The movement disorder society nonmotor rating scale: Initial validation study.

BACKGROUND: The Movement Disorder Society-sponsored Nonmotor Rating Scale is an update of the existing Parkinson's disease Nonmotor Symptoms Scale modified to address some limitations in Nonmotor Symptoms Scale scoring, structure, and symptom coverage. METHODS: PD patients were recruited from movement disorder centers in an international, multicenter study. The Movement Disorder Society Nonmotor Rating Scale, consisting of 13 domains plus a subscale for nonmotor fluctuations, was rater administered, along with the Nonmotor Symptoms Scale and other clinical assessments. Standard reliability and validity testing were conducted. RESULTS: Four hundred and two PD patients were recruited (mean age ± standard deviation, 67.42 ± 9.96 years; mean age at PD onset ± standard deviation, 59.27 ± 10.67 years; median Hoehn and Yahr stage 2 (interquartile range 2-3). Data quality was satisfactory for all Movement Disorder Society Nonmotor Rating Scale domains except sexual (6.7% missing data). There were no floor or ceiling effects for the Movement Disorder Society Nonmotor Rating Scale and nonmotor fluctuations total score; domains had no ceiling effects, but some floor effects (13.5%-83.5%). The Movement Disorder Society Nonmotor Rating Scale and nonmotor fluctuations total score internal consistency were acceptable (average Cronbach's alpha, 0.66 and 0.84, respectively); interrater reliability was excellent (intraclass correlation coefficient, >0.95); for test-retest reliability, the intraclass correlation coefficient was 0.84 for the Movement Disorder Society Nonmotor Rating Scale and 0.70 for Movement Disorder Society nonmotor fluctuations total score, and precision was excellent for the Movement Disorder Society Nonmotor Rating Scale (standard error of measurement, 25.30) and fair for nonmotor fluctuations (standard error of measurement, 7.06). Correlations between Movement Disorder Society Nonmotor Rating Scale score and the corresponding Nonmotor Symptoms Scale and Movement Disorder Society UPDRS scores were high. There were no significant sex or age effects. The Movement Disorder Society Nonmotor Rating Scale score increased with increasing PD duration, disease severity, and PD medication dose (all P < 0.001). CONCLUSIONS: The Movement Disorder Society Nonmotor Rating Scale is a valid measure for measuring the burden of a wide range of Nonmotor Rating Scale scores, including nonmotor fluctuations, in PD patients. © 2019 International Parkinson and Movement Disorder Society.

The Neuropsychiatry of Parkinson Disease: A Perfect Storm.

Affective disorders, cognitive decline, and psychosis have long been recognized as common in Parkinson disease (PD), and other psychiatric disorders include impulse control disorders, anxiety symptoms, disorders of sleep and wakefulness, and apathy. Psychiatric aspects of PD are associated with numerous adverse outcomes, yet in spite of this and their frequent occurrence, there is incomplete understanding of epidemiology, presentation, risk factors, neural substrate, and management strategies. Psychiatric features are typically multimorbid, and there is great intra- and interindividual 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 many psychiatric symptoms, although psychological factors are involved as well. There is evidence that psychiatric disorders in PD are still under-recognized and undertreated and although psychotropic medication use is common, controlled studies demonstrating efficacy and tolerability are largely lacking. Future research on neuropsychiatric complications in PD should be oriented toward determining modifiable correlates or risk factors and establishing efficacious and well-tolerated treatment strategies.

Antipsychotic Use and Physical Morbidity in Parkinson Disease.

