Parkinson Disease: Weintraub D

Schrag A, Barone P, Brown RG, Leentjens AF, McDonald WM, Starkstein S, Weintraub D, Poewe W, Rascol O, Sampaio C, Stebbins GT, Goetz CG. · University Department of Clinical Neurosciences, Royal Free and University College Medical School, London, UK. · Mov Disord. · Pubmed #17394234 links to  free full text

Abstract: Depression is a common comorbid condition in Parkinson's disease (PD) and a major contributor to poor quality of life and disability. However, depression can be difficult to assess in patients with PD due to overlapping symptoms and difficulties in the assessment of depression in cognitively impaired patients. As several rating scales have been used to assess depression in PD (dPD), the Movement Disorder Society commissioned a task force to assess their clinimetric properties and make clinical recommendations regarding their use. A systematic literature review was conducted to explore the use of depression scales in PD and determine which scales should be selected for this review. The scales reviewed were the Beck Depression Inventory (BDI), Hamilton Depression Scale (Ham-D), Hospital Anxiety and Depression Scale (HADS), Zung Self-Rating Depression Scale (SDS), Geriatric Depression Scale (GDS), Montgomery-Asberg Depression Rating Scale (MADRS), Unified Parkinson's Disease Rating Scale (UPDRS) Part I, Cornell Scale for the Assessment of Depression in Dementia (CSDD), and the Center for Epidemiologic Studies Depression Scale (CES-D). Seven clinical researchers with clinical and research experience in the assessment of dPD were assigned to review the scales using a structured format. The most appropriate scale is dependent on the clinical or research goal. However, observer-rated scales are preferred if the study or clinical situation permits. For screening purposes, the HAM-D, BDI, HADS, MADRS, and GDS are valid in dPD. The CES-D and CSDD are alternative instruments that need validation in dPD. For measurement of severity of depressive symptoms, the Ham-D, MADRS, BDI, and SDS scales are recommended. Further studies are needed to validate the CSDD, which could be particularly useful for the assessment of severity of dPD in patients with comorbid dementia. To account for overlapping motor and nonmotor symptoms of depression, adjusted instrument cutoff scores may be needed for dPD, and scales to assess severity of motor symptoms (e.g., UPDRS) should also be included to help adjust for confounding factors. The HADS and the GDS include limited motor symptom assessment and may, therefore, be most useful in rating depression severity across a range of PD severity; however, these scales appear insensitive in severe depression. The complex and time-consuming task of developing a new scale to measure depression specifically for patients with PD is currently not warranted.

Simuni T, Lyons KE, Pahwa R, Hauser RA, Comella C, Elmer L, Weintraub D. · Department of Neurology, Northwestern University, Parkinson's Disease and Movement Disorders Center, Chicago, Ill, USA. · Eur Neurol. · Pubmed #19176961 links to  free full text

Abstract: The management of early Parkinson's disease (PD) involves the treatment of motor symptoms, and, increasingly, non-motor symptoms. Given the fast pace of clinical research in PD, clinicians are faced with the challenge of integrating the latest findings into the ongoing care of individual PD patients. Part 1 of this 2-part article reviews efficacy and safety data for the newest PD treatment options, as well as for established therapies. Part 2 of the article, presented here, reviews key data relevant to the assessment of potential neuroprotective therapies and the treatment of non-motor symptoms.

Simuni T, Lyons KE, Pahwa R, Hauser RA, Comella C, Elmer L, Weintraub D. · Department of Neurology, Northwestern University, Parkinson's Disease and Movement Disorders Center, Chicago, Ill 60611, USA. · Eur Neurol. · Pubmed #19176960 links to  free full text

Abstract: The management of early Parkinson's disease (PD) involves the treatment of motor symptoms and, increasingly, non-motor symptoms. Given the fast pace of clinical research in PD, clinicians are faced with the challenge of integrating the latest findings into the ongoing care of individual PD patients. Part 1 of this 2-part article reviews motor symptom efficacy data for the newest PD treatment options, as well as for established therapies. Safety and tolerability data are also reviewed. Part 2 of the article reviews key findings relevant to the assessment of potential neuroprotective therapies and the treatment of non-motor symptoms.

