General Parkinson's Disease Population Research Articles

Access and Use of Device‐Aided Therapies for Parkinson’s Disease in Denmark

In Denmark's five regions, there is potential inequality in access to device-aided therapy (DAT) for Parkinson's disease (PD) based on structural or socioeconomic factors. It is unclear how long DAT is maintained and affects concomitant medication. To investigate access to DAT by comparing the proportion of patients with DBS, subcutaneous apomorphine infusion (SCAI), or levodopa/carbidopa intestinal gel (LCIG) in Danish regions 2008-2016 and describe demographics of patients, changes in use of comedication, and maintenance of DAT. This work is a retrospective nationwide population-based registry analysis generated by combining various registries and statistics in Denmark. From 2008 to 2016, 612 patients started DAT. There were statistically significant differences in the number of patients starting DAT between the Capital Region (99.5 per 1,000) and both Central Jutland (66.6 per 1,000) and North Jutland (70.6 per 1,000; P < 0.05). Among DBS and LCIG patients, respectively, 4% and 42% were aged ≥70 years, 68% and 63% were men (vs. 59% in the general PD population; P < 0.05 for DBS), 73% and 63% had a partner (vs. 62% in the general PD population), and 73% and 71% had a qualifying education (vs. 63% in the general PD population; P < 0.05). Use of PD-related medication decreased significantly from 4 years before to 4 years after DAT. Eighty-one percent of the patients who started LCIG, alive 4 years later, had maintained this treatment. There is unequal access to DAT in the Danish regions, and political and social considerations are warranted to address structural and socioeconomic causes.

Dementia and subthalamic deep brain stimulation in Parkinson disease: A long-term overview.

To assess the prevalence and the cumulative incidence of dementia at short-, medium- and long-term follow-up after deep brain stimulation (DBS) of the subthalamic nucleus (STN) (at 1, 5, and 10 years) and to evaluate potential risk factors for postoperative dementia. The presence of dementia (according to the DSM-V) was retrospectively evaluated at each postoperative follow-up in patients with Parkinson disease (PD) who underwent bilateral STN-DBS. Preoperative and perioperative risk factors of developing postoperative dementia were also investigated. Demographic data, disease features, medications, comorbidities, nonmotor symptoms, PD motor scales, neuropsychological scales at baseline, and perioperative complications were collected for each patient. A total of 175 patients were included, and 104 were available at 10-year follow-up. Dementia prevalence was 2.3% at 1 year, 8.5% at 5 years, and 29.8% at 10 years. Dementia cumulative incidence at 1, 5, and 10 years was 2.3%, 10.9%, and 25.7%, respectively. The corresponding dementia incidence rate was 35.6 per 1,000 person-years. Male sex, higher age, hallucinations, lower frontal score at baseline, and perioperative cerebral hemorrhage were predictors of dementia. In patients with PD with longstanding STN-DBS, dementia prevalence and incidence are not higher than those reported in the general PD population. Except for few patients with perioperative cerebral hemorrhage, STN-DBS is cognitively safe, and does not provide dementia risk factors in addition to those reported for PD itself. Identification of dementia predictors in this population may improve patient selection and information concerning the risk of poor cognitive outcome.

Long-term risk of falls in an incident Parkinson's disease cohort: the Norwegian ParkWest study.

The objective of this study is to examine the frequency, development, concomitants, and risk factors of falls in a population-based incident Parkinson's disease (PD) cohort. One hundred eighty-one drug-naïve patients with incident PD and 173 normal controls recruited from the Norwegian ParkWest study were prospectively monitored over 7years. Information on falls was obtained biannually from patients, and at baseline and after 1, 3, 5, and 7years of follow-up in control subjects. Generalized estimating equation models for correlated data were applied to investigate concomitant features of falls and risk factors for incident falls during 7years of follow-up in PD. Overall, 64.1% of patients reported falling during the study period. The 7-year cumulative incidence of falls in non-falling patients at baseline (n=153) was 57.5%, with a relative risk to controls of at least 3.1 (95% confidence interval 1.5-6.3; p<0.002). Significant concomitants of falls in patients during the study period were higher age, Unified PD Rating Scale motor score, postural instability and gait difficulties (PIGD) phenotype, dementia, and follow-up time. Higher age at baseline, PIGD phenotype at 1-year visit, and follow-up time were independent risk factors for incident falls during follow-up. Nearly two-thirds of patients in the general PD population experience falls within 7 years of diagnosis, representing a more than threefold increased risk compared to age- and gender-matched controls. Patients with higher age at baseline and early PIGD have the greatest risk of falling and may, therefore, be the prime target of specialized assessment and treatment interventions.

