Transitioning from Subtyping to Precision Medicine in Parkinson's Disease: A Purpose-Driven Approach.

The International Parkinson and Movement Disorder Society (MDS) created a task force (TF) to provide a critical overview of the Parkinson's disease (PD) subtyping field and develop a guidance on future research in PD subtypes. Based on a literature review, we previously concluded that PD subtyping requires an ultimate alignment with principles of precision medicine, and consequently novel approaches were needed to describe heterogeneity at the individual patient level. In this manuscript, we present a novel purpose-driven framework for subtype research as a guidance to clinicians and researchers when proposing to develop, evaluate, or use PD subtypes. Using a formal consensus methodology, we determined that the key purposes of PD subtyping are: (1) to predict disease progression, for both the development of therapies (use in clinical trials) and prognosis counseling, (2) to predict response to treatments, and (3) to identify therapeutic targets for disease modification. For each purpose, we describe the desired product and the research required for its development. Given the current state of knowledge and data resources, we see purpose-driven subtyping as a pragmatic and necessary step on the way to precision medicine. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Perspectives of Implementation of Closed-Loop Deep Brain Stimulation: From Neurological to Psychiatric Disorders.

BACKGROUND: Deep brain stimulation (DBS) is a highly efficient, evidence-based therapy to alleviate symptoms and improve quality of life in movement disorders such as Parkinson's disease, essential tremor, and dystonia, which is also being applied in several psychiatric disorders, such as obsessive-compulsive disorder and depression, when they are otherwise resistant to therapy. SUMMARY: At present, DBS is clinically applied in the so-called open-loop approach, with fixed stimulation parameters, irrespective of the patients' clinical state(s). This approach ignores the brain states or feedback from the central nervous system or peripheral recordings, thus potentially limiting its efficacy and inducing side effects by stimulation of the targeted networks below or above the therapeutic level. KEY MESSAGES: The currently emerging closed-loop (CL) approaches are designed to adapt stimulation parameters to the electrophysiological surrogates of disease symptoms and states. CL-DBS paves the way for adaptive personalized DBS protocols. This review elaborates on the perspectives of the CL technology and discusses its opportunities as well as its potential pitfalls for both clinical and research use in neuropsychiatric disorders.

A neural network for tics: insights from causal brain lesions and deep brain stimulation.

Brain lesions are a rare cause of tic disorders. However, they can provide uniquely causal insights into tic pathophysiology and can also inform on possible neuromodulatory therapeutic targets. Based on a systematic literature review, we identified 22 cases of tics causally attributed to brain lesions and employed 'lesion network mapping' to interrogate whether tic-inducing lesions would be associated with a common network in the average human brain. We probed this using a normative functional connectome acquired in 1000 healthy participants. We then examined the specificity of the identified network by contrasting tic-lesion connectivity maps to those seeding from 717 lesions associated with a wide array of neurological and/or psychiatric symptoms within the Harvard Lesion Repository. Finally, we determined the predictive utility of the tic-inducing lesion network as a therapeutic target for neuromodulation. Specifically, we collected retrospective data of 30 individuals with Tourette disorder, who underwent either thalamic (n = 15; centromedian/ventrooralis internus) or pallidal (n = 15; anterior segment of globus pallidus internus) deep brain stimulation and calculated whether connectivity between deep brain stimulation sites and the lesion network map could predict clinical improvements. Despite spatial heterogeneity, tic-inducing lesions mapped to a common network map, which comprised the insular cortices, cingulate gyrus, striatum, globus pallidus internus, thalami and cerebellum. Connectivity to a region within the anterior striatum (putamen) was specific to tic-inducing lesions when compared with control lesions. Connectivity between deep brain stimulation electrodes and the lesion network map was predictive of tic improvement, regardless of the deep brain stimulation target. Taken together, our results reveal a common brain network involved in tic generation, which shows potential as a therapeutic target for neuromodulation.

Resting-State Functional Connectivity in Frontostriatal and Posterior Cortical Subtypes in Parkinson's Disease-Mild Cognitive Impairment.