Poewe W, Gauthier S, Aarsland D, Leverenz JB, Barone P, Weintraub D, Tolosa E, Dubois B. · Department of Neurology, Medical University Innsbruck, Innsbruck, Austria. · Int J Clin Pract. · Pubmed #18822028 links to  free full text

Abstract: Parkinson's disease (PD) has long been considered predominantly a motor disorder. However, its frequent association with dementia, which contributes significantly to the morbidity and mortality of the condition, is gaining increasing recognition. PD dementia (PDD) has a unique clinical profile and neuropathology, distinct from Alzheimer's disease (AD). Cholinergic deficits, a feature of both AD and PDD, underlie the rationale for cholinesterase inhibitor therapy in both conditions. In clinical practice, it is important that PDD should be recognised and appropriately treated. This review aims to outline the recently proposed clinical diagnostic criteria for PDD and to summarise the guidelines/recommendations published since 2006 on the use of cholinesterase inhibitors in the management of PDD. Although the cholinesterase inhibitor rivastigmine has recently been approved for the management of PDD, there remains a need for the development of novel therapies that can affect key mechanisms of the disease or prevent/delay patients with PD and mild cognitive impairment from progressing to PDD.

Weintraub D, Comella CL, Horn S. · Department of Psychiatry and Neurology, University of Pennsylvania, 3615 Chestnut St, Philadelphia, PA 19104, USA. · Am J Manag Care. · Pubmed #18402509 links to  free full text

Abstract: The nonmotor neuropsychiatric symptoms of Parkinson's disease, particularly depression, psychosis, and cognitive impairment/dementia, are major contributors to disability and a decline in quality of life. Their effect on patients may be more disabling than motor symptoms. Increasing awareness of the importance of recognizing and treating neuropsychiatric symptoms of this disease in the medical community is a focus of specialists and organizations. This article looks at useful screening measures to help clinicians recognize neuropsychiatric symptoms and offers suggestions for their effective treatment.

Weintraub D, Comella CL, Horn S. · Department of Neurological Sciences, University of Pennsylvania, 330 S 9th St, Philadelphia, PA 19107, USA. · Am J Manag Care. · Pubmed #18402508 links to  free full text

Abstract: In the absence of a cure, the primary goals in managing Parkinson's disease (PD) are to preserve functionality and health-related quality of life. Meeting these goals can minimize healthcare-resource utilization and long-term healthcare costs. Although effective treatment of motor symptoms of the disease is a central consideration to facilitate improved outcomes, management of nonmotor symptoms is now recognized as an equally important target of intervention, since nonmotor symptoms can contribute greatly to disability. The article addresses the current treatment options of choice for reducing motor symptoms of PD and their most rational use. Cost-effectiveness is a major consideration for managed care and is also analyzed for many available treatment options.

Weintraub D, Comella CL, Horn S. · University of Pennsylvania, Philadelphia, PA, USA. · Am J Manag Care. · Pubmed #18402507 links to  free full text

Abstract: Parkinson's disease (PD) is a chronic neurodegenerative disease associated with substantial morbidity, increased mortality, and high economic burden. Of importance to managed care is that the number of cases of PD are on the rise, paralleling the advancing age of the population, and misdiagnosis is common. Effective management of PD can minimize disability and potentially improve long-term outcomes, which would minimize long-term healthcare costs and medical resource utilization. This article provides a brief review of the epidemiology, pathophysiology, clinical course, and burden of PD.

Potenza MN, Voon V, Weintraub D. · Department of Psychiatry, Yale University School of Medicine, Connecticut Mental Health Center, New Haven, CT 06519, USA. · Nat Clin Pract Neurol. · Pubmed #18046439 No free full text.

