Neuropsychiatric symptoms in Parkinson's disease

Neuropsychiatric symptoms are common in Parkinson's disease, even at the earliest stages, and have important consequences for quality of life and daily functioning, are associated with increased carer burden and increased risk for nursing home admission. In addition to cognitive impairment, a wide range of neuropsychiatric symptoms have been reported. In this article, the epidemiology, clinical course, diagnosis, and management of some of the most common neuropsychiatric symptoms in PD are discussed: depression, anxiety, apathy, fatigue, and psychotic symptoms. Although much is known regarding the prevalence and course of these symptoms, the empirical evidence for how to manage these symptoms is limited at best. There is thus an urgent need for systematic studies for the pharmacological and non‐pharmacological management of these symptoms. © 2009 Movement Disorder Society     

Depressive symptom profile in Parkinson's disease: a comparison with depression in elderly patients without Parkinson's disease

OBJECTIVE: Depression is a common neuropsychiatric syndrome in Parkinson's disease (PD), and may be etiologically related to the neurochemical changes accompanying this disease. It is still unclear whether the disturbances of neurotransmitter activities lead to a specific profile of depressive symptoms, that is characteristic for PD and differs from that in depressed patients without PD. METHOD: We compared the individual depressive symptoms of 145 non-demented depressed patients with PD and 100 depressed patients without PD by comparing item scores on the Montgomery-Asberg Depression Rating Scale by way of MANCOVA. RESULTS: The severity of depression and the level of cognitive functioning in depressed PD patients were comparable with that of depressed control subjects. However, patients with PD showed significant less reported sadness, less anhedonia, less feelings of guilt and, slightly less loss of energy, but more concentration problems than depressed control subjects. CONCLUSION: The profile of depressive symptoms in PD differs from that in depressed subjects without PD. This finding is important for the conceptualisation and clinical diagnosis of depression in PD.     

Neuropsychiatric problems in Parkinson's disease: comparisons between self and caregiver report

Introduction: This study examined the level of agreement between caregiver and Parkinson's disease (PD) patient reports of neuropsychiatric problems.

Method: Forty-three patients and 43 informants who knew the patient well (caregivers) participated in the study. Caregivers rated patients’ behaviour, as well as their own stress, using the Neuropsychiatric Inventory (NPI). Information from patients was obtained using commonly used scales (Beck Depression Inventory, Apathy Scale, Unified Parkinson's Disease Rating Scale and the Hamilton Anxiety Depression Scale). Both the patients and the caregivers also completed the Frontal Systems Behavior Scale, which assesses behaviours associated with apathy, disinhibition and executive dysfunction.

Results: The level of agreement between these self and caregiver reports was low, with only 45.8% agreement for depression, 45.0% for apathy, 28.6% for hallucinations, 26.9% for sleep problems and 6.7% for anxiety.

Conclusions: Given this low level of agreement between self and other report, these two methods of assessment cannot be considered interchangeable.     

Neuropsychiatric disturbances in Parkinson's disease clusters in five groups with different prevalence of dementia

OBJECTIVE: To investigate the inter-relationship of neuropsychiatric disturbances in Parkinson's disease (PD) by cluster analysis and describe the properties of the clusters. METHOD: A total of 139 patients were assessed using the neuropsychiatric inventory (NPI). A cluster-analysis was used to investigate the inter-relationship of NPI items. The clusters were profiled regarding dementia (PDD) and major depression. RESULTS: A total of 39 patients showed no neuropsychiatric symptoms. The remaining 100 patients (43% PDD) were divided in to five clusters. The largest group (42, 31% PDD) showed symptoms of mild depression, followed by a group (29, 79.3% PDD) with hallucinations and mild other symptoms. The third group (14, 7.1% PDD) had sleep disturbances exclusively. The fourth group (8, 25% PDD) showed apathy, anxiety and depression. The smallest group (7, 57.1% PDD) had high scores on several NPI items. CONCLUSION: Our PD sample can be divided in to clusters based on the NPI, with different prevalence of dementia and depression.     

