Differentiating drug-induced parkinsonism from Parkinson's disease: An update on non-motor symptoms and investigations

Drug-induced parkinsonism is the second most common cause of parkinsonism after Parkinson's disease and their distinction has crucial implications in terms of management and prognosis. However, differentiating between these conditions can be challenging on a clinical ground, especially in the early stages. We therefore performed a review to ascertain whether assessment of non-motor symptoms, or use of ancillary investigations, namely dopamine transporter imaging, transcranial sonography of the substantia nigra, and scintigraphy for myocardial sympathetic innervation, can be recommended to distinguish between these conditions.Among non-motor symptoms, there is evidence that hyposmia can differentiate between patients with “pure” drug-induced parkinsonism and those with degenerative parkinsonism unmasked by an anti-dopaminergic drug. However, several issues, including smoking history and cognitive functions, can influence smell function assessment. Higher diagnostic accuracy has been demonstrated for dopamine transporter imaging. Finally, preliminary evidence exists for sympathetic cardiac scintigraphy to predict dopaminergic pathway abnormalities and to differentiate between drug-induced parkinsonism and Parkinson's disease.Imaging of the dopaminergic pathway seems to be the only, reasonably available, technique to aid the differential diagnosis between drug-induced parkinsonism and Parkinson's disease.     

Characterizing motor and non-motor aspects of early-morning off periods in Parkinson's disease: An international multicenter study

IntroductionThe characteristic off periods that develop over time in subjects with Parkinson's disease (PD) on chronic levodopa therapy are usually considered to be motor complications but more recently the important contribution of non-motor off and non-motor fluctuations has also been acknowledged. Early-morning off (EMO) periods in PD patients are known to be a cause of significant disability, in addition to having a negative impact on quality of life. Yet EMOs are poorly defined, particularly in relation to non-motor symptoms (NMS).MethodsThis European, multicentre, observational study was undertaken to characterize the range and patterns of NMS that occur during EMO periods in a consecutive series of PD patients.ResultsThe results demonstrate that EMO periods are common and occur in 59.7% of subjects across all disease stages in line with other reports. However, importantly, in 88.0% of those, EMOs were found to be associated with NMS. The predominant NMS associated with EMO were urinary urgency, anxiety, dribbling of saliva, pain, low mood, limb paresthesia and dizziness. The patterns of dopaminergic treatment being taken by patients in this study suggested that a prolonged-release or continuous drug delivery strategy can alleviate some NMS associated with EMO.ConclusionsIn light of these findings it is suggested that greater awareness, recognition and appropriate treatment of EMO and NMS could improve the overall 24-h management of PD. An EMO-specific scale/questionnaire which captures both motor and NMS associated with EMO over the off time period is warranted.     

Validation of a non-motor fluctuations questionnaire in Parkinson's disease

IntroductionNon-motor fluctuations (NMF) in Parkinson's disease (PD) remain poorly recognized but have a high impact on patients’ quality of life. The lack of assessment tools limits our understanding of NMF, compromising appropriate management. Our objective was to validate a hetero-questionnaire for NMF in PD patients at different stages of the disease: without treatment, without motor fluctuations, with motor fluctuations.MethodsWe included patients in 15 centers in France. Our questionnaire, NMF-Park, resulted from previous studies, allowing us to identify the more pertinent NMF for evaluation. Patients reported the presence (yes or no) of 22 selected NMF, and their link with dopaminergic medications. The assessment was repeated at one and two years to study the progression of NMF. We performed a metrological validation of our questionnaire.ResultsWe included 255 patients (42 without treatment, 88 without motor fluctuations and 125 with motor fluctuations). After metrological validation, three dimensions of NMF were found: dysautonomic; cognitive; psychiatric. The sensory/pain dimension described in the literature was not statistically confirmed by our study.DiscussionOur questionnaire was validated according to clinimetric standards, for different stages of PD. It was clinically coherent with three homogeneous dimensions. It highlighted a link between fatigue, visual accommodation disorder, and cognitive fluctuations; and the integration of sensory/pain fluctuations as part of dysautonomic fluctuations. It focused exclusively on NMF, which is interesting considering the described differences between non-motor and motor fluctuations.ConclusionOur study validated a hetero-questionnaire of diagnosis for NMF for different stages of PD.     

