls.ResultsWe recruited 157 controls and 138 newly diagnosed, untreated PD patients (mean ages 75 and 73). The 95% control reference range for tapping scores with the dominant hand was 18–74 taps. Males and younger participants performed significantly better. PD patients performed less well (mean difference 15 taps, p < 0.001) but only 10% had tapping scores below the control range. The 95% control reference range for the get-up-and-go test was 9–27 s. Walking times increased significantly with age, but gender had no effect. PD patients were slower (median difference 4.5s, p < 0.001) but only 17% were slower than the control range.DiscussionAlthough PD patients performed more slowly than matched controls, timed tests were not helpful diagnostically because few incident patients were outside the normal reference ranges. Further work is needed on their utility in monitoring disease progression.     

Mild cognitive impairment in Parkinson’s disease

Parkinson’s disease (PD) has initially been described as a clinical syndrome, although its exact definition has changed over the past centuries. The identification of the pathological changes added another level of complexity, with Lewy bodies, synuclein deposits and neuronal loss in the substantia nigra being used alternatively as criteria. A third level of complexity was added with the recognition of genetic mutations resulting in Parkinsonism, sometimes with and sometimes without Lewy bodies or synuclein deposition. Lastly, frequent additional important pre-motor manifestations, particularly depression, anosmia and sleep-associated phenomena have been described. These different points of view on the definition of PD have important implications on the study of the etiology and even the therapy of PD. Cognitive impairment is also an important feature of PD, while the spectrum of deficits ranges from none to severe dementia. The no-man land in-between normal cognition and dementia has been termed mild cognitive impairment in PD. At present, this term lacks heuristic value or clinical utility, and remains a target for scientific research.     

Non-motor symptoms in Huntington’s disease: a comparative study with Parkinson’s disease

Journal of Neurology - The presence of non-motor symptoms in Huntington’s disease (HD) has not been systematically assessed so far. Our objective was to know their prevalence and to compare...     

Pergolide effect on cognitive functions in early-mild Parkinson’s disease

Summary. In the present study, we evaluated the effect of pergolide, a mixed D1/D2 agonist, on cognitive function in mild Parkinsons disease (PD). After a two-week wash-out phase, twenty patients with a Hoehn and Yahr score 2.5 entered a 16-week, cross-over study in which the order of administration of pergolide or 1-dopa was randomly assigned. Cognitive assessment was performed after the wash-out phase and repeated after eight weeks (before patients were switched to the other drug) and at the end of the study. There were no significant differences in test scores among the three experimental modalities (off-treatment vs. l-dopa, off-treatment vs. pergolide, pergolide vs. l-dopa).In another cohort of comparably mild PD patients we had previously demonstrated that pramipexole, a mixed D2/D3 agonist, slightly but significantly worsened verbal fluency in comparison to l-dopa; moreover, pramipexole impaired short term verbal memory and attentional-executive functions in comparison to both l-dopa and the off-treatment condition. Taken together, these findings suggest that dopamine agonists may influence cognition in PD according to their pharmacological characteristics. Unlike the D2/D3 agonist pramipexole, pergolide and l-dopa, both of which stimulate D1- and D2-receptor subtypes, do not appear to impair cognitive function.     

Hallucinations in Parkinson’s disease: cross-sectional study

The aim of this study was to estimate the prevalence and risk factors for the development of hallucinations in patients with Parkinson's disease (PD). This cross-sectional study included 180 consecutive, non-demented patients with PD. Out of them, 24 patients (13%) experienced some kind of hallucinations. Visual hallucinations were present in 22/24 (90%) subjects. Univariate logistic regression analysis has shown relationship between presence of hallucinations and the following variables: age of patients (p?=?0.025), PD duration (p?=?0.001), duration of levodopa treatment (p?=?0.001), total daily dose of levodopa (p?=?0.033), presence of levodopa-induced dyskinesia (p?=?0.002) and their duration (p?=?0.021), and experience of nightmares (p?=?0.042). Hallucinations were also associated with higher scores of the UPDRS (p?=?0.001), HDRS (p?=?0.001) and the NPI total score (p?=?0.001), and higher H-Y stages of the disease (p?=?0.001). Multivariate regression analysis has demonstrated that the duration of PD (p?=?0.024) as well as NPI total score (p?=?0.002) was significant independent risk factors for hallucinations in PD.     

