Gregory M. Pontone

Clinical features associated with impulse control disorders in Parkinson disease.

In patients with Parkinson disease (PD), impulse control disorders (ICDs) such as hypersexuality and pathologic gambling and shopping can be devastating complications of antiparkinsonian treatment. To improve their detection, we investigated clinical features associated with ICDs. Subjects were participants in a longitudinal study of PD. ICDs were associated with use of dopamine agonists and depressed mood, disinhibition, irritability, and appetite disturbance.

Neuropsychiatric Disorders and Potentially Preventable Hospitalizations in a Prospective Cohort Study of Older Americans

ABSTRACTBACKGROUNDThe relative contributions of depression, cognitive impairment without dementia (CIND), and dementia to the risk of potentially preventable hospitalizations in older adults are not well understood.OBJECTIVE(S)To determine if depression, CIND, and/or dementia are each independently associated with hospitalizations for ambulatory care-sensitive conditions (ACSCs) and rehospitalizations within 30xa0days after hospitalization for pneumonia, congestive heart failure (CHF), or myocardial infarction (MI).DESIGNProspective cohort study.PARTICIPANTSPopulation-based sample of 7,031 Americansu2009>u200950xa0years old participating in the Health and Retirement Study (1998–2008).MAIN MEASURESThe eight-item Center for Epidemiologic Studies Depression Scale and/or International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) depression diagnoses were used to identify baseline depression. The Modified Telephone Interview for Cognitive Status and/or ICD-9-CM dementia diagnoses were used to identify baseline CIND or dementia. Primary outcomes were time to hospitalization for an ACSC and presence of a hospitalization within 30xa0days after hospitalization for pneumonia, CHF, or MI.KEY RESULTSAll five categories of baseline neuropsychiatric disorder status were independently associated with increased risk of hospitalization for an ACSC (depression alone: Hazard Ratio [HR]: 1.33, 95xa0% Confidence Interval [95%CI]: 1.18, 1.52; CIND alone: HR: 1.25, 95%CI: 1.10, 1.41; dementia alone: HR: 1.32, 95%CI: 1.12, 1.55; comorbid depression and CIND: HR: 1.43, 95%CI: 1.20, 1.69; comorbid depression and dementia: HR: 1.66, 95%CI: 1.38, 2.00). Depression (Odds Ratio [OR]: 1.37, 95%CI: 1.01, 1.84), comorbid depression and CIND (OR: 1.98, 95%CI: 1.40, 2.81), or comorbid depression and dementia (OR: 1.58, 95%CI: 1.06, 2.35) were independently associated with increased odds of rehospitalization within 30xa0days after hospitalization for pneumonia, CHF, or MI.CONCLUSIONSDepression, CIND, and dementia are each independently associated with potentially preventable hospitalizations in older Americans. Older adults with comorbid depression and cognitive impairment represent a particularly at-risk group that could benefit from targeted interventions.

Association Between Change in Body Mass Index, Unified Parkinson's Disease Rating Scale Scores, and Survival Among Persons With Parkinson Disease: Secondary Analysis of Longitudinal Data From NINDS Exploratory Trials in Parkinson Disease Long-term Study 1.

IMPORTANCEnGreater body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) is associated with improved survival among persons with Huntington disease or amyotrophic lateral sclerosis. Weight loss is common among persons with Parkinson disease (PD) and is associated with worse quality of life.nnnOBJECTIVEnTo explore the association between change in BMI, Unified Parkinsons Disease Rating Scale (UPDRS) motor and total scores, and survival among persons with PD and to test whether there is a positive association between BMI at randomization and survival.nnnDESIGN, SETTING, AND PARTICIPANTSnSecondary analysis (from May 27, 2014, to October 13, 2015) of longitudinal data (3-6 years) from 1673 participants who started the National Institute of Neurological Disorders and Stroke Exploratory Trials in PD Long-term Study-1 (NET-PD LS-1). This was a double-blind randomized placebo-controlled clinical trial of creatine monohydrate (10 g/d) that was performed at 45 sites throughout the United States and Canada. Participants with early (within 5 years of diagnosis) and treated (receiving dopaminergic therapy) PD were enrolled from March 2007 to May 2010 and followed up until September 2013.nnnMAIN OUTCOMES AND MEASURESnChange across time in motor UPDRS score, change across time in total UPDRS score, and time to death. Generalized linear mixed models were used to estimate the effect of BMI on the change in motor and total UPDRS scores after controlling for covariates. Survival was analyzed using Cox proportional hazards models of time to death. A participants BMI was measured at randomization, and BMI trajectory groups were classified according to whether participants experienced weight loss (decreasing BMI), weight stability (stable BMI), or weight gain (increasing BMI) during the study.nnnRESULTSnOf the 1673 participants (mean [SD] age, 61.7 [9.6] years; 1074 [64.2%] were male), 158 (9.4%) experienced weight loss (decreasing BMI), whereas 233 (13.9%) experienced weight gain (increasing BMI). After adjusting for covariates, we found that the weight-loss groups mean (SE) motor UPDRS score increased by 1.48 (0.28) (P < .001) more points per visit than the weight-stable groups mean (SE) motor UPDRS score. The weight-gain groups mean (SE) motor UPDRS score decreased by -0.51 (0.24) (P = .03) points per visit, relative to the weight-stable group. While there was an unadjusted difference in survival between the 3 BMI trajectory groups (log-rank P < .001), this was not significant after adjusting for covariates.nnnCONCLUSIONS AND RELEVANCEnChange in BMI was inversely associated with change in motor and total UPDRS scores in the NET-PD LS-1. Change in BMI was not associated with survival; however, these results were limited by the low number of deaths in the NET-PD LS-1.nnnTRIAL REGISTRATIONnclinicaltrials.gov Identifier: NCT00449865.