BACKGROUND: The "dual syndrome hypothesis" distinguished two subtypes in mild cognitive impairment (MCI) in Parkinson's disease: frontostriatal, characterized by attentional and executive deficits; and posterior cortical, characterized by visuospatial, memory, and language deficits. OBJECTIVE: The aim was to identify resting-state functional modifications associated with these subtypes. METHODS: Ninety-five nondemented patients categorized as having normal cognition (n = 31), frontostriatal (n = 14), posterior cortical (n = 20), or mixed (n = 30) cognitive subtype had a 3 T resting-state functional magnetic resonance imaging scan. Twenty-four age-matched healthy controls (HCs) were also included. A group-level independent component analysis was performed to identify resting-state networks, and the selected components were subdivided into 564 cortical regions in addition to 26 basal ganglia regions. Global intra- and inter-network connectivity along with global and local efficiencies was compared between groups. The network-based statistics approach was used to identify connections significantly different between groups. RESULTS: Patients with posterior cortical deficits had increased intra-network functional connectivity (FC) within the basal ganglia network compared with patients with frontostriatal deficits. Patients with frontostriatal deficits had reduced inter-network FC between several networks, including the visual, default-mode, sensorimotor, salience, dorsal attentional, basal ganglia, and frontoparietal networks, compared with HCs, patients with normal cognition, and patients with a posterior cortical subtype. Similar results were also found between patients with a mixed subtype and HCs. CONCLUSION: MCI subtypes are associated with specific changes in resting-state FC. Longitudinal studies are needed to determine the predictive potential of these markers regarding the risk of developing dementia. © 2021 International Parkinson and Movement Disorder Society.

Phenomenology of Atypical Anxiety Disorders in Parkinson's Disease: A Systematic Review.

OBJECTIVE: Anxiety is a prominent concern in Parkinson's disease (PD) that negatively impacts quality of life, increases functional disability, and complicates clinical management. Atypical presentations of anxiety are under-recognized and inadequately treated in patients with PD, compromising global PD care. METHODS: This systematic review focuses on the prevalence, symptomology and clinical correlates of atypical presentations of PD-related anxiety following PRISMA guidelines. RESULTS: Of the 60 studies meeting inclusion criteria, 14 focused on 'Anxiety Not Otherwise Specified (NOS)' or equivalent, 31 reported on fluctuating anxiety symptoms, and 22 reported on 'Fear of Falling (FOF)'. Anxiety NOS accounted for a weighted mean prevalence of 14.9%, fluctuating anxiety for 34.19%, and FOF for 51.5%. These latter two exceeded the average reported overall prevalence rate of 31% for anxiety disorders in PD. We identified a diverse array of anxiety symptoms related to motor and non-motor symptoms of PD, to complications of PD medication (such as "on" and "off" fluctuations, or both), and, to a lesser extent, to cognitive symptoms. CONCLUSION: Atypical anxiety is common, clinically relevant, and heterogeneous in nature. A better understanding of the phenomenology, clinical course, and pathophysiology of varied forms of atypical anxiety in PD is needed to improve recognition, advance therapeutic development and ultimately optimize quality of life in PD.

European clinical guidelines for Tourette syndrome and other tic disorders-version 2.0. Part IV: deep brain stimulation.

In 2011 the European Society for the Study of Tourette Syndrome (ESSTS) published its first European clinical guidelines for the treatment of Tourette Syndrome (TS) with part IV on deep brain stimulation (DBS). Here, we present a revised version of these guidelines with updated recommendations based on the current literature covering the last decade as well as a survey among ESSTS experts. Currently, data from the International Tourette DBS Registry and Database, two meta-analyses, and eight randomized controlled trials (RCTs) are available. Interpretation of outcomes is limited by small sample sizes and short follow-up periods. Compared to open uncontrolled case studies, RCTs report less favorable outcomes with conflicting results. This could be related to several different aspects including methodological issues, but also substantial placebo effects. These guidelines, therefore, not only present currently available data from open and controlled studies, but also include expert knowledge. Although the overall database has increased in size since 2011, definite conclusions regarding the efficacy and tolerability of DBS in TS are still open to debate. Therefore, we continue to consider DBS for TS as an experimental treatment that should be used only in carefully selected, severely affected and otherwise treatment-resistant patients.

