Patients' perspectives on oral decitabine/cedazuridine for the treatment of myelodysplastic syndromes/neoplasms.

Background: Hypomethylating agents (HMAs) are guideline-recommended treatment for higher-risk myelodysplastic syndromes/neoplasms (MDS). However, a prior survey of patients with MDS reported challenges with intravenous (IV) and subcutaneous (SC) HMA therapies, including pain related to treatment administration and interference with daily activities; most patients also indicated a preference to switch to an oral therapy if one were available. Objectives: This study evaluated the perspectives of US patients with MDS receiving oral decitabine/cedazuridine (DEC-C), an alternative to IV/SC HMAs. Methods: An online survey was conducted among adult patients with MDS in the United States (10 November 2022 to 5 December 2022) who had filled a prescription for oral DEC-C between 2021 and 2022. Results: A total of 150 patients completed the survey; 61% were aged ⩾60 years and 63% were male. Of these, 123 (82%) were still receiving oral DEC-C, and 27 (18%) had stopped oral DEC-C treatment. Half (50%) of patients had received oral DEC-C for ⩾6 months. The majority reported that treatment was convenient (83%) and that they were satisfied with treatment (86%). Most patients also reported very little/no interference with regular daily activities (82%), social activities (78%), and productivity (78%). When queried about negative impacts on quality of life (QOL), treatment side effects were the most commonly reported (30% of respondents). Among patients who had previously received IV/SC HMAs (n = 91), most agreed that oral DEC-C interfered less with daily life (91%) and had experienced improvement in QOL (85%) compared with previous treatment; 91% reported that oral DEC-C reduced the number of times they needed to travel to a healthcare facility. Conclusion: Survey results suggest very little/no impact on regular daily activities and improved QOL with oral DEC-C relative to IV/SC HMAs, highlighting the potential for oral DEC-C to reduce the treatment burden associated with parenteral HMA therapy.

"Instead, You're Going to a Friend": Evaluation of a Community-Developed, Peer-Delivered Online Crisis Prevention Intervention.

OBJECTIVE: Online communities promote social connection and can be used for formal peer support and crisis intervention. Although some communities have programs to support their members' mental health, few programs have been formally evaluated. The authors present findings from a mixed-methods evaluation of the Stack Up Overwatch Program (StOP), a digital peer support intervention delivered in an online gaming community. METHODS: Data were collected from members of the Stack Up Discord server between June and October 2020 and included chat messages, survey responses, encounter forms (documenting information from private interactions between users and peer supporters), and interviews with peer support team members. The authors analyzed data on demographic characteristics, mental health and crises, use of and experiences with StOP, and chat posts. Thematic analysis and descriptive statistics were combined in a joint display table, with mixed-methods findings explained in narrative form. RESULTS: The findings show that StOP provides users in crisis with a source of mental health support when other options have been exhausted and that military and veteran users valued the connections and friendships they formed while using it. Participants reported that StOP met needs for support and connection when formal services were inaccessible or did not meet their needs, and volunteer peer supporters detailed how StOP's design facilitates use of the intervention. Volunteering offered members of the peer support team a "family feeling" facilitated by the unique chat room structure. CONCLUSIONS: Community-based crisis prevention programs administered through chat rooms may provide valuable support to both users and peer support providers.

Caregiver Experiences With an Internet-Delivered Insomnia Intervention: SHUTi-CARE Trial Primary Qualitative Analysis.

