Daniel Weintraub

University of Pennsylvania, Filadelfia, Pennsylvania, United States

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Publications (185)991.8 Total impact

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    ABSTRACT: Background: Mild cognitive impairment and dementia are common, clinically important features of Parkinson's disease (PD). The underlying disease pathology is heterogeneous and not yet well characterized. Biomarkers for cognitive impairment in PD could aid in diagnostic and prognostic evaluation and in the development of new cognitive enhancing treatments. Objective: To examine the relationship between CSF markers and cognition in a large, multicentre, cohort study of early, untreated PD, and compare marker concentrations between PD patients with and without MCI and healthy, age-matched controls. Methods: 414 early, untreated PD (34% with mild cognitive impairment) and 189 healthy, cognitively intact controls with baseline neuropsychological testing and CSF abeta42, t-tau, p-tau181 and α-synuclein results were included. Multiple linear regression models were constructed with a composite cognition factor, or memory-, or visuospatial- or executive-attention domains as dependent variables, and CSF markers, demographic characteristics and MDS-UPDRS III score as predictors. Results: Lower α-synuclein was associated with reduced performance on the executive-attention domain and the composite cognition factor in the whole PD-group. Abeta42 was significantly decreased in PD with mild cognitive impairment compared with controls after adjusting for covariates, while values in PD without MCI were identical to healthy controls. Conclusions: The association between reduced CSF α-synuclein concentrations and cognition suggests that α-synuclein pathology contributes to early cognitive impairment in PD, in particular to executive-attentional dysfunction. Longitudinal analyses are needed to determine if this and other CSF biomarkers in early Parkinson's disease are associated with the risk of future cognitive decline and dementia.
    11/2015; DOI:10.3233/JPD-150682
  • Kara M Smith · Sharon X Xie · Daniel Weintraub ·
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    ABSTRACT: Objective: To describe the incidence of, and clinical and neurobiological risk factors for, new-onset impulse control disorder (ICD) symptoms and related behaviours in early Parkinson disease (PD). Methods: The Parkinson's Progression Markers Initiative is an international, multicenter, prospective study of de novo patients with PD untreated at baseline and assessed annually, including serial dopamine transporter imaging (DAT-SPECT) and ICD assessment (Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease short form, QUIP). Participants were included if they screened negative on the QUIP at baseline. Kaplan-Meier curves and generalised estimating equations examined frequency and predictors of incident ICD symptoms. Results: Participants were seen at baseline (n=320), year 1 (n=284), year 2 (n=217) and year 3 (n=96). Estimated cumulative incident rates of ICD symptoms and related behaviours were 8% (year 1), 18% (year 2) and 25% (year 3) and increased each year in those on dopamine replacement therapy (DRT) and decreased in those not on DRT. In participants on DRT, risk factors for incident ICD symptoms were younger age (OR=0.97, p=0.05), a greater decrease in right caudate (OR=4.03, p=0.01) and mean striatal (OR=6.90, p=0.04) DAT availability over the first year, and lower right putamen (OR=0.06, p=0.01) and mean total striatal (OR=0.25, p=0.04) DAT availability at any post-baseline visit. Conclusions: The rate of incident ICD symptoms increases with time and initiation of DRT in early PD. In this preliminary study, a greater decrease or lower DAT binding over time increases risk of incident ICD symptoms, conferring additional risk to those taking DRT. Clinical trial registration: NCT01141023.
    Journal of neurology, neurosurgery, and psychiatry 11/2015; DOI:10.1136/jnnp-2015-311827 · 6.81 Impact Factor
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    ABSTRACT: Objective: To report the rates and predictors of progression from normal cognition to either mild cognitive impairment (MCI) or dementia using standardized neuropsychological methods. Methods: A prospective cohort of patients diagnosed with Parkinson disease (PD) and baseline normal cognition was assessed for cognitive decline, performance, and function for a minimum of 2 years, and up to 6. A panel of movement disorders experts classified patients as having normal cognition, MCI, or dementia, with 55/68 (80.9%) of eligible patients seen at year 6. Kaplan-Meier curves and Cox proportional hazard models were used to examine cognitive decline and its predictors. Results: We enrolled 141 patients, who averaged 68.8 years of age, 63% men, who had PD on average for 5 years. The cumulative incidence of cognitive impairment was 8.5% at year 1, increasing to 47.4% by year 6. All incident MCI cases had progressed to dementia by year 5. In a multivariate analysis, predictors of future decline were male sex (p = 0.02), higher Unified Parkinson's Disease Rating Scale motor score (p ≤ 0.001), and worse global cognitive score (p < 0.001). Conclusions: Approximately half of patients with PD with normal cognition at baseline develop cognitive impairment within 6 years and all new MCI cases progress to dementia within 5 years. Our results show that the transition from normal cognition to cognitive impairment, including dementia, occurs frequently and quickly. Certain clinical and cognitive variables may be useful in predicting progression to cognitive impairment in PD.