Cognitive Outcome After Deep Brain Stimulation for Refractory Obsessive-Compulsive Disorder: A Systematic Review.

INTRODUCTION: Deep brain stimulation (DBS) is an effective treatment for refractory obsessive-compulsive disorder (OCD). Neuropsychological assessment contributes to DBS treatment in several ways: it monitors the cognitive safety of the treatment, identifies beneficial or detrimental cognitive side effects, and it could aid to explain variability in treatment outcome, and possibly the treatment's working mechanism(s). BACKGROUND: This systematic review assessed the cognitive safety of DBS for OCD and explored whether changes in cognitive function may help explain its working mechanism(s). MATERIALS AND METHODS: EMBASE, PubMed/Medline, Psycinfo, and the Cochrane Library were systematically searched for studies reporting cognitive outcomes following DBS for OCD. Searches were completed in November 2020. Included studies were appraised for study design and quality according to National Heart, Lung, and Blood Institute (NHLBI) quality assessment tools. RESULTS: Five randomized controlled trials and ten observational studies comprising a total of 178 patients were analyzed collectively. Variable outcomes of DBS were observed in the domains of attention, memory, executive functioning, and in particular, cognitive flexibility. CONCLUSION: Although individual studies generally do not report cognitive deterioration after DBS for OCD, the variability of study designs and the multitude of cognitive measures used precluded a meta-analysis to confirm its safety and recognition of a cognitive pattern through which the efficacy of DBS for OCD might be explained. In the future, prospective studies should preferably include a standardized neuropsychological assessment battery specifically addressing executive functioning and have a longer-term follow-up in order to demonstrate the cognitive safety of the procedure. Such prospective and more uniform data collection may also contribute to our understanding of the working mechanisms of DBS in OCD.

Surgical and Hardware-Related Adverse Events of Deep Brain Stimulation: A Ten-Year Single-Center Experience.

INTRODUCTION: Although deep brain stimulation (DBS) is effective for treating a number of neurological and psychiatric indications, surgical and hardware-related adverse events (AEs) can occur that affect quality of life. This study aimed to give an overview of the nature and frequency of those AEs in our center and to describe the way they were managed. Furthermore, an attempt was made at identifying possible risk factors for AEs to inform possible future preventive measures. MATERIALS AND METHODS: Patients undergoing DBS-related procedures between January 2011 and July 2020 were retrospectively analyzed to inventory AEs. The mean follow-up time was 43 ± 31 months. Univariate logistic regression analysis was used to assess the predictive value of selected demographic and clinical variables. RESULTS: From January 2011 to July 2020, 508 DBS-related procedures were performed including 201 implantations of brain electrodes in 200 patients and 307 implantable pulse generator (IPG) replacements in 142 patients. Surgical or hardware-related AEs following initial implantation affected 40 of 200 patients (20%) and resolved without permanent sequelae in all instances. The most frequent AEs were surgical site infections (SSIs) (9.95%, 20/201) and wire tethering (2.49%, 5/201), followed by hardware failure (1.99%, 4/201), skin erosion (1.0%, 2/201), pain (0.5%, 1/201), lead migration (0.52%, 2/386 electrode sites), and hematoma (0.52%, 2/386 electrode sites). The overall rate of AEs for IPG replacement was 5.6% (17/305). No surgical, ie, staged or nonstaged, electrode fixation, or patient-related risk factors were identified for SSI or wire tethering. CONCLUSIONS: Major AEs including intracranial surgery-related AEs or AEs requiring surgical removal or revision of hardware are rare. In particular, aggressive treatment is required in SSIs involving multiple sites or when Staphylococcus aureus is identified. For future benchmarking, the development of a uniform reporting system for surgical and hardware-related AEs in DBS surgery would be useful.