Abstract: Impulse control disorders (ICDs) constitute a group of relatively common psychiatric conditions. ICDs typically involve pleasurable or hedonic behaviors (e.g. gambling, shopping or sex) that are performed repetitively, excessively or compulsively, to an extent that interferes in major areas of life functioning. Over the past decade, case reports, case studies and controlled examinations have reported ICDs in neurological patients, particularly those with Parkinson's disease (PD). A relationship between dopamine agonist treatment and ICDs was initially suggested on the basis of clinical observations, and subsequent systematic studies have provided more-substantial support for this association. Ongoing studies of the clinical characteristics of individuals with PD with and without ICDs suggest that certain individuals might be at increased risk of developing ICDs during PD treatment. Emerging data suggest that the association between dopamine agonists and ICDs extends into other neurological patient populations in which these agents are employed, such as those with restless legs syndrome. In this article, we summarize current knowledge regarding ICDs, review their relationships with PD and its treatments, provide practical clinical recommendations based on existing data, and suggest avenues for future research directed at advancing clinical care strategies.

Weintraub D, Hurtig HI. · Department of Psychiatry, University of Pennsylvania, 3535 Market St., Rm. 3003, Philadelphia, PA 19104, USA. · Am J Psychiatry. · Pubmed #17898337 links to  free full text

This publication has no abstract.

Weintraub D, Stern MB. · University of Pennsylvania School of Medicine, Department of Psychiatry, 3535 Market Sreet, Room 3003, Philadelphia, PA 19104, USA. · Expert Rev Neurother. · Pubmed #17563252 No free full text.

Abstract: Although Parkinson's disease is considered a movement disorder, it has a wide range and high prevalence of affective, psychotic, cognitive, behavioral and sleep-related features. To treat such features, agents including antidepressants, anxiolytics, antipsychotics and cognition-enhancing agents are commonly prescribed, although the targeted syndromes are often incompletely understood and controlled studies demonstrating a treatment's efficacy and tolerability in Parkinson's disease patients are often lacking. Nevertheless, the available information does suggest the outlines of management methods, pending expanded research to identify optimal strategies specific to Parkinson's disease.

Weintraub D, Potenza MN. · Department of Psychiatry, University of Pennsylvania, 3535 Market Street, Room 3003, Philadelphia, PA 19104, USA. · Curr Neurol Neurosci Rep. · Pubmed #16822350 No free full text.

Abstract: There is an increasing awareness that impulse control disorders (ICDs), including pathologic gambling and compulsive sexual behavior, can occur as a complication of Parkinson's disease (PD). Anecdotal experience and case reporting have suggested an association between ICDs in PD and the use of dopamine agonists. Lacking established treatments for ICDs in PD, clinical management should initially consist of modifications to or discontinuation of dopamine replacement therapy, particularly dopamine agonists. It is important that PD patients be aware that dopamine agonist use may lead to the development of an ICD, and that clinicians monitor patients as part of routine clinical care. As empirically validated treatments for ICDs are emerging, it will be important to examine their efficacy and tolerability in individuals with co-occurring PD and ICDs.

Weintraub D, Stern MB. · Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. · Am J Geriatr Psychiatry. · Pubmed #16223962 No free full text.

Abstract: Although Parkinson disease (PD) is primarily considered a movement disorder, the high prevalence of psychiatric complications suggests that it is more accurately conceptualized as a neuropsychiatric disease. Affective disorders, cognitive impairment, and psychosis are particularly common in PD and are associated with excess disability, worse quality of life, poorer outcomes, and caregiver distress. Yet, in spite of this and their frequent occurrence, there is incomplete understanding of the epidemiology, phenomenology, risk factors, neuropathophysiology, and optimal treatment strategies for these disorders. Psychiatric complications are typically comorbid, and there is great intra- and inter-individual variability in presentation. The hallmark neuropathophysiological changes that occur in PD plus the association between exposure to dopaminergic medications and certain psychiatric disorders suggest a neurobiological basis for most psychiatric symptoms, although psychological factors are probably involved in the development of affective disorders. Although antidepressants, antipsychotics, and cognition-enhancing agents are commonly prescribed in PD, controlled studies demonstrating efficacy and tolerability of these drugs are virtually nonexistent. Because of the high prevalence and complexity of psychiatric complications in PD, geriatric psychiatrists are in a position to offer valuable consultation and clinical care to this population. This article provides an overview of the epidemiology, pathophysiology, clinical presentation, and management of the most common psychiatric complications in PD.

