A prospective study of depression in French patients with Parkinson's disease. The Depar study

To investigate the prevalence and symptomatology of depression in Parkinson's disease (PD), we have studied 506 unselected patients attending the neurology services in French general hospitals during a 5 month period defined for prospective inclusion. 246 patients (48.6%) were suspected of depression according to different methods of evaluation and 168 (33.2%) were defined as definite or probable depression. According to the Montgomery and Asberg scale, 46 cases (9%) had a severity score suggestive of major depression. As a function of the cut-off score defined for severity, these patients represented from 23.2 to 43.7% of the depressive population with PD. There was no significant difference between depressed and non depressed PD patients as a function of the patient's current age or age at onset of PD. A significantly higher rate of depression was found among women with PD. A past history of depression was a risk factor for mood disorder after onset of PD. The severely depressed patients had a significantly longer duration of PD and a higher score of cognitive impairment than mildly or moderately depressed and non depressed patients with PD. Depressed patients had a significantly more advanced stage of disability than non-depressed patients with PD.     

帕金森操康复训练的临床疗效观察

目的探讨帕金森健康操对帕金森病患者运动功能和日常生活能力的影响。方法选取2013年4月至2014年7月期间我院收治的帕金森病患者38例。分为两组:治疗组给予临床常规药物治疗及常规康复治疗,并在此基础上教授帕金森健康操,每天2 h;对照组仅给予临床常规药物治疗及常规康复治疗。治疗5月及14月后观察疗效。结果两组治疗5月后UPDRSⅡ评分和UPDRSⅢ评分均较治疗前降低,差异具有统计学意义(P0.05);治疗组在治疗14月后,与治疗前比较降低更加显著(P0.01)。治疗组在治疗14月后与治疗5月后比较也有明显降低,差异具有统计学意义(P0.05)。治疗5月后和治疗14月后治疗组与对照组比较,差异均有统计学意义(P0.05)。结论帕金森健康操能提高帕金森病患者的运动功能,改善患者的日常生活活动能力,特别是长期预后具有较好的临床效果。     

Association of low serum BDNF with depression in patients with Parkinson's disease

ObjectiveIncreasing evidence shows that brain-derived neurotrophic factor (BDNF) plays a critical role in the development of depression and the mechanisms of antidepressant. Parkinson disease (PD) is associated with depression and decreased BDNF. The aim of the present study was to examine the association of BDNF with depression in PD, which has not been investigated.MethodsWe recruited 96 PD patients with (n = 46) and without depression (n = 50) and 102 healthy controls and measured the serum BDNF levels in both groups. Zung Self-Rating Depression Scale (SDS) was administered for the severity of depression and Hoehn-Yahr staging scale for motor abilities in PD patients.ResultsSerum BDNF levels were significantly lower in PD patients than healthy controls (p < 0.01). Also serum BDNF levels were significantly decreased in PD patients with than without depression (p < 0.01). BDNF levels were negatively associated with SDS in both PD patients with and without depression (both p < 0.01). Multiple regression analysis confirmed that in either PD with or without depression group, BDNF was an independent contributor to SDS (both p < 0.05).ConclusionsOur findings suggest that decreased serum BDNF may be involved in the pathophysiology of depression in PD patients.     

Prevalence and determinants of depression in Mexican patients with Parkinson's disease

Objective

To assess the prevalence and associated factors of depression in a Mexican Parkinson's disease (PD) population.

Background

Depressive symptoms are frequent in PD and have been recognized as a major determinant of quality of life. Only two previous studies have partially addressed depression in Mexican PD patients.

Methods

One hundred forty-seven non-demented PD patients were recruited at the movement disorder specialist clinic at the National Institute of Neurology and Neurosurgery, Mexico City. The following sociodemographic variables were collected: gender, age, age at onset, disease duration and disease severity in terms of Hoehn and Yahr stage. PDQ-8, NMSQuest and Beck Depression Inventory (BDI) were applied to all participants.

Results

One hundred forty-seven patients were included (49.7% female). The mean age of the sample was 62.1 ± 11.7 years, the mean age at diagnosis was 55.8 ± 12.3 and the mean duration of the disease was 6.3 ± 5 years. A total of 49 (33.3%) patients were diagnosed with current depression. Depressed patients also scored higher in the NMSQuest even when depression/anxiety items were excluded. Differences were found in gender, UPDRS III score and HY stage, but after the logistic regression analysis was performed only the NMSQuest score and low education remained as statistically significant factors for depression in Mexican PD patients.