Neuropsychiatric Complications of Parkinson Disease Treatments: Importance of Multidisciplinary Care

Although Parkinson disease (PD) is defined clinically by its motor symptoms, it is increasingly recognized that much of the disability and worsened quality of life experienced by patients with PD is attributable to psychiatric symptoms. The authors describe a model of multidisciplinary care that enables these symptoms to be effectively managed. They describe neuropsychiatric complications of PD itself and pharmacologic and neurostimulation treatments for parkinsonian motor symptoms and discuss the management of these complications. Specifically, they describe the clinical associations between motor fluctuations and anxiety and depressive symptoms, the compulsive overuse of dopaminergic medications prescribed for motor symptoms (the dopamine dysregulation syndrome), and neuropsychiatric complications of these medications, including impulse control disorders, psychosis, and manic syndromes. Optimal management of these problems requires close collaboration across disciplines because of the potential for interactions among the pathophysiologic process of PD, motor symptoms, dopaminergic drugs, and psychiatric symptoms. The authors emphasize how their model of multidisciplinary care facilitates close collaboration among psychiatrists, other mental health professionals, neurologists, and functional neurosurgeons and how this facilitates effective care for patients who develop the specific neuropsychiatric complications discussed.

Dopamine Transporter Imaging in Psychogenic Parkinsonism and Neurodegenerative Parkinsonism with Psychogenic Overlay: A Report of Three Cases

Background Differentiating psychogenic parkinsonism from neurodegenerative Parkinsons disease (PD) with psychogenic features is a diagnostic challenge. Case report We report a detailed longitudinal clinical description of three cases presenting with suspected psychogenic parkinsonism. Dopamine transporter single-photon emission computed tomography (DAT-SPECT) was used as a supplemental diagnostic study and influenced clinical management. Discussion DAT-SPECT quantified the integrity of the striatal dopaminergic system in these cases of clinically uncertain parkinsonism and supported clinical decision-making.

Postoperative symptoms of psychosis after deep brain stimulation in patients with Parkinson's disease

OBJECTnCases of postoperative psychosis in Parkinsons disease patients receiving deep brain stimulation (DBS) treatment have previously been published. However, the magnitude of symptom incidence and the clinical risk factors are currently unknown. This retrospective study sheds light on these issues by investigating psychosis in a group of 128 Parkinsons disease patients who received DBS implants.nnnMETHODSnA retrospective chart review was performed to obtain surgery dates, follow-up clinic visit dates, and associated stimulation parameter settings (contacts in use and the polarity of each along with stimulation voltage, frequency, and pulse width) for each patient. Unified Parkinsons Disease Rating Scale II Thought Disorder scores, used as a clinical assessment tool to evaluate the presence of psychosis at each visit, were also collected. The data were compiled into a database and analyzed.nnnRESULTSnThe lifetime incidence of psychosis in this cohort of patients was 28.1%. The data suggest that risk of psychosis remains fairly constant throughout the first 5 years after implantation of a DBS system and that patients older at the time of receiving the first DBS implant are not only more likely to develop psychosis, but also to develop symptoms sooner than their younger counterparts. Further analysis provides evidence that psychosis is largely independent of the clinically used electrode contact and of stimulation parameters prior to psychosis onset.nnnCONCLUSIONSnAlthough symptoms of psychosis are widely seen in patients with Parkinsons disease in the years following stimulator placement, results of the present suggest that most psychoses occurring postoperatively are likely independent of implantation and stimulation settings.

Onset and Remission of Psychosis in Parkinson's Disease: Pharmacologic and Motoric Markers

Psychosis is among the most disabling complications of Parkinsons disease (PD). The chronicity of PD psychosis remains understudied, and the relative importance of dopaminergic therapy versus the disease process itself in engendering psychosis remains unclear. The objective of this study was to examine pharmacologic and motoric correlates of PD psychosis onset and remission in a longitudinally monitored PD cohort.