    Neurology 09/2015; 85(15). DOI:10.1212/WNL.0000000000002001 · 8.29 Impact Factor
  • Mark Terrelonge · Karen S. Marder · Daniel Weintraub · Roy N. Alcalay ·
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    ABSTRACT: Low CSF β-amyloid 1-42 has been associated with cognitive decline in advanced Parkinson's disease; data from a single cohort suggest β-amyloid 1-42 may be an early marker of cognitive impairment. Newly diagnosed Parkinson's participants (mean duration, 6.9 months) in the Parkinson's Progression Markers Initiative (n = 341) were assessed at baseline (untreated state) and followed for 2 years. CSF β-amyloid 1-42, α-synuclein, total tau, and tau phosphorylated at threonine 181 were collected at baseline. Participants were classified as having cognitive impairment (CI) if scores on two of six cognitive tests were 1.5 standard deviations below the standardized mean based on published norms in healthy controls. Multivariable regression analyses were used to determine the association between baseline CSF markers with cognitive impairment, defined by neuropsychological testing performance at 2-year follow-up. Fifty-five participants (16.1 %) had CI at baseline and were not included in further analyses. Thirty-seven of the 286 participants without CI at baseline (12.9 %) developed CI at 2 years. Participants with CI at 2 years had significantly lower mean baseline CSF β-amyloid 1-42 levels than non-CI participants (343.8 vs. 380.4 pg/mL, p < 0.01); no significant difference was seen for α-synuclein, T-tau, or P-tau 181. In a regression model of 286 participants without baseline CI adjusted for age, gender, disease duration, education, motor severity, and depression status, lower baseline β-amyloid 1-42 levels were associated with higher odds of CI at 2 years. (OR10pg/mL = 1.04, 95 % CI 1.01-1.08, p < 0.05). CSF β-amyloid 1-42 level at disease onset is an independent predictor of cognitive impairment in early Parkinson's disease.
    Journal of Molecular Neuroscience 09/2015; DOI:10.1007/s12031-015-0647-x · 2.34 Impact Factor
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    ABSTRACT: Background: Placebo responses raise significant challenges for the design of clinical trials. We report changes in agitation outcomes in the placebo arm of a recent trial of citalopram for agitation in Alzheimer's disease (CitAD). Methods: In the CitAD study, all participants and caregivers received a psychosocial intervention and 92 were assigned to placebo for nine weeks. Outcomes included Neurobehavioral Rating Scale agitation subscale (NBRS-A), modified AD Cooperative Study-Clinical Global Impression of Change (CGIC), Cohen-Mansfield Agitation Inventory (CMAI), the Neuropsychiatric Inventory (NPI) Agitation/Aggression domain (NPI A/A) and Total (NPI-Total) and ADLs. Continuous outcomes were analyzed with mixed-effects modeling and dichotomous outcomes with logistic regression. Results: Agitation outcomes improved over nine weeks: NBRS-A mean (SD) decreased from 7.8 (3.0) at baseline to 5.4 (3.2), CMAI from 28.7 (6.7) to 26.7 (7.4), NPI A/A from 8.0 (2.4) to 4.9 (3.8), and NPI-Total from 37.3 (17.7) to 28.4 (22.1). The proportion of CGI-C agitation responders ranged from 21 to 29% and was significantly different from zero. MMSE improved from 14.4 (6.9) to 15.7 (7.2) and ADLs similarly improved. Most of the improvement was observed by three weeks and was sustained through nine weeks. The major predictor of improvement in each agitation measure was a higher baseline score in that measure. Conclusions: We observed significant placebo response which may be due to regression to the mean, response to a psychosocial intervention, natural course of symptoms, or nonspecific benefits of participation in a trial.