Weintraub D, Morales KH, Moberg PJ, Bilker WB, Balderston C, Duda JE, Katz IR, Stern MB. · Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Mov Disord. · Pubmed #15954137 links to  free full text

Abstract: The objective of this study was to determine effect sizes for both antidepressant treatment and placebo for depression in Parkinson's disease (PD), and to compare the findings with those reported in elderly depressed patients without PD. Recent reviews have concluded that there is little empiric evidence to support the use of antidepressants in PD; however, available data has not been analyzed to determine the effect size for antidepressant treatment in PD depression. A literature review identified antidepressant studies in PD. Suitable studies were analyzed using meta-analytic techniques, and effect sizes were compared with those from antidepressant studies in elderly patients without PD. Large effect sizes were found for both active treatment and placebo in PD, but there was no difference between the two groups. In contrast, active treatment was superior to placebo in depressed elderly patients without PD. In PD, increasing age and a diagnosis of major depression were associated with better treatment response. Results also suggest that newer antidepressants are well tolerated in PD. Despite the high prevalence of depression and antidepressant use in PD, controlled treatment research has been almost nonexistent. Meta-analysis results suggest a large but nonspecific effect for depression treatment in PD. In addition, PD patients may benefit less from antidepressant treatment, particularly selective serotonin reuptake inhibitors, than do elderly patients without PD.

Hoeh N, Gyulai L, Weintraub D, Streim J. · University of Pennsylvania, Philadelphia 19104, USA. · J Geriatr Psychiatry Neurol. · Pubmed #14653429 No free full text.

Abstract: OBJECTIVE: Psychotic symptoms are seen in numerous psychiatric illnesses afflicting the elderly. This article reviews the efficacy of the pharmacologic management of psychotic symptoms in primary psychotic disorders, affective disorders, and neurodegenerative disorders. METHOD: A comprehensive literature review. RESULTS: Evidence to support the use of pharmacologic interventions to manage psychotic symptoms in elderly patients afflicted with primary psychotic disorders and affective disorders is limited by the absence of randomized, placebo-controlled trials (RCTs). The use of low-dose clozapine is supported by RCTs in Parkinson's disease. The efficacy of risperidone and olanzapine for the treatment of psychotic symptoms has been demonstrated by large RCTs in Alzheimer's disease. CONCLUSION: There is evidence of the efficacy of antipsychotic medications to manage psychotic symptoms in elderly patients. However, the absence of published evidence from RCTs in primary psychotic and affective disorders, and the limited evidence in the neurodegenerative illnesses, is notable.

Weintraub D, Taraborelli D, Morales KH, Duda JE, Katz IR, Stern MB. · University of Pennsylvania School of Medicine, Pennsylvania, USA. · J Neuropsychiatry Clin Neurosci. · Pubmed #16963587 links to  free full text

Abstract: Depression and antidepressant use are common in Parkinson's disease, but the benefit of selective serotonin reuptake inhibitor (SSRI) treatment in this population has not been established. The authors treated 14 Parkinson's disease patients with major depression with escitalopram in an open-label study. Although treatment was well tolerated and correlated with a significant decrease in Inventory of Depressive Symptomatology score, response and remission rates were only 21% and 14%, respectively. However, half of the subjects met Clinical Global Impression-Improvement criteria for response. In Parkinson's disease, either SSRIs may have limited antidepressant effects, or the use of existing depression diagnostic and rating instruments may be problematic.

