Differences in the Presentation and Progression of Parkinson's Disease by Sex.

BACKGROUND: Previous studies reported various symptoms of Parkinson's disease (PD) associated with sex. Some were conflicting or confirmed in only one study. OBJECTIVES: We examined sex associations to PD phenotypes cross-sectionally and longitudinally in large-scale data. METHODS: We tested 40 clinical phenotypes, using longitudinal, clinic-based patient cohorts, consisting of 5946 patients, with a median follow-up of 3.1 years. For continuous outcomes, we used linear regressions at baseline to test sex-associated differences in presentation, and linear mixed-effects models to test sex-associated differences in progression. For binomial outcomes, we used logistic regression models at baseline and Cox regression models for survival analyses. We adjusted for age, disease duration, and medication use. In the secondary analyses, data from 17 719 PD patients and 7588 non-PD participants from an online-only, self-assessment PD cohort were cross-sectionally evaluated to determine whether the sex-associated differences identified in the primary analyses were consistent and unique to PD. RESULTS: Female PD patients had a higher risk of developing dyskinesia early during the follow-up period, with a slower progression in activities of daily living difficulties, and a lower risk of developing cognitive impairments compared with male patients. The findings in the longitudinal, clinic-based cohorts were mostly consistent with the results of the online-only cohort. CONCLUSIONS: We observed sex-associated contributions to PD heterogeneity. These results highlight the necessity of future research to determine the underlying mechanisms and importance of personalized clinical management. © 2020 International Parkinson and Movement Disorder Society.

Quantitative Muscle MRI Depicts Increased Muscle Mass after a Behavioral Change in Myotonic Dystrophy Type 1.

Background Patients with myotonic dystrophy type 1 (DM1) increased their physical activity and exercise capacity following a behavioral intervention. However, it is unknown what is altered in muscles of patients with DM1 as a result of this intervention. The increased exercise capacity suggests that decelerated fat infiltration or increased muscle cross-sectional area (CSA) could be involved. Purpose To assess the effect of this activity-stimulating behavioral intervention on the lower extremity muscles of patients with DM1 with longitudinal quantitative muscle MRI. Materials and Methods In this prospective trial, participants with DM1 were randomized to a behavioral intervention (n = 14) or continued regular care (standard care; n = 13); no age-matched pairing was performed. Participants underwent MRI of the lower extremities at baseline and 10-month follow-up (January 2015 to March 2016). Fat fraction (FF), muscle CSA, and muscle water T2 (T2water) as markers for fat infiltration, muscle mass, and alteration in tissue water distribution (edema), respectively, were assessed with a chemical shift-encoded Dixon sequence and multiecho spin-echo sequence. Longitudinal within-group and between-group changes were assessed with paired-samples t tests and multivariable regression models. Results A total of 27 patients with DM1 (15 men) were evaluated. Patient age was comparable between groups (intervention, 45 years ± 13 [standard deviation]; standard care, 5 years ± 12; P = .96). Muscle CSA increased 5.9 cm2 ± 7.8 in the intervention group during the 10-month follow-up (P = .03) and decreased 3.6 cm2 ± 7.2 in the standard care group (P = .13). After 10 months, the mean difference between the groups was 9.5 cm2 (P = .01). This effect was stronger in muscles with baseline FF below the mean ± standard deviation of unaffected volunteers (-0.4 cm2 ± 0.15; P < .001). FF increased 0.9% ± 1.0 in the intervention group (P = .02) and 1.2% ± 1.2 for standard care (P = .02), with no between-group difference (P = .56). T2water did not change significantly in either group (intervention, P = .08; standard care, P = .88). Conclusion A behavioral intervention targeting physical activity increased lower extremity muscle cross-sectional area in patients with myotonic dystrophy, preferentially in healthy-appearing muscle. © RSNA, 2020 Online supplemental material is available for this article.

Genomewide association study of Parkinson's disease clinical biomarkers in 12 longitudinal patients' cohorts.

