Multiple sleep disturbances are associated with apathy in individuals with Parkinson's disease.

Background: Parkinson's disease (PD) is associated with both sleep disturbances and apathy, and within PD, apathy has been associated with REM behavior disorder and excessive daytime sleepiness. Whether other forms of sleep disturbance are similarly associated with apathy in PD remains unclear. This study explored associations between a broad array of sleep disturbances and apathy in 50 individuals with idiopathic PD (PD) and 48 matched controls (MC). Methods: Participants were adults aged 53-80 (Mdn = 67), 23 % female, and 96 % white. Sleep disturbances were measured with various questionnaires (ISI, PSQI, PROMIS-SD, ESS, PROMIS-SRI, RBDSQ). Mood was measured with the STAI and BDI-II. Apathy was evaluated using the Apathy Scale (AS). Spearman correlations and regression analyses were performed between measures of sleep disturbance and AS in the total sample and each group. Group correlations were compared using 2-sample Fisher's z test. Results: The AS total score significantly correlated with PROMIS-SRI in the total sample and multiple measures of sleep disturbance in the PD group. The apathy subscales were each significantly correlated with sleep disturbance measures in the total sample, MC, and PD groups. The correlations between several sleep and apathy values were significantly stronger in the PD group than MC. When accounting for anxiety and depression most differences were no longer significant, only the PROMIS-SRI was significantly predictive of the behavioral apathy sub score. Discussion: Evidence supports an association between sleep disturbances and apathy in individuals with PD. Specifically, insomnia severity, poor sleep quality, and daytime sleepiness were uniquely associated with apathy in this group. We did not find these associations in the matched control group. Anxiety and depression are likely involved in the association between sleep and apathy in PD. Experimental studies that manipulate or improve sleep may further elucidate the mechanisms underlying the association between sleep disturbance and apathy in PD.

Anticholinergic Medication Burden and Cognitive Subtypes in Parkinson's Disease without Dementia.

OBJECTIVE: Cognitive changes are heterogeneous in Parkinson's disease (PD). This study compared whether anticholinergic burden drives differences in cognitive domain performance and empirically-derived PD-cognitive phenotypes. METHOD: A retrospective chart review contained participants (n = 493) who had idiopathic PD without dementia. Participants' medications were scored (0-3) and summed based on the anticholinergic cognitive burden scale (ACBS). We examined the ACBS' relationship to five cognitive domain composites (normative z-scores) and three (K-means clustering based) cognitive phenotypes: cognitively intact, low executive function (EF), and predominately impaired EF/memory. Analyses included Spearman correlations, analysis of covariance, and Pearson chi-squared test. RESULTS: Overall, phenotypes did not differ in anticholinergic burden, and (after false-discovery-rate corrections) no cognitive domains related. When comparing those above and below the clinically relevant ACBS cutoff (i.e., score ≥3), no significant phenotype or domain differences were found. CONCLUSIONS: Anticholinergic medication usage did not drive cognitive performance in a large clinical sample of idiopathic PD without dementia.

Greater Apathy Associated With Selective Serotonin Reuptake Inhibitor Use in Parkinson's Disease.

OBJECTIVE: Apathy, a motivational disorder, is common in Parkinson's disease (PD) and often misdiagnosed as depression. Use of selective serotonin reuptake inhibitors (SSRIs) has been associated with increased apathy in adolescents and adults with depression. Based on observations that serotonin may downregulate dopaminergic systems, we examined the relationship between apathy and SSRI use in individuals with PD. METHODS: Medications, mood/motivation scales, and clinical data were collected from a convenience sample of 400 individuals with PD. Depression and apathy were measured using the Beck Depression Inventory-II (BDI-Il) and the Apathy Scale (AS). Antidepressant medications were grouped by mechanism type. RESULTS: Of the 400 PD patients, 26% were on SSRIs. On standard mood/motivation scales, 38% of the sample exceeded clinical cut-offs for apathy and 28% for depression. Results of hierarchical regression analyses revealed that SSRIs were the only antidepressant that were significantly associated with higher apathy scores (ß = .1, P = .02). Less education (ß = -.1, P = .01) worse cognition (ß = -.1, P = .01), and greater depressive symptoms (ß = .5, P < .001) were also significant predictors of apathy. CONCLUSION: These findings suggest that use of SSRIs, but not other antidepressants, is associated with greater apathy in PD. Given the interactive relationship between serotonin and dopamine, the current findings highlight the importance of considering apathy when determining which antidepressants to prescribe to individuals with PD. Similarly, switching a SSRI for an alternative antidepressant in individuals with PD who are apathetic may be a potential treatment for apathy that needs further study.