Neuroimaging of Anxiety in Parkinson's Disease: A Systematic Review.

BACKGROUND: The aim of this systematic review was (1) to identify the brain regions involved in anxiety in Parkinson's disease (PD) based on neuroimaging studies and (2) to interpret the findings against the background of dysfunction of the fear circuit and limbic cortico-striato-thalamocortical circuit. METHODS: Studies assessing anxiety symptoms in PD patients and studies using magnetic resonance imaging, positron emission tomography, or single-photon emission computed tomography were included. RESULTS: The severity of anxiety was associated with changes in the fear circuit and the cortico-striato-thalamocortical limbic circuit. In the fear circuit, a reduced gray-matter volume of the amygdala and the anterior cingulate cortex (ACC); an increased functional connectivity (FC) between the amygdala and orbitofrontal cortex (OFC) and hippocampus and between the striatum and the medial prefrontal cortex (PFC), temporal cortex, and insula; and a reduced FC between the lateral PFC and the OFC, hippocampus, and amygdala were reported. In the cortico-striato-thalamocortical limbic circuit, a reduced FC between the striatum and ACC; a reduced dopaminergic and noradrenergic activity in striatum, thalamus, and locus coeruleus; and a reduced serotoninergic activity in the thalamus were reported. CONCLUSION: To conclude, anxiety is associated with structural and functional changes in both the hypothesized fear and the limbic cortico-striato-thalamocortical circuits. These circuits overlap and may well constitute parts of a more extensive pathway, of which different parts play different roles in anxiety. The neuropathology of PD may affect these circuits in different ways, explaining the high prevalence of anxiety in PD and also the associated cognitive, motor, and psychiatric symptoms. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Cognitive Behavioral Therapy for Anxiety in Parkinson's Disease: A Randomized Controlled Trial.

BACKGROUND: Anxiety disorders are among the most prevalent and disabling neuropsychiatric syndromes in patients with Parkinson's disease (PD), but no randomized controlled treatment trials of anxiety have been published to date. OBJECTIVE: The aim of this study was to assess the effectiveness of cognitive behavioral therapy (CBT) in the treatment of anxiety in patients with PD. METHODS: Forty-eight patients with PD with anxiety were randomized 1:1 between CBT and clinical monitoring only (CMO). The CBT program was developed to specifically address anxiety symptoms in PD and consisted of 10 weekly sessions. Assessments were conducted by blinded assessors at baseline, at the end of the intervention, after 3 months, and after 6 months (CBT group only). Main outcome measures were the Hamilton Anxiety Rating Scale (HARS) and the Parkinson Anxiety Scale (PAS). RESULTS: Both the CBT and CMO groups showed clinically relevant improvement. Although there was no between-group difference in outcome on the Hamilton Anxiety Rating Scale (6.7-point reduction in the CBT group versus 3.9-point reduction in the CMO group; P = 0.15), there was both a statistically significant and a clinically relevant between-group difference on the total PAS in favor of CBT (9.9-point reduction in the CBT group versus 5.2-point reduction in the CMO group; P = 0.012), which was due to improvement on the PAS subscales for episodic (situational) anxiety and avoidance behavior. This greater improvement was maintained at 3- and 6-month follow-ups. CONCLUSION: CBT is an effective treatment for anxiety in patients with PD and reduces situational and social anxiety, as well as avoidance behavior. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Brainstem Pathologies Correlate With Depression and Psychosis in Parkinson's Disease.