BACKGROUND: Several reports have identified different patterns of Parkinson's disease progression in individuals carrying missense variants in GBA or LRRK2 genes. The overall contribution of genetic factors to the severity and progression of Parkinson's disease, however, has not been well studied. OBJECTIVES: To test the association between genetic variants and the clinical features of Parkinson's disease on a genomewide scale. METHODS: We accumulated individual data from 12 longitudinal cohorts in a total of 4093 patients with 22,307 observations for a median of 3.81 years. Genomewide associations were evaluated for 25 cross-sectional and longitudinal phenotypes. Specific variants of interest, including 90 recently identified disease-risk variants, were also investigated post hoc for candidate associations with these phenotypes. RESULTS: Two variants were genomewide significant. Rs382940(T>A), within the intron of SLC44A1, was associated with reaching Hoehn and Yahr stage 3 or higher faster (hazard ratio 2.04 [1.58-2.62]; P value = 3.46E-8). Rs61863020(G>A), an intergenic variant and expression quantitative trait loci for α-2A adrenergic receptor, was associated with a lower prevalence of insomnia at baseline (odds ratio 0.63 [0.52-0.75]; P value = 4.74E-8). In the targeted analysis, we found 9 associations between known Parkinson's risk variants and more severe motor/cognitive symptoms. Also, we replicated previous reports of GBA coding variants (rs2230288: p.E365K; rs75548401: p.T408M) being associated with greater motor and cognitive decline over time, and an APOE E4 tagging variant (rs429358) being associated with greater cognitive deficits in patients. CONCLUSIONS: We identified novel genetic factors associated with heterogeneity of Parkinson's disease. The results can be used for validation or hypothesis tests regarding Parkinson's disease. © 2019 International Parkinson and Movement Disorder Society.

Physical therapy and occupational therapy in Parkinson's disease.

Current medical management is only partially effective in controlling the symptoms of Parkinson's disease. As part of comprehensive multidisciplinary care, physical therapy and occupational therapy aim to support people with Parkinson's disease in dealing with the consequences of their disease in daily activities. In this narrative review, we address the limitations that people with Parkinson's disease may encounter despite optimal medical management, and we clarify both the unique and shared approaches that physical therapists and occupational therapists can apply in treating these limitations.

The European Physiotherapy Guideline for Parkinson's Disease: translation for non-English speaking countries.

BACKGROUND: The use of the European Physiotherapy Guideline for Parkinson's Disease is limited in countries where the official language is not English. OBJECTIVE: To provide practical steps on how to translate the European Physiotherapy Guideline for Parkinson's Disease. METHODS: We used the translation process of the Portuguese version as an example of how to define the recommended steps. A combination of a forward-backward-translation and dual-panel approach was used. RESULTS: Ten recommended translation steps were defined: (1) authorization, (2) translation of sample chapter, (3) physiotherapy expert panel review, (4) backward translation, (5) approval by copyright holders, (6) translation of the remaining sections of the guideline, (7) review of the entire translation by expert panel, (8) review by a user panel, (9) conclude final draft, (10) publication and dissemination. Several adjustments were needed in the Portuguese version. CONCLUSION: The additional adjustments that were required for the Portuguese version justify the need for the detailed and multifaceted translation process that was outlined in this manuscript.

Design and baseline characteristics of the ParkFit study, a randomized controlled trial evaluating the effectiveness of a multifaceted behavioral program to increase physical activity in Parkinson patients.

BACKGROUND: Many patients with Parkinson's disease (PD) lead a sedentary lifestyle. Promotion of physical activities may beneficially affect the clinical presentation of PD, and perhaps even modify the course of PD. However, because of physical and cognitive impairments, patients with PD require specific support to increase their level of physical activity. METHODS: We developed the ParkFit Program: a PD-specific and multifaceted behavioral program to promote physical activity. The emphasis is on creating a behavioral change, using a combination of accepted behavioral motivation techniques. In addition, we designed a multicentre randomized clinical trial to investigate whether this ParkFit Program increases physical activity levels over two years in sedentary PD patients. We intended to include 700 sedentary patients. Primary endpoint is the time spent on physical activities per week, which will be measured every six months using an interview-based 7-day recall. RESULTS: In total 3453 PD patients were invited to participate. Ultimately, 586 patients--with a mean (SD) age of 64.1 (7.6) years and disease duration of 5.3 (4.5) years--entered the study. Study participants were younger, had a shorter disease duration and were less sedentary compared with eligible PD patients not willing to participate. DISCUSSION: The ParkFit trial is expected to yield important new evidence about behavioral interventions to promote physical activity in sedentary patients with PD. The results of the trial are expected in 2012. TRIAL REGISTRATION: http://clinicaltrials.gov (nr NCT00748488).