Conclusions

Depression prevalence in PD Mexican patients is similar to other international reports. The main associated factor was the presence of non-motor symptoms.     

Prevalence of non motor features in a cohort of Parkinson's disease patients

Background

There is a lack of awareness among physicians of the considerable disability caused by non-motor symptoms (NMS) in PD. The aim of this work is to estimate the prevalence of NMS in a series of patients with Parkinson's disease (PD).

Materials and methods

We studied 112 patients with Parkinson's disease. Motor symptoms were scored on the Unified Parkinson's Disease Rating Scale (UPDRS) part III and the Hoehn and Yahr (HY) Scale. Other symptoms were quantified with the Non-Motor Symptom Questionnaire and Scale (NMSQuest and NMSS) as well as Minimental State Examination (MNSE).

Results

Analysis of the data from the NMSS showed that mood/cognition was the most commonly affected domain (prevalence rate = 87.5%), followed by sleep disturbance/fatigue second (78.6%). However, all other non-motor symptoms scored highly: gastrointestinal and urinary (76.8% for both), sexual dysfunction (73%), cardiovascular (70.5%) with significantly higher percentage in predominantly akinetic/rigid patients. Perceptual problems/hallucinations (9.9%) were infrequent in this population. Dementia was recorded in 22.3% of patients, most of them having a mild degree of dementia. UPDRS scores were correlated with total scores in both NMSQuest and NMSS.

Conclusions

Mood/cognition, sleep disorders, GIT, and sexual disorders were common non motor manifestations in this population of PD patients.     

Trajectories of recovery in depressed Parkinson's disease patients treated with paroxetine or venlafaxine

IntroductionDepression is considered a syndrome with a constellation of symptoms that are frequently categorized into 3 domains including affective, somatic and cognitive. There has been limited research into the domain specific magnitude or relative timing of treatment response in patients with Parkinson's disease (PD). In addition, antidepressant trials involving patients with PD have demonstrated a similar robust placebo response to that seen in other populations. However, the timing of the placebo response has not been carefully studied.MethodsWe studied differential responses to antidepressant treatment in affective, somatic and cognitive domains of depression. Patients were treated for twelve weeks with placebo, venlafaxine or paroxetine as part of the Study of Antidepressants in Parkinson's Disease (SAD-PD) randomized controlled trial. Depressive symptoms were evaluated with three commonly used rating scales.ResultsAll symptom domains improved during the study period, There was a significant placebo effect, especially in the first two weeks that had diminished by week 12. Compared to placebo, the affective symptoms significantly improved during treatment as early as week 4, followed by the somatic symptoms of depression in week 6 and cognitive symptoms in week 8. The largest response was seen in the affective domain.ConclusionIn depressed PD patients treated with venlafaxine or paroxetine, affective symptoms improved first, followed by somatic symptoms and cognitive symptoms. These findings could guide patient counselling and increase patient compliance by informing about the expected treatment responses. The substantial placebo effect underlines the importance of a sufficiently long study period in future studies.     

Suicide in patients with Parkinson's disease

The purpose of this study was to estimate the risk of suicide for patients with Parkinson's disease (PD) in Denmark compared with that in the background population. The study involved 458 patients with a PD diagnosis, 226 men and 232 women. The follow-up period to either death or end of follow-up on December 31, 1990 was 0 to 17 years, mean 5.7 years. Deaths in the follow-up period amounted to 254, 135 men and 119 women. Two women committed suicide. The number of expected suicides was 1.06 for men and 0.55 for women, a total of 1.62. Neither for men nor for women was the difference between expected and observed suicides statistically significant.     

