Nonmotor symptoms are independently associated with impaired health‐related quality of life in Chinese patients with Parkinson's disease

We performed a cross‐sectional study of 82 Chinese patients with Parkinson's disease (PD) enrolled during an 18‐month period using a clinical interview to assess the prevalence of nonmotor symptoms (NMS), the association with disease severity and motor status, and the impact on patients' health‐related quality of life (Hr‐QoL). The patients' NMS, Hr‐QoL, disease severity, and motor status were assessed by the Nonmotor Symptoms Scale (NMSS), the 39‐item Parkinson's Disease Questionnaire (PDQ‐39), the modified Hoehn and Yahr staging scale (H&Y) and the Unified Parkinson's Disease Rating Scale part III (UPDRS III), respectively. We found that 100% of patients with PD presented with NMS. The NMSS significantly correlated with disease duration (Spearman's r_S = 0.276, P = 0.012), H&Y (r_S = 0.230, P = 0.038), and UPDRS III (r_S = 0.350, P = 0.001). Similarly, the PDQ‐39 SI significantly associated with the disease duration (r_S = 0.258, P = 0.019), H&Y (r_S = 0.340, P = 0.002), and UPDRS III (r_S = 0.453, P < 0.001). NMS domains that influenced the PDQ‐39 SI were sleep/fatigue, mood, gastrointestinal, urinary, and miscellaneous symptoms. This strongly suggested that the five domains played a key role in the manifestation of Hr‐QoL. NMSS explains more of the variability in Hr‐QoL than UPDRS III, when both are the model (stepwise multiple linear regression analysis R² change, 47.8% vs. 5.87%, respectively). Therefore, these findings demonstrate that NMS are independently and negatively associated with Hr‐QoL in PD and that improving NMS should be viewed as an important part in the management of PD. © 2010 Movement Disorder Society     

Delineating nonmotor symptoms in early Parkinson's disease and first‐degree relatives

Nonmotor symptoms (NMS) are an important prodromal feature of Parkinson's disease (PD). However, their frequency, treatment rates, and impact on health‐related quality of life (HRQoL) in the early motor phase is unclear. Rates of NMS in enriched at‐risk populations, such as first‐degree PD relatives, have not been delineated. We assessed NMS in an early cohort of PD, first‐degree PD relatives and control subjects to address these questions. In total, 769 population‐ascertained PD subjects within 3.5 years of diagnosis, 98 first‐degree PD relatives, and 287 control subjects were assessed at baseline across the following NMS domains: (1) neuropsychiatric; (2) gastrointestinal; (3) sleep; (4) sensory; (5) autonomic; and (6) sexual. NMS were much more common in PD, compared to control subjects. More than half of the PD cases had hyposmia, pain, fatigue, sleep disturbance, or urinary dysfunction. NMS were more frequent in those with the postural instability gait difficulty phenotype, compared to the tremor dominant (mean total number of NMS 7.8 vs. 6.2; P < 0.001). PD cases had worse HRQoL scores than controls (odds ratio: 4.1; P < 0.001), with depression, anxiety, and pain being stronger drivers than motor scores. NMS were rarely treated in routine clinical practice. First‐degree PD relatives did not significantly differ in NMS, compared to controls, in this baseline study. NMS are common in early PD and more common in those with postural instability gait difficulty phenotype or on treatment. Despite their major impact on quality of life, NMS are usually under‐recognized and untreated. © 2015 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.     

Health‐related quality of life in early Parkinson's disease: The impact of nonmotor symptoms

