A.D. Speelman's research while affiliated with Radboud University Medical Centre (Radboudumc) and other places

Parkinson's disease (PD) is a neurodegenerative disorder caused by nigrostriatal dopaminergic degeneration. Brain-derived neurotrophic factor (BDNF) is a key protein in brain plasticity and is particularly important for survival of dopaminergic neurons. The Val66Met polymorphism of BDNF (rs6265) has been associated with functional differences (mainly cognitive) between healthy adults and also with differences in the clinical expression of several other neuropsychiatric illnesses including PD. However, these studies used different outcome measures, have not been replicated, and were cross sectional, making it difficult to establish the role of BDNF in the clinical variability of PD. Here, a large cohort of 384 PD patients were followed up for 2 years, and associations between BDNF genotype and various clinical characteristics were examined. The BDNF Met-allele carriers showed a significantly smaller decline in set shifting during follow-up compared with the homozygous BDNF Val-allele carriers. Contrary to previous assumptions, these results indicate that mental flexibility is one of the cognitive processes that may benefit from the BDNF Met allele in PD patients. Copyright © 2014 Elsevier Inc. All rights reserved.

We recently completed the ParkFit study, a two-year randomized controlled trial including 586 sedentary Parkinson's disease (PD) patients, that evaluated a multifaceted intervention (ParkFit program) to promote physical activity. The results showed that the ParkFit program enables PD patients to become physically more active, suggesting that this intervention should now be further implemented into clinical practice. To facilitate this process, we here evaluate the implementation of the ParkFit program. The ParkFit program was evaluated in three ways: (a) experiences of patients and physiotherapists, as investigated using interviews and questionnaires; (b) factors associated with changed activity levels; and (c) subgroup analyses to identify differential effects in subgroups of patients based on baseline physical activity level, age, gender, disease severity, disease duration, and mobility. The ParkFit program was well received: 73% of patients indicated they would recommend the program to other patients, and 90% of physiotherapists indicated they wanted to use the ParkFit program in other patients. Multiple forward regression analysis resulted in a model with two variables: less baseline physical activity, and better mobility were associated with larger changes in levels of physical activity (R(2)=38%). The program was effective in almost all subgroups. In women, most sedentary patients and patients with higher disease severity, the estimated effect size was largest. We conclude that the ParkFit program was effective in almost all specific subgroups. Therapists and patients experienced no major hurdles. Suggestions for improvement are: (1) improve education for therapists with respect to theories about behavioral change; (2) formulate concrete and specific examples of exercise goals; and (3) pay more specific attention to patients with co morbidities, cognitive dysfunction and a lack of motivation during education.

To evaluate whether a multifaceted behavioural change programme increases physical activities in patients with Parkinson's disease. Multicentre randomised controlled trial. 32 community hospitals in the Netherlands, collaborating in a nationwide network (ParkinsonNet). 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). 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). 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). 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%). 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. Clinical trials NCT00748488.

Background: patients with Parkinson's disease (PD) have a high risk of sustaining osteoporotic fractures as a result of falls and reduced bone mass. Objective: to summarise the underlying pathophysiological mechanisms of bone loss in PD by reviewing the available literature. Methods: a Medline search was performed for articles published between January 1975 and January 2011, using the keywords 'bone mineral density', 'bone loss', 'bone metabolism', 'osteoporosis', 'osteopenia', 'Parkinson's disease' and 'Parkinsonism'. Results: PD patients have a lower bone mineral density (BMD) than age-matched controls. Bone loss in PD is multifactorial, resulting from immobility, decreased muscle strength, and low body weight. Vitamin D deficiency is also important, not only because it reduces BMD, but also because cell function in the substantia nigra depends on vitamin D. Lastly, hyperhomocysteinaemia, an independent risk factor for osteoporosis, is common in PD, due to levodopa use, as well as vitamin B12 and folic acid deficiency. A few studies have demonstrated that treatment with bisphosphonates, vitamin D and calcium can increase BMD and reduce fractures in PD patients. Conclusion: bone loss in PD is multifactorial. It is clinically important because of the concomitant risk of fractures. Screening for osteoporosis should be considered more often, and therapeutic interventions should be initiated.

Bone loss is more common in Parkinson's disease (PD) than in the general population. Several factors may be involved in the development of bone loss, including malnutrition, immobilization, low body mass index, decreased muscle strength, vitamin D deficiency and medication use. This study investigates the prevalence of osteoporosis and possible risk factors associated with bone loss in early stage PD. In 186 PD patients (Hoehn and Yahr stage 1-2.5, mean age 64.1 years, 71 % men) bone mineral density (BMD) measurements were performed with DEXA. T- and Z-scores were calculated. Univariate linear regression analysis was performed to identify variables that contributed to BMD. 25-OH-vitamin D status of PD patients was compared with 802 controls (mean age 63.3 years, 50 % men) using linear regression analysis. Osteoporosis (11.8 %) and osteopenia (41.4 %) were common in PD patients. Mean Z-score for the hip was 0.24 (SD 0.93), and for the lumbar spine 0.72 (SD 1.91). Female gender, low weight, and low 25-OH-vitamin D were significantly correlated with BMD of the hip and lumbar spine. PD patients had lower 25(OH)D serum levels than controls (B = -10, p = 0.000). More than half of the patients with early stage PD had an abnormal BMD. Female gender, low weight, and low vitamin D concentration were associated with bone loss. Furthermore, vitamin D concentrations were reduced in PD patients. These results underscore the importance of proactive screening for bone loss and vitamin D deficiency, even in early stages of PD.

Background: Patients with Parkinson's disease (PD) are physically less active than controls, and autonomic dysfunction may contribute to this sedentary lifestyle. Specifically, an altered cardiovascular response to physical effort may restrict physical activities. Objective: To assess the cardiovascular responses to a submaximal exercise test in PD patients and controls, 546 sedentary PD patients and 29 sedentary healthy controls performed the Åstrand-Rhyming submaximal cycle exercise test. Methods: Average heart rate was used to estimate maximal oxygen consumption (VO2max). Variables that may affect submaximal activity in PD patients, including disease severity, fatigue, and level of physical activity in daily life, were recorded. Results: Fewer PD patients (46%) completed the submaximal exercise test successfully than the controls (86%). The estimated VO2max of patients with a successful test was 34% lower than the controls (p < 0.001). Multivariate regression analyses revealed that higher body weight, lower systolic blood pressure, lower resting heart rate, and lower maximal workload were associated with an increased risk of an inadequate heart rate increase during submaximal exercise (R2 = 27%). PD patients with a successful submaximal exercise test had lower estimated VO2max values than controls. Conclusions: Importantly, half of the PD patients had an inadequate heart rate increase during submaximal exercise, which was likely caused by cardiac sympathetic denervation leading to autonomic dysfunction. PD patients should therefore be screened to identify their limitations in exercise performance. Caution should be applied when prescribing beta blockers, as they might limit physical activities further.