Daniel Weintraub

University Hospital Donostia, San Sebastián, Basque Country, Spain

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Publications (141)770.69 Total impact

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    ABSTRACT: The Parkinson Anxiety Scale is a new scale developed to measure anxiety severity in Parkinson's disease specifically. It consists of three dimensions: persistent anxiety, episodic anxiety, and avoidance behavior. This study aimed to assess the measurement properties of the scale while controlling for the rater (self- vs. clinician-rated) effect. The Parkinson Anxiety Scale was administered to a cross-sectional multicenter international sample of 362 Parkinson's disease patients. Both patients and clinicians rated the patient's anxiety independently. A many-facet Rasch model design was applied to estimate and remove the rater effect. The following measurement properties were assessed: fit to the Rasch model, unidimensionality, reliability, differential item functioning, item local independency, interrater reliability (self or clinician), and scale targeting. In addition, test–retest stability, construct validity, precision, and diagnostic properties of the Parkinson Anxiety Scale were also analyzed. A good fit to the Rasch model was obtained for Parkinson Anxiety Scale dimensions A and B, after the removal of one item and rescoring of the response scale for certain items, whereas dimension C showed marginal fit. Self versus clinician rating differences were of small magnitude, with patients reporting higher anxiety levels than clinicians. The linear measure for Parkinson Anxiety Scale dimensions A and B showed good convergent construct with other anxiety measures and good diagnostic properties. Parkinson Anxiety Scale modified dimensions A and B provide valid and reliable measures of anxiety in Parkinson's disease that are comparable across raters. Further studies are needed with dimension C. © 2014 International Parkinson and Movement Disorder Society
    Movement Disorders 12/2014; · 5.63 Impact Factor
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    ABSTRACT: Background There is compelling evidence from over 60 epidemiological studies that smoking significantly reduces the risk of Parkinson's disease (PD). In general, those who currently smoke cigarettes, as well as those with a past history of such smoking, have a reduced risk of PD compared to those who have never smoked. Recently it has been suggested that a cardinal nonmotor sensory symptom of PD, olfactory dysfunction, may be less severe in PD patients who smoke than in PD patients who do not, in contrast to the negative effect of smoking on olfaction described in the general population.Methods We evaluated University of Pennsylvania Smell Identification Test (UPSIT) scores from 323 PD patients and 323 controls closely matched individually on age, sex, and smoking history (never, past, or current).ResultsPatients exhibited much lower UPSIT scores than did the controls (P < 0.0001). The relative decline in dysfunction of the current PD smokers was less than that of the never- and past-PD smokers (respective Ps = 0.0005 and 0.0019). Female PD patients outperformed their male counterparts by a larger margin than did the female controls (3.66 vs. 1.07 UPSIT points; respective Ps < 0.0001 and 0.06). Age-related declines in UPSIT scores were generally present (P < 0.0001). No association between the olfactory measure and smoking dose, as indexed by pack-years, was evident.ConclusionsPD patients who currently smoke do not exhibit the smoking-related decline in olfaction observed in non-PD control subjects who currently smoke. The physiological basis of this phenomenon is yet to be defined. © 2014 International Parkinson and Movement Disorder Society
    Movement Disorders 12/2014; · 5.63 Impact Factor
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    ABSTRACT: Cognitive impairment is one of the earliest, most common, and most disabling non-motor symptoms in Parkinson's disease (PD). Thus, routine screening of global cognitive abilities is important for the optimal management of PD patients. Few global cognitive screening instruments have been developed for or validated in PD patients. The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Dementia Rating Scale-2 (DRS-2) have been used extensively for cognitive screening in both clinical and research settings. Determining how to convert the scores between instruments would facilitate the longitudinal assessment of cognition in clinical settings and the comparison and synthesis of cognitive data in multicenter and longitudinal cohort studies. The primary aim of this study was to apply a simple and reliable algorithm for the conversion of MoCA to MMSE scores in PD patients. A secondary aim was to apply this algorithm for the conversion of DRS-2 to both MMSE and MoCA scores. The cognitive performance of a convenience sample of 360 patients with idiopathic PD was assessed by at least two of these cognitive screening instruments. We then developed conversion scores between the MMSE, MoCA, and DRS-2 using equipercentile equating and log-linear smoothing. The conversion score tables reported here enable direct and easy comparison of three routinely used cognitive screening assessments in PD patients. © 2014 International Parkinson and Movement Disorder Society
    Movement Disorders 11/2014; · 5.63 Impact Factor
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    ABSTRACT: Impulse control disorders (ICDs), including compulsive gambling, buying, sexual behavior, and eating, are a serious and increasingly recognized psychiatric complication in Parkinson's disease (PD). Other impulsive-compulsive behaviors (ICBs) have been described in PD, including punding (stereotyped, repetitive, purposeless behaviors) and dopamine dysregulation syndrome (DDS; compulsive PD medication overuse). ICDs have been most closely related to the use of dopamine agonists (DAs), perhaps more so at higher doses; in contrast, DDS is primarily associated with shorter-acting, higher-potency dopaminergic medications, such as apomorphine and levodopa. Possible risk factors for ICDs include male sex, younger age and younger age at PD onset, a pre-PD history of ICDs, and a personal or family history of substance abuse, bipolar disorder, or gambling problems. Given the paucity of treatment options and potentially serious consequences, it is critical for PD patients to be monitored closely for development of ICDs as part of routine clinical care. © 2014 International Parkinson and Movement Disorder Society
    Movement Disorders 10/2014; · 5.63 Impact Factor
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    ABSTRACT: Cognitive impairment is a common and disabling problem in Parkinson disease (PD) that is not well understood and is difficult to treat. Identification of genetic variants that influence the rate of cognitive decline or pattern of early cognitive deficits in PD might provide a clearer understanding of the etiopathogenesis of this important nonmotor feature.
