Pain in Parkinson's Disease: Current Concepts and a New Diagnostic Algorithm.

BACKGROUND: Pain is a significant burden for patients with Parkinson's disease (PD) with a high impact on quality of life. The present article aims at summarizing epidemiological, pathophysiological, clinical, and neurophysiological data regarding pain in PD. METHODS: In this domain, a procedure of systematic assessment is still lacking for the syndromic diagnosis and should take into account pain characteristics, effects of dopaminergic treatment, motor fluctuations, and non-PD-associated pain. FINDINGS: We propose an original questionnaire addressing an algorithm suitable for daily clinical practice. The questionnaire is based on a three-step approach addressing first the relationship between pain and PD (including temporal relationship with the course of the disease, association with motor fluctuations, and impact of antiparkinsonian treatment), before classifying pain into one of three main syndromes (i.e., musculoskeletal pain, psychomotor restlessness pain, and neuropathic pain). CONCLUSIONS: The proposed questionnaire allows the characteristics of each pain type to be determined according to its relationship with the disease and its treatment. The validation of the clinical use of this questionnaire will be the goal of a forthcoming work.

[Psychosis in Parkinson's disease]. / Psykose ved Parkinsons sykdom.

BACKGROUND: Psychosis is common in Parkinson's disease, and occurs with increasing frequency as the disease progresses. Assessment and treatment are often complicated and involve several clinical specialists in addition to the general practitioner. We describe the prevalence, form, causes and treatment of psychosis in Parkinson's disease. MATERIAL AND METHOD: The article is based on a literature search in PubMed for controlled pharmacological treatment studies and a discretionary selection of articles based on the authors' clinical and research experience. RESULTS: About 1 % of patients with newly diagnosed Parkinson's disease have psychotic symptoms. In later stages, complicated by dementia, these symptoms occur in about half of the patients. A false sense of presence, optical illusions and visual hallucinations occur most frequently, but delusions and hallucinations involving other senses have been reported. Various theories to explain the underlying etiology and pathology are explored. A further medical assessment is recommended when psychotic symptoms occur. Clozapine is still the only antipsychotic drug documented effective against psychotic symptoms in Parkinson's disease. INTERPRETATION: The prevalence of psychotic symptoms in various stages of Parkinson''s disease has been thoroughly documented. Non-pharmacological treatment is often effective, but the documentation is inadequate. Pharmacological treatment with clozapine has proved effective against psychosis in Parkinson's disease, but new drugs that are easier to administer are needed.

Depression in Parkinson disease--epidemiology, mechanisms and management.

Depression occurs in around 35% of patients with Parkinson disease (PD) and is often persistent. Symptoms of depression can be evident in individuals at the time of diagnosis and might develop in the premotor stage of the disease. The underlying mechanisms of depression in PD are not known in detail, but changes in brain structure, signaling by neurotransmitters, and levels of inflammatory and neurotrophic factors are all suggested to contribute to its development. Psychosocial factors and pain could also have roles in depression. Changes in dopaminergic, noradrenergic and serotonergic systems in patients with PD might help to explain the incidence of depression in these individuals. Antidepressants that have dual serotonergic and noradrenergic effects are the drugs of choice for treating depression in PD. However, antiparkinsonian drugs might have beneficial effects not only on the motor symptoms of disease, but also on a patient's mood. Deep brain stimulation can worsen depression in some patients, but a preliminary study has suggested that transcranial magnetic stimulation could improve symptoms of depression. This Review describes the frequency and course of depression in patients with PD. The mechanisms that underlie depression in this disease are also discussed, and the management strategies for these patients are highlighted.

Depressive symptoms in Alzheimer's disease and lewy body dementia: a one-year follow-up study.