    International Psychogeriatrics 08/2015; DOI:10.1017/S1041610215001106 · 1.93 Impact Factor
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    ABSTRACT: To assess potential genetic influences on citalopram treatment efficacy for agitation in individuals with Alzheimer dementia (AD). Six functional genetic variants were studied in the following genes: serotonin receptor 2A (HTR2A-T102C), serotonin receptor 2C (HTR2C-Cys23Ser), serotonin transporter (5HTT-LPR), brain-derived neurotropic factor (BDNF-Val66Met), apolipoprotein E (ε2, ε3, ε4 variants), and cytochrome P450 (CYP2C19). Treatment response by genotype was measured by (1) the agitation domain of the Neurobehavioral Rating Scale, (2) the modified Alzheimer Disease Cooperative Study-Clinical Global Impression of Change scale (mADCS-CGIC), (3) the agitation domain of the Neuropsychiatric Inventory (NPI), and (4) the Cohen-Mansfield Agitation Inventory. We utilized data from the Citalopram for Agitation in Alzheimer's Disease (CitAD) database. CitAD was a 9-week randomized, double-blind, placebo-controlled multicenter clinical trial showing significant improvement in agitation and caregiver distress in patients treated with citalopram. Proportional odds logistic regression and mixed effects models were used to examine the above-mentioned outcome measures. Significant interactions were noted on the NPI agitation domain for HTR2A (likelihood ratio [LR] = 6.19, df = 2, P = .04) and the mADCS-CGIC for HTR2C (LR = 4.33, df = 2, P = .02) over 9 weeks. Treatment outcomes in CitAD showed modest, although statistically significant, influence of genetic variation at HTR2A and HTR2C loci. Future studies should continue to examine the interaction of known genetic variants with antidepressant treatment in patients with AD having agitation. © The Author(s) 2015.
    Journal of Geriatric Psychiatry and Neurology 08/2015; DOI:10.1177/0891988715601735 · 2.24 Impact Factor
  • Jennifer G Goldman · Daniel Weintraub ·
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    ABSTRACT: Cognitive impairment in Parkinson's disease (PD) is a frequent complication, with significant interindividual variability in clinical symptoms, severity, timing, and neural substrates. Recent studies have focused not only on understanding PD dementia, but also mild cognitive impairment in PD, which may represent a prodromal stage for dementia. In recent years, there have been important advances regarding clinical characterizations, definitions, associated biomarkers, and risk factors for both mild cognitive impairment in PD and PD dementia. However, there is a paucity of effective therapies for cognitive impairment in PD, whether for mild symptoms or for moderate to severe dementia. At present, only rivastigmine is U.S. Food and Drug Administration approved for PD dementia, an indication received nearly a decade ago. Given the frequency of PD cognitive impairment and its substantial impact on both patients and families, the lack of available and effective treatments represents a striking gap in the field, especially when compared to the large number of available therapies for PD motor symptoms and complications. Improved symptomatic therapies, as well as potential disease-modifying agents, for PD cognitive impairment are needed. Most therapeutic trials for PD dementia and mild cognitive impairment in PD have focused on drugs developed for and tested in Alzheimer's disease, such as cholinesterase inhibitors and the N-methyl-D-aspartate receptor antagonist, memantine, though recent and ongoing trials examine the effects of pharmacological agents affecting other neurotransmitters, as well as nonpharmacological therapies, including mental and physical exercise and neurostimulation. This review summarizes the design and outcomes of trials for PD cognitive impairment published since 2013 and highlights future therapeutic research opportunities and challenges. © 2015 International Parkinson and Movement Disorder Society
    Movement Disorders 08/2015; 30(11). DOI:10.1002/mds.26352 · 5.68 Impact Factor
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    ABSTRACT: The Parkinson Associated Risk Syndrome Study identified a cohort of healthy adults with hyposmia and dopamine transporter binding reduction to characterize individuals at risk for Parkinson's disease (PD). We describe the cognitive profile of this cohort. Individuals older than 50 y without PD were recruited. Two hundred twenty-five completed cognitive testing and were included in the final analysis. A neuropsychological test battery was administered and normative scores created for global cognition, memory, executive function/working memory, processing speed/attention, visuospatial abilities, and language domains. Other non-motor symptoms (constipation, depression, anxiety, and rapid eye movement sleep behavior disorder) were assessed through questionnaires. Individuals with both hyposmia and reduced dopamine transporter binding (n = 38) had lower mean scores for global cognition, executive function/working memory, and memory compared with all other participants (n = 187). In separate multivariate logistic regression models, lower global cognition (odds ratio, 1.97, P = 0.004), and specifically executive function/working memory (odds ratio, 1.84, P = 0.004) scores were associated with membership in the hyposmia with dopamine transporter reduction group. Combining hyposmia with relative impairment on specific cognitive domains increased the odds of dopamine transporter binding reduction compared with hyposmia alone, with the greatest increase in odds for hyposmia plus executive function/working memory relative impairment (68% increase in odds from 4.14 to 6.96). Changes in global cognitive abilities, and specifically executive function/working memory, are present in individuals at risk for PD. Combining non-motor features, including cognition, improves prediction of dopamine transporter binding reduction. © 2015 International Parkinson and Movement Disorder Society. © 2015 International Parkinson and Movement Disorder Society.