Clinical and posturographic correlates of falling in Parkinson's disease

Various clinical tests and balance scales have been used to assess postural stability and the risk of falling in patients with idiopathic Parkinson's disease (IPD). Quantitative posturography allows a more objective assessment but the findings in previous studies have been inconsistent and few studies have investigated which posturographic measures correlate best with a history of falling. The purpose of this study was to determine the efficacy of clinical tests, balance scales, and stable‐platform posturography in detecting postural instability and discriminating between fallers and non‐fallers in a home‐dwelling PD cohort. Forty‐eight PD subjects (Hoehn & Yahr stage 1–3) and 17 age‐matched controls had the following assessments: Activities‐specific Balance Confidence scale, Berg Balance Scale, Unified Parkinson's Disease Rating Scale (UPDRS) (motor), pull‐test, timed up‐and‐go, static posturography, and dynamic posturography to assess multidirectional leaning balance. Of the clinical assessments, all but the pull‐test were closely correlated with a history of falling. Static posturography discriminated between PD fallers and controls but not between PD fallers and non‐fallers, whereas dynamic posturography (reaction time, velocity, and target hit‐time) also discriminated between fallers and non‐fallers. Our findings suggest that this combination of clinical and posturographic measures would be useful in the prospective assessment of falls risk in PD patients. A further prospective study is now required to assess their predictive value. © 2013 Movement Disorder Society     

Rasch analysis of the hospital anxiety and depression scale in Parkinson's disease

The hospital anxiety and depression scale (HADS) is commonly used to assess mood in Parkinson's disease (PD) patients. Very few studies analyze the scale from the standpoint of item response theory. This article sought to analyze how the HADS fits the Rasch model in PD. The HADS was administered to 387 PD patients. Three sets of Rasch analyses were performed for the HADS total score, and anxiety and depression subscales (HADS‐T, ‐A, and ‐D, respectively). Although the HADS‐T and HADS‐A displayed a good fit, with little threshold disordering and no differential item functioning, the HADS‐D failed to fit the model. The person separation index, a reliability measure, was 0.87 (HADS‐T) and 0.80 (HADS‐A). Both HADS‐T and HADS‐A showed unidimensionality. Our results supported the use of HADS‐T as a measure of psychological distress in PD patients. Moreover, the HADS‐A was also an adequate anxiety measure. Further research is required to address the use of HADS‐D in PD. © 2008 Movement Disorder Society     

Reduced mind wandering in patients with Parkinson's disease

BackgroundMind Wandering (MW) refers to the process of disengaging from the immediate external environment and participating in internally driven mentation. This process has been suggested to be supported by a distributed set of brain regions, collectively referred to as the Default Mode Network (DMN). Recently, reduced recruitment and connectivity of the DMN has been described in Parkinson's disease (PD) patients compared to healthy controls. We thus aimed to explore whether PD patients with normal cognitive test scores show differential MW capabilities compared to healthy controls.MethodsThirty PD patients and thirty age-matched controls, all with a Montreal cognitive assessment (MoCA) score of 26 or above, performed a novel yet validated thought-sampling paradigm used to assess the frequency and extent of MW irrespective of cognitive load in which participants were asked to observe a series of geometric shapes and describe their thoughts after watching them. Shapes were presented one at a time for varying durations across nine trials.ResultsPD patients showed significantly less MW compared to the control. ANCOVA revealed a significant interaction indicating that the difference in MW scores was driven by trials with short stimulus presentation times.ConclusionsThese findings provide evidence for decreased MW in PD patients. We propose that this is due to difficulties in performing MW within short time frames.     

Neural networks associated with quality of life in patients with Parkinson's disease

IntroductionThe neural underpinnings of health-related quality of life in Parkinson's disease remain unclear. This study was conducted to unravel which motor and non-motor symptoms in Parkinson's disease influence health-related quality of life and reveal neural networks most likely linked to it.MethodsComprehensive clinical assessments were conducted for 247 Parkinson's disease patients and image analyses were performed for 181 patients. Clinical scores commonly used to assess various symptoms related to health-related quality of life were investigated. Factor and resting-state functional magnetic resonance imaging analyses were reviewed to reveal health-related quality of life-associated brain networks.ResultsThe Spearman's rank correlation coefficient for the Parkinson's disease Questionnaire-39 summary index was high in the Activities-specific Balance Confidence Scale, Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part 2, Freezing of Gait Questionnaire, and Self-reported Autonomic Symptoms in Parkinson's disease. Multiple regression and Random Forest regression analyses indicated that health-related quality of life-associated factors were Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part 1, Depression Rating Scales, and the above-mentioned scales. The resting-state functional magnetic resonance imaging analysis revealed decreased functional connectivity between the anterior cingulate cortex and right temporo-parietal junction as health-related quality of life worsened.ConclusionFear of falling, daily living activities, gait freezing, and autonomic dysfunction have notable effects on health-related quality of life in Parkinson's disease. Brain networks consisting of the anterior cingulate cortex and temporo-parietal junction may be associated with the emotion-related and social factors of health-related quality of life in Parkinson's disease.     