The association between non-motor symptoms in Parkinson's disease and age at onset

Objective

Age at onset is likely to be related to a wide range of problems in Parkinson's disease (PD), including cardinal motor features, motor complications and non-motor symptoms (NMS). This study investigated the effect of the age at onset on NMS.

Methods

Two hundred and thirty patients were examined and classified into one of three groups based on age at onset: early onset PD (EOPD) group (<45 years), middle-age onset group (45–64 years) and old-age onset group (≥65 years). The trends relating to NMS were compared across the three groups. The EOPD and old-age onset groups were separately studied to determine their association to the appearance of non-motor features using logistic regression analysis.

Results

There were upward trends in the occurrence of dribbling (P = 0.009; all P values are stated for trend), impaired taste/smelling (P = 0.016), constipation (P = 0.006), urinary urgency (P = 0.002), nocturia (P = 0.018), hallucinations (P = 0.016) and acting out during dreams (P = 0.011) with the increase of age at onset. Older age at onset is an independent risk factor for dementia (OR = 8.42, CI 3.16–22.44), dribbling (OR = 4.14, CI 1.93–8.87), impaired taste/smelling (OR = 2.23, CI 1.20–4.13), constipation (OR = 3.42, CI 1.88–6.24), incomplete bowel emptying (OR = 2.23, CI 1.19–4.20), urinary urgency (OR = 2.58 CI 1.46–4.57), nocturia (OR = 2.65, CI 1.49–4.71), hallucinations (OR = 5.32, CI 1.78–15.97), dizziness (OR = 3.03, CI 1.59–5.79), falling (OR = 3.60, CI 1.67–7.77), insomnia (OR = 2.29, CI 1.28–4.11), intense vivid dreaming (OR = 2.10, CI 1.21–3.66) and acting out during dreams (OR = 2.23, CI 1.24–4.01).

Conclusions

PD patients with different ages at onset present clinically different symptoms in terms of NMS. Old-age onset PD is characterized by more olfactory and sensory symptoms, autonomic symptoms, sleep disorders, dementia and psychosis compared to EOPD.     

Rotigotine and specific non-motor symptoms of Parkinson's disease: Post hoc analysis of RECOVER

BackgroundNon-motor symptoms of Parkinson's disease (PD) represent major causes of morbidity. RECOVER, a randomized controlled trial of rotigotine transdermal system, was the first prospective controlled trial to use the Non-Motor Symptoms Scale (NMSS) as an exploratory outcome for assessment of treatment effects on non-motor symptoms in PD. Rotigotine improved NMSS total score compared with placebo, and the “Sleep/fatigue” and “Mood/apathy” domains. This post hoc analysis further characterizes the effects of rotigotine on sleep/fatigue and mood/apathy.MethodsPatients with PD and unsatisfactory early-morning motor impairment were randomized to transdermal patches of rotigotine (2–16 mg/24 h) or placebo. Treatment was titrated to optimal dose over 1–8 weeks, maintained for 4 weeks. The NMSS was assessed at baseline and end of treatment. Post hoc analyses are presented for individual items of the “Sleep/fatigue” and “Mood/apathy” domains. The interpretation of p-values is considered exploratory in nature.ResultsOf 287 patients randomized, NMSS data were available for 267 patients (178 rotigotine, 89 placebo). Within the “Sleep/fatigue” domain there was a significant difference, in favor of rotigotine, in change from baseline score in 1 of 5 items: “fatigue (tiredness) or lack of energy” (ANCOVA, p < 0.0001). Within the “Mood/apathy” domain, there were significant differences in favor of rotigotine in 4 of 7 items: “lost interest in surroundings” (p < 0.0001), “lost interest in doing things” (p < 0.0001), “seems sad or depressed” (p < 0.01), and “difficulty experiencing pleasure” (p < 0.05).ConclusionsRotigotine transdermal system may improve non-motor symptoms such as fatigue, symptoms of depression, anhedonia, and apathy in patients with PD; further prospective controlled studies are required to confirm this post hoc analysis.     