Risk and course of motor complications in a population-based incident Parkinson's disease cohort

BackgroundMotor complications may become major challenges in the management of patients with Parkinson's disease. In this study, we sought to determine the incidence, risk factors, evolution, and treatment of motor fluctuations and dyskinesias in a population-representative, incident Parkinson's disease cohort. MethodsIn this prospective population-based 5-year longitudinal study, we followed 189 incident and initially drug-naïve Parkinson's disease patients biannually for detailed examination of dyskinesias and motor fluctuations as defined by the Unified Parkinson's disease Rating Scale. We performed Kaplan–Meier survival and Cox regression analyses to assess cumulative incidence and risk factors of these motor complications. ResultsThe 5-year cumulative incidence of motor complications was 52.4%. Motor fluctuations occurred in 42.9% and dyskinesias in 24.3%. Besides higher motor severity predicting both motor fluctuations (p = 0.016) and dyskinesias (p < 0.001), lower age at diagnosis predicted motor fluctuations (p = 0.001), whereas female gender predicted dyskinesias (p = 0.001). Actual levodopa dose at onset of motor fluctuations (p = 0.037) or dyskinesias (p < 0.001) rather than initial treatment with levodopa (p > 0.1) independently predicted development of motor complications. Motor fluctuations reversed in 37% and dyskinesias in 49% of patients on oral treatment and remained generally mild in those with persistent complications. No patients received device-aided therapies during the study. ConclusionsMore than 50% in the general Parkinson's disease population develop motor complications within 5 years of diagnosis. However, they remain mild in the vast majority and are reversible in a substantial proportion of patients.

A 12-year population-based study of freezing of gait in Parkinson's disease.

Freezing of gait (FOG) is a potentially disabling motor problem in Parkinson's disease (PD) with uncertain etiology. Longitudinal studies of FOG in PD are scarce. We determined the prevalence, incidence, and associated clinical risk factors and concomitants of FOG during prospective long-term follow-up of a population-based PD cohort. A community-based prevalent cohort of 232 PD patients was followed prospectively over 12 years. Reassessments were conducted at 4 and 8 years, and then annually. FOG, as well as severity of parkinsonism, motor complications, and psychotic symptoms were assessed by the Unified PD Rating Scale, and cognitive impairment by the Mini-Mental State Examination. Generalized estimating equations were applied to investigate baseline risk factors and concomitants of FOG over time. The point prevalence of FOG at baseline was 27% (95% confidence interval (95%-CI) 22-33%). By study end, 63% (95%-CI 56-69%) of patients had developed FOG. The incidence rate of FOG was 124.2 (95%-CI 101.5-152.1) per 1000 person-years. Motor fluctuations (odds ratio (OR) 3.45; p = 0.036) and higher levodopa dose (OR 1.30/100 mg, p = 0.009) at baseline were independent risk factors of incident FOG. Prevalent FOG over time was additionally associated with features thought to reflect extrastrial, non-dopaminergic pathologies, including PIGD (postural instability/gait difficulty, OR 6.30/10 points, p < 0.001) and psychosis (OR 1.85; p = 0.016). These findings demonstrate that FOG affects the majority of patients in the general PD population and provide support to the hypothesis that alterations in both basal ganglia and extrastriatal brain areas are involved in the pathogenesis of FOG in PD.