Anhedonia in Japanese patients with Parkinson's disease: analysis using the Snaith-Hamilton Pleasure Scale

Background

Anhedonia, a lowered ability to experience physical or social pleasure, has recently been recognized as a non-motor symptom of Parkinson's disease.

Objective

To identify the frequency of anhedonia and the factors influencing hedonic tone in Japanese patients with Parkinson's disease.

Patients and methods

We recruited 86 consecutive outpatients with a clinical diagnosis of PD attending two Japanese hospitals (one university hospital and one community hospital) in February 2010. We used the self-rating Snaith–Hamilton Pleasure Scale (SHAPS) translated into Japanese language from the original English version to assess and quantify hedonic tone as a subjectively experienced phenomenon. We studied the association of anhedonia with the variables age, age at onset, gender, disease duration, disease severity and antiparkinsonian drugs.

Results

Thirty-nine patients (45%) were male and 47 (55%) were female. Mean age was 72.01 ± 9.07 (49–89) years, with mean age at onset of 64.93 ± 11.42 (31–88) years. Mean disease duration was 7.20 ± 5.54 (1–23) years. The mean Hoehn and Yahr scale was 2.76 ± 0.78. The mean SHAPS score of the total sample was 1.19 ± 1.86. The SHAPS score of 14 patients (16.3%) was 3 or more, indicating anhedonia. The mean SHAPS score was lower in patients taking pramipexole (0.58 ± 0.97) than in patients not taking pramipexole (1.57 ± 2.16). Multiple linear regression analysis identified pramipexole as a significant negative influencing factor on the SHAPS score, while disease severity and entacapone treatment were identified as positive influencing factors. The age, onset age, gender, disease duration, and use of pergolide, amantadine, zonisamide, selegiline, anticholinergic agents and droxidopa did not significantly affect the SHAPS score.

Conclusion

Anhedonia is not rare non-motor symptom in Japanese patients with Parkinson's disease. This study suggests an anti-anhedonic property of pramipexole.     

Fatigue correlates with LRRK2 G2385R variant in Chinese Parkinson's disease patients

IntroductionFatigue is common in patients with Parkinson's disease (PD). The leucine-rich repeat kinase 2 (LRRK2) G2385R variant predisposes individuals to develop PD in China. The aim of this study was to evaluate whether the LRRK2 G2385R variant is associated with fatigue in patients with PD.MethodsFatigue was evaluated by the Parkinson Fatigue Scale (PFS) in 329 PD patients and 180 controls, a cut-off score of ≥3.3 was used to define the presence of fatigue. All the enrolled PD patients were assessed by a comprehensive battery of motor and non-motor questionnaires. PD patients were genotyped for the G2385R variant. Associations of fatigue with the clinical assessments and with the G2385R variant in PD patients were analyzed by logistic regression.ResultsFatigue frequency was 55.62%. A logistic regression model found that the female sex (OR = 10.477; 95%CI: 2.806–39.120; p < 0.001), motor function (OR = 1.060; 95%CI: 1.012–1.110; p = 0.013), sleep disturbance (OR = 0.943; 95%CI: 0.910–0.976; p = 0.001) and depression severity (OR = 0.843; 95%CI: 0.736–0.965; p = 0.013) collectively predict the presence of fatigue in PD patients. After adjustment for demographics and associated clinical factors, the G2385R variant was associated with an increased risk for the presence of fatigue (OR = 10.699; 95% CI = 2.387–47.958; p = 0.002) in the PD population in this study.ConclusionWe confirm that fatigue in PD patients is common, and we have strengthened the associations between fatigue and female sex, motor severity and non-motor symptoms, particularly depression and sleep disturbances. Overall, we found that carriers of the G2385R variant were more prone to fatigue than non-carriers in PD patients.     