    JAMA Neurology 09/2014; 71(11). · 7.01 Impact Factor
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    ABSTRACT: Parkinson's disease (PD) significantly impacts both patients' and spouses' emotional and physical health. However, despite the importance of social relationships for wellbeing, few studies have examined relationship quality and their correlates in individuals with PD and their partners. Specifically, no known studies have examined the association between benefit finding, or the experience of personal growth and other positive changes in the face of a stressor, and perceived marital quality. To address these gaps in the field, 25 married couples participated in a cross-sectional, pilot study. Patients were veterans diagnosed with idiopathic PD receiving care at the Philadelphia VA Medical Center. Each patient and spouse independently completed self-reported measures of sociodemographics, physical and mental wellbeing, caregiver burden, marital quality, and perceived benefits associated with having PD. Actor-partner interdependence models revealed that, after adjusting for covariates, greater perceived benefits from either having PD or living with a spouse with PD was associated with greater marital quality, both for that individual and their partner. Thus, perceiving positive consequences, such as personal growth, as a result of personally having PD or living with a spouse with PD is related to greater marital quality for both members of the marital dyad. Findings may inform individual and couples-based interventions that address the value of benefit finding and incorporate other techniques of positive reappraisal. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
    Journal of Family Psychology 09/2014; 28(5). · 1.89 Impact Factor
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    ABSTRACT: The discovery of novel plasma-based biomarkers could lead to new approaches in the treatment of Parkinson's disease (PD). Here, we explore the role of plasma apolipoprotein A1 (ApoA1) as a risk marker for PD and evaluate the influence of APOA1 promoter variation on plasma ApoA1 levels. Plasma ApoA1 and the single-nucleotide polymorphism, rs670, were assayed in a discovery cohort (cohort 1) of 301 PD patients, 80 normal controls (NCs), and 165 subjects with other neurodegenerative diseases, as well as a cohort (cohort 2) of 158 PD patients from a second clinical site. Additionally, rs670 was genotyped in a third cohort of 1,494 PD and 925 NC subjects from both clinical sites. Compared to both normal and disease controls, PD patients have lower plasma ApoA1 (P < 0.001 for both comparisons). Moreover, in PD patients, plasma ApoA1 levels are correlated with genotype at the APOA1 promoter polymorphism, rs670. Specifically, lower plasma ApoA1 levels were found in rs670 major allele (G) homozygotes in both cohort 1 (P = 0.009) and in a replication cohort (cohort 2; n = 158 PD patients; P = 0.024). Finally, evaluating rs670 genotype frequencies in 1,930 PD cases versus 997 NCs, the rs670 GG genotype shows a trend toward association (odds ratio: 1.1; P = 0.10) with PD. Our results are compatible with a model whereby circulating ApoA1 levels may be useful in risk-stratifying subjects for the development of PD, with higher ApoA1 levels suggesting relative protection. Future studies evaluating modulation of ApoA1 as a novel therapeutic strategy in PD are warranted. © 2014 International Parkinson and Movement Disorder Society
    Movement Disorders 09/2014; · 5.63 Impact Factor
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    ABSTRACT: To evaluate the course and predictors of neuropsychiatric symptoms (NPS) and cognition in patients with de novo Parkinson disease (PD).