Physiotherapy in Parkinson's Disease: A Meta-Analysis of Present Treatment Modalities.

BACKGROUND: Physiotherapy is a commonly prescribed intervention for people with Parkinson's disease (PD). Conventional types of physiotherapy have been studied extensively, while novel modalities are being developed and evaluated. OBJECTIVE: To evaluate the effectiveness of conventional and more recent physiotherapy interventions for people with PD. The meta-analysis performed as part of the 2014 European Physiotherapy Guideline for PD was used as the starting point and updated with the latest evidence. METHODS: We performed a systematic search in PubMed, CINAHL, Embase, and Web of Science. Randomized controlled trials comparing any physiotherapy intervention with no intervention or sham treatment were included. Trials were classified into 12 categories: conventional physiotherapy, resistance training, treadmill training, strategy training, dance, martial arts, aerobic exercises, hydrotherapy, balance and gait training, dual tasking, exergaming, and Nordic walking. Outcomes included motor symptoms, balance, gait, and quality of life, and are presented as standardized mean differences. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used to systematically appraise methodological quality. RESULTS: A total of 191 trials with 7998 participants were included. Conventional physiotherapy significantly improved motor symptoms, gait, and quality of life. Resistance training improved gait. Treadmill training improved gait. Strategy training improved balance and gait. Dance, Nordic walking, balance and gait training, and martial arts improved motor symptoms, balance, and gait. Exergaming improved balance and quality of life. Hydrotherapy improved balance. Finally, dual task training did not significantly improve any of the outcomes studied. CONCLUSIONS: This meta-analysis provides a comprehensive overview of the evidence for the effectiveness of different physiotherapy interventions in the management of PD, allowing clinicians and patients to make an evidence-based decision for specific treatment modalities. Further work is needed to directly compare the relative efficacy of the various treatments.

Recommendations for the Organization of Multidisciplinary Clinical Care Teams in Parkinson's Disease.

BACKGROUND: Optimal management in expert centers for Parkinson's disease (PD) usually involves pharmacological and non-pharmacological interventions, delivered by a multidisciplinary approach. However, there is no guideline specifying how this model should be organized. Consequently, the nature of multidisciplinary care varies widely. OBJECTIVE: To optimize care delivery, we aimed to provide recommendations for the organization of multidisciplinary care in PD. METHODS: Twenty expert centers in the field of multidisciplinary PD care participated. Their leading neurologists completed a survey covering eight themes: elements for optimal multidisciplinary care; team members; role of patients and care partners; team coordination; team meetings; inpatient versus outpatient care; telehealth; and challenges towards multidisciplinary care. During a consensus meeting, outcomes were incorporated into concept recommendations that were reviewed by each center's multidisciplinary team. Three patient organizations rated the recommendations according to patient priorities. Based on this feedback, a final set of recommendations (essential elements for delivery of multidisciplinary care) and considerations (desirable elements) was developed. RESULTS: We developed 30 recommendations and 10 considerations. The patient organizations rated the following recommendations as most important: care is organized in a patient-centered way; every newly diagnosed patient has access to a core multidisciplinary team; and each team has a coordinator. A checklist was created to further facilitate its implementation. CONCLUSION: We provide a practical tool to improve multidisciplinary care for persons with PD at the organizational level. Future studies should focus on implementing these recommendations in clinical practice, evaluating their potential applicability and effectiveness, and comparing alternative models of PD care.