Co-Occurrence of Apathy and Impulse Control Disorders in Parkinson Disease: Variation across Multiple Measures.

OBJECTIVE: To determine if the co-occurrence of apathy and impulse control disorders (ICDs) in Parkinson disease is dependent on instrument selection and assess the concurrent validity of three motivation measures by examining interrelationships between them. METHOD: Ninety-seven cognitively normal individuals with idiopathic Parkinson disease (PD) completed the Questionnaire for Impulsive-Compulsive Disorders in Parkinson Disease-Rating Scale (QUIP-RS) and three apathy measures: the Apathy Scale, Lille Apathy Rating Scale, and Item 4 of the Movement Disorder Society-Unified Parkinson Disease Rating Scale. RESULTS: Fifty (51.5%) participants were classified as apathetic on at least one measure, and only four individuals (4.3%) obtained clinically elevated scores on all three measures. The co-occurrence of apathy and ICD varied across measures. CONCLUSIONS: We observed a co-occurrence of apathy and ICDs in PD patients with each apathy instrument; however, limited concurrent validity exists across measures. This is important for future investigations into shared pathophysiology and the design of future clinical trials aimed at improving the early detection and treatment of these debilitating syndromes.

Responsive deep brain stimulation for the treatment of Tourette syndrome.

To report the results of 'responsive' deep brain stimulation (DBS) for Tourette syndrome (TS) in a National Institutes of Health funded experimental cohort. The use of 'brain derived physiology' as a method to trigger DBS devices to deliver trains of electrical stimulation is a proposed approach to address the paroxysmal motor and vocal tic symptoms which appear as part of TS. Ten subjects underwent bilateral staged DBS surgery and each was implanted with bilateral centromedian thalamic (CM) region DBS leads and bilateral M1 region cortical strips. A series of identical experiments and data collections were conducted on three groups of consecutively recruited subjects. Group 1 (n = 2) underwent acute responsive DBS using deep and superficial leads. Group 2 (n = 4) underwent chronic responsive DBS using deep and superficial leads. Group 3 (n = 4) underwent responsive DBS using only the deep leads. The primary outcome measure for each of the 8 subjects with chronic responsive DBS was calculated as the pre-operative baseline Yale Global Tic Severity Scale (YGTSS) motor subscore compared to the 6 month embedded responsive DBS setting. A responder for the study was defined as any subject manifesting a ≥ 30 points improvement on the YGTSS motor subscale. The videotaped Modified Rush Tic Rating Scale (MRVTRS) was a secondary outcome. Outcomes were collected at 6 months across three different device states: no stimulation, conventional open-loop stimulation, and embedded responsive stimulation. The experience programming each of the groups and the methods applied for programming were captured. There were 10 medication refractory TS subjects enrolled in the study (5 male and 5 female) and 4/8 (50%) in the chronic responsive eligible cohort met the primary outcome manifesting a reduction of the YGTSS motor scale of ≥ 30% when on responsive DBS settings. Proof of concept for the use of responsive stimulation was observed in all three groups (acute responsive, cortically triggered and deep DBS leads only). The responsive approach was safe and well tolerated. TS power spectral changes associated with tics occurred consistently in the low frequency 2-10 Hz delta-theta-low alpha oscillation range. The study highlighted the variety of programming strategies which were employed to achieve responsive DBS and those used to overcome stimulation induced artifacts. Proof of concept was also established for a single DBS lead triggering bi-hemispheric delivery of therapeutic stimulation. Responsive DBS was applied to treat TS related motor and vocal tics through the application of three different experimental paradigms. The approach was safe and effective in a subset of individuals. The use of different devices in this study was not aimed at making between device comparisons, but rather, the study was adapted to the current state of the art in technology. Overall, four of the chronic responsive eligible subjects met the primary outcome variable for clinical effectiveness. Cortical physiology was used to trigger responsive DBS when therapy was limited by stimulation induced artifacts.