    Movement Disorders 08/2015; DOI:10.1002/mds.26373 · 5.68 Impact Factor
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    ABSTRACT: Loss-of-function mutations in the GBA gene are associated with more severe cognitive impairment in PD, but the nature of these deficits is not well understood and whether common GBA polymorphisms influence cognitive performance in PD is not yet known. We screened the GBA coding region for mutations and the E326K polymorphism in 1,369 PD patients enrolled at eight sites from the PD Cognitive Genetics Consortium. Participants underwent assessments of learning and memory (Hopkins Verbal Learning Test-Revised), working memory/executive function (Letter-Number Sequencing Test and Trail Making Test A and B), language processing (semantic and phonemic verbal fluency), visuospatial abilities (Benton Judgment of Line Orientation), and global cognitive function (MoCA). We used linear regression to test for association between genotype and cognitive performance with adjustment for important covariates and accounted for multiple testing using Bonferroni's corrections. Mutation carriers (n = 60; 4.4%) and E326K carriers (n = 65; 4.7%) had a higher prevalence of dementia (mutations, odds ratio = 5.1; P = 9.7 × 10(-6) ; E326K, odds ratio = 6.4; P = 5.7 × 10(-7) ) and lower performance on Letter-Number Sequencing (mutations, corrected P[Pc ] = 9.0 × 10(-4) ; E326K, Pc = 0.036), Trail Making B-A (mutations, Pc = 0.018; E326K, Pc = 0.018), and Benton Judgment of Line Orientation (mutations, Pc = 0.0045; E326K, Pc = 0.0013). Both GBA mutations and E326K are associated with a distinct cognitive profile characterized by greater impairment in working memory/executive function and visuospatial abilities in PD patients. The discovery that E326K negatively impacts cognitive performance approximately doubles the proportion of PD patients we now recognize are at risk for more severe GBA-related cognitive deficits. © 2015 International Parkinson and Movement Disorder Society. © 2015 International Parkinson and Movement Disorder Society.