Nonmotor symptoms (NMS) are common in patients with established Parkinson's disease (PD) and have a major impact upon quality of life. We investigated the significance of NMS in relation to health‐related quality of life (HRQoL) in patients with newly diagnosed PD. Patients and healthy controls were recruited as part of the Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation in Parkinson's Disease Study. Prevalence of NMS was determined with the Non‐Motor Symptom Questionnaire. HRQoL was recorded with the 39‐item Parkinson's Disease Quality of Life Questionnaire (PDQ‐39). Further assessments included measures of motor disability, depression, sleep, and cognition. One hundred and fifty‐eight patients with newly diagnosed PD and 99 controls participated in this cross‐sectional study. Patients reported greater numbers of NMS than controls (mean 8.3 ± 4.3 versus 2.8 ± 2.5 symptoms; P < 0.001). Patients reported lowest HRQoL in the domains assessing bodily discomfort, mobility, and activities of daily living. Motor and nonmotor symptoms impacted negatively upon HRQoL scores. Patients with the postural instability and gait difficulty motor subtype reported worse HRQoL, compared with those with tremor‐dominant disease. Depression (P < 0.001), incomplete bowel emptying (P < 0.001), anxiety (P < 0.001), impaired concentration (P < 0.001), memory complaints (P < 0.001), and insomnia (P = 0.001) had the greatest negative impact upon HRQoL. NMS are common in patients with early PD and represent a significant cause of poorer health‐related quality of life. Cognitive, neuropsychiatric, and sleep disturbances are particularly associated with reduced well‐being. Screening and management of these symptoms should be prioritized at the time of diagnosis. © 2013 International Parkinson and Movement Disorder Society     

Motor laterality asymmetry and nonmotor symptoms in Parkinson's disease

Background: In patients with Parkinson's disease (PD), asymmetric motor signs provide an interesting model to evaluate whether asymmetric nigrostriatal degeneration can affect neuropsychological function and other nonmotor symptoms (NMS). This study was designed to evaluate the predominant laterality of motor symptoms and its relationship with cognition and other NMS in idiopathic PD. Methods: Nationwide, longitudinal, and multicenter study (ELEP Registry) using outpatients with PD. Left PD (LPD) and right PD (RPD) was defined based on the motor signs on the SCOPA‐motor scale. To include the clinical spectrum of asymmetric PD patients, we considered two groups of patients with mild‐moderate and extreme asymmetry. Predominant LPD or RPD with mild‐moderate versus extreme asymmetry were compared using the following scales: cognition, psychosis (Parkinson Psychosis Rating Scale), anxiety/depression, sleep (and autonomic dysfunction at baseline and 1 year later. Nonparametric tests were used for comparison. Results: One hundred forty‐nine PD patients (74 RPD and 75 LPD) with mild‐moderate asymmetry and 90 (47 RPD and 43 LPD) with extreme asymmetry and a mean age of 64.5 (10.4) years were included. Extreme RPD had higher Parkinson Psychosis Rating Scale scores over time (P = 0.005) compared with LPD, but no significant differences were observed between LPD and RPD in terms of other NMS. Conclusions: These findings suggest that damage to left‐hemisphere plays a disproportionately greater role in PD‐related psychosis over time. In contrast, motor laterality does not consistently affect other NMS, suggesting that NMS are related to a more widespread brain disorder. © 2009 Movement Disorder Society     

What are the most important nonmotor symptoms in patients with Parkinson's disease and are we missing them?

Nonmotor symptoms (NMS) are increasingly recognized as important and neglected aspects of Parkinson's disease (PD). We evaluated their relative frequency and comparative impact on health‐related quality of life (Hr‐QoL) using validated questionnaires. In addition, we assessed the rate of reporting of NMS in neurology clinics compared with their subjective impact on patients. We used a range of validated clinimetric scales of motor and nonmotor symptoms and Hr‐QoL to assess consecutive patients with PD. Reporting of NMS was assessed by comparison with case note documentation. A mean of 11 of 30 NMS per patient were elicited on the NMS questionnaire of which on average 4.8 were reported in the clinical notes (44%). The most common NMS were autonomic (particularly urinary). The Hr‐QoL scores correlated most strongly with autonomic dysfunction (r = 0.84; particularly urinary and gastrointestinal symptoms), mood (r = 0.74), fatigue (r = 0.74), sleep problems (nocturnal r = 0.55; daytime somnolence r = 0.65), pain (r = 0.56), and psychosis (r = 0.55, all p < 0.0001) followed by UPDRS motor score (r = 0.48, p < 0.0001). Greater motor fluctuations (r = 0.57) and dyskinesia (r = 0.43, both p < 0.0001) were also associated with worse Hr‐QoL. In multivariate analysis, depression had the strongest association with Hr‐QoL (adjusted R² = 0.53, p = 0.005) followed by fatigue, thermoregulatory, gastrointestinal, and cardiovascular autonomic function (especially orthostatic hypotension), daytime somnolence, and urinary problems. This study demonstrates that a autonomic dysfunction, psychiatric complications, pain, fatigue, and sleep problems are major correlates of poor Hr‐QoL. However, whilst psychiatric problems are increasingly documented, many symptoms (particularly those possibly perceived as embarrassing or unrelated) remain under‐reported. © 2010 Movement Disorder Society     