BACKGROUND: The pathological hallmarks of Parkinson's disease include intraneuronal Lewy bodies, neuronal loss, and gliosis. We aim to correlate Parkinson's disease neuropsychiatric symptoms, (e.g., depression, psychosis, and anxiety) with the severity of neuropathology in the substantia nigra and locus coeruleus. METHODS: The brains of 175 participants with a primary pathologic diagnosis of Parkinson's disease were analyzed semi-quantitatively to ascertain the burden of neuronal loss and gliosis and Lewy body pathology within the locus coeruleus and substantia nigra. Participants' history of anxiety, depression, and psychosis were determined using a chart-extracted medical history or record of formal psychiatric evaluation. RESULTS: Of the sample, 56% (n = 98), 50% (n = 88), and 31.25% (n = 55) of subjects had a diagnosis of psychosis, depression, and anxiety, respectively. Psychosis (χ2 = 7.1, p = 0.008, df = 1) and depression (χ2 = 7.2, p = 0.007, df = 1) were associated with severe neuronal loss and gliosis in the substantia nigra but not in the locus coeruleus. No association was observed between anxiety and neuronal loss and gliosis in either region. No neuropsychiatric symptoms were associated with Lewy body score. After controlling for disease duration and dementia, psychosis (odds ratio [OR]: 3.1, 95% confidence interval [CI]: 1.5-6.4, χ2 = 9.4, p = 0.012, df = 1) and depression (OR: 2.6, 95% CI: 1.3-5.0, χ2 = 7.9, p = 0.005, df = 1) remained associated with severe neuronal loss and gliosis in the substantia nigra. CONCLUSION: These results suggest that psychosis and depression in Parkinson's disease are associated with the underlying neurodegenerative process and demonstrate that cell loss and gliosis may be a better marker of neuropsychiatric symptoms than Lewy body pathology.

Structural connectivity predicts clinical outcomes of deep brain stimulation for Tourette syndrome.

Deep brain stimulation may be an effective therapy for select cases of severe, treatment-refractory Tourette syndrome; however, patient responses are variable, and there are no reliable methods to predict clinical outcomes. The objectives of this retrospective study were to identify the stimulation-dependent structural networks associated with improvements in tics and comorbid obsessive-compulsive behaviour, compare the networks across surgical targets, and determine if connectivity could be used to predict clinical outcomes. Volumes of tissue activated for a large multisite cohort of patients (n = 66) implanted bilaterally in globus pallidus internus (n = 34) or centromedial thalamus (n = 32) were used to generate probabilistic tractography to form a normative structural connectome. The tractography maps were used to identify networks that were correlated with improvement in tics or comorbid obsessive-compulsive behaviour and to predict clinical outcomes across the cohort. The correlated networks were then used to generate 'reverse' tractography to parcellate the total volume of stimulation across all patients to identify local regions to target or avoid. The results showed that for globus pallidus internus, connectivity to limbic networks, associative networks, caudate, thalamus, and cerebellum was positively correlated with improvement in tics; the model predicted clinical improvement scores (P = 0.003) and was robust to cross-validation. Regions near the anteromedial pallidum exhibited higher connectivity to the positively correlated networks than posteroventral pallidum, and volume of tissue activated overlap with this map was significantly correlated with tic improvement (P < 0.017). For centromedial thalamus, connectivity to sensorimotor networks, parietal-temporal-occipital networks, putamen, and cerebellum was positively correlated with tic improvement; the model predicted clinical improvement scores (P = 0.012) and was robust to cross-validation. Regions in the anterior/lateral centromedial thalamus exhibited higher connectivity to the positively correlated networks, but volume of tissue activated overlap with this map did not predict improvement (P > 0.23). For obsessive-compulsive behaviour, both targets showed that connectivity to the prefrontal cortex, orbitofrontal cortex, and cingulate cortex was positively correlated with improvement; however, only the centromedial thalamus maps predicted clinical outcomes across the cohort (P = 0.034), but the model was not robust to cross-validation. Collectively, the results demonstrate that the structural connectivity of the site of stimulation are likely important for mediating symptom improvement, and the networks involved in tic improvement may differ across surgical targets. These networks provide important insight on potential mechanisms and could be used to guide lead placement and stimulation parameter selection, as well as refine targets for neuromodulation therapies for Tourette syndrome.

Ventral Capsule/Ventral Striatum Stimulation in Obsessive-Compulsive Disorder: Toward a Unified Connectomic Target for Deep Brain Stimulation?