BACKGROUND: Digital health interventions show potential to increase caregivers' access to psychosocial care; however, it is unclear to what extent existing interventions may need to be tailored to meet caregivers' unique needs. PURPOSE: This study aimed to determine whether-and if so, how-an efficacious Internet-delivered insomnia program should be modified for caregivers. The generalizability of these findings beyond the tested program was also examined. METHODS: Higher-intensity family caregivers (N = 100; age M = 52.82 [SD = 13.10], 75% non-Hispanic White, 66% ≥college degree) received access to an Internet-based cognitive-behavioral therapy for insomnia (CBT-I) program. Participants who completed one or more intervention "Cores" provided open-ended feedback on their experience; nonusers (completed no Cores) shared their barriers. RESULTS: Most caregivers who used the program (n = 82, 82%) found it feasible, citing its user-friendly, fully automated online format. Many reported that CBT-I strategies were helpful, although some faced challenges in implementing these strategies due to the unpredictability of their caregiving responsibilities. Opinions were divided on the utility of tailoring the program for caregivers. Nonusers (n = 18, 18%) primarily cited concerns about time burden and lifestyle compatibility as usage barriers. CONCLUSIONS: Delivering fully automated behavioral interventions through the Internet appears suitable for many caregivers. Extensive tailoring may not be required for most caregivers to benefit from an existing online CBT-I program, although additional guidance on integrating CBT-I strategies in the context of challenging sleep schedules and environments may help a subset of caregivers. Future research should explore how such tailoring may enhance digital health intervention uptake and effectiveness for caregivers.

This study examined family caregivers' experiences using an online cognitive-behavioral therapy for insomnia program. The aim was to determine if the program needed changes to better fit caregivers' needs. Researchers gave 100 caregivers with insomnia access to Sleep Healthy Using the Internet (SHUTi), an online insomnia program that had no caregiver-specific tailoring. Of the 82 caregivers who used the program, most found the program easy to use and helpful, although some struggled with behavioral strategies because of their unpredictable caregiving duties. There was no clear consensus among caregivers on whether tailoring would be helpful. The 18 caregivers who did not use the program most commonly said that they did not have enough time to use the program or that they felt it would not work well with their lifestyle. Overall, findings suggest that providing interventions via the Internet is a good fit for many caregivers. Many caregivers benefitted from an online insomnia program without being tailored specifically for caregivers, although some additional guidance on how to follow behavioral strategies may be helpful to some caregivers.

The Intersection of Successful Aging and Family Caregiving.

For the millions of older adults who rely on the support of a family caregiver, successful aging is not an individual achievement but a cooperative process between a care receiver and a caregiver. Yet, family caregivers are rarely incorporated into theoretical models of successful aging. Family caregivers also play an essential role in recent healthcare delivery movements that seek to better align care delivery with successful aging. Greater reliance on family caregivers by the US healthcare system is occurring as an increasingly vocal constituency is tasking policymakers with developing and implementing federal and state health policies that would help build the national infrastructure needed to support them. This paper provides a critical discussion of how family caregivers actualize successful aging for older adults. We highlight the key role of family caregivers in healthcare delivery innovations aimed at facilitating successful aging and discuss policies that support family caregivers. As successful aging continues to evolve as a dominating framework in the literature, we conclude with key recommendations for how research, policy, and practice efforts in successful aging can be more inclusive and supportive of family caregivers.

Impact of Acute Dopamine Replacement on Cognitive Function in Parkinson's Disease.

BACKGROUND: PD causes striatal dopaminergic denervation in a posterior/dorsal to anterior/ventral gradient, leaving motor and associative cortico-striato-pallido-thalamic loops differentially susceptible to hyperdopaminergic effects with treatment. As the choice and titration of symptomatic PD medications are guided primarily by motor symptoms, it is important to understand their cognitive implications. OBJECTIVE: To investigate the effects of acute dopaminergic medication administration on executive function in Parkinson's disease (PD). METHODS: Participants with idiopathic PD were administered the oral Symbol Digit Modalities Test (SDMT; n = 181) and the Stroop test (n = 172) in the off-medication and "best on" medication states. ANCOVA was used to test for differences between off-medication and on-medication scores corrected for age and years of education. RESULTS: After administration of symptomatic medications, scores worsened on the SDMT (F = 11.70, P < 0.001, d = -0.13), improved on the Stroop color (F = 26.89, P < 0.001, d = 0.184), word (F = 6.25, P = 0.013, d = 0.09), and color-word (F = 13.22, P < 0.001, d = 0.16) test components, and the Stroop difference and ratio-based interference scores did not significantly change. Longer disease duration correlated with lower scores on the SDMT, Stroop color, word, and color-word scores; however, longer disease duration and higher levodopa-equivalents correlated with higher Stroop difference-based interference scores. CONCLUSIONS: Symptomatic medication differentially affects performance on two cognitive tests in PD. After acute treatment, core Stroop measures improved, Stroop interference was unchanged, and SDMT performance worsened, likely reflecting complex changes in processing speed and executive function related to acute treatment. When considering motor symptom therapies in PD, an individual's cognitive demands and expectations, especially regarding executive function, should be considered.