Association between ubiquitin carboxy-terminal hydrolase-L1 S18Y variant and risk of Parkinson's disease: the impact of ethnicity and onset age.

The Ubiquitin carboxy-terminal hydrolase-L1 (UCHL1) is a candidate risk gene for Parkinson' disease (PD), and a function SNP (rs5030732) in the coding region of this gene has been studied for the association with the disease extensively among worldwide populations, but the results were inconsistent and controversial. Here, to estimate the association between UCHL1 S18Y polymorphism and risk of PD in general population, we conducted a systematic meta-analysis by combining all available case-control subjects in Asian, European, and American populations, with a total of 7742 PD cases and 8850 healthy controls, and the pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for UCHL1 S18Y polymorphism and PD were calculated using the Mantel-Haenszel method with a fixed- or random-effects model. Subgroup analysis was also performed in different onset age-matched groups. Among high-quality studies, UCHL1 S18Y polymorphism was moderately associated with the risk of PD (allele contrasts, OR = 1.063, 95% CI 1.008-1.122; p = 0.024; regressive genetic model, OR = 1.078, 95% CI 1.005-1.157; p = 0.035). When stratifying for ethnicity, none association were observed in subgroups. Analysis of early-onset PD (EOPD) and late-onset PD (LOPD) revealed that the polymorphism was not associated with the risk of PD. In conclusion, our meta-analysis suggests that UCHL1 S18Y polymorphism is moderately associated with susceptibility to PD, and more studies are needed to confirm our conclusion.

Dopamine dysregulation syndrome in Parkinson's disease: from clinical and neuropsychological characterisation to management and long-term outcome

ObjectiveDopamine dysregulation syndrome (DDS) refers to a compulsive pattern of dopaminergic drug misuse complicating Parkinson's disease (PD). To date, few data are available on DDS risk factors, cognitive profile and...

Lack of Short-Term Effectiveness of Rotating Treadmill Training on Turning in People with Mild-to-Moderate Parkinson's Disease and Healthy Older Adults: A Randomized, Controlled Study

Since turning is often impaired in Parkinson's disease (PD) and may lead to falls, it is important to develop targeted treatment strategies for turning. We determined the effects of rotating treadmill training on turning in individuals with PD. This randomized controlled study evaluated 180° in-place turns, functional turning (timed-up-and-go), and gait velocity before and after 15 minutes of rotating treadmill training or stepping in place in 26 people with PD and 27 age-matched controls. A subset of participants with PD (n = 3) completed five consecutive days of rotating treadmill training. Fast as possible gait velocity, timed-up-and-go time, 180° turn duration, and steps to turn 180° were impaired in PD compared to controls (P < 0.05) and did not improve following either intervention (P > 0.05). Preferred pace gait velocity and timing of yaw rotation onset of body segments (head, trunk, pelvis) during 180° turns were not different in PD (P > 0.05) and did not change following either intervention. No improvements in gait or turning occurred after five days of rotating treadmill training, compared to one day. The rotating treadmill is not recommended for short-term rehabilitation of impaired in-place turning in the general PD population.

Prevalence of hypersexual behavior in Parkinson&amp;rsquo;s disease patients: Not restricted to males and dopamine agonist use

This study investigates the prevalence and demographic characteristics of hypersexuality in Parkinson's disease (PD). Impulse control disorders in PD patients have been associated with dopamine agonist therapy. Moreover, hypersexuality and pathological gambling have been associated with males, while females may be inherently thought to be more likely to participate in compulsive shopping and binge-eating behaviors. In this study, a screening mail-in survey was sent to all PD patients at a single Movement Disorders Center. One hundred forty one of 400 (35.3%) research packets were returned completed. Fifteen of 141 patients met initial screening criteria for hypersexual behavior. After detailed interview, only 6/141 (4.3%) of PD patients met criteria for pathologic hypersexual behavior. These behaviors included: compulsive masturbation, prostitution, and paraphilias. Patients with a younger age of PD onset were more likely to exhibit hypersexual behavior. Unlike previous report, no significant association was found between hypersexuality and gender or dopamine agonist use. Rather, this study suggests that physicians should be vigilant for hypersexual behavior in all PD patients, regardless of gender and PD medication regimen. Ultimately, given the innate sensitivity of the topic and survey limitations, it is very likely that hypersexual behavior in our cohort, as it is in the general PD population, has been under-reported.