REM Sleep Behavior and Motor Findings in Parkinson’s Disease: A Cross-sectional Analysis

Background Parkinsons disease (PD) represents a major public health challenge that will only grow in our aging population. Understanding the connection between PD and associated prodromal conditions, such as rapid eye movement sleep behavioral disorder (RBD), is critical to identifying prevention strategies. However, the relationship between RBD and severity of motor findings in early PD is unknown. This study aims to examine this relationship. Methods The study population consisted of 418u2005PD patients who completed the Movement Disorders Society-United Parkinsons Disease Rating Scale (MDS-UPDRS) and rapid eye movement sleep (REM) disorder questionnaires at the baseline visit of the Michael J. Foxs Parkinsons Progression Markers Initiative (PPMI). Cross-sectional analysis was carried out to assess the association between REM Sleep Behavior Screening Questionnaire score and MDS UPDRS-3 (motor) score categories. Correlation with a higher score category was described as “worse motor findings”. A score of 5 on the REM disorder questionnaire was defined as predictive of RBD. Results Out of the 418u2005PD patients, 113 (27.0%) had RBD. With univariate logistic regression analysis, individuals with scores predictive of RBD were 1.66 times more likely to have worse motor findings (pu200a=u200a0.028). Even with age, gender, and Geriatric Depression Scale scores taken into account, individuals with scores predictive of RBD were 1.69 times more likely to have worse motor findings (pu200a=u200a0.025). Discussion PD patients with RBD symptoms had worse motor findings than those unlikely to have RBD. This association provides further evidence for the relationship between RBD and PD.

Application of Depression Rating Scales in Patients with Parkinson's Disease with and without Co-Occurring Anxiety

BACKGROUNDnIn patients with Parkinsons disease (PD), depressive symptom rating scales facilitate identification of depressive disorders, which are common and disabling. Anxiety disturbances in PD, which lack valid assessment scales, frequently co-occur with PD-depression, are under-recognized, and require different interventions than depressive disorders. Whether high anxiety rates in PD confound depression scale performance or if any depression scales also predict anxiety disturbances is not known.nnnOBJECTIVEnTo test the impact of co-occurring anxiety disorders on psychometric properties of depression rating scales in depressed PD patients and compare disability between PD patients with anxiety, depression, and comorbid anxiety and depressive disorders.nnnMETHODSnPD subjects (n = 229) completed self-report and clinician-administered depression scales. Receiver operating characteristic curves were developed to estimate psychometric properties of each scale in those with depression alone, anxiety alone, and comorbid depression and anxiety. Between-group differences on all measures were examined.nnnRESULTSnComorbid anxiety did not affect the psychometric properties of any scale when identifying depressive disorders, but is associated with greater symptom severity and disability. Depression-scale scores were not significantly different between subjects with anxiety disorders only and those without depressive or anxiety diagnoses.nnnCONCLUSIONSnCo-occurring anxiety disorders do not impact performance of depression rating scales in depressed PD patients. However, depression rating scales do not adequately identify anxiety disturbances alone or in patients with depression.

Dopamine transporter availability reflects gastrointestinal dysautonomia in early Parkinson disease

BACKGROUNDnConstipation is a prodromal feature of Parkinsons disease (PD) and the gastrointestinal (GI) tract is implicated in the pathogenesis of PD. However, no studies have demonstrated ante-mortem relationships between nigrostriatal dysfunction and GI dysautonomia in PD.nnnMETHODSnThe Scale for Outcomes in Parkinsons disease for Autonomic Symptoms (SCOPA-AUT) assesses dysautonomia in the multi-center Parkinsons Progression Marker Initiative (PPMI). We used linear mixed-effects models and reliable change indices (RCIs) to examine longitudinal associations between dysautonomia and dopamine transporter (DAT) striatal binding ratios (SBRs) measured by single-photon emission computerized tomography in PPMI participants over four years (nu202f=u202f397u202fat baseline).nnnRESULTSnAdjusted mixed-models of longitudinal data showed that constipation-but not orthostatic hypotension or urinary dysfunction-was associated with reduced SBR in both caudate (Pu202f<u202f0.001) and putamen (Pu202f=u202f0.040). In both regions, SBR reductions between baseline and 4-year follow-up were significant and measurable (Pu202f<u202f0.0001), with larger decline and variance in the caudate nucleus. Four-year change in caudate-but not putaminal-SBR was significantly associated with RCI-indicated progression of GI dysautonomia (Pu202f=u202f0.031), but not other types of dysautonomia. These associations remained after adjusting for the use of medications or supplements to control constipation. Consistent with prior PPMI reports, motor impairment progression was not associated with SBR reduction.nnnCONCLUSIONSnGI dysautonomia correlates with reductions in DAT availability; constipation is most closely associated with caudate-DAT reduction. Worsening GI-dysautonomia and reduced bowel movements may accompany advancing nigral degeneration or changes in nigrostriatal dopamine function.