OBJECTIVE: To explore the course of depression in people with mild dementia and identify predictors for depression at 1-year follow-up. METHODS: Patients with mild dementia (n = 199) were assessed using Montgomery and Åsberg Depression Rating Scale (MADRS) and the depression item from Neuropsychiatric Inventory (NPI) at baseline and after 1 year. A score above 6 on MADRS indicates at least mild depression. Linear and logistic regression analyses were performed to identify predictors of change in depression scores. RESULTS: Among subjects with depression at baseline, 68.1% remained depressed at follow-up, whereas 31.9% had remitted, based on MADRS. Among patients without depression at baseline, 77.1% remained non-depressed at follow-up, whereas 22.9% had incident depression. The proportion with persistent depression was higher in the combined dementia with Lewy bodies (DLB)/Parkinson's disease with dementia (PDD) group (45.5%) compared to AD (28%) (p < 0.05). Greater decline on the Mini Mental State Examination (p < 0.001) and higher baseline MADRS score (p < 0.001) were significant predictors of increased MADRS score. CONCLUSION: Two thirds of patients with depression at baseline were still depressed at follow-up, more so in DLB with PDD compared to AD. Cognitive decline was associated with worsening of depressive symptoms.

Depression in mild dementia: associations with diagnosis, APOE genotype and clinical features.

BACKGROUND: Depression is common in dementia, with important clinical implications. Few studies of depression in dementia with Lewy bodies are available, and the results are inconsistent. OBJECTIVE: To examine the frequency of depression and its characteristics and correlates, in people with mild dementia. METHODS: All referrals for patients with a first time diagnosis of dementia to geriatric and older psychiatry outpatient clinics in the counties of Rogaland and Hordaland in Western Norway from March 2005 to March 2007 were screened for the study. Participants and their caregivers underwent a comprehensive and standardised diagnostic and assessment procedure. The depression subitem of the neuropsychiatric inventory (NPId) and Montgomery and Åsberg depression rating scale (MADRS) were used to estimate depression. Cut-off scores for any depression were 0/1 (NPId) and 6/7 (MADRS), and for clinically significant depression 3/4 and 14/15, respectively. RESULTS: Two hundered and twenty-three subjects with dementia participated, of whom 59 and 50% showed symptoms of depression assessed by NPI or MADRS, respectively, and 25 and 16% had clinically significant depression as measured by NPI and MADRS, respectively. Depression was more frequent in dementia with Lewy bodies (DLB) than in Alzheimer's disease (AD; p < 0.05). APOE genotype was available in 153 patients, and in AD, but not in DLB, a general linear model showed that the presence of APOEε4 allele was significantly associated with depression (F = 4.14; p = 0.045). CONCLUSION: Depression is common even in mild dementia, and more common and severe in DLB compared to AD. Future studies should explore the longitudinal course of depression in DLB, and the neural underpinnings of depression in DLB.

Use of drugs with anticholinergic effect and impact on cognition in Parkinson's disease: a cohort study.

BACKGROUND: Cognitive decline is common in Parkinson's disease (PD). Although some of the aetiological factors are known, it is not yet known whether drugs with anticholinergic activity (AA) contribute to this cognitive decline. Such knowledge would provide opportunities to prevent acceleration of cognitive decline in PD. OBJECTIVE: To study whether the use of agents with anticholinergic properties is an independent risk factor for cognitive decline in patients with PD. METHODS: A community-based cohort of patients with PD (n=235) were included and assessed at baseline. They were reassessed 4 and 8 years later. Cognition was assessed using the Mini-Mental State Examination (MMSE). A detailed assessment of the AA of all drugs prescribed was made, and AA was classified according to a standardised scale. Relationships between cognitive decline and AA load and duration of treatment were assessed using bivariate and multivariate statistical analyses. RESULTS: More than 40% used drugs with AA at baseline. During the 8-year follow-up, the cognitive decline was higher in those who had been taking AA drugs (median decline on MMSE 6.5 points) compared with those who had not taken such drugs (median decline 1 point; p=0.025). In linear regression analyses adjusting for age, baseline cognition and depression, significant associations with decline on MMSE were found for total AA load (standardised beta=0.229, p=0.04) as well as the duration of using AA drugs (standardised beta 0.231, p=0.032). CONCLUSION: Our findings suggest that there is an association between anticholinergic drug use and cognitive decline in PD. This may provide an important opportunity for clinicians to avoid increasing progression of cognitive decline by avoiding drugs with AA. Increased awareness by clinicians is required about the classes of drugs that have anticholinergic properties.