OBJECTIVE: To determine if antipsychotic (AP) use in Parkinson disease (PD) patients is associated with increased physical morbidity. METHODS: Veterans Health Administration data (1999-2010) was used to examine physical morbidity risk associated with AP use in idiopathic PD patients with stable recent physical health. We compared 180-day morbidity rates in patients initiating an AP with matched non-AP users who survived for 180 days (matched on age, sex, race, index year, presence and duration of dementia, PD duration, delirium, hospitalization, Charlson Comorbidity Index, and new non-psychiatric medications; covarying for psychosis). Outcomes were 180-day emergency department (ED), and inpatient and outpatient visits. RESULTS: There were 6,679 matched PD pairs. Any AP use was associated with an increased risk of ED visit (HR: 1.64, 95% CI: 1.51, 1.77), inpatient care (HR: 1.58, 95% CI: 1.46, 1.71), and outpatient visits (IRR: 1.08, 95% CI: 1.05, 1.12). The risk was significantly higher for atypical AP use compared with nonuse for all three morbidity outcomes, and was similar for atypical and typical AP use. CONCLUSIONS: Any AP use, and atypical AP use, are associated with significantly increased physical morbidity risk in PD patients, as evidenced by increased ED, inpatient, and outpatient visits. These findings, which require replication, extend the risk associated with use of APs in this population from mortality to a broader range of adverse outcomes, and further highlight the need to use APs cautiously in PD patients.

Rivastigmine for mild cognitive impairment in Parkinson disease: a placebo-controlled study.

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.

Validating virtual administration of neuropsychological testing in Parkinson disease: a pilot study.

Background COVID-19 has highlighted the need for remote cognitive testing. Virtual testing may lessen burden and can reach a larger patient population. The reliability and validity of virtual cognitive testing in Parkinson disease (PD) is unknown. Objectives To validate neuropsychological tests for virtual administration in PD. Methods Participants enrolled in an observational, cognition-focused study completed a rater-administered cognitive battery in-person and via video conference 3-7 days apart. Order of administration was counterbalanced. Analyses to compare performance by type of administration (virtual versus in-person) included paired t-test, intraclass correlation (ICC) and linear mixed-effects models. Results Data for 35 (62.9% male) PD participants (62.5% normal cognition, 37.5% cognitive impairment) were analyzed. Only the semantic verbal fluency test demonstrated a difference in score by administration type, with a significantly better score when administered virtually (paired t-test p = 0.011 and linear mixed-effects model p = 0.012). Only the Dementia Rating Scale-2, Trails A test and phonemic verbal fluency demonstrated good reliability (ICC value 0.75-0.90) for virtual versus in-person administration, and values for visit 1 versus visit 2 were similarly low overall. Trail making tests were successfully administered virtually to only 18 (51.4%) participants due to technical issues. Conclusions Virtual cognitive testing overall is feasible in PD, and virtual and in-person cognitive testing generate similar scores at the group level, but reliability is poor or moderate for most tests. Given that mode of test administration, learning effects and technical difficulties explained relatively little of the low test-retest reliability observed, there may be significant short-term variability in cognitive performance in PD in general, which has important implications for clinical care and research.

Validating virtual administration of neuropsychological testing in Parkinson disease: a pilot study.

COVID-19 has highlighted the need for remote cognitive testing, but the reliability and validity of virtual cognitive testing in Parkinson disease (PD) is unknown. Therefore, we assessed PD participants enrolled in an observational, cognition-focused study with an extensive cognitive battery completed both in-person and via video conference close in time. Data for 35 PD participants with normal cognition to mild dementia were analyzed. Only one test (semantic verbal fluency) demonstrated a difference in score by administration type, with a significantly better score virtually. Only three tests demonstrated good reliability for in-person versus virtual testing, but reliability values for visit 1 versus visit 2 were similarly low overall. Trail Making Test B was successfully administered virtually to only 18 participants due to technical issues. Virtual and in-person cognitive testing generate similar scores at the group level, but with poor to moderate reliability for most tests. Mode of test administration, learning effects, and technical difficulties explained little of the low test-retest reliability, indicating possible significant short-term variability in cognitive performance in PD in general, which has implications for clinical care and research. In-person cognitive testing with a neuropsychologist remains the gold standard, and it remains to be determined if virtual cognitive testing is feasible in PD.

Course of Impulse Control Disorder Symptoms in Parkinson's Disease: Deep Brain Stimulation Versus Medications.