INTRODUCTION: Obsessive-compulsive disorder (OCD) is among the most disabling chronic psychiatric disorders and has a significant negative impact on multiple domains of quality of life. Deep brain stimulation (DBS) is a treatment option for severe therapy-resistant OCD. OBJECTIVE: To provide a detailed clinical description and treatment outcome analysis in a cohort of eight refractory OCD patients receiving ventral capsule/ventral striatum (VC/VS) stimulation with the intention to validate discriminating fiber bundles previously associated with clinical response. MATERIALS AND METHODS: The primary outcome measure (the Yale-Brown Obsessive Compulsive Scale [Y-BOCS]) and secondary outcomes depressive symptoms, anxiety, and quality of life were retrospectively analyzed. DBS leads were warped into standard stereotactic space. A normative connectome was used to identify the neural network associated with clinical outcome. RESULTS: With a median stimulation duration of 26 months, patients exhibited a mean Y-BOCS reduction of 10.5 resulting in a response rate of 63%. Modulation of a fiber bundle traversing the anterior limb of the internal capsule (ALIC) was associated with Y-BOCS reduction. This fiber bundle connected the frontal regions to the subthalamic nucleus (STN) and was functionally identified as the hyperdirect pathway of the basal ganglia circuitry. CONCLUSION: Our findings show that in VC/VS stimulation, the neural network associated with clinical outcome shows overlap with that of previously described for other targets namely the anterior limb of the internal capsula, the nucleus accumbens, or the STN, which supports the evolvement from the concept of an optimal gray matter target to conceiving the target as part of a symptom modulating network.

Texture features of magnetic resonance images: A marker of slight cognitive deficits in Parkinson's disease.

BACKGROUND: Cognitive impairment is a frequent nonmotor symptom of Parkinson's disease. Depending on severity, patients are considered to have mild cognitive impairment or dementia. However, among the cognitively intact patients, some may have deficits in a less severe range. The early detection of such subtle symptoms may be important for the initiation of care strategies. OBJECTIVE: To identify imaging markers of early cognitive symptoms, potentially before usual signs, such as atrophy, become manifest. METHODS: A total of 102 patients with Parkinson's disease and 17 age-matched cognitively intact healthy controls underwent extensive neuropsychological assessment and T1-weighted magnetic resonance imaging. Parkinson's disease patients were separated into 3 groups according to their cognitive status: intact, with slight slowing, and with mild deficits in executive functions. Texture features as measured by first-order and second-order statistics were computed in the following 6 brain regions: the hippocampus, thalamus, amygdala, putamen, caudate nucleus, and pallidum. They were tested between the groups, and their correlation with cognition was examined. Volumetric measurements were made for comparison. RESULTS: Texture analysis showed significant between-group differences for 2 features-skewness and entropy in the hippocampus, the thalamus, and the amygdala-and the volume analysis revealed no between-group difference. These features were significantly correlated with cognitive performance. CONCLUSION: These results support the assumption that signal alterations associated with Parkinson's disease-related cognitive decline can be captured very early by texture analysis. As these changes appear to reflect clinical phenomena, texture analysis may be a promising marker for helping cognitive phenotyping in Parkinson's disease. © 2019 International Parkinson and Movement Disorder Society.

Usability of the Experience Sampling Method in Parkinson's Disease on a Group and Individual Level.

BACKGROUND: Around 50% of PD patients experience motor fluctuations, which are often accompanied by mood fluctuations. The nature of the relationship between motor and mood fluctuations remains unknown. It is suggested that the experience sampling method can reveal such associations on both a group and individual level. Revealing group patterns may enhance our understanding of symptom interactions and lead to more general treatment recommendations, whereas analyses in individual patients can be used to establish a personalized treatment plan. OBJECTIVES: To explore the usability of routinely collected experience sampling method data over a brief period of time to detect associations between motor fluctuations, affective state, and contextual factors in PD patients with motor fluctuations on a group level and on an individual level. METHODS: Eleven patients with motor fluctuations collected data at 10 semirandom moments over the day for 5 consecutive days. RESULTS: On a group level, multilevel analyses showed significant associations between all motor symptoms and positive affect. Being at home was associated with increased balance problems and rigidity. Analyses on an individual level revealed much less significant associations that mostly, but not always, were in line with the results on a group level. CONCLUSION: This exploratory study showed significant associations between affective state, motor symptoms, and contextual factors in a group of PD patients with motor fluctuations, but less so in individual patients. Given that the ultimate aim is to use the experience sampling method as an aid to personalize treatments, the sensitivity of the approach needs to be increased. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Performance and Symptom Validity Assessment in Patients with Apathy and Cognitive Impairment.