Frontal-temporal regional differences in brain energy metabolism and mitochondrial function using 31P MRS in older adults.

Aging is a major risk for cognitive decline and transition to dementia. One well-known age-related change involves decreased brain efficiency and energy production, mediated in part by changes in mitochondrial function. Damaged or dysfunctional mitochondria have been implicated in the pathogenesis of age-related neurodegenerative conditions like Alzheimer's disease (AD). The aim of the current study was to investigate mitochondrial function over frontal and temporal regions in a sample of 70 cognitively normal older adults with subjective memory complaints and a first-degree family history of AD. We hypothesized cerebral mitochondrial function and energy metabolism would be greater in temporal as compared to frontal regions based on the high energy consumption in the temporal lobes (i.e., hippocampus). To test this hypothesis, we used phosphorous (31P) magnetic resonance spectroscopy (MRS) which is a non-invasive and powerful method for investigating in vivo mitochondrial function via high energy phosphates and phospholipid metabolism ratios. We used a single voxel method (left temporal and bilateral prefrontal) to achieve optimal sensitivity. Results of separate repeated measures analyses of variance showed 31P MRS ratios of static energy, energy reserve, energy consumption, energy demand, and phospholipid membrane metabolism were greater in the left temporal than bilateral prefrontal voxels. Our findings that all 31P MRS ratios were greater in temporal than bifrontal regions support our hypothesis. Future studies are needed to determine whether findings are related to cognition in older adults.

Dose response of transcranial near infrared light stimulation on brain functional connectivity and cognition in older adults-A randomized comparison.

Photobiomodulation, also called low-level light therapy, has been reported in animal studies to have an effect on brain activity and cognition. However, studies in humans regarding its effect on cognition and brain functional connectivity, and the required dose threshold for achieving the same have been very limited. We compared the effects of different doses of photobiomodulation (PBM) on cognition and resting state brain functional connectivity in 25 cognitively normal adults aged 55-70 years. They were randomized to a single session of the sham group, "low-dose" and "high-dose" groups receiving NIR light with transcranial fluence of 26 and 52 J/cm2 respectively, and intranasal fluence of 9 and 18 J/cm2 respectively. There was a significant increase in resting state functional connectivity of the left superior frontal gyrus (SFG) with the left planum temporale (PT), p = 0.0016, and with the left inferior frontal gyrus, pars triangularis, p = 0.0235 in the "high-dose" group only compared to the "sham" group. There was also a significant improvement in visual search and processing speed (p = 0.012) in the "high-dose" group. Replication of these findings in an adequately powered randomized sham-controlled study in healthy older adults can pave the way for clinical application of NIRL as a therapeutic modality in patients with Alzheimer's disease.

Perception of cognitive change by individuals with Parkinson's disease or essential tremor seeking deep brain stimulation: Utility of the cognitive change index.