Weintraub D, Newberg AB, Cary MS, Siderowf AD, Moberg PJ, Kleiner-Fisman G, Duda JE, Stern MB, Mozley D, Katz IR. · Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. · J Nucl Med. · Pubmed #15695780 links to  free full text

Abstract: We studied the correlation of striatal dopamine transporter (DAT) imaging with anxiety and depression symptoms in Parkinson's disease (PD). METHODS: Patients with idiopathic PD (n = 76) and age-matched healthy volunteers (n = 46) underwent SPECT brain scans with (99m)Tc-TRODAT-1, a radiolabeled tropane that selectively binds to the DAT. TRODAT-1 distribution volume ratios, a reflection of DAT availability, were calculated from the SPECT scan data for 6 regions of interest (ROIs) in the caudate and putamen. The association between neuropsychiatric symptoms (anxiety, depression, and fatigue) and DAT availability was explored for both subject groups, and the impact of disease severity on this association was examined in the PD group. RESULTS: PD patients showed lower DAT availability than did healthy volunteers in all examined regions (for all ROIs, P < 0.001). In PD patients, higher individual affective measures (for anxiety, r = -0.30 and P = 0.01; and for depression, r = -0.24 and P = 0.05) and total affect scores (r = -0.31; P = 0.01) were associated with diminished left anterior putamen DAT availability. The association between total affect scores and DAT availability was present only in the subset of patients with less severe PD (r = -0.35; P = 0.04), but subjects with the highest DAT availability did not show high total affect scores. No association between neuropsychiatric measures and DAT availability was found in the controls. CONCLUSION: These preliminary findings suggest that decreased DAT availability may be necessary for but not invariably associated with the development of affective symptoms in PD. This suggestion is consistent with previous research showing a link between depression and basal ganglia impairment, particularly involving the left hemisphere, and extends this finding to include anxiety.

Weintraub D, Moberg PJ, Culbertson WC, Duda JE, Stern MB. · Parkinson's Disease Research, Education and Clinical Center (PADRECC), Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA. · Cogn Behav Neurol. · Pubmed #15622014 No free full text.

Abstract: OBJECTIVE: The purpose of the study was to determine whether patients with Parkinson disease (PD) demonstrate different memory profiles. Specifically, we sought to ascertain whether the memory performance of PD patients can be categorized as fitting an unimpaired, an impaired retrieval, or an impaired encoding memory profile. BACKGROUND: Cognitive impairment in PD is usually described as subcortical-frontal in nature. However, neuropathophysiological changes consistent with diffuse cortical disease are also reported. Establishing memory subtypes in PD could potentially assist in reducing the observed heterogeneity of disease presentation, establishing prognosis, making clinical decisions, and defining endpoints in clinical trials. METHODS:: A sample of 63 PD patients was evaluated with the Hopkins Verbal Learning Test-Revised (HVLT-R). Cluster analysis was used to classify patients into three memory subgroups based on performance on free recall, intrusion errors, and recall enhancement with recognition. Subgroup comparisons were made for demographic and clinical characteristics. RESULTS: An "unimpaired" group (n = 30) demonstrated intact free recall and few intrusion errors. "Impaired retrieval" (n = 22) and "impaired encoding" (n = 11) subgroups with similar impairment on free recall were also identified, but the impaired retrieval group demonstrated greater memory improvement with recognition (P < 0.001) and had fewer intrusion errors (P < 0.001) than the impaired encoding group. CONCLUSIONS: A majority of PD patients demonstrate memory impairment, which can be categorized as either a primary retrieval or a primary encoding deficit. Further research is needed to confirm memory subtypes in PD and determine their diagnostic, prognostic, and therapeutic significance.

Nazem S, Siderowf AD, Duda JE, Have TT, Colcher A, Horn SS, Moberg PJ, Wilkinson JR, Hurtig HI, Stern MB, Weintraub D. · Department of Psychiatry, University of Pennsyvania, Philadelphia, USA. · J Am Geriatr Soc. · Pubmed #19170786 No free full text.