Goal Setting for Aging Adults and Care Partners: A Scoping Review.

Background and Objectives: Evidence demonstrates that goal-setting and care partner support help aging adults improve their health. Less is known about how aging adults and care partners collaboratively participate in goal setting, revealing a potential gap in care delivery processes. The current review describes the scope of the literature on this topic. Research Design and Methods: A search was conducted in several relevant databases and 1,231 articles were screened for the following inclusion criteria: (a) participants included aging adults (50+ years) and care partners, (b) goal setting was conducted, and (c) articles were in English. Results: Common goals reported by aging adults were independence, improving or maintaining functioning, addressing symptoms, and remaining socially active. Care partners listed similar goals but also identified accessing services and supports as important. The level of care partner involvement varied across articles, with some care partners serving in a supportive role, some setting goals concurrently with the aging adult, and others setting goals on behalf of the aging adult. Discussion and Implications: This review revealed concordant and discordant prioritization of goals within dyads. These findings illustrate the importance and potential complexity of including care partners in the goal-setting process. We also found that collaborative goal-setting and care partner-directed goals are scarce, indicating the need for additional work in this area. Collaborative goal setting aligns with person and family-centered care approaches and can contribute to better care plans that meet the needs of aging adults and their care partners.

Effects of Caregiver Sleep Disturbances on Relationship Quality With Their Care Recipient.

OBJECTIVES: Sleep problems are highly prevalent and disruptive for caregivers. Although the connection between caregivers' sleep and outcomes like caregiver burden and quality of life is well established, the potential influence of caregivers' sleep on their reported relationship quality with the care recipient is not known. The current study sought to address this gap. METHODS: We analyzed data from the 2017 National Health and Aging Trends Study and linked it with data from the 2017 National Study of Caregiving. Our dependent variable was caregiver-reported relationship quality, and our predictor variable of interest was caregiver sleep problems. We also included several covariates related to the caregiver and care recipient. We used a generalized linear model to examine the relationship between caregiver sleep problems and relationship quality, controlling for other potentially influential factors. RESULTS: Sleep problems were significantly related to relationship quality. Compared to caregivers who reported no sleep problems, those who reported at least one sleep problem (ß: -0.23, 95% CI: -0.46 to -0.01) had lower relationship quality with the care recipient. Other factors that remained related to relationship quality in the generalized linear model were negative aspects of caregiving, emotional difficulties, caregiver race, relationship type, care recipient depressive symptoms, and care recipient sex. DISCUSSION: Sleep problems are influential health behaviors that are related to relationship quality for caregivers. Therefore, it is critical that sleep is more systematically assessed and addressed in caregiving populations.

Association of caregiver strain with the trajectory of quality of life in Parkinson's disease.

We aimed to identify caregiver characteristics associated with the trajectory of quality of life (QoL) in Parkinson's disease (PD). We fit a growth mixture model to longitudinal data from the Parkinson Foundation Parkinson's Outcomes Project (POP) to identify the heterogeneity of QOL trajectories in PD. We then used multinomial logistic regression to model baseline factors that predicted class membership. Baseline growth models were fit to QOL scores measured over 4 disease duration time points. A random intercept and slope model was determined to best fit the data. Next, growth mixture models (1, 2, 3, 4, and 5-class) were fit with covariates (Hoehn & Yahr, sex, and depression) and a three-class model was found to provide the best fit. Class 1 (problematic class (10.0%)) represented individuals with poor QOL at baseline and minor improvement over time. Class 2 (moderate class (32.6%)) represented individuals with moderate QOL at baseline with slight worsening over time. Class 3 (favorable class (56.9%)) represented individuals with good QOL at baseline and slight worsening over time. Multinomial regression revealed that lower caregiver strain, better mobility, and better verbal fluency at baseline predicted membership in the favorable compared to the moderate class. Worse mobility and younger age predicted membership in the problematic compared to the moderate class. While previous studies have reported on the association between mobility and cognition, the novel finding of an association between caregiver strain and PD QOL trajectory suggests caregiver strain is important to measure and address in future research and practice.