Background: The effect of surgery on impulse control disorders (ICDs) remains unclear in Parkinson's disease (PD) patients undergoing deep brain stimulation (DBS). Objective: To examine changes in ICD symptoms in PD patients undergoing DBS compared to a medication-only control group. Methods: The study was a 2-center, 12-month, prospective, observational investigation of PD patients undergoing DBS and a control group matched on age, sex, dopamine agonist use, and baseline presence of ICDs. Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) and total levodopa equivalent daily dose (LEDD) were collected at baseline, 3, 6, and 12 months. Linear mixed-effects models assessed changes in mean QUIP-RS score (sum of buying, eating, gambling, and hypersexuality items). Results: The cohort included 54 participants (DBS = 26, controls = 28), mean (SD) age 64.3 (8.1) and PD duration 8.0 (5.2) years. Mean baseline QUIP-RS was higher in the DBS group at baseline (8.6 (10.7) vs. 5.3 (6.9), P = 0.18). However, scores at 12 months follow-up were nearly identical (6.6 (7.3) vs. 6.0 (6.9) P = 0.79). Predictors of change in QUIP-RS score were baseline QUIP-RS score (ß = 0.483, P < 0.001) and time-varying LEDD (ß = 0.003, P = 0.02). Eight patients (four in each group) developed de novo ICD symptoms during follow-up, although none met diagnostic criteria for an impulse control disorder. Conclusions: ICD symptoms (including de novo symptoms) at 12 months follow-up were similar between PD patients undergoing DBS and patients treated with pharmacological therapy only. Monitoring for emergence of ICD symptoms is important in both surgically- and medication-only-treated PD patients.

Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale.

Impulse control disorders and related disorders (hobbyism-punding and dopamine dysregulation syndrome) occur in 15% to 20% of Parkinson's disease (PD) patients. We assessed the validity and reliability of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS), a rating scale designed to measure severity of symptoms and support a diagnosis of impulse control disorders and related disorders in PD. A convenience sample of PD patients at a movement disorders clinic self-completed the QUIP-RS and were administered a semistructured diagnostic interview by a blinded trained rater to assess discriminant validity for impulse control disorders (n = 104) and related disorders (n = 77). Subsets of patients were assessed to determine interrater reliability (n = 104), retest reliability (n = 63), and responsiveness to change (n = 29). Adequate cutoff points (both sensitivity and specificity values >80% plus acceptable likelihood ratios) were established for each impulse control disorder and hobbyism-punding. Interrater and retest reliability (intraclass correlation coefficient r) were >0.60 for all disorders. Participants in an impulse control disorder treatment study who experienced full (t = 3.65, P = .004) or partial (t = 2.98, P = .01) response demonstrated significant improvement on the rating scale over time, while nonresponders did not (t = 0.12, P = .91). The QUIP-RS appears to be valid and reliable as a rating scale for impulse control disorders and related disorders in PD. Preliminary results suggest that it can be used to support a diagnosis of these disorders, as well as to monitor changes in symptom severity over time.

Perfusion Imaging of Fatigue and Time-on-Task Effects in Patients With Parkinson's Disease.

Fatigue is a highly prevalent and debilitating non-motor symptom in Parkinson's disease (PD), yet its' neural mechanisms remain poorly understood. Here we combined arterial spin labeling (ASL) perfusion functional magnetic resonance imaging (fMRI) with a sustained mental workload paradigm to examine the neural correlates of fatigue and time-on-task effects in PD patients. Twenty-one PD patients were scanned at rest and during continuous performance of a 20-min psychomotor vigilance test (PVT). Time-on-task effects were measured by the reaction time changes during the PVT and by self-reported fatigue ratings before and after the PVT. PD subjects demonstrated significant time-on-task effects, including progressively slower reaction time on the PVT and increased post-PVT fatigue ratings compared to pre-PVT. Higher levels of general fatigue were associated with larger increases in mental fatigue ratings after the PVT. ASL imaging data showed increased CBF in the right middle frontal gyrus (MFG), bilateral occipital cortex, and right cerebellum during the PVT compared to rest, and decreased CBF in the right MFG at post-task rest compared to pre-task rest. The magnitude of regional CBF changes in the right MFG and right inferior parietal lobe correlated with subjective fatigue rating increases after the PVT task. These results demonstrate the utility of continuous PVT paradigm for future studies of fatigue and cognitive fatigability in patients, and support the key role of the fronto-parietal attention network in mediating fatigue in PD.

