Risk of Dementia in Parkinson's Disease: A Systematic Review and Meta-Analysis.

Estimates of the risk of dementia in Parkinson's disease (PDD) vary widely. We aimed to review the incidence of PDD and in a meta-analysis estimate the pooled annual incidence and relative risk of PDD while also exploring factors that may contribute to heterogeneity between studies. Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines were followed and MEDLINE and EMBASE were searched for articles reporting the number of cases of dementia in a population, followed longitudinally, with a minimum of 100 dementia-free Parkinson's disease (PD) patients at baseline. Meta-analyses and meta-regressions were used to estimate the pooled incidence rate of PDD and the relative risk of PDD versus healthy controls (HC). A total of 32 studies were identified, 25 reporting the incidence of PDD and 10 reporting the relative risk of PDD versus HC. The pooled incidence rate of PDD was 4.45 (95% confidence interval [CI], 3.91-4.99) per 100 person-years at risk, equating to a 4.5% annual risk of dementia in a PD prevalent population. The relative risk of PDD was estimated to be 3.25 (95% CI, 2.62-4.03) times greater than HC. Factors contributing to study heterogeneity and disparities in the estimated risk of PDD include the age of patients, year of recruitment, and study location. Significant gaps remain with no studies identified in several geographical regions. Future studies should stratify by age and standardize reporting to reduce overall heterogeneity. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

A general clinical overview of the non-motor symptoms in Parkinson's disease: Neuropsychiatric symptoms.

The heterogeneity of non-motor features observed in people with Parkinson's disease (PD) is often dominated by one or more symptoms belonging to the neuropsychiatric spectrum, such as cognitive impairment, psychosis, depression, anxiety, and apathy. Due to their high prevalence in people with PD (PwP) and their occurrence in every stage of the disease, from the prodromal to the advanced stage, it is not surprising that PD can be conceptualised as a complex neuropsychiatric disorder. Despite progress in understanding the pathophysiological mechanisms underlying the neuropsychiatric signs and symptoms in PD, and better identification and diagnosis of these symptoms, effective treatments are still a major unmet need. The impact of these symptoms on the quality of life of PwP and caregivers, as well as their contribution to the overall non-motor symptom burden can be greater than that of motor symptoms and require a personalised, holistic approach. In this chapter, we provide a general clinical overview of the major neuropsychiatric symptoms of PD.

Clinical trials in dementia with Lewy bodies: the evolving concept of co-pathologies, patient selection and biomarkers.

PURPOSE OF REVIEW: Currently, no disease modifying therapies (DMTs) have been approved for use in dementia with Lewy bodies (DLB). Clinical trials face difficulties due to the clinical and neuropathological heterogeneity of the condition with a diverse array of neuropathogenic mechanisms contributing to the clinical phenotype. The purpose of this review is to describe how recent advances in the development of biofluid biomarkers may be used in clinical trials to tackle some of these challenges. RECENT FINDINGS: Biomarkers are essential both to support the accurate diagnosis of DLB and to delineate the influence of coexisting pathologies. Recent advances in the development of α-synuclein seeding amplification assays (SAA) allow accurate identification of α-synuclein from the prodromal stages in DLB. Additionally, validation of plasma phosphorylated tau assays in DLB is ongoing and offers an accessible biomarker to indicate the existence of AD co-pathology. Use of biomarkers for diagnosis and group stratification in clinical trials of DLB is growing and likely to be of increasing importance in the future. SUMMARY: In vivo biomarkers can enhance patient selection in clinical trials allowing greater diagnostic accuracy, a more homogeneous trial population, and stratification by co-pathology to create subgroups most likely to derive therapeutic benefit from DMTs.

Dementia with Lewy Bodies Drug Therapies in Clinical Trials: Systematic Review up to 2022.

INTRODUCTION: Reviews of randomized clinical trials (RCTs) in dementia with Lewy bodies (DLB) are essential for informing ongoing research efforts of symptomatic therapies and potentially disease-modifying therapies (DMTs). METHODS: We performed a systematic review of all clinical trials conducted until September 27, 2022, by examining 3 international registries: ClinicalTrials.gov, the European Union Drug Regulating Authorities Clinical Trials Database, and the International Clinical Trials Registry Platform, to identify drugs in trials in DLB. RESULTS: We found 25 agents in 40 trials assessing symptomatic treatments and DMTs for DLB: 7 phase 3, 31 phase 2, and 2 phase 1 trials. We found an active pipeline for drug development in DLB, with most ongoing clinical trials in phase 2. We identified a recent trend towards including participants at the prodromal stages, although more than half of active clinical trials will enroll mild to moderate dementia patients. Additionally, repurposed agents are frequently tested, representing 65% of clinical trials. CONCLUSION: Current challenges in DLB clinical trials include the need for disease-specific outcome measures and biomarkers, and improving representation of global and diverse populations.

NMDA Receptor Antibodies and Neuropsychiatric Symptoms in Parkinson's Disease.