Apathy in untreated early‐stage Parkinson disease: Relationship with other non‐motor symptoms

Apathy is a frequent and disabling behavioral disorder in patients with Parkinson's disease (PD). Its prevalence in treatment‐naive patients with early‐stage PD has not been extensively investigated. Moreover, whether apathy is related to other non‐motor symptoms in early‐stage PD is unknown. Our objective was to determine the prevalence and features of apathy and associated factors in a group of treatment‐naive patients with early‐stage PD. Ninety‐five treatment‐naive patients with early‐stage PD participated in the study. Apathy, depression, motor symptoms, and overall cognitive efficiency were assessed. The presence of the main non‐motor symptoms was checked during a detailed clinical interview. Group comparisons were carried out to investigate the association with apathy. Eighteen patients (18.95%) were diagnosed as apathetic, and five of the latter had concomitant depression. Apathetic patients had significantly more severe motor symptoms (P < 0.001) and a lower cognitive status (P = 0.032) than non‐apathetic patients. When considering non‐motor symptoms, apathy was significantly associated only with fatigue (P = 0.007) and anhedonia (P = 0.010), both of which were more prevalent in apathetic patients than in non‐apathetic patients. In treatment‐naive patients with early‐stage PD, apathy was significantly associated with more severe motor symptoms and a lower cognitive status. After adjustment for these factors, apathy appeared to be a relatively isolated, independent symptom because the only other associated non‐motor symptoms were fatigue and anhedonia. © 2014 International Parkinson and Movement Disorder Society     

Rhinorrhea: A common nondopaminergic feature of Parkinson's disease

We compared the frequency of rhinorrhea between 34 Parkinson's disease (PD) subjects and 15 normal controls (NC) and explored relationships between rhinorrhea and clinical functions, and degree of nigrostriatal dopaminergic denervation using [¹¹C]dihydrotetrabenazine (DTBZ) brain positron emission tomography imaging. Sixty‐eight percent (23 of 34) of PD subjects reported rhinorrhea of any cause compared with 27% (4 of 15) of NC (χ² = 7.07, P = 0.008). Rhinorrhea frequency remained higher in the PD group after excluding possible rhinitic etiologies: 35% (12 of 34) of PD versus 7% (1 of 15) of NC (χ² = 4.38, P = 0.04). There were no differences in demographics, nigrostriatal dopaminergic denervation, and clinical motor or nonmotor variables between PD subjects with and without rhinorrhea, except that more PD subjects with rhinorrhea complained of lightheadedness (52% vs. 9%, χ² = 5.85, P = 0.02). Rhinorrhea is a common nondopaminergic feature of PD, unrelated to olfactory or motor deficits. Further investigations are needed to determine if rhinorrhea correlates with sympathetic denervation or other autonomic symptoms in PD. © 2010 Movement Disorder Society     

Cerebral blood flow changes induced by pedunculopontine nucleus stimulation in patients with advanced Parkinson's disease: A [15O] H2O PET study