    Movement Disorders 08/2015; DOI:10.1002/mds.26359 · 5.68 Impact Factor
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    ABSTRACT: Accurate diagnosis and early detection of complex diseases, such as Parkinson's disease, has the potential to be of great benefit for researchers and clinical practice. We aimed to create a non-invasive, accurate classification model for the diagnosis of Parkinson's disease, which could serve as a basis for future disease prediction studies in longitudinal cohorts. We developed a model for disease classification using data from the Parkinson's Progression Marker Initiative (PPMI) study for 367 patients with Parkinson's disease and phenotypically typical imaging data and 165 controls without neurological disease. Olfactory function, genetic risk, family history of Parkinson's disease, age, and gender were algorithmically selected by stepwise logistic regression as significant contributors to our classifying model. We then tested the model with data from 825 patients with Parkinson's disease and 261 controls from five independent cohorts with varying recruitment strategies and designs: the Parkinson's Disease Biomarkers Program (PDBP), the Parkinson's Associated Risk Study (PARS), 23andMe, the Longitudinal and Biomarker Study in PD (LABS-PD), and the Morris K Udall Parkinson's Disease Research Center of Excellence cohort (Penn-Udall). Additionally, we used our model to investigate patients who had imaging scans without evidence of dopaminergic deficit (SWEDD). In the population from PPMI, our initial model correctly distinguished patients with Parkinson's disease from controls at an area under the curve (AUC) of 0·923 (95% CI 0·900-0·946) with high sensitivity (0·834, 95% CI 0·711-0·883) and specificity (0·903, 95% CI 0·824-0·946) at its optimum AUC threshold (0·655). All Hosmer-Lemeshow simulations suggested that when parsed into random subgroups, the subgroup data matched that of the overall cohort. External validation showed good classification of Parkinson's disease, with AUCs of 0·894 (95% CI 0·867-0·921) in the PDBP cohort, 0·998 (0·992-1·000) in PARS, 0·955 (no 95% CI available) in 23andMe, 0·929 (0·896-0·962) in LABS-PD, and 0·939 (0·891-0·986) in the Penn-Udall cohort. Four of 17 SWEDD participants who our model classified as having Parkinson's disease converted to Parkinson's disease within 1 year, whereas only one of 38 SWEDD participants who were not classified as having Parkinson's disease underwent conversion (test of proportions, p=0·003). Our model provides a potential new approach to distinguish participants with Parkinson's disease from controls. If the model can also identify individuals with prodromal or preclinical Parkinson's disease in prospective cohorts, it could facilitate identification of biomarkers and interventions. National Institute on Aging, National Institute of Neurological Disorders and Stroke, and the Michael J Fox Foundation. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Lancet Neurology 08/2015; 14(10). DOI:10.1016/S1474-4422(15)00178-7 · 21.90 Impact Factor
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    ABSTRACT: The aim of this work was to describe the development and psychometric analysis of the Penn Parkinson's Daily Activities Questionnaire. The questionnaire is an item response theory-based tool for rating cognitive instrumental activities of daily living in PD. Candidate items for the Penn Parkinson's Daily Activities Questionnaire were developed through literature review and focus groups of patients and knowledgeable informants. Item selection and calibration of item-response theory parameters were performed using responses from a cohort of PD patients and knowledgeable informants (n = 388). In independent cohorts of PD patients and knowledgeable informants, assessments of test-retest reliability (n = 50), and construct validity (n = 68) of the questionnaire were subsequently performed. Construct validity was assessed by correlating questionnaire scores with measures of motor function, cognition, an existing activities of daily living measure, and directly observed daily function. Fifty items were retained in the final questionnaire item bank. Items were excluded owing to redundancy, difficult reading level, and when item-response theory parameters could not be calculated. Test-retest reliability was high (intraclass correlation coefficient = 0.97; P < 0.001). The questionnaire correlated strongly with cognition (r = 0.68; P < 0.001) and directly observed daily function (r = 0.87; P < 0.001), but not with motor impairment (r = 0.08; P = 0.53). The questionnaire score accurately discriminated between PD patients with and without dementia (receiver operating characteristic curve = 0.91; 95% confidence interval: 0.85-0.97). The Penn Parkinson's Daily Activities Questionnaire shows strong evidence of reliability and validity. Item response theory-based psychometric analysis suggests that this questionnaire can discriminate across a range of daily functions. © 2015 International Parkinson and Movement Disorder Society. © 2015 Movement Disorder Society.