Intravenous amantadine on freezing of gait in Parkinson’s disease: a randomized controlled trial

To compare the effects of intravenous amantadine and placebo therapy on freezing of gait in patients with Parkinson’s disease, this randomized, double-blind, placebo-controlled, multicenter trial compared the efficacy of 5 days intravenous amantadine and placebo treatments on freezing of gait in 42 subjects randomly allocated 2:1 to amantadine or placebo groups. Changes in freezing of gait questionnaire (FOG-Q) scores and in unified Parkinson’s disease rating scale (UPDRS) scores, from baseline to immediately (V1) and 1 month (V2) after treatments, were assessed. Among the 42 patients (amantadine n = 29, placebo n = 13, a mean age 65.5 ± 9.4 years and a mean FOG-Q score 17.4 ± 3.2), 40 subjects completed treatment. There was no significant group difference on the primary outcome measure as total FOG-Q score changes at V1. However a significant beneficial effect of amantadine on freezing was seen at V2 in the UPDRS Part II freezing and FOG-Q item 3 scores, and there was significant improvement in the UPDRS Part IV total score and in the UPDRS Part II getting out of bed score in the amantadine group at both V1 and V2. There was no serious adverse event reported during the study. The intravenous amantadine therapy did not show a significant improvement on overall FOG-Q scores in patients with moderate-to-severe freezing; however, it might be beneficial by attenuating freezing severity and improving patients’ mobility. To prove this finding further studies with larger sample sizes are warranted in the future.     

Cognitive training in Alzheimer’s disease: a controlled randomized study

This controlled randomized single-blind study evaluated the effects of cognitive training (CT), compared to active music therapy (AMT) and neuroeducation (NE), on initiative in patients with mild to moderate Alzheimer’s disease (AD). Secondarily, we explored the effects of CT on episodic memory, mood, and social relationships. Thirty-nine AD patients were randomly assigned to CT, AMT, or NE. Each treatment lasted 3 months. Before, at the end, and 3 months after treatment, neuropsychological tests and self-rated scales assessed initiative, episodic memory, depression, anxiety, and social relationships. At the end of the CT, initiative significantly improved, whereas, at the end of AMT and NE, it was unchanged. Episodic memory showed no changes at the end of CT or AMT and a worsening after NE. The rates of the patients with clinically significant improvement of initiative were greater after CT (about 62%) than after AMT (about 8%) or NE (none). At the 3-month follow-up, initiative and episodic memory declined in all patients. Mood and social relationships improved in the three groups, with greater changes after AMT or NE. In patients with mild to moderate AD, CT can improve initiative and stabilize memory, while the non-cognitive treatments can ameliorate the psychosocial aspects. The combining of CT and non-cognitive treatments may have useful clinical implications.     

The effect of real and virtual visual cues on walking in Parkinson’s disease

Patients with Parkinson’s disease (PwPD) have a slow, shuffling gait, marked by sporadic freezing of gait (FoG) during which effective stepping ceases temporarily. As these gait problems are not commonly improved by medical and surgical treatments, alternative approaches to manage these problems have been adopted. The aim of this study was to evaluate the effect of real and virtual visual cues on walking in PD. We assessed 26 mid-stage PwPD, on and off medication, on a laboratory-based walking task which simulated real world challenges by incorporating FoG triggers and using appropriate placebo conditions. Cueing interventions were presented via virtual reality glasses (VRG rhythmic, visual flow and static placebo cues), and as transverse lines (TL) on the walkway. Objective measures of gait (task completion time; velocity, cadence, stride length; FoG frequency) and self-rated fear of falling (FoF) were recorded. Cueing intervention affected task completion time only off medication. Whereas placebo VRG cues provided no improvement in walking, visual flow VRG cues marginally reduced the task completion time. TL on the floor elicited more substantial improvements in gait with reduced cadence, increased stride length and reduced FoG frequency. VRG rhythmic cueing impaired overall walking. Notably, a final no-intervention condition yielded quicker task completion, greater walking velocity, increased stride length and less frequent FoG. Although the VRG produced modest improvements only in the visual flow condition, their flexibility is an advantage. These results endorse the use of TL and justify further testing and customisation of VRG cues for individual PwPD.     

Mild cognitive impairment exists in Parkinson’s disease

Cognitive impairment exists in Parkinson’s disease (PD) as a transitional state between cognitively intact and demented PD patients. It seems to be a risk factor for the development of dementia in PD, but the precise criteria and unfavorable cognitive profile of mild cognitive impairment in PD (MCI-PD) have not yet been established. The concept may turn to be different from that in Alzheimer’s disease since we search for those already diagnosed PD patients who are at risk of developing dementia. In addition, clinical variables specific for PD also play role. Importantly, MCI possesses a metabolic basis in PD. Various biomarkers particularly including neuropsychological testing and the brain imaging hold promise in identification of MCI-PD patients with unfavorable prognoses. Well-designed longitudinal studies in MCI-PD cohorts are needed to assess the sensitivity and specificity of the PD-MCI designation as far as dementia development is concerned.