Pain and its relationship to depression in Parkinson disease.

BACKGROUND: Depression and pain are common in Parkinson disease (PD). An association between pain and depression has been demonstrated in non-PD groups, but little is known about this relationship in PD. The authors examined the relationship between pain and depression in a community-based sample of patients with PD. METHODS: Two hundred twenty-seven patients with PD were drawn from a community-based prevalence study. A random sample of 100 healthy elderly comparable regarding age and sex were included for comparison. Pain was assessed by employing the pain section of the Nottingham Health Profile and depression by the Montgomery-Asberg Depression Rating Scale (MADRS) and the Beck Depression Inventory (BDI). General linear models and regression analyses were used to study the relationship between pain and depression. RESULTS: Sixty-seven percent of PD patients suffered from pain, compared with 39% of the control group. PD subjects with pain had higher scores on MADRS and BDI, and were more likely to have major depression, than PD patients without pain. In multivariate analyses, the presence of pain was significantly associated with depression scores, even after adjusting for demographic and clinical variables. CONCLUSION: A significant relationship between pain and depression was found. Pain issues should be integrated in the evaluation and management of depression in PD, and vice versa.

Frequency and case identification of dementia with Lewy bodies using the revised consensus criteria.

OBJECTIVE: To find the proportion of dementia with Lewy bodies (DLB) in a referral cohort of patients with a first-time diagnosis of mild dementia. BACKGROUND: The proportion of DLB among the dementia sufferers is not known and the clinical consensus criteria have low sensitivity. We employed the revised DLB criteria to study the proportion with DLB in a community sample of patients with mild dementia. METHODS: From March 2005 to March 2007, we included 196 patients from referrals to all geriatric medicine, old age psychiatry and neurology outpatient clinics in Rogaland and Hordaland counties in Western Norway. Standardized clinical instruments and diagnostic criteria were employed. RESULTS: 65% had Alzheimer dementia, 20% DLB (16% probable DLB), 5.6% vascular dementia, 5.6% Parkinson disease with dementia, 2.0% frontotemporal dementia and 1.5% alcoholic dementia. There were no significant differences in the proportion with DLB according to age bands and dementia severity groups. The revised criteria for a clinical diagnosis of DLB increased the proportion of probable DLB by 25% compared to the previous criteria. CONCLUSION: DLB is common in patients with mild dementia, and is the second most common type of dementia. The introduction of new clinical criteria for DLB leads to an increase in the proportion diagnosed with probable DLB.

[Neuropsychiatric and cognitive symptoms in Parkinson disease]. / Nevropsykiatriske og kognitive symptomer ved Parkinsons sykdom.

BACKGROUND: A variety of neuropsychiatric symptoms commonly occur in Parkinson's disease. Extensive research the last 10 years has provided new knowledge in the field. MATERIAL AND METHODS: This review is based on literature retrieved from a Medline search and own research and clinical experience. RESULTS AND INTERPRETATION: Neuropsychiatric symptoms occur in the majority of patients with Parkinson's disease, and are associated with impaired quality of life for patients and relatives, additional deterioration of function and increased use of health resources. Medical and surgical therapies can induce or worsen such symptoms. Cognitive impairment and dementia are among the most common and severe complications to Parkinson's disease. No disease-modifying treatment is available, but rivastigmine was effective in one large randomised trial. Visual hallucinations are common and often persistent, but can be treated with klozapin if reducing the number and dose of antiparkinson agents are not helpful. Depression occurs frequently, usually mild, but there is little evidence of treatment efficacy. Apathy, anxiety and sleep disturbances are additional commonly occurring neuropsychiatric symptoms. Neuropsychiatric symptoms are so frequent in Parkinson's disease that they should be considered an integral part of the disease; it is important that clinicians are aware of these symptoms.

Cortical serotonin 1A receptor levels are associated with depression in patients with dementia with Lewy bodies and Parkinson's disease dementia.