Patients with advanced Parkinson's disease (PD) develop disabling axial symptoms, including gait disturbances, freezing and postural instability poorly responsive to levodopa replacement therapy. The pedunculopontine nucleus (PPN) is involved in locomotion, control of posture, and behavioral states [i.e. wakefulness, rapid eye movement sleep]. Recent reports suggested that PPN modulation with deep brain stimulation (DBS) may be beneficial in the treatment of axial symptoms. However, the mechanisms underlying these effects are still unknown. We used [¹⁵O] H₂O PET to investigate regional cerebral blood flow in three patients with advanced PD who underwent a new experimental surgical procedure with implantation of unilateral PPN‐DBS. Patients were studied Off‐medication with stimulator Off and On, both at rest and during a self‐paced alternating motor task of the lower limbs. We used SPM2 for imaging data analysis, threshold P < 0.05 corrected at the cluster level. Stimulation induced significant regional cerebral blood flow increment in subcortical regions such as the thalamus (P < 0.006), cerebellum (P < 0.001), and midbrain region (P < 0.001) as well as different cortical areas involving medial sensorimotor cortex extending into caudal supplementary motor area (BA 4/6; P < 0.001). PPN‐DBS in advanced PD resulted in blood flow and presumably neuronal activity changes in subcortical and cortical areas involved in balance and motor control, including the mesencephalic locomotor region (e.g. PPN) and closely interconnected structures within the cerebello‐(rubro)‐thalamo‐cortical circuit. Whether these findings are associated with the DBS‐PPN clinical effect remains to be proven. However, they suggest that PPN modulation may induce functional changes in neural networks associated with the control of lower limb movements. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Extra‐nigral pathological conditions are common in Parkinson's disease with freezing of gait: An in vivo positron emission tomography study

Cholinergic denervation has been associated with falls and slower gait speed and β‐amyloid deposition with greater severity of axial motor impairments in Parkinson disease (PD). However, little is known about the association between the presence of extra‐nigral pathological conditions and freezing of gait (FoG). Patients with PD (n = 143; age, 65.5 ± 7.4 years, Hoehn and Yahr stage, 2.4 ± 0.6; Montreal Cognitive Assessment score, 25.9 ± 2.6) underwent [¹¹C]methyl‐4‐piperidinyl propionate acetylcholinesterase and [¹¹C]dihydrotetrabenazine dopaminergic PET imaging, and clinical, including FoG, assessment in the dopaminergic “off” state. A subset of subjects (n = 61) underwent [¹¹C]Pittsburgh compound‐B β‐amyloid positron emission tomography (PET) imaging. Normative data were used to dichotomize abnormal β‐amyloid uptake or cholinergic deficits. Freezing of gait was present in 20 patients (14.0%). Freezers had longer duration of disease (P = 0.009), more severe motor disease (P < 0.0001), and lower striatal dopaminergic activity (P = 0.013) compared with non‐freezers. Freezing of gait was more common in patients with diminished neocortical cholinergic innervation (23.9%, χ² = 5.56, P = 0.018), but not in the thalamic cholinergic denervation group (17.4%, χ² = 0.26, P = 0.61). Subgroup analysis showed higher frequency of FoG with increased neocortical β‐amyloid deposition (30.4%, Fisher Exact test: P = 0.032). Frequency of FoG was lowest with absence of both pathological conditions (4.8%), intermediate in subjects with single extra‐nigral pathological condition (14.3%), and highest with combined neocortical cholinopathy and amyloidopathy (41.7%; Cochran‐Armitage trend test, Z = 2.63, P = 0.015). Within the group of freezers, 90% had at least one of the two extra‐nigral pathological conditions studied. Extra‐nigral pathological conditions, in particular the combined presence of cortical cholinopathy and amyloidopathy, are common in PD with FoG and may contribute to its pathophysiology. © 2014 International Parkinson and Movement Disorder Society     

Prevalence and Clinical Aspects of Mild Cognitive Impairment in Parkinson's Disease: A Meta-Analysis