The impact of caregiving on quality of life in Parkinson's disease: A systematic review.

OBJECTIVE: Parkinson's disease (PD) is a progressive neurodegenerative disease that can reduce quality of life (QOL). Previous research has explored patient specific factors that influence QOL; but understanding external factors that may also affect patient QOL, such as caregiver characteristics, can provide additional intervention targets that may improve QOL for both the person with PD and their caregiver. METHODS: We conducted a systematic review of existing literature on caregiver factors that are related to QOL for the person with PD. We developed a tailored search strategy in six databases and performed a screening procedure according to PRISMA guidelines. We synthesized findings from articles that met inclusion criteria using a narrative approach and identified themes categorizing caregiver factors associated with PD QOL. RESULTS: We found 32 full-text articles that fulfilled the inclusion criteria and passed the quality appraisal. Seven themes were identified, including: (1) burden, (2) strain, (3) QOL and satisfaction, (4) demographic factors, (5) psychological factors, (6) relationship factors, and (7) caregiver input. CONCLUSIONS: Our review presents critical insights into the role of the caregiver in the QOL of a person with PD. Findings reveal several targets for intervention to improve QOL in this population.

'Anxious fluctuators' a subgroup of Parkinson's disease with high anxiety and problematic on-off fluctuations.

Anxiety that occurs in association with on-off dopamine medication fluctuations is a major cause of distress, dysfunction, and lower quality of life in people with Parkinson's disease (PD). However, the association between anxiety and on-off fluctuations is poorly understood and it is difficult to predict which patients will suffer from this atypical form of anxiety. To understand whether fluctuating anxiety in PD exists as part of an endophenotype that is associated with other signs or symptoms, we prospectively assessed the change in anxiety and a battery of clinical variables when transitioning from the off-dopamine medication state to the on state in 200 people with PD. We performed latent profile analysis with observed variables as latent profile indicators measuring the on-off-state difference in anxiety, depression, motor function, daily functioning, and the wearing off questionnaire 19 item scale (WOQ-19) in order to model unobserved (i.e., latent) profiles. A two-class model produced the best fit. The majority of participants, 69%, were categorized as having a 'typical on-off response' compared to a second profile constituting 31% of the sample who experienced a worsening in anxiety in the off state that was three times that of other participants. This profile referred to as "anxious fluctuators" had a Hamilton Anxiety Rating Scale change between the off and on medication state of 10.22(32.85) compared to 3.27 (7.62), higher depression scores, greater disability and was less likely to improve on select WOQ-19 items when in the on-state. Anxious fluctuators were more likely to be male and have a family history of anxiety disorder. Given the adverse impact of this profile we believe it may be important to distinguish patients with a typical on-off response from those with this more problematic course of fluctuations.

Wellness, sexual health, and nonmotor Parkinson's.

Nonmotor symptoms of Parkinson's disease (PD) range from neuropsychiatric and cognitive to sleep, sensory, and genito-urinary disorders, and occur as a result of the disease process as well as due to side effects of drug treatment for PD. Sexual dysfunction is an important aspect of the nonmotor profile of Parkinson's but is rarely discussed. Sexual health is considered an integral element of holistic health, thus sexual dysfunction can also significantly impact quality of life in people with Parkinson's. The effect of sexual dysfunction of PD, both disease related and drug induced, on the concept of "wellness" of patients and their intimate partners is poorly understood, inadequately researched and a key unmet need in care and support. In this chapter we discuss the concept of "wellness" as applied to the treatment of PD, the ways in which nonmotor symptoms and other aspects of living may affect wellness in PD, and strategies for addressing sexual health utilizing a wellness model.

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.

Bidirectional Correlations Between Dopaminergic Function and Motivation in Parkinson's Disease.