    Neurology 08/2014; · 8.30 Impact Factor
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    ABSTRACT: Impulse control disorders (ICDs) in Parkinson disease (PD) are common and can be difficult to manage. The objective of this study was to determine the efficacy and tolerability of naltrexone, an opioid antagonist, for the treatment of ICDs in PD.METHODS: Patients with PD (n = 50) and an ICD were enrolled in an 8-week, randomized (1:1), double-blind, placebo-controlled study of naltrexone 50-100 mg/d (flexible dosing). The primary outcome measure was response based on the Clinical Global Impression-Change score, and the secondary outcome measure was change in symptom severity using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) ICD score.RESULTS: Forty-five patients (90%) completed the study. The Clinical Global Impression-Change response rate difference favoring naltrexone in completers was 19.8% (95% confidence interval [CI] -8.7% to 44.2%). While this difference was not significant (odds ratio = 1.6, 95% CI 0.5-5.2, Wald χ(2) [df] = 0.5 [1], p = 0.5), naltrexone treatment led to a significantly greater decrease in QUIP-RS ICD score over time compared with placebo (regression coefficient for interaction term in linear mixed-effects model = -7.37, F[df] = 4.3 [1, 49], p = 0.04). The estimated changes in QUIP-RS ICD scores from baseline to week 8 were 14.9 points (95% CI 9.9-19.9) for naltrexone and 7.5 points (95% CI 2.5-12.6) for placebo.CONCLUSIONS: Naltrexone treatment was not efficacious for the treatment of ICDs in PD using a global assessment of response, but findings using a PD-specific ICD rating scale support further evaluation of opioid antagonists for the treatment of ICD symptoms in PD.CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in patients with PD and an ICD, naltrexone does not significantly increase the probability of achieving response. However, the study lacked the precision to exclude an important difference in response rates.
    Neurology 07/2014; · 8.30 Impact Factor
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    ABSTRACT: Cognitive impairment is a common occurrence in Parkinson's disease (PD), although the severity and specific presentation varies across patients. Initial deficits, including mild cognitive impairment (PD-MCI), may remain stable or in many cases, may progress over variable lengths of time to Parkinson's disease dementia (PDD). As there are currently no marketed treatments for milder forms of cognitive impairment, an opportunity exists to define the path for therapeutic development in this area. In the absence of a well-defined path for the approval of therapies that target PD-MCI, pharmaceutical companies are unlikely to pursue this indication. In order to move forward and improve the quality of life for PD patients, it is imperative for the field to have consensus on the definition of PD-MCI, the best instruments to measure cognitive decline, and a strategy for future clinical trials.
    Journal of Parkinson's disease. 07/2014;
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    ABSTRACT: Cognitive impairment, including dementia, is common in Parkinson's disease (PD). The Mini-Mental State Examination (MMSE) has been recommended as a screening tool for Parkinson's disease dementia (PDD), with values below 26 indicative of possible dementia. Using a detailed neuropsychological battery, we examined the range of cognitive impairment in PD patients with an MMSE score of 26 or higher. In this multicenter, cross-sectional, observational study, we performed neuropsychological testing in a sample of 788 PD patients with MMSE scores of 26 or higher. Evaluation included tests of global cognition, executive function, language, memory, and visuospatial skills. A consensus panel reviewed results for 342 subjects and assigned a diagnosis of no cognitive impairment, mild cognitive impairment, or dementia. Sixty-seven percent of the 788 subjects performed 1.5 standard deviations below the normative mean on at least one test. On eight of the 15 tests, more than 20% of subjects scored 1.5 standard deviations or more below the normative mean. Greatest impairments were found on Hopkins Verbal Learning and Digit Symbol Coding tests. The sensitivity of the MMSE to detect dementia was 45% in a subset of participants who underwent clinical diagnostic procedures. A remarkably wide range of cognitive impairment can be found in PD patients with a relatively high score on the MMSE, including a level of cognitive impairment consistent with dementia. Given these findings, clinicians must be aware of the limitations of the MMSE in detecting cognitive impairment, including dementia, in PD. © 2014 International Parkinson and Movement Disorder Society
    Movement Disorders 07/2014; · 5.63 Impact Factor
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    ABSTRACT: A Food and Drug Administration (FDA) safety communication in August 2011 warned that citalopram was associated with a dose dependent risk of QT prolongation and recommended dose restriction in patients over the age of 60 but did not provide data for this age group.