OBJECTIVE: Performance and symptom validity tests (PVTs and SVTs) measure the credibility of the assessment results. Cognitive impairment and apathy potentially interfere with validity test performance and may thus lead to an incorrect (i.e., false-positive) classification of the patient's scores as non-credible. The study aimed at examining the false-positive rate of three validity tests in patients with cognitive impairment and apathy. METHODS: A cross-sectional, comparative study was performed in 56 patients with dementia, 41 patients with mild cognitive impairment, and 41 patients with Parkinson's disease. Two PVTs - the Test of Memory Malingering (TOMM) and the Dot Counting Test (DCT) - and one SVT - the Structured Inventory of Malingered Symptomatology (SIMS) - were administered. Apathy was measured with the Apathy Evaluation Scale, and severity of cognitive impairment with the Mini Mental State Examination. RESULTS: The failure rate was 13.7% for the TOMM, 23.8% for the DCT, and 12.5% for the SIMS. Of the patients with data on all three tests (n = 105), 13.5% failed one test, 2.9% failed two tests, and none failed all three. Failing the PVTs was associated with cognitive impairment, but not with apathy. Failing the SVT was related to apathy, but not to cognitive impairment. CONCLUSIONS: In patients with cognitive impairment or apathy, failing one validity test is not uncommon. Validity tests are differentially sensitive to cognitive impairment and apathy. However, the rule that at least two validity tests should be failed to identify non-credibility seemed to ensure a high percentage of correct classification of credibility.

Electroencephalography-based machine learning for cognitive profiling in Parkinson's disease: Preliminary results.

BACKGROUND: Cognitive symptoms are common in patients with Parkinson's disease. Characterization of a patient's cognitive profile is an essential step toward the identification of predictors of cognitive worsening. OBJECTIVE: The aim of this study was to investigate the use of the combination of resting-state EEG and data-mining techniques to build characterization models. METHODS: Dense EEG data from 118 patients with Parkinson's disease, classified into 5 different groups according to the severity of their cognitive impairments, were considered. Spectral power analysis within 7 frequency bands was performed on the EEG signals. The obtained quantitative EEG features of 100 patients were mined using 2 machine-learning algorithms to build and train characterization models, namely, support vector machines and k-nearest neighbors models. The models were then blindly tested on data from 18 patients. RESULTS: The overall classification accuracies were 84% and 88% for the support vector machines and k-nearest algorithms, respectively. The worst classifications were observed for patients from groups with small sample sizes, corresponding to patients with the severe cognitive deficits. Whereas for the remaining groups for whom an accurate diagnosis was required to plan the future healthcare, the classification was very accurate. CONCLUSION: These results suggest that EEG features computed from a daily clinical practice exploration modality in-that it is nonexpensive, available anywhere, and requires minimal cooperation from the patient-can be used as a screening method to identify the severity of cognitive impairment in patients with Parkinson's disease. © 2018 International Parkinson and Movement Disorder Society.

Scales to assess impulsive and compulsive behaviors in Parkinson's disease: Critique and recommendations.