Genetic prediction of impulse control disorders in Parkinson's disease.

OBJECTIVE: To develop a clinico-genetic predictor of impulse control disorder (ICD) risk in Parkinson's disease (PD). METHODS: In 5770 individuals from three PD cohorts (the 23andMe, Inc.; the University of Pennsylvania [UPenn]; and the Parkinson's Progression Markers Initiative [PPMI]), we used a discovery-replication strategy to develop a clinico-genetic predictor for ICD risk. We first performed a Genomewide Association Study (GWAS) for ICDs anytime during PD in 5262 PD individuals from the 23andMe cohort. We then combined newly discovered ICD risk loci with 13 ICD risk loci previously reported in the literature to develop a model predicting ICD in a Training dataset (n = 339, from UPenn and PPMI cohorts). The model was tested in a non-overlapping Test dataset (n = 169, from UPenn and PPMI cohorts) and used to derive a continuous measure, the ICD-risk score (ICD-RS), enriching for PD individuals with ICD (ICD+ PD). RESULTS: By GWAS, we discovered four new loci associated with ICD at p-values of 4.9e-07 to 1.3e-06. Our best logistic regression model included seven clinical and two genetic variables, achieving an area under the receiver operating curve for ICD prediction of 0.75 in the Training and 0.72 in the Test dataset. The ICD-RS separated groups of PD individuals with ICD prevalence of nearly 40% (highest risk quartile) versus 7% (lowest risk quartile). INTERPRETATION: In this multi-cohort, international study, we developed an easily computed clinico-genetic tool, the ICD-RS, that substantially enriches for subgroups of PD at very high versus very low risk for ICD, enabling pharmacogenetic approaches to PD medication selection.

Olfactory dysfunction is associated with neuropsychiatric manifestations in Parkinson's disease.

Hyposmia, psychiatric disorders, and cognitive problems are common nonmotor manifestations in Parkinson's disease, but how they are related remains unclear. We investigated the relationship between olfactory dysfunction and neuropsychiatric manifestations and performed a cross-sectional study of 248 patients at two movement disorders clinics at academic medical centers. Psychiatric measures were the Geriatric Depression Scale-15, Inventory of Depressive Symptomatology, State Anxiety Inventory, Apathy Scale, and Parkinson's Psychosis Rating Scale. Cognitive measures were the Mini-Mental State Examination, Hopkins Verbal Learning Test-Revised, Digit Span, Tower of London-Drexel, and the Stroop Color Word Test. Olfaction was tested with the University of Pennsylvania Smell Identification Test. There was no significant association between olfaction and mood measures, but psychotic symptoms were more common in patients with olfaction scores below the median (30% vs. 12%; P < 0.001). Worse olfaction was associated with poorer memory (Hopkins Verbal Learning Test-Revised delayed recall items: mean [standard deviation], 6.2 [3.2] vs. 8.4 [2.8]; P < 0.001) and executive performance (Tower of London total moves, 52 [38] vs. 34 [21]; P < 0.001). Odor-identification score was a significant predictor of abnormal performance on these cognitive tests after adjustment for age, sex, and disease characteristics in logistic regression models. The relationship between hyposmia, psychosis, and specific cognitive impairments may reflect the anatomic distribution of Lewy pathology and suggests that olfactory dysfunction could be a biomarker of additional extranigral disease. Future prospective studies are warranted to assess whether hyposmia, a very early feature of Parkinson's disease, might be used to predict the appearance of other common nonmotor symptoms.

Psychometric Properties of the Clinical Dementia Rating Scale Sum of Boxes in Parkinson's Disease.