Abstract: OBJECTIVES: To examine Montreal Cognitive Assessment (MoCA) performance in patients with Parkinson's disease (PD) with "normal" global cognition according to Mini-Mental State Examination (MMSE) score. DESIGN: A cross-sectional comparison of the MoCA and the MMSE. SETTING: Two movement disorders centers at the University of Pennsylvania and the Philadelphia Veterans Affairs Medical Center. PARTICIPANTS: A convenience sample of 131 patients with idiopathic PD who were screened for cognitive and psychiatric complications. MEASUREMENTS: Subjects were administered the MoCA and MMSE, and only subjects defined as having a normal age- and education-adjusted MMSE score were included in the analyses (N=100). As previously recommended in patients without PD, a MoCA score less than 26 was used to indicate the presence of at least mild cognitive impairment (MCI). RESULTS: Mean MMSE and MoCA scores+/-standard deviation were 28.8+/-1.1 and 24.9+/-3.1, respectively. More than half (52.0%) of subjects with normal MMSE scores had cognitive impairment according to their MoCA score. Impairments were seen in numerous cognitive domains, including memory, visuospatial and executive abilities, attention, and language. Predictors of cognitive impairment on the MoCA using univariate analyses were male sex, older age, lower educational level, and greater disease severity; older age was the only predictor in a multivariate model. CONCLUSION: Approximately half of patients with PD with a normal MMSE score have cognitive impairment based on the recommended MoCA cutoff score. These results suggest that MCI is common in PD and that the MoCA is a more sensitive instrument than the MMSE for its detection.

Weintraub D. · Department of Psychiatry, University of Pennsylvania School of Medicine, Parkinson's Disease Research, Education and Clinical Center, Philadelphia, PA, USA. · Ann Neurol. · Pubmed #19127573 No free full text.

Abstract: There is an increasing awareness that impulse control disorders (ICDs), including compulsive gambling, buying, sexual behavior, and eating, can occur as a complication of Parkinson's disease (PD). In addition, other impulsive or compulsive disorders have been reported to occur, including dopamine dysregulation syndrome (DDS) and punding. Case reporting and prospective studies have reported an association between ICDs and the use of dopamine agonists (DAs), particularly at greater dosages, whereas dopamine dysregulation syndrome has been associated with greater dosages of levodopa or short-acting DAs. Data suggest that risk factors for an ICD may include male sex, younger age or younger age at PD onset, a pre-PD history of ICD symptoms, personal or family history of substance abuse or bipolar disorder, and a personality style characterized by impulsiveness. Although psychiatric medications are used clinically in the treatment of ICDs, there is no empiric evidence supporting their use in PD. Therefore, management for clinically significant ICD symptoms should consist of modifications to dopamine replacement therapy, particularly DAs, and there is emerging evidence that such management is associated with an overall improvement in ICD symptomatology. It is important that PD patients be aware that DA use may lead to the development of an ICD, and that clinicians monitor patients as part of routine clinical care. As empirically validated treatments for ICDs are emerging, it will be important to examine their efficacy and tolerability in individuals with cooccurring PD and ICDs.

Leentjens AF, Dujardin K, Marsh L, Martinez-Martin P, Richard IH, Starkstein SE, Weintraub D, Sampaio C, Poewe W, Rascol O, Stebbins GT, Goetz CG. · Department of Psychiatry, Maastricht University Hospital, Maastricht, the Netherlands. · Mov Disord. · Pubmed #18792121 links to  free full text