Lower extremity muscle pathology in myotonic dystrophy type 1 assessed by quantitative MRI.

OBJECTIVE: To determine the value of quantitative MRI in providing imaging biomarkers for disease in 20 different upper and lower leg muscles of patients with myotonic dystrophy type 1 (DM1). METHODS: We acquired images covering these muscles in 33 genetically and clinically well-characterized patients with DM1 and 10 unaffected controls. MRIs were recorded with a Dixon method to determine muscle fat fraction, muscle volume, and contractile muscle volume, and a multi-echo spin-echo sequence was used to determine T2 water relaxation time (T2water), reflecting putative edema. RESULTS: Muscles in patients with DM1 had higher fat fractions than muscles of controls (15.6 ± 11.1% vs 3.7 ± 1.5%). In addition, patients had smaller muscle volumes (902 ± 232 vs 1,097 ± 251 cm3), smaller contractile muscle volumes (779 ± 247 vs 1,054 ± 246 cm3), and increased T2water (33.4 ± 1.0 vs 31.9 ± 0.6 milliseconds), indicating atrophy and edema, respectively. Lower leg muscles were affected most frequently, especially the gastrocnemius medialis and soleus. Distribution of fat content per muscle indicated gradual fat infiltration in DM1. Between-patient variation in fat fraction was explained by age (≈45%), and another ≈14% was explained by estimated progenitor CTG repeat length (r 2 = 0.485) and somatic instability (r 2 = 0.590). Fat fraction correlated with the 6-minute walk test (r = -0.553) and muscular impairment rating scale (r = 0.537) and revealed subclinical muscle involvement. CONCLUSION: This cross-sectional quantitative MRI study of 20 different lower extremity muscles in patients with DM1 revealed abnormal values for muscle fat fraction, volume, and T2water, which therefore may serve as objective biomarkers to assess disease state of skeletal muscles in these patients. CLINICALTRIALSGOV IDENTIFIER: NCT02118779.

Genetic risk of Parkinson disease and progression:: An analysis of 13 longitudinal cohorts.

OBJECTIVE: To determine if any association between previously identified alleles that confer risk for Parkinson disease and variables measuring disease progression. METHODS: We evaluated the association between 31 risk variants and variables measuring disease progression. A total of 23,423 visits by 4,307 patients of European ancestry from 13 longitudinal cohorts in Europe, North America, and Australia were analyzed. RESULTS: We confirmed the importance of GBA on phenotypes. GBA variants were associated with the development of daytime sleepiness (p.N370S: hazard ratio [HR] 3.28 [1.69-6.34]) and possible REM sleep behavior (p.T408M: odds ratio 6.48 [2.04-20.60]). We also replicated previously reported associations of GBA variants with motor/cognitive declines. The other genotype-phenotype associations include an intergenic variant near LRRK2 and the faster development of motor symptom (Hoehn and Yahr scale 3.0 HR 1.33 [1.16-1.52] for the C allele of rs76904798) and an intronic variant in PMVK and the development of wearing-off effects (HR 1.66 [1.19-2.31] for the C allele of rs114138760). Age at onset was associated with TMEM175 variant p.M393T (-0.72 [-1.21 to -0.23] in years), the C allele of rs199347 (intronic region of GPNMB, 0.70 [0.27-1.14]), and G allele of rs1106180 (intronic region of CCDC62, 0.62 [0.21-1.03]). CONCLUSIONS: This study provides evidence that alleles associated with Parkinson disease risk, in particular GBA variants, also contribute to the heterogeneity of multiple motor and nonmotor aspects. Accounting for genetic variability will be a useful factor in understanding disease course and in minimizing heterogeneity in clinical trials.

Solving a mental rotation task in congenital hemiparesis: motor imagery versus visual imagery.