BACKGROUND: A composite measure that assesses both cognitive and functional abilities in Parkinson's disease (PD) would be useful for diagnosing mild cognitive impairment (MCI) and PD dementia (PDD) and as an outcome measure in randomized controlled trials. The Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) was designed to assess both cognition and basic-instrumental activities of daily living in Alzheimer's disease but has not yet been validated in PD. OBJECTIVE: To validate the CDR-SOB as a composite cognitive-functional measure for PD patients, as well as to assess its sensitivity to change. METHODS: The CDR-SOB and a comprehensive cognitive and functional battery was administered to 101 PD patients at baseline (39 normal cognition [NC], 41 MCI and 21 PDD by expert consensus panel), and re-administered to 64 patients after 1-2 years follow-up (32 NC and 32 cognitive impairment [CI] at baseline). RESULTS: Cross-sectionally, CDR-SOB and domain scores were correlated with corresponding neuropsychological or functional measures and were significantly different between cognitive subgroups both at baseline and at follow-up. In addition, CDR-SOB ROC curves distinguished between normal cognition and dementia with high sensitivity, but did not distinguish well between NC and MCI. Longitudinal changes in the CDR-SOB and domain scores were not significant and were inconsistent in predicting change in commonly-used cognitive and functional tests. CONCLUSION: The CDR-SOB detects dementia-level cognitive impairment in PD but may not be appropriate for predicting longitudinal combined cognitive-functional changes in patients without significant cognitive impairment at baseline.

The experience of care partners of patients with Parkinson's disease psychosis.

BACKGROUND: Parkinson's disease psychosis (PDP) has a major impact on quality of life and care partner burden; however, little is known about the lived experiences of care partners in managing PDP. OBJECTIVE: To understand how care partners of individuals with PDP experience their role and articulate their needs related to psychosis. METHODS: This was a qualitative study of semi-structured telephone interviews. Recruitment was conducted online via the clinical study matching tool, Fox Trial Finder; study activities took place remotely via telephone interviews. Transcripts of the phone interviews were analyzed by grounded theory methods, and a codebook of key themes that emerged from the analysis was developed. RESULTS: Nine care partners (all female) were interviewed. Discussion topics in the codebook included (1) care partner burden and guilt; (2) communication with medical professionals; (3) coping strategies; (4) emotional reactions of the care partner to psychosis; (5) sources of knowledge about PD psychosis; (6) attitudes towards medications for PDP; (7) strategies to care for loved ones with psychosis; (8) psychosis triggers. CONCLUSIONS: This qualitative analysis uncovers important aspects of the care partner experience, including challenges in navigating the medical system and communicating with professionals. Providers treating patients with PDP should be aware of these constraints and provide added support for strained care partners.

Decreased ventral striatal activity with impulse control disorders in Parkinson's disease.

A range of impulse control disorders (ICDs) are reported to occur in Parkinson's disease (PD). However, alterations in brain activity at rest and during risk taking occurring with ICDs in PD are not well understood. We used both arterial spin labeling perfusion functional magnetic resonance imaging (fMRI) to directly quantify resting cerebral blood flow (CBF) and blood oxygenation level dependent (BOLD) fMRI to measure neural responses to risk taking during performance on the Balloon Analogue Risk Task (BART). Eighteen PD patients, either with a diagnosis of one or more ICDs (N = 9) or no lifetime ICD history (N = 9), participated. BOLD fMRI data demonstrated that PD patients without an ICD activate the mesocorticolimbic pathway during risk taking. Compared with non-ICD patients, ICD patients demonstrated significantly diminished BOLD activity in the right ventral striatum during risk taking and significantly reduced resting CBF in the right ventral striatum. ICDs in PD are associated with reduced right ventral striatal activity at rest and diminished striatal activation during risk taking, suggesting that a common neural mechanism may underlie ICDs in individuals with PD and those without PD. Thus, treatments for ICDs in non-PD patients warrant consideration in PD patients with ICDs.

Understanding the Lexicon of Fatigue in Parkinson's Disease.