Malignant syndrome in Parkinson's disease without dopaminergic drug withdrawal

Malignant syndrome is a rare complication occurring during the course of drug treatment for Parkinson''s disease. It resembles neuroleptic malignant syndrome and is characterized by fever, marked rigidity, altered consciousness, leucocytosis and elevated creatine kinase. Malignant syndrome is a potentially fatal condition and awareness of this condition is imperative for prevention and treatment. The commonest precipitating factor is dopaminergic drug withdrawal or dose reduction. We report malignant syndrome (precipitated by hyponatremia) in a case of Parkinson''s disease, in the absence of dopaminergic drug withdrawal. A 60-year-old man presented with fever, severe rigidity and altered sensorium following repeated vomiting. On investigation, he was found to have hyponatremia precipitated malignant syndrome. Treatment with hydration, cooling, correction of hyponatremia and dopaminergic drugs reversed his condition. The triad of fever, severe rigidity and altered sensorium should prompt evaluation for malignant syndrome in Parkinson''s disease.     

Comorbid cancer in Parkinson's disease

The aim of this article was to evaluate cancer occurrence before and after diagnosis of Parkinson's disease (PD). We investigated 692 patients newly diagnosed with PD and 761 age‐ and sex‐matched control subjects identified during two periods (1994–1995 and 2000–2003) within Kaiser Permanente Medical Care Program of Northern California. Primary cancers were searched and dated, and all participants were followed up until the end of membership, death, or December 31, 2008. We used unconditional logistic regression to evaluate the PD–cancer association before the date of PD diagnosis or the index date and Cox proportional hazards regression to evaluate the PD–cancer association after the index date. Nearly 20% (140 of 692) of the PD patients and 25% (188 of 761) of the non‐PD controls had ever had a cancer diagnosis. Before the index date, the prevalence of cancer was not significantly lower in patients with PD (8.1% PD vs. 9.2% controls; OR = 0.83; 95% CI 0.54–1.3). After the index date, the risk of developing a cancer did not differ between PD cases and controls (relative risk [RR] = 0.94; 95% CI 0.70–1.3). Among specific cancers, melanoma was more common among PD cases (before PD, OR = 1.5; 95% CI 0.40–5.2; after PD, RR = 1.6; 95% CI 0.71–3.6), but independent of dopaminergic therapy. Cancer occurrence is not significantly lower among patients with PD. The positive association between PD and subsequent melanoma merits further investigation, as it does not seem to be attributable to dopaminergic therapy, pigmentation, or confounding by smoking. © 2010 Movement Disorder Society.     

Comparing cerebral perfusion in Alzheimer's disease and Parkinson's disease dementia: an ASL-MRI study

Emerging evidence suggests that Alzheimer''s disease (AD) and Parkinson''s disease dementia (PDD) share neurodegenerative mechanisms. We sought to directly compare cerebral perfusion in these two conditions using arterial spin labeling magnetic resonance imaging (ASL-MRI). In total, 17 AD, 20 PDD, and 37 matched healthy controls completed ASL and structural MRI, and comprehensive neuropsychological testing. Alzheimer''s disease and PDD perfusion was analyzed by whole-brain voxel-based analysis (to assess absolute blood flow), a priori specified region of interest analysis, and principal component analysis (to generate a network differentiating the two groups). Corrections were made for cerebral atrophy, age, sex, education, and MRI scanner software version. Analysis of absolute blood flow showed no significant differences between AD and PDD. Comparing each group with controls revealed an overlapping, posterior pattern of hypoperfusion, including posterior cingulate gyrus, precuneus, and occipital regions. The perfusion network that differentiated AD and PDD groups identified relative differences in medial temporal lobes (AD<PDD) and right frontal cortex (PDD<AD). In conclusion, the pattern of cerebral hypoperfusion is very similar in AD and PDD. This suggests closely linked mechanisms of neurodegeneration mediating the evolution of dementia in both conditions.     

Characterization of diplopia in non-demented patients with Parkinson's disease

IntroductionAlthough diplopia is considered a frequent symptom of Parkinson's disease (PD), little is known about its clinical manifestation, associated mechanisms and treatment. Here we characterized binocular diplopia in non-demented PD patients in an interdisciplinary setting.MethodsPD patients were prospectively screened for diplopia, visual hallucinations, problems with spatial perception, contrast sensitivity, presence of blurred vision, and history of ophthalmological comorbidities via interview. Two groups of PD patients, one with and one without diplopia, underwent clinical and ophthalmological assessment to characterize diplopia in these patients. Clinical features were investigated using the Unified Parkinson's Disease Rating Scale and the Non-Motor Symptoms Scale.ResultsThe frequency of binocular diplopia was 29.6% (n = 37) in our cohort of 125 Parkinson's disease patients. Related mechanisms were heterogeneous including convergence insufficiency, strabismus, and motor fluctuations, as well as symptoms related to visual hallucinations. Diplopia was associated with other visual disturbances like visual hallucinations, blurred vision and problems with spatial perception. Beyond that, diplopia was found to be a predictive factor (3.2, odds ratio) for the occurrence of visual hallucinations in PD.ConclusionBinocular diplopia represents a frequent and relevant symptom in PD patients. Different subtypes should be considered due to different associated mechanisms including ophthalmic pathology and motor fluctuation, as well as intermediate to higher level visual processes. Diplopia seems to be part of a continuous spectrum of positive visual symptoms in Parkinson's disease.     