BACKGROUND: Serotonin 1A receptors (5-HT(1A)) have not been studied in dementia with Lewy bodies (DLB) or Parkinson's disease dementia (PDD) patients with depression. AIM: To examine 5-HT(1A) in DLB and PDD postmortem in relation to depression. METHODS: [(3)H]8-hydroxy-2-dipropylaminotetralin binding to 5-HT(1A) was determined in temporal cortex (Brodmann areas, BA20 and BA36) from 10 DLB patients, 17 PDD patients and 9 controls. RESULTS: 5-HT(1A) density was significantly higher in BA36 in combined DLB/PDD patients with depression, but was unaltered in BA20. CONCLUSION: Higher BA36 5-HT(1A) density in PDD and DLB patients than in control is dependent on whether the patient had experienced depression during life, not DLB/PDD diagnosis. A 5-HT(1A) antagonist adjuvant may improve treatment of depression in dementia.

A systematic review of prevalence studies of depression in Parkinson's disease.

Prevalence rates of depressive disorders in Parkinson's disease (PD) vary widely across studies, ranging from 2.7% to more than 90%. The aim of this systematic review was to calculate average prevalences of depressive disorders taking into account the different settings and different diagnostic approaches of studies. Using Medline on Pubmed, a systematic literature search was carried out for studies of depression in Parkinson's disease. A total of 104 articles were included and assessed for quality; 51 articles fulfilled the quality criteria. Multiple publications from the same database were not included in the meta-analysis. In the remaining 36 articles, the weighted prevalence of major depressive disorder was 17% of PD patients, that of minor depression 22% and dysthymia 13%. Clinically significant depressive symptoms, irrespective of the presence of a DSM defined depressive disorder, were present in 35%. In studies using a (semi) structured interview to establish DSM criteria, the reported prevalence of major depressive disorder was 19%, while in studies using DSM criteria without a structured interview, the reported prevalence of major depressive disorder was 7%. Population studies report lower prevalence rates for both major depressive disorder and the clinically significant depressive symptoms than studies in other settings. This systematic review suggests that the average prevalence of major depressive disorder in PD is substantial, but lower than generally assumed.

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.

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.

Psychiatric aspects of Parkinson's disease.

PURPOSE OF REVIEW: Recently, there has been much interest and rapid progress in understanding the neuropsychiatry of Parkinson's disease. This paper reviews the most important papers published during 2004 on dementia and cognitive impairment, depression and psychosis in Parkinson's disease. RECENT FINDINGS: Many new studies of cognitive impairment and dementia in Parkinson's disease have been published during 2004. Cognitive impairment has been demonstrated even during the first 1-2 years after onset of disease. Whereas executive and attentional impairment is typical, learning deficits occur early in some patients. Both functional and structural imaging suggest that in addition to fronto-subcortical deficits, temporal and parietal changes occur early as well. In the first large placebo-controlled trial, the cholinesterase inhibitor rivastigmine improved cognition, daily functioning and psychiatric symptoms without worsening of parkinsonism. The frequency and characteristics of depression, anxiety and hallucinations have been explored in several studies. Unfortunately, there is still little scientific evidence available to guide the treatment of these important aspects of Parkinson's disease, and adequately designed clinical trials are needed. Although subthalamic stimulation, in addition to improvement of movement, is frequently associated with some affective and cognitive improvement, permanent and significant worsening may occur in some. Future studies should aim at identifying at-risk patients, as well as identifying the optimal pharmacological and stimulation treatments for individual patients. SUMMARY: These findings provide a deeper understanding of the neurobiological substrate of cognitive impairment and dementia in Parkinson's disease, and provide new information regarding the assessment and management of dementia and other neuropsychiatric aspects of Parkinson's disease.

TEMPS-a scale in 'mixed' and 'pure' manic episodes: new data and methodological considerations on the relevance of joint anxious-depressive temperament traits.