OBJECTIVE: The Cognitive Change Index (CCI-20) is a validated questionnaire that assesses subjective cognitive complaints (SCCs) across memory, language, and executive domains. We aimed to: (a) examine the internal consistency and construct validity of the CCI-20 in patients with movement disorders and (b) learn how the CCI-20 corresponds to objective neuropsychological and mood performance in individuals with Parkinson's disease (PD) or essential tremor (ET) seeking deep brain stimulation (DBS). METHODS: 216 participants (N = 149 PD; N = 67 ET) underwent neuropsychological evaluation and received the CCI-20. The proposed domains of the CCI-20 were examined via confirmatory (CFA) and exploratory (EFA) factor analyses. Hierarchical regressions were used to assess the relationship among subjective cognitive complaints, neuropsychological performance and mood symptoms. RESULTS: PD and ET groups were similar across neuropsychological, mood, and CCI-20 scores and were combined into one group who was well educated (m = 15.01 ± 2.92), in their mid-60's (m = 67.72 ± 9.33), predominantly male (63%), and non-Hispanic White (93.6%). Previously proposed 3-domain CCI-20 model failed to achieve adequate fit. Subsequent EFA revealed two CCI-20 factors: memory and non-memory (p < 0.001; CFI = 0.924). Regressions indicated apathy and depressive symptoms were associated with greater memory and total cognitive complaints, while poor executive function and anxiety were associated with more non-memory complaints. CONCLUSION: Two distinct dimensions were identified in the CCI-20: memory and non-memory complaints. Non-memory complaints were indicative of worse executive function, consistent with PD and ET cognitive profiles. Mood significantly contributed to all CCI-20 dimensions. Future studies should explore the utility of SCCs in predicting cognitive decline in these populations.

The Relationship Between Autonomic Dysfunction and Mood Symptoms in De Novo Parkinson's Disease Patients Over Time.

BACKGROUND: Autonomic dysfunction is prevalent in Parkinson's disease (PD) and can worsen quality of life. We examined: (a) whether specific autonomic symptoms were more strongly associated with anxiety or depression in PD and (b) whether overall autonomic dysfunction predicted mood trajectories over a 5-year period. METHODS: Newly diagnosed individuals with PD (N = 414) from the Parkinson's Progression Markers Initiative completed self-report measures of depression, anxiety, and autonomic symptoms annually. Cross-sectional linear regressions examined relationships between specific autonomic subdomains (gastrointestinal, cardiovascular, thermoregulatory, etc.) and mood. Multilevel modeling examined longitudinal relationships with total autonomic load. RESULTS: Gastrointestinal symptoms were associated with both higher anxiety (b = 1.04, 95% CI [.55, 1.53], P < .001) and depression (b = .24, 95% CI [.11, .37], P = .012), as were thermoregulatory symptoms (anxiety: b = 1.06, 95% CI [.46, 1.65], P = .004; depression: b = .25, 95% CI [.09, .42], P = .013), while cardiovascular (b = .36, 95% CI [.10, .62], P = .012) and urinary symptoms (b = .10, 95% CI [.01, .20], P = .037) were associated only with depression. Longitudinally, higher total autonomic load was associated with increases in both depression (b = .01, 95% CI [.00, .02], P = .015) and anxiety (b = .04, 95% CI [.01, .06], P < .001) over time, as well as occasion-to-occasion fluctuations (depression: b = .08, 95% CI [.05, .10], P < .001; anxiety: b = .24, 95% CI [.15, .32], P < .001). CONCLUSION: Findings suggest autonomic dysfunction, particularly gastrointestinal and thermoregulatory symptoms, may be an indicator for elevated anxiety/depression and a potential treatment target early on in PD.

Frontal adenosine triphosphate markers from 31P MRS are associated with cognitive performance in healthy older adults: preliminary findings.

Aging is associated with declines in mitochondrial efficiency and energy production which directly impacts the availability of adenosine triphosphate (ATP), which contains high energy phosphates critical for a variety of cellular functions. Previous phosphorous magnetic resonance spectroscopy (31P MRS) studies demonstrate cerebral ATP declines with age. The purpose of this study was to explore the functional relationships of frontal and posterior ATP levels with cognition in healthy aging. Here, we measured frontal and posterior ATP levels using 31P MRS at 3 Tesla (3 T) and assessed cognition using the Montreal Cognitive Assessment (MoCA) in 30 healthy older adults. We found that greater frontal, but not posterior, ATP levels were significantly associated with better MoCA performance. This relationship remained significant after controlling for age, sex, years of education, and brain atrophy. In conclusion, our findings indicate that cognition is related to ATP in the frontal cortex. These preliminary findings may have important implications in the search for non-invasive markers of in vivo mitochondrial function and the impact of ATP availability on cognition. Future studies are needed to confirm the functional significance of regional ATP and cognition across the lifespan.