Parkinson's disease: The quintessential neuropsychiatric disorder

Although diagnosed by characteristic motor features, Parkinson's disease may be preceded, and is frequently accompanied by, a wide range of cognitive and neuropsychiatric features. In addition to the most commonly studied disorders of dementia, depression, and psychosis, other relatively common and clinically significant psychiatric complications include impulse control disorders, anxiety symptoms, disorders of sleep and wakefulness, and apathy. These problems may be underrecognized and are frequently undertreated. The emergent focus on nonmotor aspects of Parkinson's disease over the past quarter of a century is highlighted by a nonlinear increase in the number of articles published devoted to this topic. Although the development of newer antidepressants, atypical antipsychotics, and cholinesterase inhibitors in recent years has had a positive benefit on the management of these troublesome and distressing symptoms, responses are frequently suboptimal, and this remains an area of major unmet therapeutic need. © 2011 Movement Disorder Society     

Measuring therapy adherence in Parkinson's disease: a comparison of methods

The objective of this study was to assess different methods of measuring therapy adherence in Parkinson's disease (PD). In a single centre observational study, 112 patients with idiopathic PD were randomised to a crossover trial of active monitoring (n = 69, simple tablet count and electronic monitoring), or to no monitoring (n = 43, control group). All patients completed a self report and visual analogue scale (VAS) indicating therapy intake. In the active monitoring group, 56 (81% of cases) used > or = 80% of their medication, and 13 (19% of cases) used <80%, based on electronic monitoring. Median adherence for self report was 100% (interquartile range (IQR) 100 to 100) and for VAS was 100% (IQR 95 to 100), in both active and control groups. Patients taking > or = 80% of prescribed medication had a median total adherence of 98% (IQR 93 to 101) by electronic monitoring, which was similar to that from other METHODS: self report 100%, IQR 100 to 100; VAS 100%, IQR 95 to 100; simple tablet count 98%, IQR 89 to 100. Median total adherence in patients taking <80% of medication was significantly lower by electronic monitoring (69%, IQR 44 to 74) than by other methods: self report 100%, IQR 100 to 100; VAS 100%, IQR 95 to 100; and simple tablet count 90%, IQR 78 to 100 (all p<0.0001). Sensitivities of self report (10%), VAS (17%), and simple tablet count (50%) were all low for detecting suboptimal medicine intake. Self report, VAS, and simple tablet counts are insensitive as predictors of suboptimal medicine usage in PD. How patients take their medicines influences interpretation of the therapy response and consequent management decisions, with implications for clinical trial analysis and clinical practice.     

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.     

Suicidal and death ideation in Parkinson's disease

Parkinson's disease (PD) is a chronic, disabling illness affecting primarily the elderly and is associated with a high prevalence of depression. Although these are known risk factors for suicidal and death ideation, little is known about the prevalence and correlates of such ideation in PD. A convenience sample of 116 outpatients with idiopathic PD at two movement disorders centers were administered a modified Paykel Scale for suicidal and death ideation, as well as an extensive psychiatric, neuropsychological, and neurological battery. Univariate and multivariate logistic regression models were used to determine the correlates of suicidal or death ideation. Current death ideation (28%) or suicide ideation (11%) were present in 30% of the sample, and 4% had a lifetime suicide attempt. On univariate logistic regression analysis, increasing severity of depression (odds ratio = 2.92, 95% CI 2.01–4.24, P < 0.001), impulse control disorder (ICD) behaviors sometime during PD (odds ratio = 6.08, 95% CI 1.90–19.49, P = 0.002), and psychosis (odds ratio = 2.45, 95% CI 1.05–5.69, P = 0.04) were associated with either ideation. On multivariate logistic regression analysis, only increasing severity of depressive symptoms (odds ratio = 2.76, 95% CI 1.88–4.07, P < 0.001) predicted suicidal or death ideation. In conclusion, active suicidal or death ideation occurs in up to one‐third of PD patients. Comorbid psychiatric disorders, more than PD‐related disease variables, are associated with this ideation, highlighting the need for a comprehensive approach to the clinical care of PD patients. © 2008 Movement Disorder Society     