OBJECTIVE: To test the hypothesis that striatal dopamine function influences motivational alterations in Parkinson disease (PD), we compared vesicular monoamine transporter 2 (VMAT2) and dopamine transporter (DaT) imaging data in PD patients with impulse control disorders (ICDs), apathy, or neither. METHODS: We extracted striatal binding ratios (SBR) from VMAT2 PET imaging (18F-AV133) and DaTscans from the Parkinson's Progression Markers Initiative (PPMI) multicenter observational study. Apathy and ICDs were assessed using the Movement Disorders Society-revised Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP), respectively. We used analysis of variance (ANOVA) and log-linear mixed-effects (LME) regression to model SBRs with neurobehavioral metrics. RESULTS: Among 23 participants (mean age 62.7 years, mean disease duration 1.8 years) with VMAT2 imaging data, 5 had apathy, 5 had an ICD, and 13 had neither. ANOVA indicated strong groupwise differences in VMAT2 binding in right anterior putamen [F(2,20) = 16.2, p < 0.0001), right posterior putamen [F(2,20) = 16.9, p < 0.0001), and right caudate [F(2,20) = 6.8, p = 0.006)]. Post-hoc tests and repeated-measures analysis with LME regression also supported right striatal VMAT2 elevation in the ICD group and reduction in the apathy group relative to the group with neither ICD nor apathy. DaT did not exhibit similar correlations, but normalizing VMAT2 with DaT SBR strengthened bidirectional correlations with ICD (high VMAT2/DaT) and apathy (low VMAT2/DaT) in all striatal regions bilaterally. CONCLUSIONS: Our findings constitute preliminary evidence that striatal presynaptic dopaminergic function helps describe the neurobiological basis of motivational dysregulation in PD, from high in ICDs to low in apathy.

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

OBJECTIVE: The mechanisms and neuronal networks associated with anxiety in Parkinson's disease (PD) are incompletely understood. One of the best tools for investigating both component function and neuronal networks associated with psychiatric symptoms is functional MRI (fMRI). Unlike structural scans, functional scans, whether task-based or resting-state, are more likely to be clinically relevant and sensitive to changes related to treatment. The investigators provide a comprehensive review of and present results for imaging studies of anxiety in PD. METHODS: A systematic review of the literature on fMRI and anxiety in PD was conducted, and the quality of all included studies was simultaneously assessed. Eighteen studies were included: 15 studies assessed anxiety directly, and three evaluated emotional processing. Imaging methodology and behavioral assessments varied across studies, preventing direct comparison of results in most cases. RESULTS: There was a convergence in findings across methods, implicating involvement of the amygdala, caudate, and putamen in association with anxiety in PD. For both task-based activation and resting-state connectivity, dopamine medication status was associated with differences in activation and behavioral function. CONCLUSIONS: Although there is little consensus in the current fMRI literature studying anxiety in PD, these results suggest an overlap between structures classically involved in the brain's fear circuit (particularly the amygdala) and the alterations in the nigro-striatal system (e.g., the caudate and putamen and on-off dopamine findings) related to PD and its dopaminergic treatments.

Attentional dysfunction and the punding spectrum in Parkinson's disease.

BACKGROUND: Punding is a complication of Parkinson's disease (PD) treatment and stimulant abuse that features excessive preoccupation with repetitive and/or aimless behaviors. We hypothesized that cognitive impairment and functional limitations influence how punding behaviors manifest in PD. METHODS: We extracted data on punding, hobbyism, and cognition from the Parkinson's Progression Marker Initiative (PPMI). Punding and hobbyism were measured with the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP) scale. We determined how cognition predicted punding and hobbyism behaviors-adjusting for levodopa dose, Hoehn & Yahr stage, disease duration, and age-using generalized estimating equation (GEE) logistic regression. Activities of daily living (ADL) and motor impairment were measured with the MDS-UPDRS scale. RESULTS: In GEE logistic regression models, punding was selectively associated with lower scores on the Letter Number Sequencing test (LNS), the primary attention test in PPMI (Odds ratio: 0.87 (95% CI: 0.79-0.96); p = 0.022). This was corroborated by a subscale-analysis of Montreal Cognitive Assessment (MoCA) scores, as only the attention subscale was significantly associated with punding (OR: 0.59 (0.45-0.77); p < 0.001). Baseline impairment in LNS (Hazard ratio: 2.52 (1.22-5.20); p = 0.012) and MoCA attention (HR: 2.68 (1.32-5.42); p = 0.006) predicted earlier punding in Cox regression. In turn, ADL dysfunction predicted punding (OR: 1.55 (1.20-2.00); p < 0.001), but not hobbyism. CONCLUSION: Attentional dysfunction is a domain-specific cognitive biomarker of punding risk in PD. Further, attentional capacity and functional impairment may determine the complexity of perseverative behaviors on the continuum from rudimentary punding to semi-purposeful hobbyism.