Early rapid eye movement sleep behavior disorder predicts incident cognitive impairment in Parkinson's disease across ages.

This study demonstrated possible rapid eye movement sleep behavior disorder (RBD)'s relationship to longitudinal, incident cognitive impairment in the Parkinson's Progression Markers Initiative (PPMI) database. Age did not moderate this relationship, suggesting that RBD serves as a cognitive risk factor across individuals of all ages with recently diagnosed Parkinson's disease.

A Pilot Trial of Dopamine Replacement for Dynamic Facial Expressions in Parkinson's Disease.

Background: Current conflict exists regarding the potential beneficial effects of dopamine medications on facial expressivity in Parkinson's disease. Via digital video analysis software, we previously found reduced facial movement (entropy) and slower time to reach peak entropy in individuals with Parkinson's disease compared to controls. Objectives: We aimed to determine whether levodopa medications improved parameters of dynamic facial expressions (amplitude, speed). Methods: A total of 34 individuals with idiopathic Parkinson's disease were videotaped making voluntary facial expressions (happy, fear, anger, disgust) when "on" and "off" levodopa. Participants were 52 to 80 years old, early to mid-stage disease, non-demented, and included more men (65%). Expressions were digitized and analyzed using software that extracted three variables: two indices of movement change (total entropy, percent entropy change) and time to reach peak expression. Results: Indices of facial movement (total entropy, peak entropy) and timing were significantly improved when patients were "on" vs "off" medication (all F's ≥ 3.00, P < 0.05). For total movement and time to reach peak entropy, levodopa-related improvements were emotion nonspecific. Levodopa-related improvement for peak entropy was driven primarily by happy expressions. There was no relationship between quantitative indices and clinical measures of mood (depression, anxiety) and motor disease severity. Conclusion: The effects of levodopa on Parkinson's disease voluntary facial movement and on timing were robust and consistent with those of levodopa on other intentional movements in Parkinson's disease. This improvement possibly occurred because of levodopa enhanced activation of face representation areas in fronto-cortical regions or because of less movement-based suppression.

What does the Dementia Rating Scale-2 measure? The relationship of neuropsychological measures to DRS-2 total and subscale scores in non-demented individuals with Parkinson's disease.

OBJECTIVE: The Dementia Rating Scale-2 (DRS-2) is recommended for assessing global cognition in Parkinson's disease (PD) by the Movement Disorder Society. However, empirical evidence is limited regarding the degree to which the DRS-2 corresponds to traditional neurocognitive domains (i.e., construct validity) in PD. Thus, this study aims to determine the construct validity of the DRS-2 in a non-demented sample of PD patients. METHOD: Patients with PD (n = 359; mean age = 64.50 ± 8.53, education = 14.97 ± 2.73, disease duration = 8.48 ± 4.87, UPDRS Part III motor scale scores = 25.23 ± 10.17) completed the DRS-2 as part of a comprehensive neuropsychological assessment consisting of attention/working memory, executive function, language, delayed recall, and visuoperceptual-spatial skills.Bootstrapped bias-corrected Spearman rho's correlations andhierarchical linear regressions were performed to examine construct validity of DRS-2 total and subscale scores. RESULTS: Speeded measures of set-shifting, rapid word generation to letter and semantic cues, and simple visuoperceptual skills largely accounted for variance in DRS-2 total scores. Most DRS-2 subscale scores showed weak relationships with theoretically related neuropsychological measures. CONCLUSIONS: DRS-2 total scores reflect impairment across a range of cognitive domains (i.e., executive, language, and visuoperception), while DRS-2 subscale scores have limited construct validity. Together, the DRS-2 does not appear to have utility beyond screening for global cognition in PD.