Mild cognitive impairment associated with Parkinson's disease (PD) is a risk factor for the development of dementia. Despite the importance of early identification of mild cognitive impairment in PD, its prevalence and clinical correlates are still debated. The present meta-analysis provides a robust estimate of prevalence rate of mild cognitive impairment in PD according to the Movement Disorder Society clinical criteria and to explore the differences between PD patients with and without mild cognitive impairment in demographic, clinical, and neuropsychiatric features. A systematic literature search was performed up to April 2019 using PsycInfo (PROQUEST), PubMed, and Scopus. From 4706 titles and abstracts, 41 studies were selected (n = 7053 patients). Pooled mild cognitive impairment prevalence was 40% on a total sample of 7053 PD patients (95% confidence interval = 36–44; Q = 490.14, P < 0.0001; I² = 91.84%) with a higher frequency for the multiple domain subtype (31%; 95% confidence interval = 23–41, Q = 93.24; P < 0.0001; I² = 92.49%). Meta-regression analysis revealed that stage of PD moderate prevalence estimates of mild cognitive impairment (β = 2.80; P = 0.008). Mild cognitive impairment in PD was associated with older age, lower education, longer disease duration, higher levodopa equivalent daily dose, more severe motor symptoms, and postural instability/gait difficulty motor subtype, poorer quality of life, higher levels of apathy, and depression. The present meta-analysis indicated that mild cognitive impairment in PD is a frequent cognitive status deserving to be early detected by means of standardized cognitive assessments in clinical practice. © 2019 International Parkinson and Movement Disorder Society     

β‐amyloid and postural instability and gait difficulty in Parkinson's disease at risk for dementia

Although motor impairments in Parkinson's disease (PD) are attributed to nigrostriatal dopaminergic denervation, postural instability and gait difficulty (PIGD) features are less responsive to dopaminergic medications. PIGD features are a risk factor also for the development of dementia in PD (PDD). These observations suggest that nondopaminergic mechanisms may contribute to axial motor impairments. The aim was to perform a correlative PET study to examine the relationship between neocortical β‐amyloid deposition ([¹¹C]‐Pittsburgh Compound B), nigrostriatal dopaminergic denervation ([¹¹C]‐dihydrotetrabenazine), and PIGD feature severity in PD patients at risk for dementia. This was a cross‐sectional study of 44 PD patients (11 female and 33 male; 69.5 ± 6.6 years of age; 7.0 ± 4.8 years motor disease duration; mean H & Y stage: 2.7 ± 0.5) who underwent PET, motor feature severity assessment using the Movement Disorder Society revised UPDRS, and the Dementia Rating Scale (DRS). Linear regression (R²_adj = 0.147; F_4,39 = 2.85; P = 0.036) showed that increased PIGD feature severity was associated with increased neocortical [¹¹C]‐Pittsburgh Compound B binding (β = 0.346; t₃₉ = 2.13; P = 0.039) while controlling for striatal [¹¹C]‐dihydrotetrabenazine binding, age, and DRS total score. Increased neocortical β‐amyloid deposition, even at low‐range levels, is associated with higher PIGD feature severity in PD patients at risk for dementia. This finding may explain why the PIGD motor phenotype is a risk factor for the development of PDD. © 2012 Movement Disorder Society     

LINGO1 gene analysis in Parkinson's disease phenotypes

Background: Parkinson's disease (PD) and essential tremor (ET) may share some etiopathogenic factors. A genome‐wide association study has shown that LINGO1 gene variants are associated with increased risk of ET. We hypothesized that LINGO1 variants could increase susceptibility to PD. Methods: A large series of PD subjects and healthy controls were genotyped for rs9652490 and rs11856808 LINGO1 single nucleotide polymorphisms (SNPs). Results: We found an increased frequency of the rs11856808^T/T genotype in PD compared with controls (odds ratio = 1.46; corrected P value = 0.02). A recessive genetic model was the best fit for rs11856808 influence on PD (recessive gene action test: corrected P value = 0.01). Stratification analysis showed that rs11856808^T/T genotype frequency was higher in the tremor‐dominant PD and the classical PD (C‐PD) subgroups (recessive gene action test for the C‐PD subgroup: corrected P value = 0.004). Discussion: Our results indicate that LINGO1 variants could increase risk of PD, specifically those presenting the non‐rigid‐akinetic phenotypes, which suggests that LINGO1 may have a role in the etiology of tremor in PD at least in the Spanish population. © 2010 Movement Disorder Society     

Cerebrospinal fluid,plasma, and saliva in the BioFIND study: Relationships among biomarkers and Parkinson's disease Features