Response of non-motor symptoms to levodopa in late-stage Parkinson's disease: Results of a levodopa challenge test

BackgroundNon-motor symptoms (NMS) are extremely common among late-stage Parkinson's disease (LSPD) patients. Levodopa (L-dopa) responsiveness seems to decrease with disease progression but its effect on NMS in LSPD still needs to be investigated.ObjectiveTo assess the response of blood pressure (BP), pain, fatigue and anxiety to L-dopa in LSPD patients.Methods20 LSPD patients, defined as Schwab and England ADL Scale <50 or Hoehn Yahr Stage >3 (MED ON) and 22 PD patients treated with subthalamic deep brain stimulation (advanced PD group) underwent an L-dopa challenge. BP and orthostatic hypotension (OH) assessment, a visual analogue scale (VAS) for pain and fatigue and the Strait Trait Anxiety (STAI) were evaluated before and after the L-dopa challenge.ResultsSystolic BP dropped significantly after L-dopa intake (p < 0.05) in LSPD patients, while there was no change in pain, fatigue or anxiety. L-dopa significantly improved (p < 0.05) pain and anxiety in the advanced PD group, whereas it had no effect on BP or fatigue. L-dopa-related adverse effects (AEs), namely OH and sleepiness, were more common among LSPD patients. 40% and 65% of LSPD patients were not able to fill out the VAS and the STAI, respectively, while measurement of orthostatic BP was not possible in four LSPD patients.ConclusionsThis exploratory study concludes that some non-motor variables in LSPD do not benefit from the acute action of L-dopa while it can still induce disabling AEs. There is a need for assessment tools of NMS adapted to these disabled LSPD patients.     

Relationship between sleep disorders and other non-motor symptoms in Parkinson's disease

BackgroundThe association between sleep disorders and other non-motor symptoms (NMS) in Parkinson's disease (PD) has been scarcely investigated.ObjectiveTo describe the prevalence of insomnia and hypersomnia in PD and analyze their relationship with other NMS.MethodsCross-sectional, multicenter study including 388 PD patients evaluated with Hoehn and Yahr, Clinical Impression of Severity Index for PD, Scales for Outcomes in Parkinson's Disease (SCOPA)-Sleep(S), SCOPA-Cognition, SCOPA-Psychiatric Complications, SCOPA-Autonomic, Hospital Anxiety and Depression Scale, and fatigue and pain visual analogue scales. Spearman correlation coefficients, Mann–Whitney test and multiple linear regression analysis were applied.ResultsMean age (54% male) was 65.9 ± 11.2 years old, with disease duration of 8.1 ± 6.0 years and median HY = 2 (range: 1–5). Mean SCOPA-S nocturnal sleep (NS) was 5.4 ± 4.0 (range: 0–15), daytime sleepiness (DS) was 3.76 ± 3.04 (range: 0–15). Most of the sample declared nocturnal or daytime sleep problems (87.4%). Weak-to-moderate correlations were found between sleep disturbances and other NMS (range: 0.14–0.37). SCOPA-S subscales showed higher scores with the presence of most other NMS such as psychiatric complications and autonomic dysfunctions (p < 0.05). Regression models showed that fatigue, depression, urinary, cardiovascular, and thermoregulatory dysfunctions were significant determinants of SCOPA-NS score (variance: 23%); cognitive impairment, urinary, cardiovascular, and pupillomotor disorders influenced SCOPA-DS score (variance: 14%).ConclusionsInsomnia and daytime sleepiness are extremely prevalent in PD. Depression, fatigue, cognitive impairment, cardiovascular, urinary and thermoregulatory dysfunctions may contribute to insomnia/hypersomnia. This is the first clinical study to relate cardiovascular and thermoregulatory dysfunctions with sleep in PD.     

The impact of non-motor symptoms on the Health-Related Quality of Life of Parkinson's disease patients from Southwest China