Unpacking the NIH Toolbox Emotion Battery in Persons With Parkinson's disease.

OBJECTIVE: Examine the relationship between the National Institutes of Health Toolbox Emotion Battery (Emotion Toolbox) and traditional measures in Parkinson's disease (PD). METHOD: Persons with PD (n = 30) and cognitively healthy older adults (OA; n = 40) completed the Emotion Toolbox consisting of Well-Being, Negative Affect, and Social Satisfaction scores along with traditional measures of depression (Beck Depression Inventory-II [BDI-II]), anxiety (State-Trait Anxiety Inventory [STAI]), and apathy (Apathy Scale [AS]); total raw scores). RESULTS: Separate bootstrapped analyses of covariance indicated that the PD group scored higher on BDI-II and STAI-State compared to OA (ps < .01); groups did not differ on Emotion Toolbox. In the PD group, bootstrapped partial correlations indicated that Negative Affect was positively related to BDI-II and STAI (ps ≤ .001). Social Satisfaction was negatively related to BDI-II and STAI-Trait (.05 < ps < .004). Psychological Well-Being was negatively related to BDI-II, AS, and STAI (p < .004). No relationships emerged in OA. In the PD group, separate binary logistic regressions showed that traditional measures (BDI-II, AS, and STAI-Trait) correctly classified 79.6% those with formal psychiatric diagnoses (presence vs. absence; p < .011), whereas Emotion Toolbox measures correctly classified 73.3% (p < .019). CONCLUSIONS: The Emotion Toolbox showed moderate-strong correlations with traditional measures in persons with PD. Even so, it did not capture the group differences between PD and OA and had a somewhat lower classification accuracy rate for persons with PD who had a formal psychiatric diagnosis than traditional measures. Together, findings question the utility of the Emotion Toolbox as a stand-alone emotion screener in PD.

From pleasure to punding: Distinct patterns of anhedonia and impulsivity linked to motivational disturbances in Parkinson disease.

INTRODUCTION: Apathy and impulse control disorders (ICD) are common comorbid motivational syndromes in Parkinson disease (PD). This study aimed to determine if patients with these motivational disturbances exhibit different patterns of anhedonia and trait impulsivity. METHODS: Sixty-four non-demented patients with PD completed questionnaires assessing apathy and ICD symptoms, which were used to classify participants into one of the following groups: apathy only, ICD only, both, and neither. Participants also completed multidimensional measures of anhedonia and trait impulsivity, which were compared across groups defined by motivational status. RESULTS: Individuals with both apathy and ICD had significantly greater symptoms of positive and negative urgency than all other groups and had significantly greater consummatory anhedonia and lack of premeditation and perseverance than those with ICD only and neither. Patients with apathy only also reported significantly greater anticipatory anhedonia than those with ICD only and the neither group. There were no significant between-group differences in sensation seeking. CONCLUSION: Distinct patterns of impulsivity and anhedonia characterize unique behavioral phenotypes of motivational disturbances in PD and may reflect important differences in the underlying neurobiological mechanisms. Clinicians should be aware that motivational disturbances may be more severe in cases where apathy co-occurs with one or more ICD.HIGHLIGHTSHighlights are mandatory for all submissions except letters. They consist of a short collection of bullet points that convey the core findings of the article and should be submitted in a separate file in the online submission system. Please use "Highlights" in the file name and include 3-5 bullet points (maximum 85 characters, including spaces, per bullet point). See https://www.elsevier.com/highlights for examples.

Online vs Face-to-Face Administration of Impulse Control Disorder Questionnaires in Parkinson Disease: Does Method Matter?