Objective: Examine relationships among neurodegenerative biomarkers and PD motor and nonmotor symptoms. Background: CSF alpha‐synuclein is decreased in PD versus healthy controls, but whether plasma and saliva alpha‐synuclein differentiate these groups is controversial. Correlations of alpha‐synuclein among biofluids (CSF, plasma, saliva) or biomarkers (eg, beta‐amyloid, tau [total, phosphorylated]) are not fully understood. The relationships of these biomarkers with PD clinical features remain unclear. Methods: BioFIND, a cross‐sectional, observational study, examines clinical and biomarker characteristics in moderate‐advanced PD and matched healthy controls. We compared alpha‐synuclein concentrations across diagnosis, biofluids, and CSF biomarkers. Correlations of CSF biomarkers and MDS‐UPDRS, motor phenotype, MoCA, and rapid eye movement sleep behavior disorder questionnaire scores in PD were examined. Results: CSF alpha‐synuclein was lower in PD versus controls (P = .01), controlling for age, gender, and education. Plasma and saliva alpha‐synuclein did not differ between PD and controls, and alpha‐synuclein did not significantly correlate among biofluids. CSF beta‐amyloid_1‐42 was lower in PD versus controls (P < .01), and correlated weakly with MoCA recall scores (r = 0.23, P = .02). CSF alpha‐synuclein was lower in the postural instability/gait difficulty phenotype than other motor phenotypes (P < .01). No CSF biomarkers predicted or correlated with total motor or rapid eye movement sleep behavior disorder scores. CSF alpha‐synuclein correlated with beta‐amyloid_1‐42, total‐tau, and phosphorylated‐tau (r = 0.41, 0.81, 0.43, respectively; Ps < .001). Conclusion: Lower CSF alpha‐synuclein is associated with diagnosis and motor phenotype in moderate‐advanced PD. Plasma and saliva alpha‐synuclein neither correlate with CSF alpha‐synuclein, nor distinguish PD from controls. CSF beta‐amyloid_1‐42 remains a potential biomarker for cognitive impairment in PD. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.     

Neuropathological findings in benign tremulous Parkinsonism

Benign tremulous parkinsonism, a tremor dominant syndrome with a relatively slow rate of deterioration, is recognized by clinicians although its pathological basis is not well understood. A systematic review of Queen Square Brain Bank donors was carried out to determine the natural history and pathology of individuals who had tremor dominant parkinsonism with mild non‐tremor components and minimal gait disability for at least 8 years. We identified 16 cases of pathologically proved benign tremulous Parkinson's disease (PD); another 5 individuals conformed to the definition but did not have the pathology of PD. Patients with verified benign tremulous PD had less severe neuronal loss in the substantia nigra than controls (χ²: P = .003). Twelve of these had been correctly diagnosed with PD at their first neurological evaluation, whereas the other 4 were originally thought to have another tremor disorder. The only consistent distinguishing feature of the 5 pathologically disproved cases, who may have had either essential tremor with associated rest tremor or dystonic tremor, was a failure to develop unequivocal bradykinesia within a decade of onset of tremor at rest. Our findings support the existence of a distinct subgroup of benign tremulous PD. The slower rate of clinical progression correlates with less severe nigral cell loss at postmortem, although many of these patients transgress the benign tremulous parkinsonism definition by the final third of their disease course and develop the common features of advanced PD. © 2012 Movement Disorder Society     

Anxious and depressive symptoms in Parkinson's disease: The French cross‐sectionnal DoPaMiP study