Apathy and Anxiety in De Novo Parkinson's Disease Predict the Severity of Motor Complications.

BACKGROUND: Neuropsychiatric and affective symptoms are prevalent in prodromal and clinical Parkinson's disease (PD). Some evidence suggests that they may also signify risk for motor complications (motor fluctuations and dyskinesias) of dopamine replacement therapy (DRT). OBJECTIVE: To determine whether neuropsychiatric symptoms present in de novo PD (ie, before DRT initiation) predict the severity of eventual motor complications of DRT. METHODS: We used clinical, demographic, neurobehavioral, and neuroimaging data from the Parkinson's Progression Markers Initiative (PPMI), a multicenter observational PD study. Participants were unmedicated at enrollment and 361 initiated DRT during PPMI follow-up. We used Cox proportional hazard and multivariate ordinal mixed-effects regression models to evaluate the relationship between baseline neuropsychiatric symptoms and motor complications as measured by the Movement Disorders Society-revised Unified Parkinson's Disease Rating Scale (MDS-UPDRS). RESULTS: The cumulative incidences of dyskinesias and motor fluctuations during follow-up (6.0 ± 1.5 years) were 34.3% and 59.9%, respectively. Both apathy and high trait-anxiety (top quartile) conveyed over two-fold increases in hazard for dyskinesia onset and for adverse impact on activities of daily living caused by both dyskinesias and motor fluctuations. The longitudinal severity of motor fluctuations and dyskinesias was significantly predicted by baseline trait-anxiety and apathy, but not depression. Models were adjusted for dimensionally related symptoms (eg autonomic dysfunction) and potential confounding variables (eg DRT dose). CONCLUSIONS: Apathy and anxiety levels in de novo PD may be neuropsychiatric biomarkers of vulnerability to earlier and more disabling motor complications of DRT.

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.

Effect of STN DBS on vesicular monoamine transporter 2 and glucose metabolism in Parkinson's disease.

INTRODUCTION: Deep brain stimulation (DBS) is an established treatment for Parkinson's Disease (PD). Despite the improvement of motor symptoms in most patients by sub-thalamic nucleus (STN) DBS and its widespread use, the neurobiological mechanisms are not completely understood. The objective of the present study was to elucidate the effects of subthalamic nucleus (STN) DBS in PD on the dopamine system and neural circuitry, employing high-resolution positron emission tomography (PET) imaging. The hypotheses tested were that STN DBS would decrease the striatal vesicular monoamine transporter (VMAT2), secondary to an increase in dopamine concentrations, and would decrease striatal cerebral metabolism and increase cortical cerebral metabolism. METHODS: PET imaging of the vesicular monoamine transporter (VMAT2) and cerebral glucose metabolism was performed prior to DBS surgery and after 4-6 months of STN stimulation in seven PD patients (mean age 67 ±â€¯7). RESULTS: The patients demonstrated significant improvement in motor and neuropsychiatric symptoms after STN DBS. Decreased VMAT2 was observed in the caudate, putamen and associative striatum and in extra-striatal, cortical and limbic regions. Cerebral glucose metabolism was decreased in striatal sub-regions and increased in temporal and parietal cortices and the cerebellum. Decreased striatal VMAT2 was correlated with decreased striatal and increased cortical and limbic metabolism. Improvement of depressive symptoms was correlated with decreased VMAT2 in striatal and extra-striatal regions and with striatal decreases and cortical increases in metabolism. CONCLUSIONS: The present results support further investigation of the role of VMAT2, and associated changes in neural circuitry in the improvement of motor and non-motor symptoms with STN DBS in PD.

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).