Background and Objective: Social desirability bias, the tendency to underreport undesirable behaviors, may be one reason patients with Parkinson disease (PD) underreport symptoms of impulse control disorders (ICDs). Methods: We compared rates of ICD endorsement on questionnaires administered face-to-face and online in 60 patients with mild-to-moderate idiopathic PD. Participants also completed a self-report measure of social desirability. Results: We found a significantly higher prevalence of any ICD based on online (56.7%) vs in-person (33.3%) administration. Significantly higher endorsement of items related to hypersexuality in men and compulsive eating and buying in women were found with online administration. Social desirability bias was positively correlated with ICD symptom endorsement across all items and subscales. Discussion: The results highlight the importance of social context/setting and the need for sensitivity and discretion when screening for ICD symptoms. Although a higher level of symptom endorsement does not necessarily imply a greater level of accuracy, more work is needed to determine which method of administration is most accurate for clinical and research practice.

Embedded Human Closed-Loop Deep Brain Stimulation for Tourette Syndrome: A Nonrandomized Controlled Trial.

Importance: Because Tourette syndrome (TS) is a paroxysmal disorder, symptomatic relief in individuals with TS may be possible through the application of stimulation only during the manifestation of human tic neural signatures. This technique could be capable of suppressing both motor and vocal tics and would have similar effectiveness to conventional continuous deep brain stimulation (DBS). Objective: To evaluate the feasibility, safety, and clinical effectiveness of bilateral centromedian-parafascicular complex thalamic closed-loop DBS as a treatment for medication-refractory TS. Design, Setting, and Participants: This single-center double-blinded safety and feasibility trial was conducted between February 2014 and June 2020. Six individuals with TS were screened and recruited from the Norman Fixel Institute at the University of Florida. The primary outcome was measured at 6 months, and participants were followed up for the duration of the neurostimulator battery life. Independent ratings that compared closed-loop and conventional DBS were videotaped. The first 2 of 6 individuals with TS were excluded from the study because the technology for embedded closed-loop capability was not yet available. The date of analysis was August 2020. Interventions: DBS therapy controlled by an embedded closed-loop stimulation system. Main Outcomes and Measures: The primary clinical outcome measure was a minimum of a 40% reduction in the YGTSS score at 6 months following DBS. There was also a comparison of conventional DBS with closed-loop DBS using the Modified Rush Videotape Rating Scale for Tic. Results: The mean (SD) age at TS diagnosis for the cohort was 8.5 (2.9), and the mean (SD) disease duration was 23.7 (5.8) years. Four individuals with TS were analyzed (2 male, 2 female; mean [SD] age, 23.7 [5.8] years). The study showed the closed-loop approach was both feasible and safe. One of the novelties of this study was that a patient-specific closed-loop paradigm was created for each participant. The features and stimulation transition speed were customized based on the signal quality and the tolerance to adverse reactions. The mean (SD) therapeutic outcome with conventional DBS was 33.3% (35.7%) improvement on the YGTSS and 52.8% (21.9%) improvement on the Modified Rush Videotape Rating Scale. Two of 4 participants had a primary outcome variable improvement of 40% meeting the primary efficacy target. When comparing closed-loop DBS with conventional DBS using a Wilcoxon sign-rank test, there was no statistical difference between tic severity score and both approaches revealed a lower tic severity score compared with baseline. The study was feasible in all 4 participants, and there were 25 total reported adverse events with 3 study-related events (12%). The most common adverse events were headache and anxiety. Conclusions and Relevance: Embedded closed-loop deep DBS was feasible, safe, and had a comparable outcome to conventional TS DBS for the treatment of tics. Trial Registration: ClinicalTrials.gov Identifier: NCT02056873.

Central Nervous System Manifestations of COVID-19: A Critical Review and Proposed Research Agenda.