OBJECTIVE: N-methyl-d-aspartate receptor (NMDAR) encephalitis is an autoantibody-mediated neurological syndrome with prominent cognitive and neuropsychiatric symptoms. The clinical relevance of NMDAR antibodies outside the context of encephalitis was assessed in this study. METHODS: Plasma from patients with Parkinson's disease (PD) (N=108) and healthy control subjects (N=89) was screened at baseline for immunoglobulin A (IgA), IgM, and IgG NMDAR antibodies, phosphorylated tau 181 (p-tau181), and the neuroaxonal injury marker neurofilament light (NfL). Clinical assessment of the patients included measures of cognition (Mini-Mental State Examination [MMSE]) and neuropsychiatric symptoms (Hospital Anxiety and Depression Scale; Non-Motor Symptoms Scale for Parkinson's Disease). A subgroup of patients (N=61) was followed annually for up to 6 years. RESULTS: Ten (9%) patients with PD tested positive for NMDAR antibodies (IgA, N=5; IgM, N=6; IgG, N=0), and three (3%) healthy control subjects had IgM NMDAR antibodies; IgA NMDAR antibodies were detected significantly more commonly among patients with PD than healthy control subjects (χ2=4.23, df=1, p=0.04). Age, gender, and disease duration were not associated with NMDAR antibody positivity. Longitudinally, antibody-positive patients had significantly greater decline in annual MMSE scores when the analyses were adjusted for education, age, disease duration, p-tau181, NfL, and follow-up duration (adjusted R2=0.26, p=0.01). Neuropsychiatric symptoms were not associated with antibody status, and no associations were seen between NMDAR antibodies and p-tau181 or NfL levels. CONCLUSIONS: NMDAR antibodies were associated with greater cognitive impairment over time in patients with PD, independent of other pathological biomarkers, suggesting a potential contribution of these antibodies to cognitive decline in PD.

Quantitative EEG as a Prognostic Tool in Suspected Anti-N-Methyl- d -Aspartate Receptor Antibody Encephalitis.

PURPOSE: Anti-N-methyl- d -aspartate receptor (anti-NMDAR) encephalitis is a form of autoimmune encephalitis associated with EEG abnormalities. In view of the potentially severe outcomes, there is a need to develop prognostic tools to inform clinical management. The authors explored whether quantitative EEG was able to predict outcomes in patients with suspected anti-NMDAR encephalitis. METHODS: A retrospective, observational study was conducted of patients admitted to a tertiary clinical neuroscience center with suspected anti-NMDAR encephalitis. Peak power and peak frequency within delta (<4 Hz), theta (4-8 Hz), alpha (8 - 13 Hz), and beta (13-30 Hz) frequency bands were calculated for the first clinical EEG recording. Outcome was based on the modified Rankin Scale (mRS) score at 1 year after hospital discharge. Binomial logistic regression using backward elimination was performed with peak frequency and power, anti-NMDAR Encephalitis One-Year Functional Status score, age, and interval from symptom onset to EEG entered as predictors. RESULTS: Twenty patients were included (mean age 48.6 years, 70% female), of which 7 (35%) had a poor clinical outcome (mRS 2-6) at 1 year. There was no association between reported EEG abnormalities and outcome. The final logistic regression model was significant (χ 2 (1) = 6.35, P < 0.012) with peak frequency in the delta range (<4 Hz) the only retained predictor. The model explained 38% of the variance (Nagelkerke R2 ) and correctly classified 85% of cases. Higher peak frequency in the delta range was significantly associated ( P = 0.04) with an increased likelihood of poor outcome. CONCLUSIONS: In this exploratory study, it was found that quantitative EEG on routinely collected EEG recordings in patients with suspected anti-NMDAR encephalitis was feasible. A higher peak frequency within the delta range was associated with poorer clinical outcome and may indicate anti-NMDAR-mediated synaptic dysfunction. Quantitative EEG may have clinical utility in predicting outcomes in patients with suspected NMDAR antibody encephalitis, thereby serving as a useful adjunct to qualitative EEG assessment; however, given the small sample size, replication in a larger scale is indicated.

Neuropathological correlates of neuropsychiatric symptoms in dementia.

INTRODUCTION: Neuropsychiatric symptoms (NPS) are common in Lewy body disease (LBD), but their etiology is poorly understood. METHODS: In a population-based post mortem study neuropathological data was collected for Lewy body (LB) neuropathology, neurofibrillary tangles (NFT), amyloid beta burden, TDP-43, lacunar infarcts, cerebral amyloid angiopathy (CAA), and hyaline atherosclerosis. Post mortem interviews collected systematic information regarding NPS and cognitive status. A total of 1038 cases were included: no pathology (NP; n = 761), Alzheimer's disease (AD; n = 189), LBD (n = 60), and AD+LBD (n = 28). RESULTS: Hallucinations were associated with higher LB Braak stages, while higher NFT Braak staging was associated with depression, agitation, and greater number of symptoms in the Neuropsychiatric Inventory. Cases with dual AD+LBD pathology had the highest risk of hallucinations, agitation, apathy, and total symptoms but a multiplicative interaction between these pathologies was not significant. DISCUSSION: LB and AD pathology contribute differentially to NPS likely with an additive process contributing to the increased burden of NPS.