BACKGROUND: Fatigue in Parkinson's disease (PD) is multifaceted and associated with reduced quality of life. In turn, the language used by people with PD to describe fatigue is variable and poorly understood. We sought to elucidate the lexicon of fatigue using a qualitative grounded theory approach. OBJECTIVE: The objective of this study was to understand how patients with PD describe fatigue. METHODS: A pre-study phase of online journaling (Phase 1) provided information regarding topics of importance to patients. Following this, two independent samples of fatigued subjects were studied. Individuals with PD participated in a telephone interview (Phase 2); interview transcripts were analyzed to develop a detailed codebook. To ensure trustworthiness of the findings, an online survey (Phase 3) was administered to individuals with self-reported PD participating in the online study Fox Insight. The survey included the following question: "How do you define fatigue? Please provide your definition in the space below." The codebook developed from Phase 2 was applied to the Phase 3 responses. RESULTS: Fifteen individuals participated in Phase 2 and 413 individuals completed Phase 3. Fatigue was subdivided into three domains: cognitive, emotional, and physical. Nearly all individuals experienced more than one domain of fatigue. The most common themes included tiredness, lack of energy, and negative motivation. CONCLUSION: Fatigue in PD is multidimensional. Questionnaires that only assess the physical impact of fatigue may not be adequate to capture the broad range of experiences of fatigue among people with PD.

Mild cognitive impairment is common in Parkinson's disease patients with normal Mini-Mental State Examination (MMSE) scores.

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.

Long-term follow-up of impulse control disorders in Parkinson's disease.

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.

Association of Antipsychotic Use With Mortality Risk in Patients With Parkinson Disease.

IMPORTANCE: As many as 60% of patients with Parkinson disease (PD) experience psychosis, 80% develop dementia, and the use of antipsychotics (APs) in the population with PD is common. The use of APs by patients with dementia in the general population is associated with increased mortality, but whether this risk extends to patients with PD remains unknown. OBJECTIVE: To determine whether AP use in patients with PD is associated with increased mortality. DESIGN, SETTING, AND PARTICIPANTS: This retrospective matched-cohort study used data from a Veterans Health Administration database from fiscal years 1999 to 2010 to examine the risk associated with AP use in a cohort of patients with idiopathic PD and recent stable physical health. The rates of 180-day mortality were compared in 7877 patients initiating AP therapy and 7877 patients who did not initiate AP therapy (matched for age ±2.5 years, sex, race, index year, presence and duration of dementia, PD duration, delirium, hospitalization, Charlson Comorbidity Index, and new nonpsychiatric medications). Data were analyzed from October 19, 2012, to September 21, 2015. MAIN OUTCOMES AND MEASURES: Mortality rates at 180 days in those patients who initiated AP therapy compared with matched patients who did not use APs. Cox proportional hazards regression models were used with intent-to-treat (ITT) and exposure-only analyses. RESULTS: The study population included 7877 matched pairs of patients with PD (65 women [0.8%] and 7812 men [99.2%] in each cohort; mean [SD] age, 76.3 [7.7] years for those who initiated AP therapy and 76.4 [7.6] years for those who did not). Antipsychotic use was associated with more than twice the hazard ratio (HR) of death compared with nonuse (ITT HR, 2.35; 95% CI, 2.08-2.66; P < .001). The HR was significantly higher for patients who used typical vs atypical APs (ITT HR, 1.54; 95% CI, 1.24-1.91; P < .001). Among the atypical APs used, HRs relative to nonuse of APs in descending order were 2.79 (95% CI, 1.97-3.96) for olanzapine, 2.46 (95% CI, 1.94-3.12) for risperidone, and 2.16 (95% CI, 1.88-2.48) for quetiapine fumarate. CONCLUSIONS AND RELEVANCE: Use of APs is associated with a significantly increased mortality risk in patients with PD, after adjusting for measurable confounders. This finding highlights the need for cautious use of APs in patients with PD. Future studies should examine the role of nonpharmacologic strategies in managing psychosis in PD. In addition, new pharmacologic treatments that do not increase mortality in patients with neurodegenerative diseases need to be developed.