Abstract: Anxiety syndromes are common in patients with Parkinson's disease (PD) with up to 30% suffering from panic disorder, and up to 11% from generalized anxiety disorder (GAD). Anxiety is associated with increased subjective motor symptoms, more severe gait problems, dyskinesias, freezing, and on/off fluctuations. Anxiety has a negative impact on health related quality of life and is strongly associated with depressive syndromes. Since a variety of anxiety scales have been used in PD patients, the Movement Disorder Society commissioned a task force to assess the clinimetric properties of these scales in PD. A systematic review was conducted to identify anxiety scales that have either been validated or used in patients with PD. Six anxiety rating scales were identified. These were the Beck anxiety inventory, the hospital anxiety and depression scale, the Zung self-rating anxiety scale and anxiety status inventory, the Spielberger state trait anxiety inventory, and the Hamilton anxiety rating scale. In addition, Item 5 (anxiety) of the neuropsychiatric inventory was included in the review. No scales met the criteria to be "recommended," and all scales were classified as "suggested." Essential clinimetric information is missing for all scales. Because several scales exist and have been used in PD, the task force recommends further studies of these instruments. If these studies show that the clinimetric properties of existing scales are inadequate, development of a new scale to assess anxiety in PD should be considered.

Leentjens AF, Dujardin K, Marsh L, Martinez-Martin P, Richard IH, Starkstein SE, Weintraub D, Sampaio C, Poewe W, Rascol O, Stebbins GT, Goetz CG. · Department of Psychiatry, Maastricht University Hospital, Maastricht, The Netherlands. · Mov Disord. · Pubmed #18709683 links to  free full text

Abstract: Apathy is a common condition in Parkinson's disease (PD) and is generally defined as a lack of motivation. It is associated with more severe cognitive dysfunction and a decrease in activities of daily living (ADL) performance. Anhedonia, the inability to experience pleasure, can be a symptom of both depressive and apathetic syndromes. The Movement Disorder Society (MDS) commissioned a task force to assess the clinimetric properties of apathy and anhedonia scales in PD patients. A systematic literature review was conducted to identify scales that have either been validated or used in PD patients. Apathy scales identified for review include the Apathy Evaluation Scale (AES), the Apathy Scale (AS), the Apathy Inventory (AI), and the Lille Apathy Rating Scale (LARS). In addition, item 4 (motivation/initiative) of the Unified Parkinson's Disease Rating Scale (UPDRS) and item 7 (apathy) of the Neuropsychiatric Inventory (NPI) were included. Anhedonia scales identified for review were the Snaith-Hamilton Pleasure Scale (SHAPS) and the Chapman scales for physical and social anhedonia. Only the AS is classified as "recommended" to assess apathy in PD. Although item 4 of the UPDRS also meets the criteria to be classified as recommended, it should be considered for screening only because of the obvious limitations of a single item construct. For the assessment of anhedonia, only the SHAPS meets the criteria of "Suggested." Information on the validity of apathy and anhedonia scales is limited because of the lack of consensus on diagnostic criteria for these conditions.

Nazem S, Siderowf AD, Duda JE, Brown GK, Ten Have T, Stern MB, Weintraub D. · Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Mov Disord. · Pubmed #18618660 links to  free full text

Abstract: 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.

Mamikonyan E, Moberg PJ, Siderowf A, Duda JE, Have TT, Hurtig HI, Stern MB, Weintraub D. · Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA. · Parkinsonism Relat Disord. · Pubmed #18595765 links to  free full text

Abstract: PURPOSE: Cognitive impairment occurs in the majority of Parkinson's disease (PD) patients, but little is known about detection of mild cognitive impairment (MCI) in this population. We report on the frequency and characteristics of cognitive deficits in PD patients with intact global cognition based on Mini-Mental State Examination (MMSE) performance. METHODS: One hundred and six PD patients with normal age- and education-adjusted MMSE scores (mean [SD] score=29.1 [1.1]) were administered standardized neuropsychological tests assessing memory, executive function, and attention. Impairment on a cognitive domain was a low score (i.e., >or=1.5 SD below the published normative mean) on at least two measures or tests (for memory and executive abilities) or a single measure (for attention). RESULTS: Mild cognitive impairment was found in 29.2% of PD patients, with 17.9% demonstrating single domain and 11.3% multiple domain impairment. Memory and attention impairment were most common (15.1% and 17.0%, respectively), followed by executive impairment (8.5%). Depending on the measure of disease severity chosen, increasing age and disease severity, anti-anxiety medication use, and a suggestion for increasing severity of daytime sleepiness were independent predictors of cognitive impairment. CONCLUSIONS: Cognitive deficits are common in PD patients with "normal" cognition based on MMSE performance, suggesting that MCI is under-recognized in clinical practice due to routine use of insensitive screening instruments. In contrast with some previous reports, early memory impairment may be as common as either executive or attentional deficits in PD. In addition, psychiatric medication use and daytime sleepiness may be reversible or treatable contributors to cognitive impairment.