Prevalence and clinical correlates of apathy in Parkinson's disease: A community-based study

The objective of this study was to examine the prevalence and clinical correlates of apathy in a population-based sample of patients with Parkinson's disease (PD) and to assess whether apathy may present as a primary behavioural disturbance independent from depression and cognitive impairment. A total of 232 patients derived from an epidemiological study of PD in Rogaland county, Western Norway, completed a comprehensive evaluation of motor, cognitive, and depressive symptoms. Apathy was assessed with the motivation/initiative item of the Unified Parkinson's Disease Rating Scale. The majority of the population had mild to moderate PD with mean disease duration of 9.1 ± 5.7 years. Apathy was diagnosed in 38% of the 232 patients. In 11% of the total sample apathy coexisted with depression and dementia, whereas 10% had apathy and depression without dementia, 6.5% apathy and dementia without depression, and 9% were apathetic without dementia or depression (data missing in 1.5% patients). Apathy was significantly associated with higher depression scores, lower cognitive functioning, and more severe motor symptoms. When excluding patients with depression, dementia, cognitive impairment with no dementia (population-based age- and education-corrected norms for the Mini-Mental State Examination), and those using psychotropic medication, 5% of the 232 patients had apathy. In conclusion, our study shows that apathy is common in the general PD population, may present as an independent behavioural disorder, and suggests that apathy in PD may be related to dysfunction of the nigro-striatal pathway or that brain pathology underlying apathy and progression of motor symptoms develops in parallel.

Exploring the relationship between Parkinson's disease and hemifacial spasm

Case reports of co-existent Parkinson's disease (PD) and hemifacial spasm (HFS) suggest that there may be a relationship between these conditions. Three of 300 (1%) PD patients presented with HFS compared with 0/300 (0%) controls. The mean age of the three PD patients with HFS was 68.7 +/- 8.0 (60-76) years, with the majority having left-sided HFS. All three patients developed HFS symptoms at around the onset of PD and they were significantly older than the 100 patients with HFS alone (P < 0.05). Our study demonstrated no significant increased risk of HFS amongst the general PD population and hence HFS symptoms are unlikely to be of clinical importance for most PD patients.

Young‐onset Parkinson's disease revisited—clinical features, natural history, and mortality

The authors report on clinical features and mortality rates in a group of 149 patients with apparent idiopathic parkinsonism starting before the age of 40 years. Ten had juvenile parkinsonism (JP; onset before age 21 years) and 139 had young-onset Parkinson's disease (YOPD; onset at age 21 to 40 years). Included were 60 patients originally reported 10 years ago. Fifty percent of the JP group had a positive family history of parkinsonism in a first-degree relative, and clinical presentation was heterogeneous. Mortality risk was threefold that of the normal population. In the YOPD group, the mortality risk was double that of the normal population. Poor initial response to L-dopa was a risk factor for early death. In two previously reported patients, the diagnosis had been changed to multiple system atrophy and Machado-Joseph disease. After a median disease duration of 18 years, cognitive impairment was found in only 19% of YOPD patients (13% of those younger than 60 years and 43% of those 60 years or older). Age was the most important factor for development of dementia, but female sex and positive family history of parkinsonism also had more modest predictive value. After a disease duration of 10 years or less, only 5% of patients were experiencing falls and 30% freezing, but all patients had developed L-dopa-related fluctuations and dyskinesias. The authors conclude that the mortality rate in parkinsonism starting before the age of 40 is increased in comparison to the normal population and is similar to the general Parkinson's disease population. Intellectual function and postural reflexes are usually well preserved for many years despite a long history of parkinsonism and the early and frequent occurrence of treatment complications, provided the patients remain biologically and chronologically young.