BACKGROUND: Temperament is an important factor in affective illness. There is some indication that mixed episodes result from an admixture of inverse temperamental factors (e.g. depressive and/or anxious) to a manic syndrome. To test this hypothesis, which has been first formulated by Akiskal [Clin. Neuropharmacol. 15 (Suppl. 1A) (1992) 632-633], we compared the temperament of non-acute bipolar affective patients with and without the history of a previous mixed episode. METHODS: Patients who had been hospitalized for a bipolar disorder were re-assessed at least 6 months after their last in-patient treatment. Those who met the criteria for a partially remitted or full affective or psychotic episode at re-assessment were excluded from the study. Data concerning illness history, current psychopathology (SCID-I interview), depression (BDI), mania (Self-Report Manic Inventory) and temperament (TEMPS-A scale) were obtained. Patients with and without a history of previous mixed episodes were compared. RESULTS: Of 49 eligible former patients, 22 subjects with and 23 subjects without a former mixed episode in bipolar affective disorder fulfilled the inclusion criteria. Subjects suffering from bipolar affective disorder exhibited significantly more depressive and anxious and less hyperthymic temperament, if they had experienced a mixed episode previously. Concerning cyclothymic and irritable temperament, bipolar affective patients with a former mixed episode presented non-significantly higher scores. Patients with a former mixed episode presented with higher depression scores than patients without such a history. No group differences were found concerning current mania scores. LIMITATIONS: (1). This is a preliminary report from an ongoing study. (2). Temperament had not been assessed premorbidly. (3). Although group comparisons revealed significant differences, these did not seem great enough to fully explain the emergence of a mixed episode. CONCLUSION: Our findings support the study's hypothesis that mixed episodes occur more often in subjects with an inverse temperament (e.g. depressive and anxious), although it cannot be ruled out that subsyndromal features of the bipolar illness had an effect on temperament assessment.

Frequency of comorbid personality disorders in bipolar and unipolar affective disorders.

One expression of the complex relationship between personality and affective disorder is the comorbidity of personality disorders (PDs) with affective disorders. In a sample of 117 patients with unipolar and 60 with bipolar affective disorders, we assessed DSM-III-R PDs with the Structured Clinical Interview for DSM-IV Personality Disorders (SCID-II) and compared them with personality factors as obtained by the five-factor model (FFM-NEO Five-Factor Inventory). Fifty-one percent of the unipolar and 38% of the bipolar disorders fulfilled criteria for a comorbid PD. The three most frequent PDs were obsessive-compulsive PD, borderline PD, and narcissistic (bipolar) or avoidant (unipolar) PD. Cluster C PDs and especially avoidant PD occurred significantly more frequently in unipolar than in bipolar patients, while narcissistic PD occurred significantly more often in bipolar than in unipolar patients. The FFM results supported the validity of our PD diagnoses. In a logistic regression analysis, higher depression score at the time of the SCID-II interview and shorter duration of the illness were weakly related to a higher frequency of PDs. Our results indicate that PDs are frequent in affective disorders and that there are subtle differences between unipolar and bipolar patients concerning such comorbid disorders.

Consequences of comorbid personality disorders in major depression.

To describe consequences of the presence of a comorbid personality disorder (PD) in inpatients with a major depressive disorder (MDD) on variables connected to course and outcome of the unipolar affective illness, 117 inpatients with a major depressive episode were assessed at various times during inpatient treatment. Trait markers (including personality and PDs) were obtained toward the end of the treatment, when acute psychopathology had largely remitted. Fifty-one percent of all patients fulfilled the criteria for a DSM-III-R PD, 15% met the criteria for two or more PDs, and 18% fulfilled the criteria for at least one cluster A or B PD. Except for age of onset, number of suicide attempts and quality of life all other outcome and course variables were unrelated to the presence or absence of a comorbid PD. In this sample, one comorbid PD in patients with MDD was of limited relevance to the course of the affective illness, especially if it was a cluster C PD. Two or more comorbid PDs in patients with unipolar depression tended to reduce quality of life and have an earlier age of onset. Patients with cluster A or B PD and MDD had attempted suicide more often than patients with a cluster C PD and MDD. Although comorbid cluster C PDs were seen in all age groups of patients with an MDD, cluster A or B PDs and the presence of more than one PD were mainly seen in younger patients with an MDD.