BackgroundThe impact of non-motor symptoms (NMS) on the Health-Related Quality of Life (HRQoL) of patients with Parkinson's disease (PD) in the Chinese population are largely unknown.ObjectivesTo study the impact of NMS on the HRQoL in Chinese PD patients.MethodsA total of 693 PD patients from Southwest China were included in the study. NMS of patients were evaluated by non-motor symptoms scale (NMSS) and Parkinson's disease questionnaire-39 item version (PDQ-39) was used to evaluate the HRQoL of PD.ResultsThe mean total score of NMSS was 37.2 ± 33.0 and the most prevalent NMS domain was sleep/fatigue (79.8%). There was a significant strong positive correlation between total NMSS score (r_s = 0.71, P < 0.01), sleep/fatigue domain (r_s = 0.60, P < 0.01) and PDQ-39 SI. Mood/apathy (r_s = 0.55, P < 0.01), attention/memory (r_s = 0.42, P < 0.01), gastrointestinal (r_s = 0.44, P < 0.01) and Miscellany domains (r_s = 0.46, P < 0.01) moderately correlated with PDQ-39 SI. A strong correlation was found between PDQ-39 SI (r_s = 0.71, P < 0.01), emotional well-being (r_s = 0.62, P < 0.01), cognitions (r_s = 0.62, P < 0.01), and the total score of NMSS. Moderate correlation was found between mobility (r_s = 0.45, P < 0.01), activities of daily living (r_s = 0.43, P < 0.01), stigma (r_s = 0.42, P < 0.01), communication (r_s = 0.47, P < 0.01), bodily discomfort (r_s = 0.46, P < 0.01) and the total score of NMSS. Female, H–Y stage, UPDRS-III and NMSS total score were the potential determinants of worse HRQoL of PD patients.ConclusionsNMS have close association with various aspects of the HRQoL. Severe NMS may be related to dramatic decline of the HRQoL of PD patients.     

Comparison of sleep and other non-motor symptoms between SWEDDs patients and de novo Parkinson's disease patients

BackgroundSWEDDs (Scans Without Evidence of Dopaminergic Deficits) was defined from a series of pharmaceutical trials on Parkinson's disease (PD). Non-motor features including sleep-related problems are common even in early-stage PD patients; however, little is known about the burden of the non-motor symptoms in SWEDDs patients.MethodsThe Non-motor Symptoms Assessment Scale (NMSS), revised version of the Parkinson's Disease Sleep Scale (PDSS-2), Epworth Sleepiness Scale (ESS), and EuroQol 5-Dimension (EQ-5D) were applied to evaluate 17 SWEDDs patients and 28 de novo PD patients. The presence of clinically probable rapid eye movement sleep behavior disorder (cpRBD) was assessed using the International Classification of Sleep Disorders-Revised (ICSD-R) criteria.ResultsThe total NMSS score for the SWEDDs group was significantly lower than for the de novo PD group (p = 0.032). The most distinct difference was in taste or smell change (p < 0.000). Prevalence of cpRBD was higher in de novo PD patients than in SWEDDs patients (p = 0.030), though no significant differences in the PDSS-2 total score (p = 0.496) or the ESS score (p = 0.517) were found. The SWEDDs patients did not significantly differ from the de novo PD patients with regard to quality of life, as measured by the EQ-5D index score (p = 0.177).ConclusionsThe patients with SWEDDs have less non-motor problems than newly diagnosed untreated PD patients. Given the difficulty distinguishing between SWEDDs and early PD, identifying some of non-motor symptoms, such as RBD or olfactory impairment, could aid clinicians in their work.     

Subcutaneous apomorphine and non-motor symptoms in Parkinson's disease

Non-motor symptoms (NMS) are now recognized to occur across all stages of Parkinson's disease (PD) and as a result there has been an increasing focus on their diagnosis, quantification and effective management. While in some subjects, NMS may be present before diagnosis, in advanced PD, NMS can contribute to hospitalization, severe disability and a shortened life expectancy. Strategies for continuous drug delivery have been reported to have a beneficial effect on NMS in PD and while the efficacy of apomorphine on motor function in PD has been confirmed in a number of studies, in addition to its possible anti-dyskinetic effect, a number of reports have also outlined the possible beneficial effect of apomorphine on NMS. This review sets out to examine the efficacy of apomorphine in non-motor aspects of PD, including its effect on neuropsychiatric and gastrointestinal symptoms, sleep (including restless legs syndrome), urinary dysfunction, pain and impulse control disorders. The analysis takes into consideration case reports, and open-label and comparative case–control studies published to date. Results of this review suggest that although data on the effect of apomorphine on NMS in PD patients are limited there is a strong suggestion of a beneficial effect that warrants further investigation in double-blind studies.     