OBJECTIVE: On March 11, 2020, the World Health Organization declared an outbreak of a new viral entity, coronavirus 2019 (COVID-19), to be a worldwide pandemic. The characteristics of this virus, as well as its short- and long-term implications, are not yet well understood. The objective of the current paper was to provide a critical review of the emerging literature on COVID-19 and its implications for neurological, neuropsychiatric, and cognitive functioning. METHOD: A critical review of recently published empirical research, case studies, and reviews pertaining to central nervous system (CNS) complications of COVID-19 was conducted by searching PubMed, PubMed Central, Google Scholar, and bioRxiv. RESULTS: After considering the available literature, areas thought to be most pertinent to clinical and research neuropsychologists, including CNS manifestations, neurologic symptoms/syndromes, neuroimaging, and potential long-term implications of COVID-19 infection, were reviewed. CONCLUSION: Once thought to be merely a respiratory virus, the scientific and medical communities have realized COVID-19 to have broader effects on renal, vascular, and neurological body systems. The question of cognitive deficits is not yet well studied, but neuropsychologists will undoubtedly play an important role in the years to come.

Cognitive subtypes in individuals with essential tremor seeking deep brain stimulation.

Objective: Essential tremor (ET) is a common neurological disorder that has been associated with 60% increased risk of developing dementia. The goals of the present study were to: (a) learn whether individuals with advanced ET symptoms seeking deep brain stimulation (DBS) surgery would fall into distinct cognitive subgroups, and (b) learn how empirically derived subgroups map onto criteria for mild cognitive impairment (MCI). Method: Patients with ET (N = 201; mean age = 68.9 ± 8.9 years) undergoing pre-surgical evaluation for DBS completed a multi-domain neurocognitive assessment consisting of memory, executive function, visuospatial skill, language, and processing speed. Two cluster analytic approaches (K-means, hierarchical) were independently conducted to classify cognitive patterns using domain composites. Demographics, clinical characteristics, and proportion of cases meeting neuropsychologically defined criteria for MCI were examined among clusters. Results: A three-cluster solution reflected a Low Executive group (N = 64), Low Memory Multi-Domain group (N = 41), and Cognitively Normal group (N = 96). The Cognitively Normal group was older and more educated, with a higher Dementia Rating Scale-2 score. In total, 27.4% of participants met criteria for MCI. Of the MCI cases, most were in the Low Executive (41.8%) or Low Memory Multi-Domain groups (49.1%). In the latter, 65.9% of its members were classified as MCI versus 35.9% in the Low Executive group. Conclusions: Our study identified three cognitive subtypes of ET patients presenting for DBS. Future work should examine the subgroups for progression to dementia, particularly the Low Memory Multi-Domain subgroup which may be at highest risk.

Differential contributions of depression, apathy, and anxiety to neuropsychological performance in Parkinson's disease versus essential tremor.

INTRODUCTION: Mood symptoms are common features of Parkinson's disease (PD) and essential tremor (ET) and have been linked to worse cognition. The goals of the present study were to compare the severity of anxiety, apathy, and depressive symptoms in PD, ET, and healthy controls (HC) and to examine differential relationships between mood and cognition. METHOD: Older adults with idiopathic PD (N = 448), ET (N = 128), or HC (N = 136) completed a multi-domain neuropsychological assessment consisting of memory, executive function, and attention/working memory domains. Participants also completed self-reported mood measures. Between-group differences in mood and cognition were assessed, and hierarchical regression models were conducted to examine relationships between mood and cognition in each group. RESULTS: Relative to the HC group, the PD and ET groups reported more mood symptoms and scored lower across all cognitive measures. There were no differences between the two movement disorder groups. Mood variables explained 3.9-13.7% of the total variance in cognitive domains, varying by disease group. For PD, apathy was the only unique predictor of executive function (ß = -.114, p = .05), and trait anxiety was the only unique predictor of attention/working memory (ß = -.188, p < .05). For ET, there were no unique predictors, though the overall models significantly predicted performance in the executive function and attention/working memory domains. CONCLUSIONS: In a large cohort of ET and PD, we observed that the two groups had similar self-reported mood symptoms. Mood symptoms were differentially associated with cognition in PD versus ET. In PD, increased apathy was associated with worse executive function and higher trait anxiety predicted worse attention/working memory. For ET, there were no unique predictors, though the overall mood symptom severity was related to cognition. Our study highlights the importance of considering the relationship between mood and neuropsychological performance in individuals with movement disorders.