Neural correlates of minor hallucinations in non-demented patients with Parkinson's disease

BackgroundHallucinations are a frequent and severe complication in Parkinson's disease (PD). Minor hallucinations are generally not disturbing, but likely progress to well-structured hallucinations with loss of insight and a great impact on quality of life. Knowledge on the neural bases of minor hallucinations may help to describe those systems associated with the early development of psychotic phenomena in PD.In this study, we aimed to identify the pattern of structural brain alterations associated with minor hallucinations in PD by using voxel-based morphometry (VBM).MethodsWe prospectively collected a sample of 46 non-demented PD patients, with (N = 17) and without (n = 29) minor hallucinations (passage and/or presence hallucinations), and 15 healthy controls. Groups were matched for age, education and global cognitive function. Presence and type of minor psychotic phenomena was assessed by the new MDS-UPDRS. Three dimensional T1-weighted MRI images were acquired with a 1.5 T magnet, and analyzed using optimized VBM.ResultsCompared to controls, PD with minor hallucinations (PD-mH) showed reduced gray matter volume bilaterally in different areas of the dorsal visual stream, and in functionally related midbrain and cerebellar structures. Additionally, bilateral gray matter volume increases were observed in the PD-mH group in limbic and paralimbic regions.ConclusionsOur data support a major role of the dorsal visual stream in the genesis of minor hallucinations in PD, reinforcing the importance of posterior cortical regions for the development of cognitive and psychiatric complications in PD.     

Subthreshold depression in patients with Parkinson's disease and dementia--clinical and demographic correlates

BACKGROUND: About 40% of the patients with Parkinson's disease (PD) have depressive symptoms, either major depression (MD) or subthreshold depression. Depression was found to be associated with age and age at onset of PD, female gender, more severe parkinsonism, in particular with left-sided and akinetic-rigid symptoms, more functional impairment and cognitive impairment.However, the findings are inconsistent and partly contradictory and most of the studies focused on major depression in PD without dementia.The aim of this study was to examine the relationship between subthreshold depression and other clinical features in 538 PD patients with dementia but without MD drawn from a randomized, placebo-controlled multicentre trial of rivastigmine in PD. RESULTS: One hundred and sixteen patients (21%) had subthreshold depression. Depression was associated with a younger age and age at onset and female gender, but not with severity of parkinsonism, cognition or activities of daily living or laterality of motor symptoms. However, in male patients, an association between depression and left-sided parkinsonism was found. CONCLUSION: In contrast to previous findings in PD patients with major depression but without dementia, we found no relationship between subthreshold depression and other clinical symptoms in patients with PDD.     

Volumetric correlates of cognitive functioning in nondemented patients with Parkinson's disease

A challenge in Parkinson's disease (PD) is to identify biomarkers of early cognitive change because functioning in some domains may be more prognostic of dementia. Few studies have investigated whether structural magnetic resonance imaging (MRI) correlates in a regionally specific manner with functioning in different cognitive domains. The aim of this study was to identify neuroanatomical correlates of executive functioning, memory, and visual cognition in PD without dementia. 3T MRI was conducted in 51 PD patients and 39 control participants. Brain volumes were measured in structures comprising the frontostriatal cognitive‐control system, the medial temporal memory system, the ventral object‐based system, and the dorsal spatial‐based system. Measures of executive functioning (Stroop Test; Letter Fluency), memory (California Verbal Learning Test), visuospatial cognition (Judgment of Line Orientation), and visuoconstruction (Pentagon Copy) were correlated with volumes comprising each system. Poorer executive functioning largely correlated with decreased frontostriatal volumes. Poorer memory correlated with decreased volumes in all medial temporal regions, but also with frontostriatal volumes. Poorer visuospatial cognition correlated with decreased volumes in the object‐based system, whereas poorer visuoconstruction correlated with decreased frontal and object‐based system volumes. These relationships were nonsignificant in the control group. This is the first study to demonstrate that subtle changes in multiple cognitive domains in PD without dementia correlate with regional volumes in specific systems implicated in the development of cognitive impairment. The findings suggest that structural MRI holds promise as a marker of early changes in different brain systems, some of which may predict future cognitive deterioration. © 2013 Movement Disorder Society     