    PLoS ONE 07/2014; 9(6):e98426. · 3.53 Impact Factor
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    ABSTRACT: Impulse control disorders (ICDs) are a relatively recent addition to the behavioral spectrum of PD-related non-motor symptoms. Social and economic factors may play a role on the ICD phenotype of PD patients.
    Parkinsonism & Related Disorders 06/2014; · 4.13 Impact Factor
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    ABSTRACT: Our aim was to assess cortical thickness in a large multicenter cohort of drug-naive patients with early Parkinson disease (PD), with and without mild cognitive impairment (MCI), and explore the cognitive correlates of regional cortical thinning. One hundred twenty-three newly diagnosed patients with PD and 56 healthy controls with 3-tesla structural MRI scans and complete neuropsychological assessment from the Parkinson's Progression Markers Initiative were included. Modified Movement Disorders Society Task Force level II criteria were applied to diagnose MCI in PD. FreeSurfer image processing and analysis software was used to measure cortical thickness across groups and the association with cognitive domains and tests. In patients with MCI, atrophy was found in temporal, parietal, frontal, and occipital areas compared with controls. Specific regional thinning in the right inferior temporal cortex was also found in cognitively normal patients. Memory, executive, and visuospatial performance was associated with temporoparietal and superior frontal thinning, suggesting a relationship between cognitive impairment and both anterior and posterior cortical atrophy in the whole patient sample. These findings confirm that MCI is associated with widespread cortical atrophy. In addition, they suggest that regional cortical thinning is already present at the time of diagnosis in patients with early, untreated PD who do not meet the criteria for MCI. Together, the results indicate that cortical thinning can serve as a marker for initial cognitive decline in early PD.
    Neurology 05/2014; · 8.30 Impact Factor
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    ABSTRACT: Existing anxiety rating scales have limited construct validity in patients with Parkinson's disease (PD). This study was undertaken to develop and validate a new anxiety rating scale, the Parkinson Anxiety Scale (PAS), that would overcome the limitations of existing scales. The general structure of the PAS was based on the outcome of a Delphi procedure. Item selection was based on a canonical correlation analysis and a Rasch analysis of items of the Hamilton Anxiety Rating Scale (HARS) and the Beck Anxiety Inventory (BAI) from a previously published study. Validation was done in a cross-sectional international multicenter study involving 362 patients with idiopathic PD. Patients underwent a single screening session in which the PAS was administered, along with the Hamilton Depression Rating Scale, the HARS, and the BAI. The Mini International Neuropsychiatric Interview was administered to establish Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnoses of anxiety and depressive disorders. The PAS is a 12-item observer or patient-rated scale with three subscales, for persistent, episodic anxiety and avoidance behavior. Properties for acceptability and reliability met predetermined criteria. The convergent and known groups validity was good. The scale has a satisfactory factorial structure. The area under the receiver operating characteristics curve and Youden index of the PAS are higher than that of existing anxiety rating scales. The PAS is a reliable and valid anxiety measure for use in PD patients. It is easy and brief to administer, and has better clinimetric properties than existing anxiety rating scales. The sensitivity to change of the PAS remains to be assessed. © 2014 International Parkinson and Movement Disorder Society
    Movement Disorders 05/2014; · 5.63 Impact Factor
  • David Burn, Daniel Weintraub, Trevor Robbins
    Movement Disorders 04/2014; 29(5):581-3. · 5.63 Impact Factor
  • David Burn, Daniel Weintraub, Bernard Ravina, Irene Litvan
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    ABSTRACT: Cognitive impairment and dementia associated with movement disorders represent a major management challenge and area of unmet need. This article has focused upon Parkinson's disease as an exemplar condition, but many of the roadblocks and efforts to overcome these are applicable, in a general sense, to other disorders. Short of a “penicillin moment”—a chance discovery or piece of unintended good fortune—progress is likely to be incremental. Cognitive therapies may end up being multiple and possibly multimodal, parallel with the cancer therapy field. Ultimately, benefit for one condition may extend to others as commonality in protein aggregation, synergistic pathological effects between proteins, and pathological spread emerges. © 2014 International Parkinson and Movement Disorder Society
    Movement Disorders 04/2014; 29(5). · 5.63 Impact Factor
  • Dag Aarsland, John-Paul Taylor, Daniel Weintraub
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    ABSTRACT: Neuropsychiatric symptoms (NPS) such as depression, hallucinations and apathy commonly occur in Parkinson's disease (PD) and have major clinical consequences including a negative impact on quality of life. This review discusses the epidemiology, clinical features, diagnostic procedures and treatment issues of NPS in PD and related disorders in the perspective of cognitive impairment, focusing on depression, anxiety, visual hallucinations, apathy, sleep disturbances, impulse control disorder and non-motor fluctuations. The majority of NPS are more common in PD patients with dementia, possibly related to shared underlying pathologies. Recent studies also suggest that NPS are associated with mild cognitive impairment in PD, in particular with the amnestic type. Accurate diagnosis of NPS is important but can be difficult, due to overlapping symptoms and similar appearance of symptoms of motor symptoms of parkinsonism, cognitive impairment, mood disorders and apathy. There are few systematic studies focusing on the management of NPS in PD with cognitive impairment. © 2014 International Parkinson and Movement Disorder Society.