Anxiety has been less extensively studied than depression in Parkinson's disease (PD). The DoPaMiP survey allowed assessing simultaneously anxiety and depressive symptoms in PD and comparing correlations of both symptoms with clinical and therapeutic features of the disease. Cross sectional survey conducted prospectively in 450 ambulatory nondemented PD patients and 98 patients with other disorders than PD. Anxiety and depressive symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS), parkinsonism using the Unified Parkinson's Disease Rating Scale (UPDRS). Other clinical factors were measured using a structured standardized examination/questionnaire. The mean HADS‐A (anxiety) subscore was higher in PD patients than in the others (8.2 ± 3.9 vs. 6.5 ± 3.2, P < 10^?4) as was the HADS‐D (depressive) subscore (6.6 ± 3.8 vs. 3.9 ± 3.2, P < 10^?4). Patients with possible/probable anxious signs (HADS‐A ≥ 8) were more prevalent in PD (51% vs. 29%, P < 10^?4) as were those with depressive symptoms (40% vs. 10%, P < 10^?4). Conversely, anxiolytic and antidepressant medications consumption was not different between the 2 groups. Patients with anxious symptoms were more frequently female and younger than those without such symptoms, while those with depressive symptoms had more severe indices of parkinsonism, more comorbidities and lower cognitive function (Mini Mental State Exam). The logistic regression model revealed that patients with depressive symptoms received more frequently levodopa and less frequently a dopamine agonist. Anxiety and depressive symptoms were more frequent in PD patients than in medical control group. Both symptoms were commonly associated in the same PD patients, but were correlated with different clinical/therapeutic features, suggesting different underlying pathophysiological mechanisms. © 2009 Movement Disorder Society     

Autonomic and sensory symptoms and signs in incident,untreated Parkinson's disease: Frequent but mild

Although nonmotor symptoms are increasingly recognized as key features in Parkinson's disease (PD), the occurrence and severity of autonomic and sensory symptoms in patients with very early and untreated PD are poorly documented. Two hundred seven patients with newly diagnosed, untreated PD and 175 controls from the population‐based Norwegian ParkWest study were included. Postural blood pressure and olfactory function were measured and eight autonomic and sensory symptoms assessed using interview‐based rating scales. Autonomic and sensory symptoms were more frequent in patients compared with controls (mean number of symptoms 2.9 vs. 1.1; P < 0.001) and in the postural instability and gait difficulty motor‐subtype vs. tremor dominant subtype (mean 3.3 vs. 2.5; P = 0.008). In the patient group, reduced olfaction (59%), urinary problems (47%), increased saliva or drooling (42%), constipation (39%), and sensory complaints (34%) were the most frequent symptoms. Daily activities were not affected by these symptoms in 58% of the patients, and the influence on daily activities was rated as “mild” or less for all of these symptoms in 90%. A higher Hoehn and Yahr stage was associated with a higher number of autonomic and sensory symptoms and with the occurrence of gastrointestinal symptoms. Autonomic and sensory symptoms are common in patients with untreated, early PD although the severity of these symptoms is mild, with little or no influence on daily activities. The high prevalence of increased saliva or drooling close to the time of diagnosis is noteworthy and not described earlier. © 2010 Movement Disorder Society     

Cardiac sympathetic degeneration correlates with olfactory function in Parkinson's disease

Autonomic and olfactory dysfunctions are considered markers for preclinical diagnosis in Parkinson's disease (PD), because pathological changes in these systems can start before motor symptoms develop. We investigated whether cardiac sympathetic function and olfactory function are associated in PD. Participants comprised 40 nondemented patients with idiopathic PD, and age‐matched controls. Cardiac sympathetic function was evaluated by ¹²³ I‐metaiodobenzylguanidine (MIBG) uptake, in terms of the heart to mediastinum (H/M) ratio in both early and delayed images, and the washout rate (WR). Olfactory function was evaluated using the Odor Stick Identification Test for Japanese, which evaluates the detection of 12 odorants familiar to Japanese participants. Smell identification scores were significantly lower (P < 0.001) in patients with PD than in controls. Smell identification scores correlated positively with early (P < 0.05) and delayed H/M ratios (P < 0.01), and inversely with the WR (P < 0.005) especially in patients with early PD (below 5 years of the start of motor symptoms), whereas smell identification scores did not correlate with any parameters of MIBG in the advanced PD (above 5 years of the start of motor symptoms). There was no correlation between motor symptom scores and smell identification scores, H/M ratios, or WR. The results suggest that the cardiac sympathetic nervous system might degenerate in parallel with the olfactory system in patients with early PD, and that these two systems might degenerate at a different rate of speed in advanced PD. © 2010 Movement Disorder Society     