The Lille apathy rating scale (LARS), a new instrument for detecting and quantifying apathy: validation in Parkinson's disease

BACKGROUND: Apathy is usually defined as reduced interest and participation in various activities. It is a frequent consequence of neurological and psychiatric disorders. Although various scoring methods have been proposed, there is a lack of validated, standardised instruments for detecting apathy and assessing its severity. OBJECTIVE: To develop an apathy rating scale using a structured standardised interview capable of distinguishing between the condition's various features. METHODS: The Lille Apathy Rating Scale (LARS) is based on a structured interview. It includes 33 items, divided into nine domains. Responses are scored on a dichotomous scale. The participants used to validate the scale consisted of 159 patients with probable Parkinson's disease and 58 healthy control subjects. The Marin Apathy Scale, the Montgomery and Asberg Depression Rating Scale, and the Mattis Dementia Rating Scale were also administered. RESULTS: Principal component analysis showed that the LARS probed a single construct which forms the root of an oblique factor structure reflecting four dimensions: intellectual curiosity, self awareness, emotion, and action initiation. The main psychometric properties of the LARS (internal consistency, inter-rater and test-retest reliability) were satisfactory. Concurrent validity was evaluated by reference to the Marin scale and to judgements provided by expert clinicians. CONCLUSIONS: Standard validity indices showed that the LARS is sensitive and capable of distinguishing between apathy and depression. As a screening tool, the scale is able to support dichotomous judgements accurately and, when greater measurement sensitivity is required, also determine the severity of apathy within a four category classification.     

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。     

Cognitive Impairment in Parkinson's Disease without Dementia: Subtypes and Influences of Age

Background and Purpose

Cognitive impairments are common in Parkinson''s disease (PD), although the severity of these impairments does not significantly impair the patient''s daily activities. The aim of this study was to determine the frequency of mild cognitive impairment (MCI) of Parkinson''s disease (PDMCI) and its subtypes in nondemented PD patients. We also evaluated the influence of age on the pattern of subtypes of PDMCI.

Methods

A total of 141 consecutive, nondemented PD patients underwent a comprehensive neuropsychological assessment covering the five cognitive domains: attention, language, visuospatial, memory, and executive functions. PDMCI was defined as impaired performance in at least one of these five cognitive domains. The influence of age on the distribution of subtypes of PDMCI was assessed by comparing patients in two groups dichotomized according to their age at assessment (younger vs. older).

Results

Fifty-seven (40.4%) of the nondemented PD patients had an impairment in at least one domain, and were therefore considered as having PDMCI. The age at assessment and age at disease onset were significantly higher in the PDMCI patients. The amnestic type of PDMCI was the most frequent, followed by the visuospatial, linguistic, executive, and attention types in that order. The frequency of PDMCI was higher for all subtypes in the older group; the domain that was influenced the most by age was executive function.

Conclusions

MCI was common in PD and the subtypes were diverse. Age was found to be an important risk factor for the development of PDMCI, particularly for the executive subtype. These results indicate that the concept of MCI should be introduced in PD.     

Scoliosis in Patients with Parkinson's Disease

Background and purpose

Scoliosis is more common in patients with Parkinson''s disease (PD) than in the general elderly population. We compared clinical characteristics between PD patients with and without scoliosis, to identify the relationship between the direction of scoliosis and the laterality of the dominant symptoms of PD. We also studied the associations between dopaminergic pharmacotherapy and scoliosis (defined by a spinal curvature deviation of 10° or larger).

Methods

The study population comprised 97 patients (42 men and 55 women) with idiopathic PD. All of the patients submitted to a whole-spine scanograph to allow measurement of the degree of scoliosis by Cobb''s method.

Results

True scoliosis was found in 32 of the 97 PD patients, and was observed more frequently in women than in men (28 vs. 4, respectively; p=0.006). The age of patients without scoliosis was significantly lower than that of those with scoliosis (66.5±9.2 years vs. 72.8±7.3 years, respectively, mean±SD, p<0.001). There was no correlation between PD symptom laterality and scoliosis. The rate of occurrence of scoliosis did not differ between de novo and levodopa (L-dopa)-treated patients.

Conclusions

We suggest that neither L-dopa treatment nor the laterality of the initial symptoms of PD is related to the appearance of scoliosis.