    Movement Disorders 08/2015; DOI:10.1002/mds.26339 · 5.68 Impact Factor
  • Inger van Steenoven · Dag Aarsland · Daniel Weintraub ·

    Movement Disorders 07/2015; DOI:10.1002/mds.26367 · 5.68 Impact Factor
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    ABSTRACT: Apathy is a common, troublesome symptom in Parkinson's disease (PD). However, little is known about its relationship with long-term cognition. We sought to determine if a caregiver-reported apathy measure predicts the development of PD dementia. Non-demented PD patients were recruited as part of a longitudinal study of cognition. Demographics, medications, Dementia Rating Scale-2, Unified Parkinson's Disease Rating Scale, Geriatric Depression Scale and the Neuropsychiatric Inventory-Questionnaire (NPI-Q) ratings were obtained. Apathy was defined as an NPI-Q apathy score ≥1. Participants were evaluated annually with cognitive and functional assessments until the end of the study period or a physician consensus diagnosis of dementia was assigned. Cox proportional hazard models were used to assess the effects of baseline apathy on dementia development while controlling for other clinical and demographic factors. Of 132 PD patients 12.1% (N = 16) scored in the apathetic range at baseline. A total of 19.6% (N = 26) individuals developed dementia over the course of the study, 8 of whom (30.8% of future dementia patients) had baseline apathy. In bivariate analyses baseline apathy, older age, and worse cognitive, motor, and depressive symptom scores predicted the development of dementia. In a multivariate analysis the predictive effects of baseline apathy were still significant (HR = 3.56; 95% CI = 1.09-11.62; p = 0.04). A simple, caregiver-reported measure of apathy is an independent predictor of progression to dementia in PD. This highlights the importance of apathy as a clinical characteristic of PD and could prove useful for the prediction of future dementia. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Parkinsonism & Related Disorders 06/2015; 21(8). DOI:10.1016/j.parkreldis.2015.06.009 · 3.97 Impact Factor
  • Daniel Weintraub · Kimberly Papay · Sharon X Xie ·

    Neurology 05/2015; 84(13):1386-7. · 8.29 Impact Factor
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    ABSTRACT: Agitation is a common and significant problem in Alzheimer disease (AD). In the recent Citalopram for Agitation in Alzheimer's Disease (CitAD) study, citalopram was efficacious for the treatment of AD agitation. Here we examined the time course and predictors of response to treatment. Response in CitAD was defined as a modified Alzheimer Disease Cooperative Study Clinical Global Impression of Change (CGIC) score of 1 or 2 or a Neurobehavioral Rating Scale agitation subscale (NBRS-A) score reduction ≥ 50% from baseline. "Stable early response" was defined as meeting the aforementioned criteria at both weeks 3 and 9, "late response" was response at week 9 but not at week 3, and "unstable response" was response at week 3 but not at week 9. In the primary analyses, citalopram was superior to placebo on both the CGIC and the NBRS-A response measures. Little between-group differences were found in response rates in the first 3 weeks of the study (21% versus 19% on the CGIC). Citalopram patients were more likely than placebo patients to be a late responder (18% versus 8% on CGIC, Fisher's exact p = 0.09; 31% versus 15% on NBRS-A, Fisher's exact p = 0.02). Approximately half of citalopram responders (45%-56%) at end of study achieved response later in the study compared with 30%-44% of placebo responders. Treatment with citalopram for agitation in AD needs to be at least 9 weeks in duration to allow sufficient time for full response. Study duration is an important factor to consider in the design of clinical trials for agitation in AD. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.
    The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 05/2015; DOI:10.1016/j.jagp.2015.05.006 · 4.24 Impact Factor

  • 05/2015; 2(2). DOI:10.1002/mdc3.12130
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    ABSTRACT: In Parkinson's disease (PD), neuropsychiatric symptoms (NPS) can be particularly burdensome for caregivers. The main goal of this study was to assess the impact of NPS, assessed by means of a new specific scale, on caregiver burden. A sample of 584 pairs of PD patients and their primary caregivers was studied. Patients' NPS were measured with the Scale for Evaluation of Neuropsychiatric Disorders in PD (SEND-PD), and the Zarit Caregiver Burden Inventory was used to quantify caregiver burden. Three linear regression models were built to check factors associated with caregiver burden, one for the total sample and two for subgroups stratified by the presence of dementia. The most frequent NPS were depression (in 66% of the sample), anxiety (65%) and mental fatigue (57%). Patients with dementia (n = 94; 16% of sample) consistently presented more NPS than patients without dementia (p < 0.001). On linear regression models, the main determinants of caregiver burden (for the total sample and the sample of patients without dementia) were SEND-PD dimensions mood/apathy and psychosis, PD-related disability and disease duration. For patients with dementia, the only significant caregiver burden determinants were SEND-PD psychosis and mood/apathy subscale scores. NPS in PD are highly associated with and are determinants of caregiver burden, and are more prevalent and burdensome in patients with dementia. Detailed assessment and specific interventions aimed at NPS could alleviate caregiver burden. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Parkinsonism & Related Disorders 04/2015; 5(6). DOI:10.1016/j.parkreldis.2015.03.024 · 3.97 Impact Factor