Association between nocturia and anxiety in Parkinson's disease

Abstract

Objective:

The objective of the study was to determine whether there exists any relationship between nocturia and anxiety in patients with Parkinson's disease (PD). Although the exact cause of anxiety and nocturia in PD is unknown, we hypothesized that there is a relationship between these two PD symptoms. Anxiety may exacerbate nocturia or an opposite relationship may be present in which nocturia may result in heightened levels of anxiety.

Methods:

Our study consisted of 314 PD patients, selected at random, and divided into groups based on the presence or absence of anxiety and nocturia. The occurrence of anxiety and nocturia was studied individually and collectively within these groups.

Results:

The study found a significant association between anxiety and nocturia primarily driven by all PD patients (P?<?0.0001), with greater significance found for the male patients (P?<?0.0001) than female patients (P?=?0.021).

Discussion:

Based on these findings, we can conclude that anxiety and nocturia are not entirely independent symptoms in all PD patients. Thus, addressing anxiety may improve nocturia in PD or vice versa.     

Long-term effect of bilateral STN-DBS on non-motor symptoms in Parkinson's disease: A four-year observational,prospective study

BackgroundSeveral studies have shown beneficial effects of bilateral stimulation of the subthalamic nucleus (STN-DBS) on motor as well as on non-motor symptoms (NMS) up to 36 months post-surgery in advanced Parkinson's disease (PD) patients. We set to explore the long-term effect of STN-DBS on NMS in a four-year follow-up, prospective, observational study.MethodsForty patients were enrolled and assessed at baseline. Twenty-eight were followed-up at 6, 12, 24, 36 and 48 months after the operation. The effect of post-operative time on NMS was analyzed by six-level repeated measures ANOVA. In a post-hoc analysis the follow-up scores were compared to baseline using a paired t-test.ResultsThe following scores stayed improved up to 24 months after surgery, presented as baseline/24 months, p-value (t-test): total Non-Motor Symptoms Scale score (54.0 ± 5.6/44.9 ± 5.0, p = 0.029), Hamilton Anxiety Scale (14.3 ± 1.3/11.3 ± 1.2, p = 0.019) and PDQ39 (53.4 ± 4.5/40.2 ± 2.9, p = 0.012). PD Sleep Scale 2 remained improved throughout the study (17.4 ± 2.0/12.8 ± 1.3 at 48 months, p = 0.032), while Beck Depression Inventory only at six months post-surgery (9.5 ± 1.2/6.7 ± 0.7 at 6 months, p = 0.006). Montreal Cognitive Assessment remained stable up to 24 months and then declined at 36 months (26.3 ± 0.5/25.4 ± 0.5 at 36 months, p = 0.003), Starkstein Apathy Scale deteriorated throughout the study (7.6 ± 0.7/12.7 ± 0.9 at 48 months, p = 0.006).ConclusionsWe observed beneficial effect of STN-DBS in several but not all domains of NMS at least up to 24 months post-op in advanced PD. Further long-term studies on larger cohorts of PD patients and longer follow-up need to be conducted to better understand the long-term effect of STN-DBS on NMS.     

Survival in Parkinson's disease. Relation with motor and non-motor features

BackgroundSurvival in patients with Parkinson's disease is reduced as compared to the general population. We aimed to identify motor and non-motor features that predict mortality in Parkinson's disease.MethodsA broad range of motor and non-motor features were assessed in a hospital-based cohort of 414 patients with Parkinson's disease, who underwent five annual follow-up examinations including vital status assessment. Multivariable Cox's proportional hazards regression analysis was used to evaluate the association between baseline characteristics and mortality risk. Stepwise regression with backward elimination was carried out to determine the best model to predict mortality in Parkinson's disease.ResultsAfter a mean follow-up period of 4.3 years, 49 (11.8%) patients had died. In the stepwise regression model, predictors of mortality in Parkinson's disease were higher age, male sex, cognitive impairment, higher postural instability gait disorder score, and the presence of psychotic symptoms.ConclusionsHigher age, male sex, cognitive impairment, higher postural instability gait disorder score, and the presence of psychotic symptoms are independent predictors of decreased survival in Parkinson's disease. Mortality in Parkinson's disease thus seems to be affected mainly by non-dopaminergic and non-motor features.     