Impulse control disorders (ICDs) and related impulsive and compulsive behaviors (together called ICBs) have been increasingly recognized in the context of Parkinson's disease (PD) and treatment. The International Parkinson's and Movement Disorder Society commissioned a task force to assess available clinical screening instruments and rating scales, including their clinimetric properties, make recommendations regarding their utility, and suggest future directions in scale development and validation. The literature was systematically searched for scales measuring a range of reported ICBs in PD. A scale was designated "recommended" if the scale had been employed in PD studies, been used beyond the group that developed it, and had adequate clinimetric data published for PD. Numerous diagnostic screening tools and severity rating scales were identified for a range of ICBs, including compulsive medication use, punding/hobbyism, walkabout, pathological gambling, hypersexuality, compulsive or binge eating, compulsive buying, reckless driving, compulsive exercise, pyromania, trichotillomania, hoarding, kleptomania, intermittent explosive disorder, and internet addiction. For screening across the range of ICBs (except compulsive medication use), the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease (QUIP) and QUIP-Rating Scale (QUIP-RS) are recommended, and for severity rating across the range of ICBs the QUIP-RS and the Ardouin Scale of Behavior in Parkinson's Disease are recommended. The Scale for Outcomes in Parkinson's Disease-Psychiatric Complications is recommended for rating of hypersexuality and the compulsive behaviors gambling/shopping. Further testing of established scales against gold standard diagnostic criteria is urgently required for all other individual ICBs in PD. © 2019 International Parkinson and Movement Disorder Society © 2019 International Parkinson and Movement Disorder Society.

Social role functioning in Parkinson's disease: A mixed-methods systematic review.

OBJECTIVES: Parkinson's disease (PD) is a progressive neurodegenerative disease that often impedes activities of daily living (ADL) and social functioning. Impairment in these areas can alter social roles by interfering with employment status, household management, friendships, and other relationships. Understanding how PD affects social functioning can help clinicians choose management strategies that mitigate these changes. METHODS: We conducted a mixed-methods systematic review of existing literature on social roles and social functioning in PD. A tailored search strategy in five databases identified 51 full-text reports that fulfilled the inclusion criteria and passed the quality appraisal. We aggregated and analyzed the results from these studies and then created a narrative summary. RESULTS: Our review demonstrates how PD causes many people to withdraw from their accustomed social roles and experience deficits in corresponding activities. We describe how PD symptoms (eg, tremor, facial masking, and neuropsychiatric symptoms) interfere with relationships (eg, couple, friends, and family) and precipitate earlier departure from the workforce. Additionally, several studies demonstrated that conventional PD therapy has little positive effect on social role functioning. CONCLUSIONS: Our report presents critical insight into how PD affects social functioning and gives direction to future studies and interventions (eg, couple counseling and recreational activities).

Network analysis of symptoms in a Parkinson patient using experience sampling data: An n = 1 study.

BACKGROUND: Around 50% of Parkinson's disease patients experience motor fluctuations after long-term treatment with levodopa. These fluctuations may be accompanied by mood fluctuations. Routine cross-sectional assessments cannot capture the extent of these motor and mood fluctuations and their possible associations. Experience sampling techniques that use frequently repeated measurements of symptoms over time are able to capture such fluctuations. Based on such data, longitudinal associations between symptoms can be studied using network analysis. AIM: The purpose of this study is to identify longitudinal associations between motor symptoms and mood states in a patient with Parkinson's disease. METHODS: A 53-year-old man with Parkinson's disease and motor fluctuations collected experience sampling data during 34 consecutive days. A set of dependent variables included tremor, rigidity, balance problems, and "on/off" state, and the mood variables anxiety, cheerful, and "down." Independent variables were the same variables assessed at the preceding measurement. Regression coefficients were calculated and presented in a network graph. RESULTS: In this patient, anxiety and cheerfulness had a central position within the symptom network. Higher anxiety was prospectively associated with increased rigidity and tremor and with feeling "down." Cheerfulness was associated with less tremor. Balance problems were not influenced by cheerfulness nor anxiety, but increased balance problems were associated with reduced cheerfulness at the next assessment. Feeling "down" did not influence self-reported motor symptom severity at the next assessment. CONCLUSION: This n = 1 study shows that network analysis of experience sampling data may reveal longitudinal associations of self-reported motor symptoms and mood states that may have relevance for treatment strategies. © 2018 International Parkinson and Movement Disorder Society.