    Movement Disorders 04/2014; 29(5):651-62. · 5.63 Impact Factor
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    ABSTRACT: Consensus diagnostic criteria for multiple system atrophy consider dementia as a nonsupporting feature, despite emerging evidence demonstrating that cognitive impairments are an integral part of the disease. Cognitive disturbances in multiple system atrophy occur across a wide spectrum from mild single domain deficits to impairments in multiple domains and even to frank dementia in some cases. Frontal-executive dysfunction is the most common presentation, while memory and visuospatial functions also may be impaired. Imaging and neuropathological findings support the concept that cognitive impairments in MSA originate from striatofrontal deafferentation, with additional contributions from intrinsic cortical degeneration and cerebellar pathology. Based on a comprehensive evidence-based review, the authors propose future avenues of research that ultimately may lead to diagnostic criteria for cognitive impairment and dementia associated with multiple system atrophy. © 2014 International Parkinson and Movement Disorder Society
    Movement Disorders 04/2014; · 5.63 Impact Factor
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    ABSTRACT: Impulsive-compulsive disorders are frequent in patients with Parkinson's disease (PD). Recently, a screening questionnaire and rating scale were developed for these disorders: the questionnaire for impulsive-compulsive disorders (QUIP) and QUIP-rating scale (QUIP-RS). We assessed the validity of these instruments in the German language in order to reevaluate the benefit and to obtain German screening tools in clinical practice. A convenience sample of 156 patients was assessed in Kiel and Vienna. The patients filled out the QUIP-current, the QUIP-anytime and the QUIP-RS. We validated the questionnaires against a gold standard diagnosis via receiver operating characteristic curves and determined optimal cut-off scores for the instruments. Excluding walkabout, which was not shown to be valid, sensitivities ranged from 60-92 % for the QUIP-current, 68-91 % for the QUIP-anytime, and 73-100 % for the QUIP-RS. Specificities were >71 % for QUIP-current, >69 % for QUIP-anytime and >62 % for QUIP-RS. With its very good sensitivities, the QUIP-RS is a valid instrument to assess impulsive-compulsive disorders and makes an early detection of behavioral disorders in PD possible. The QUIP-anytime was also shown to be a valid screening instrument. Both are expected to prove useful in scientific and clinical practice.
    Journal of Neurology 03/2014; · 3.84 Impact Factor

Publication Stats

4k Citations
770.69 Total Impact Points

Institutions

  • 2014
    • University Hospital Donostia
      San Sebastián, Basque Country, Spain
  • 2003–2014
    • University of Pennsylvania
      • • Perelman School of Medicine
      • • Department of Psychiatry
      Philadelphia, Pennsylvania, United States
  • 2013
    • University of Florida
      Gainesville, Florida, United States
  • 2012
    • University of Washington Seattle
      • Department of Psychiatry and Behavioral Sciences
      Seattle, WA, United States
    • Johns Hopkins Medicine
      • Department of Psychiatry and Behavioral Sciences
      Baltimore, Maryland, United States
  • 2011
    • University of Louisville
      • Department of Neurology
      Louisville, KY, United States
    • University of Naples Federico II
      Napoli, Campania, Italy
  • 2005–2011
    • Hospital of the University of Pennsylvania
      • • Department of Psychiatry
      • • Division of Geriatrics
      Philadelphia, Pennsylvania, United States
    • Alpert Medical School - Brown University
      • Department of Neurology
      Providence, Rhode Island, United States
  • 2009
    • Royal Melbourne Hospital
      Melbourne, Victoria, Australia
    • University of Rochester
      • Department of Neurology
      Rochester, NY, United States
    • Northwestern University
      • Parkinson's Disease and Movement Disorders Center
      Evanston, IL, United States
  • 2008
    • Yale University
      • Department of Psychiatry
      New Haven, CT, United States
    • Johns Hopkins University
      Baltimore, Maryland, United States
  • 2004
    • Drexel University
      Philadelphia, Pennsylvania, United States