Mamikonyan E, Siderowf AD, Duda JE, Potenza MN, Horn S, Stern MB, Weintraub D. · Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Mov Disord. · Pubmed #17960796 links to  free full text

Abstract: Recent studies have linked dopamine agonist (DA) usage with the development of impulse control disorders (ICDs) in Parkinson's disease (PD). Little is known about optimal management strategies or the long-term outcomes of affected patients. To report on the clinical interventions and long-term outcomes of PD patients who developed an ICD after DA initiation. Subjects contacted by telephone for a follow-up interview after a mean time period of 29.2 months. They were administered a modified Minnesota Impulse Disorder Interview for compulsive buying, gambling, and sexuality, and also self-rated changes in their ICD symptomatology. Baseline and follow-up dopamine replacement therapy use was recorded and verified by chart review. Of 18 subjects, 15 (83.3%) participated in the follow-up interview. At follow-up, patients were receiving a significantly lower DA levodopa equivalent daily dosage (LEDD) (Z = -3.1, P = 0.002) and a higher daily levodopa dosage (Z = -1.9, P = 0.05), but a similar total LEDD dosage (Z = -0.47, P = 0.64) with no changes in Unified Parkinson's Disease Rating Scale motor score (Z = -1.3, P = 0.19). As part of ICD management, 12 (80.0%) patients discontinued or significantly decreased DA treatment, all of whom experienced full or partial remission of ICD symptoms by self-report, and 10 (83.3%) of whom no longer met diagnostic criteria for an ICD. For PD patients who develop an ICD in the context of DA treatment, discontinuing or significantly decreasing DA exposure, even when offset by an increase in levodopa treatment, is associated with remission of or significant reduction in ICD behaviors without worsening in motor symptoms.

Moberg PJ, Balderston CC, Rick JH, Roalf DR, Weintraub D, Kleiner-Fisman G, Stern MB, Duda JE. · Parkinson's Disease Research, Education, and Clinical Center, Philadelphia Veterans Affairs Medical Center, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. · Cogn Behav Neurol. · Pubmed #17846512 No free full text.

Abstract: OBJECTIVE: To examine phenylthiocarbamide (PTC) sensitivity in Parkinson disease (PD) patients and healthy volunteers to determine whether taster status represented a simple vulnerability marker for PD. BACKGROUND: The inability to taste PTC has been associated with a number of medical illnesses not typically associated with taste impairment. Abnormalities in the function/expression of G protein-signaling pathways have been implicated in PTC perception and also in dopamine expression and regulation in PD. No study has yet probed whether PTC tasting is disrupted in PD. METHOD: PTC sensitivity was assessed in a small sample of 36 male PD patients and 20 healthy male comparison subjects using a standardized psychophysical method. RESULTS: A higher proportion of nontasters were found in patients relative to healthy comparison subjects. These differences were not explained by alterations in perception of basic taste intensity or age. Among patients, nontasters and tasters of PTC did not differ with regard to duration of illness, age of onset, severity of motor symptoms, or overall illness severity. CONCLUSIONS: These data suggest an increase in the frequency of PTC nontaster status in PD. As phenotypic variation in PTC sensitivity is genetic in origin, this may represent a surrogate risk factor for the development of PD.