  • Eugenia Mamikonyan · Sharon X. Xie · Emilie Melvin · Daniel Weintraub ·
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    ABSTRACT: Mild cognitive impairment (MCI) in Parkinson's disease (PD) may be associated with subtle functional impairment and worse quality of life. The objective of this study was to determine the efficacy and tolerability of rivastigmine for PD-MCI. Patients with PD-MCI (n = 28) were enrolled in a 24-week, randomized, double-blind, placebo-controlled, crossover, single-site study of the rivastigmine transdermal patch. The primary outcome measure was the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC). Secondary outcomes included the Montreal Cognitive Assessment (MoCA), Dementia Rating Scale-2 (DRS-2), Neurotrax computerized cognitive battery, the Everyday Cognition Battery (ECB), and the Parkinson's Disease Questionnaire (PDQ-8). Twenty-six participants (92.9%) completed both study phase assessments, and 23 (82.1%) completed both phases on study medication. The CGIC response rate demonstrated a trend effect in favor of rivastigmine (regression coefficient for interaction term in linear mixed-effects model = 0.44, F[df] = 3.01 [1, 24], P = 0.096). For secondary outcomes, a significant rivastigmine effect on the ECB (regression coefficient = -2.41, F[df] = 5.81 [1, 22.05], P = 0.03) was seen, but no treatment effect was found on any cognitive measures. Trend effects also occurred in favor of rivastigmine on the PDQ-8 (regression coefficient = 4.55, F[df] = 3.93 [1, 14. 79], P = 0.09) and the State Anxiety Inventory (regression coefficient = -1.24, F[df] = 3.17 [1, 33], P = 0.08). Rivastigmine in PD-MCI showed a trend effect for improvements on a global rating of cognition, disease-related health status, and anxiety severity, and significant improvement on a performance-based measure of cognitive abilities. © 2015 International Parkinson and Movement Disorder Society. © 2015 International Parkinson and Movement Disorder Society.
    Movement Disorders 04/2015; 30(7). DOI:10.1002/mds.26236 · 5.68 Impact Factor

  • Neurology 03/2015; 84(13):1386-7. DOI:10.1212/WNL.0000000000001458 · 8.29 Impact Factor
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    ABSTRACT: Prescribing practice patterns and factors associated with treatment changes in older patients initiating antipsychotic treatment for the behavioral and psychological symptoms of dementia is not well known. The objective of this study is to study 90-day prescribing practice patterns across the three most commonly prescribed antipsychotics. This is a retrospective study using national data from the US Department of Veterans Affairs (VA). The study included patients older than 65 years diagnosed with dementia who began outpatient treatment with an antipsychotic medication between 2005 and 2008. Patients were followed for 90 days from their antipsychotic start. The primary event of interest was changing to another psychotropic medication. Cumulative incidence of treatment change was determined with antipsychotic discontinuation and death as competing risks. Covariate-adjusted hazard ratios for treatment change were determined using competing risk regression models. During the study period, 15,435 patients initiated an atypical antipsychotic; 14,791 started olanzapine, quetiapine, or risperidone. Over half (55%) of the patients discontinued index treatment within 90 days, 36% continued, 3% died while on index treatment, and 6% changed to another psychotropic medication. Compared with quetiapine, the adjusted hazard of treatment change was higher by 43% (p = 0.005) for olanzapine and by 12% (p = 0.08) for risperidone. The higher hazard of treatment change with olanzapine suggests patients either responded worse to or experienced more adverse events with olanzapine compared with quetiapine. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
    International Journal of Geriatric Psychiatry 03/2015; DOI:10.1002/gps.4281 · 2.87 Impact Factor

Publication Stats

7k Citations
991.80 Total Impact Points


  • 2004-2015
    • University of Pennsylvania
      • Department of Psychiatry
      Filadelfia, Pennsylvania, United States
    • Drexel University
      Philadelphia, Pennsylvania, United States
  • 2014
    • University Hospital Donostia
      San Sebastián, Basque Country, Spain
  • 2009-2014
    • William Penn University
      Filadelfia, Pennsylvania, United States
  • 2012
    • Johns Hopkins Medicine
      • Department of Psychiatry and Behavioral Sciences
      Baltimore, Maryland, United States
  • 2011
    • Brown University
      • Department of Neurology
      Providence, Rhode Island, United States
  • 2006
    • University of California, Los Angeles
      Los Angeles, California, United States
  • 2001
    • University of Louisville
      • Department of Psychiatry and Behavioral Sciences
      Louisville, Kentucky, United States