Cognitive correlates of visual hallucinations in non-demented Parkinson's disease patients

BackgroundVisual hallucinations (VH) in Parkinson's disease (PD) are associated with PD dementia and have been related to cognitive impairments in non-demented PD patients. Reports on the specific cognitive domains affected are conflicting. The aim of the present study was to investigate the presence of specific cognitive impairments in non-demented PD patients with VH, compared to those without VH.MethodsWe compared the clinical characteristics and neuropsychological test scores of 31 non-demented PD patients with VH with those of 31 PD patients without VH that were carefully matched for sex, age, disease duration and educational level. Several non-motor symptoms, including depression, anxiety and sleep disturbances, were also taken into account, as these may influence cognitive performance.ResultsThe PD with VH group performed significantly worse on the Trail Making Test part A (p = 0.01) and the Rey Auditory Verbal Learning Test, immediate recall (p = 0.01). In addition, PD patients with VH were more anxious, more depressed and reported more sleep disturbances. Verbal learning scores were not associated with levels of anxiety, depression or sleep disruption, whereas worse Trail Making Test A performance was associated with concomitant sleep disturbances.ConclusionsIn non-demented PD patients, the presence of VH is associated with a cognitive profile characterized by impairments in verbal learning and probably attention. Since these cognitive functions are believed to be non-dopaminergic mediated functions, the present results support the hypothesis that multiple neurotransmitter systems, other than dopamine, contribute to the pathophysiology of VH in PD.     

Mirror movements in patients with Parkinson's disease

Mirror movements (MM) refer to ipsilateral involuntary movements that appear during voluntary activity in contralateral homologous body regions. This study aimed to compare the frequency and distribution of MM in an unselected sample of 274 patients with Parkinson's disease (PD) and 100 healthy subjects, and to check a possible relationship between MM and parkinsonian features. MM of the hand were scored according to the Woods and Teuber scale. The frequency of MM was lower in PD patients than in healthy subjects (29% vs. 71%, P < 0.0001). The distribution of MM also differed in the two groups being often bilateral in healthy subjects, invariably unilateral in PD patients. When parkinsonian signs were unilateral, MM always manifested on the unaffected side; when parkinsonian signs were bilateral, MM manifested on the less affected side. PD patients manifesting MM scored significantly lower on Hohen and Yahr staging than patients without MM. Likewise, there was a significant inverse correlation between the intensity of MM as rated by the Woods and Teuber score and HY staging (r = ?0.16, P < 0.01). The low frequency of MM in PD probably relates to the complex interactions between the pathophysiological mechanisms leading to parkinsonian signs and the mechanisms responsible for movement lateralization. © 2007 Movement Disorder Society     

Rest tremor correlates with reduced contralateral striatal dopamine transporter binding in Parkinson's disease

IntroductionIn vivo dopamine transporter imaging is a useful tool for distinguishing nigrostriatal pathologies (e.g. Parkinson's disease) from other causes of tremor. However, while many of the motoric features of Parkinson's disease (e.g. bradykinesia, rigidity, hypomimia) correlate well with reduced striatal dopamine transporter binding, the same relationship has not been demonstrated for tremor. We investigated the relationship between striatal dopamine transporter binding and quantitative measures of tremor.Methods23 participants with Parkinson's disease underwent standardised clinical assessment including structured, videotaped clinical examination, tremor neurophysiology study of both upper limbs using accelerometry and surface EMG, and Technitium-99 m TRODAT-1 brain SPECT imaging. Normalised striatal uptake values were calculated. Tremor EMG and accelerometry time series were processed with Fourier transformation to identify peak tremor power within a window of 3–10Hz and to calculate the tremor stability index (TSI).ResultsSpearman correlation analyses revealed an association between tremor power and contralaterally reduced striatal uptake in a number of recording conditions. This association was strongest for rest tremor, followed by postural tremor, with the weakest association observed for kinetic tremor. Lower TSI was also associated with lower contralateral striatal uptake in a number of rest and postural conditions.ConclusionThese data suggest a relationship between Parkinsonian rest tremor and contralateral reduction in striatal dopamine binding. Use of quantitative neurophysiology techniques may allow the demonstration of clinico-pathophysiological relationships in tremor that have remained occult to previous studies.