Influence of istradefylline on non-motor symptoms of Parkinson's disease: A subanalysis of a 1-year observational study in Japan (J-FIRST)

IntroductionThe non-motor symptoms (NMSs) of Parkinson's disease (PD) significantly impact the patient's health-related quality of life. This subanalysis of the J-FIRST study evaluated the effect of istradefylline, a selective adenosine A_2A receptor antagonist, on NMSs in istradefylline-naïve Japanese patients with PD.MethodsPatients with PD and ≥1 NMS and ‘wearing-off’ with their current antiparkinsonian treatment were observed for up to 52 weeks. The effect of istradefylline on NMSs was measured in terms of changes in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part 1 total, individual sub-items scores and the 8 item PD questionnaire (PDQ-8) estimated by the marginal structural model.ResultsOverall, 732 patients were istradefylline-naïve prior to the study, of whom 171 were treated with istradefylline for ≥8 weeks during the observation period (istradefylline-treated patients). At baseline, istradefylline-treated patients were more likely to have a dyskinesia (49.7% vs 40.8%) and received a significantly higher daily dose of levodopa (462.8 mg vs 413.0 mg) than those who did not receive istradefylline (n = 561). MDS-UPDRS Part 1 total score at the end of the 52-week observational period slightly increased in patients who received istradefylline and those who did not (0.49 ± 0.41 vs 0.07 ± 0.20; P = 0.36). There were no statistically significant differences between the two groups of patients in terms of changes in the MDS-UPDRS Part 1 total score or any sub-items, or in the PDQ-8 total score.ConclusionNMSs remained generally controlled in istradefylline-treated Japanese patients with PD who exhibited wearing-off with their current antiparkinsonian treatment. Istradefylline could be a feasible treatment option for patients with advanced PD, without worsening existing NMSs.     

早期初诊帕金森病患者非运动症状的临床特征及影响因素分析

目的探讨早期帕金森病(PD)患者非运动症状(NMS)的临床特征及影响因素。方法收集门诊首次就诊且发病在1a内的早期PD患者105例和健康对照者100例,采用帕金森病非运动症状调查问卷(NMSQuest)进行NMS评估,结合临床特征等因素分析非运动症状发生的主要影响因素。结果 PD组NMS评分显著高于对照组(P0.05),发生率较高的症状依次为便秘(58例,55.2%)、记忆力下降(51例,48.6%)、情绪低落(43例,40.9%)。回归分析显示,H-Y分级、年龄及PD临床亚型是NMS评分的主要影响因素(P0.05),性别、文化程度、病程则与其无关。结论 NMS在早期PD患者中较常见且临床表现多样,需提高认识并及时干预。     

MIBG myocardial scintigraphy in pre-motor Parkinson's disease: A review

ObjectivesDetecting very early markers of neurodegeneration that predate the diagnosis of idiopathic Parkinson's disease (PD) is a crucial research topic for the development of disease-modifying therapeutic interventions. Recently ¹²³I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy has become widely used for this purpose, since this test shows high sensitivity and specificity in the diagnosis of PD, based on evidence that cardiac sympathetic nerve fibers are affected early and commonly in PD. We reviewed the literature to determine the role of MIBG myocardial scintigraphy for diagnosing pre-motor PD.MethodsWe performed a systematic review of the literature to identify the use of MIBG myocardial scintigraphy in relation to the constellation of pre-motor symptoms in PD.ResultsMild memory disorder, autonomic failure (constipation and postural hypotension), depression/anxiety, visual hallucination/psychosis (in the elderly), sleep disorder (REM sleep behavior disorder), and impaired olfaction are reported to appear as sole initial symptoms of PD. All clinical features except for impaired olfaction are accompanied by low MIBG uptake, suggestive of very early PD in situ.ConclusionIdentifying persons with mild memory disorder, constipation/postural hypotension, depression/anxiety, visual hallucination/psychosis (in the elderly), and REM sleep behavior disorder associated with low MIBG uptake may provide a unique opportunity to detect very early PD in situ within a pre-clinical window. Future prospective studies to investigate further the findings of these early cases are warranted.     