Analysis of video‐polysomnographic sleep findings in dementia with Lewy bodies

Knowledge of sleep architecture and disorders of nocturnal sleep in dementia with Lewy bodies (DLB) is limited by a lack of systematic video‐polysomnographic (video‐PSG) investigations. We describe video‐PSG findings in 29 consecutive subjects diagnosed with DLB. All the patients underwent a clinical interview and overnight video‐PSG monitoring. Twenty‐nine nondemented patients with Parkinson's disease (PD) matched for age and sex with the DLB cases were selected for comparison. The DLB subjects showed less 1NREM sleep (P = .000) and more 2NREM sleep (P = .000) than the PD subjects. Sleep apnea (30.7% vs. 34.8%) and periodic limb movements (60.9% versus 50.0%) were frequent in both groups. Disruptive motor behavioral manifestations were more frequent in subjects with DLB (69.6% vs. 26.9%, P = .008) and consisted of not only REM sleep behavior disorder (RBD) but also confusional events (30.3% vs. 3.8%, P = .020) and arousal‐related episodes mimicking RBD. Subjects with DLB in whom a sleep disturbance had been the presenting symptom performed better than those with other onset symptoms on both the Mini–Mental State Examination (22.2 ± 4.1 vs. 18.1 ± 4.6, P = .019) and the Frontal Assessment Battery (15.8 vs. 10.3, P = .010). Polysomnographic findings in DLB show a complex mix of overlapping sleep alterations: impaired sleep structure, sleep comorbidities, and various motor‐behavioral events (not restricted to RBD). Clinicians should be aware of the possibility of misleading symptoms and of the risk of overlooking sleep comorbidities, and consider performing polysomnographic sleep investigations in selected cases. We found evidence that a sleep disturbance as the presenting symptom might indicate a different phenotype of the disease, characterized by milder cognitive impairment. © 2013 International Parkinson and Movement Disorder Society     

Therapeutic effect of repetitive transcranial magnetic stimulation in Parkinson's disease: Analysis of [11C] raclopride PET study

Repetitive transcranial magnetic stimulation (rTMS) has been used as a potential therapeutic tool in Parkinson's disease (PD). However, the therapeutic value and/or the placebo effect of rTMS on PD remain to be elucidated. To investigate the therapeutic value and/or placebo effect of rTMS in PD, we compared the motor section of unified PD rating scale (UPDRS III) and the amount of extracellular dopamine concentration using [¹¹C] raclopride PET before and after two sessions of rTMS in 9 PD patients. During a consecutive 2 days while off‐medication, two series of 15 trains of 5 Hz‐frequency rTMS (intensity, 90% of the resting motor threshold) were applied to the hand area of more severely symptomatic motor cortex (MC). After unilateral rTMS of MC, mean raclopride binding potentials (BPs) were reduced not only in putaminal and caudate areas on the stimulated side (?4.9% and ?6.5%, respectively) (P > 0.05) but also in putaminal and caudate areas of nonstimulated hemispheres (?6.6%, P > 0.05 and ?12.1%, P = 0.049, respectively). UPDRS III scores were significantly decreased (35.0 ± 14.1 to 32.0 ± 13.4, P = 0.049). A reduction of raclopride BP in nonstimulated ventral striatum by unilateral rTMS supports the placebo response during rTMS. © 2007 Movement Disorder Society     

Follow-up study of cardiac 123I-MIBG scintigraphy in idiopathic REM sleep behavior disorder

Background: Cardiac ¹²³I‐metaiodobenzylguanidine (¹²³I‐MIBG) uptake in patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is markedly reduced, as in Parkinson’s disease (PD). Methods: We performed ¹²³I‐MIBG scintigrams on patients with iRBD and PD. After the initial ¹²³I‐MIBG scintigram, we retested subjects after a mean of 2.8 years. Results: The delayed heart‐to‐mediastinum (H/M) ratio of cardiac ¹²³I‐MIBG uptake was not significantly reduced between the first and second study in either group (P = 0.050, P = 0.091, respectively) . Follow‐up imaging revealed a mean decline of 4.21 ± 9.06% or 6.40 ± 19.02% in the delayed H/M ratio in those with iRBD or PD, respectively. Conclusions: The ¹²³I‐MIBG uptake findings might indicate progression early in the course of iRBD or PD, but the progression is heterogeneous and independent of development of motor symptoms.