A recent study showed that motor imagery was compromised after right congenital hemiparesis. In that study, posture of the displayed stimuli and the actual posture of the hand making the response were incongruent. Ample evidence exists that such an incongruency may negatively influence laterality judgements in a mental rotation task. In the present study, three participant groups (controls, left hemiparesis, right hemiparesis [all n=11]) performed a mental rotation task in which posture of the displayed hand and the responding hand were congruent. A small amount of errors were made and linear relations between reaction times and rotation angles of the stimuli were found for all groups, suggesting intact motor imagery. However, reaction times for the participants with hemiparesis were consistently slower compared to controls and no asymmetry in responding between the affected and less-affected hand was found, suggesting a visual imagery strategy. Collectively, these results suggest that the ability to mentally rotate stimuli is still intact in right hemiparesis. The results are discussed in relation to two strategies that may have been used to solve the task: visual imagery and motor imagery.

BDNF polymorphism associates with decline in set shifting in Parkinson's disease.

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.

Evaluation of implementation of the ParkFit program: A multifaceted intervention aimed to promote physical activity in patients with Parkinson's disease.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Involvement of specific executive functions in mobility in Parkinson's disease.

Postural instability and gait disorders (PIGD) in Parkinson's disease (PD) seem to be associated with executive dysfunction. We investigated which specific executive functions are associated with functional mobility in mildly affected PD patients. Functional mobility (Timed Up&Go Test, TUG), PIGD score, (spatial) working memory, set shifting, response inhibition and response generation were assessed in a large cohort of 232 non-demented PD patients. Both performance on the TUG and PIGD score were weakly associated with working memory and response generation (semantic and phonemic fluency). TUG also correlated with semantic fluency when corrected for disease severity and age. These results indicate that response generation and working memory are associated with (and possibly also causally related to) gait and balance deficits. In order to fully interpret gait and postural stability of PD patients in everyday situations, the role of impairments in working memory and response generation should be taken into account.

Promotion of physical activity and fitness in sedentary patients with Parkinson's disease: randomised controlled trial.

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.

Cardiovascular responses during a submaximal exercise test in patients with Parkinson's disease.

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.

How might physical activity benefit patients with Parkinson disease?

Parkinson disease (PD) is a neurodegenerative disorder characterized by progressive motor and nonmotor impairments. These impairments incline many patients towards a sedentary lifestyle, which has many deleterious consequences. Accumulating evidence suggests that patients with PD might benefit from physical activity and exercise in a number of ways, from general improvements in health to disease-specific effects and, potentially, disease-modifying effects (suggested by animal data). Many issues remain to be addressed, including the need to perform clinical trials to demonstrate these presumed benefits of physical activity and exercise in patients with PD. These trials must also address safety issues, such as an increased risk of falls and cardiovascular complications in more-active patients. Identifying ways to induce a sustained behavioral change, using specifically tailored programs that address potential barriers such as depression, apathy and postural instability, may lead to an improved quality of life in individuals with PD.

Physical inactivity in Parkinson's disease.

Patients with Parkinson's disease (PD) are likely to become physically inactive, because of their motor, mental, and emotional symptoms. However, specific studies on physical activity in PD are scarce, and results are conflicting. Here, we quantified daily physical activities in a large cohort of PD patients and another large cohort of matched controls. Moreover, we investigated the influence of disease-related factors on daily physical activities in PD patients. Daily physical activity data of PD patients (n = 699) were collected in the ParkinsonNet trial and of controls (n = 1,959) in the Longitudinal Aging Study Amsterdam (LASA); data were determined using the LAPAQ, a validated physical activity questionnaire. In addition, variables that may affect daily physical activities in PD were recorded, including motor symptoms, depression, disability in daily life, and comorbidity. Patients were physically less active; a reduction of 29% compared to controls (95% CI, 10-44%). Multivariate regression analyses demonstrated that greater disease severity, gait impairment, and greater disability in daily living were associated with less daily physical activity in PD (R (2) = 24%). In this large study, we show that PD patients are about one-third less active compared to controls. While disease severity, gait, and disability in daily living predicted part of the inactivity, a portion of the variance remained unexplained, suggesting that additional determinants may also affect daily physical activities in PD. Because physical inactivity has many adverse consequences, work is needed to develop safe and enjoyable exercise programs for patients with PD.