Nonmotor features of Parkinson's disease subtypes

Parkinson's disease is highly heterogeneous in early clinical features and later outcomes. This makes classifying subgroups of PD relevant to clinical research and practice, particularly if they are prognostically relevant. Subgroups have been defined both on the basis of motor and nonmotor features, and subgroups have been determined either empirically, based on clinical observation, or using data‐driven analytic techniques. Previous studies have examined both the overall number and the nature of nonmotor symptoms and signs in tremor‐dominant compared with non‐tremor‐dominant subtypes, and longitudinal studies identify nonmotor symptoms as important markers of prognosis and important defining features of PD subtypes. Autonomic features seem to preferentially affect individuals with non‐tremor‐dominant PD subtype early in the disease. Later in the disease cognitive disturbance distinguishes this phenotype. Pathological and neuroimaging studies provide substantial evidence for fundamental biological differences between tremor‐dominant and postural instability gait disorder/akinetic‐rigid subtypes. Biomarker studies point toward non‐tremor‐dominant PD as representing more advanced and diffuse neurodegeneration than tremor‐dominant PD, encompassing dopaminergic and nondopaminergic as well as synuclein and nonsynuclein (Abeta) pathologies. This aligns with clinical studies that find a higher burden of nonmotor symptoms in non‐tremor‐dominant PD. The mounting evidence for the relevance of nonmotor features in PD subtypes behooves us to begin to investigate the biological underpinnings of subtypes defined by both motor and nonmotor features. This may be challenging, as PD subtypes are unlikely to be distinct nonoverlapping entities but are more likely to represent typical phenotypes within a multidimensional spectrum resulting from variable contributions of a number of simultaneous pathological processes. © 2016 International Parkinson and Movement Disorder Society     

Parkinsonism and Parkinson's disease in the elderly: a community-based survey in Brazil (the Bambuí study).

Several community-based surveys on the prevalence of Parkinsonism and Parkinson's disease have been conducted worldwide, with variations on their methodology and results. The objective of this study is to assess the prevalence of Parkinsonism and its causes in a cohort of individuals age 64 years or older in Bambuí, a Brazilian town. In phase I, 1,186 people older than 64 years responded to a 9-question screening questionnaire for Parkinsonism. In phase II, all subjects who scored > or = 2 points on the test were examined independently by at least 2 movement disorder-trained physicians. A movement disorder senior specialist excluded or confirmed the diagnosis in all suspected cases. The response rate was high for both phases (96% for phase I and 94% for phase II). The prevalence rate per 100 population over 64 years of age in this group was 7.2% for Parkinsonism of all types (n = 86). The most frequent causes were idiopathic Parkinson's disease and drug-induced Parkinsonism, with prevalence rates of 3.3% (n = 39) and 2.7% (n = 32), respectively. The prevalence of vascular Parkinsonism was 1.1% (n = 13). We found 1 case of posttraumatic Parkinsonism and another with multiple system atrophy. In this first population-based study of Parkinsonism conducted in Brazil, the prevalence in a cohort of elderly subjects was higher than the observed in other populations worldwide, especially because of the high rates of drug-induced and vascular Parkinsonism. The prevalence of Parkinson's disease was similar to that observed in elderly people in door-to-door surveys in other American, European, and Eastern countries.     

Reasons driving treatment modification in Parkinson's disease: Results from the cross-sectional phase of the REASON study

ObjectivesTo assess the association between clinical and socio-demographic features and anti-Parkinson drug (APD) treatment modifications in patients with PD and to describe neurologist and patient opinions regarding the need for changes in APD therapy.MethodsSubjects with PD with stable APD treatment over ≥3 months prior to baseline were enrolled and evaluated for socio-demographic data, disability, disease severity and neurologist and patient views on the need to modify APD treatment.Results775 Patients were included, 51% with Hoehn and Yahr (HY) stage 1–2 (early PD) and 49% with HY stage 2.5–4 (advanced PD). Neurologists modified APD treatment in 255 patients, 97 (25%) early PD and 158 (41%; p < 0.0001) advanced PD. APD modification was strongly associated with a low educational level and UPDRS part IV score. The most common reasons behind the APD therapy changes among neurologists were presence/worsening of motor or non-motor symptoms (88% and 37% of subjects respectively). Out of 216 patients, 92% and 51% were willing to undergo APD changes to therapy because of the presence/worsening of motor or non-motor symptoms.ConclusionsNeurologist decision to change APD therapy and patients reasons for dissatisfaction with it can be prevalently attributed to the presence/worsening of motor symptoms and motor fluctuations in the advanced stages. Non-motor symptoms were considered more often by patients. The patient educational level played a key role in treatment decision.