Plasma p-tau181, neurofilament light chain and association with cognition in Parkinson's disease.

Early identification of cognitive impairment in Parkinson's disease (PD) has important clinical and research implications. The aim of our study was to investigate the role of plasma tau phosphorylated at amino acid 181 (p-tau181) and plasma neurofilament light chain (NfL) as biomarkers of cognition in PD. Baseline concentrations of plasma p-tau181 and NfL were measured in a cohort of 136 patients with PD and 63 healthy controls (HC). Forty-seven PD patients were followed up for up to 2 years. Cross-sectional and longitudinal associations between baseline plasma biomarkers and cognitive progression were investigated using linear regression and linear mixed effects models. At baseline, plasma p-tau181 concentration was significantly higher in PD subjects compared with HC (p = 0.026). In PD patients, higher plasma NfL was associated with lower MMSE score at baseline, after adjusting for age, sex and education (p = 0.027). Baseline plasma NfL also predicted MMSE decline over time in the PD group (p = 0.020). No significant association between plasma p-tau181 concentration and baseline or longitudinal cognitive performance was found. While the role of p-tau181 as a diagnostic biomarker for PD and its relationship with cognition need further elucidation, plasma NfL may serve as a feasible, non-invasive biomarker of cognitive progression in PD.

Plasma Neurofilament Light and p-tau181 and Risk of Psychosis in Parkinson's Disease.

BACKGROUND: Neuropsychiatric symptoms are common and important to people with Parkinson's disease (PD), but their etiology is poorly understood. Plasma neurofilament light (NfL) and p-tau181 are biomarkers of neuro-axonal degeneration and tau pathology respectively, which have yet to be explored in association with the affective and psychotic symptoms in PD. OBJECTIVE: To investigate the relationship between plasma NfL and p-tau181 with the affective and psychotic symptoms in PD. METHODS: We assessed the baseline concentration of plasma NfL and p-tau181 in a cohort of 108 patients with PD and 38 healthy controls. A subgroup of patients (n = 63) were assessed annually with clinical measures for up to 7 years. Psychotic symptoms were assessed using the Non-Motor Symptom Scale and affective symptoms were measured in the Hospital Anxiety and Depression Scale. RESULTS: Baseline plasma NfL was a significant predictor of psychotic symptoms longitudinally across the study adjusted for age, Hoehn and Yahr stage, duration of follow up, duration of disease, baseline levodopa and dopamine agonist medication, and baseline cognition: (OR 8.15 [95% CI 1.40-47.4], p = 0.020). There was no association between NfL concentration and the cumulative prevalence of affective symptoms. Plasma p-tau181 concentration was not associated with psychotic or affective symptoms. CONCLUSION: These findings suggest psychotic symptoms are associated with greater neurodegeneration in PD. Further studies are needed to explore NfL as a potential biomarker for psychosis in PD.

Incorporating medical students into school-based asthma education improves asthma knowledge in children.

OBJECTIVES: Asthma affects 1.1 million children in the UK, substantially impacting quality of life and leading to significant morbidity and mortality. Effective asthma self-management, education and empowerment can lead to a reduction in asthma related morbidity and mortality. We hypothesized that medical students can significantly improve school children's knowledge and awareness of asthma, at least in the short term. We sought to implement a medical student-led educational intervention program tailored to school-aged children, measure immediate improvements in asthma-related knowledge among participants, and determine if any population factors were associated with a difference in knowledge improvement. METHODS: Children were recruited from schools in Greater London. A 20-minute presentation was given by medical students which covered basic physiology of asthma, triggers, treatment, how to recognize a peer who is having an acute asthma attack and common misconceptions about asthma. The children's knowledge was tested using questionnaires completed before and immediately after the presentation. RESULTS: Medical students taught 1711 children aged 5 to 11 both with and without asthma. The average questionnaire score was 4.67/13 (SD 2.82) at baseline and 10.15/13 (SD 2.92) following the program. An improvement in scores was observed in all age groups and was greatest in children aged 10 and 11 (p = 0.016 and 0.049 respectively). CONCLUSION: We successfully implemented a medical student led asthma education program for school aged children in the UK. This novel approach was well received and led to a significant improvement in asthma knowledge amongst participants.

Neuronal surface autoantibodies in dementia: a systematic review and meta-analysis.

INTRODUCTION: Neuronal antibodies can cause encephalopathy syndromes often presenting with subacute cognitive impairment, sometimes resembling neurodegenerative dementias. METHODS: We searched Medline and Embase for studies reporting associations between neuronal surface antibodies in all-cause dementia versus controls. Random-effects meta-analysis was used to pool adjusted estimates across studies. RESULTS: Six studies were included, all reporting frequency of serum NMDAR antibodies in dementia with four also reporting frequency in atypical dementias. Both IgG [OR = 8.09 (1.51; 56.85), p = 0.036] and IgA/IgM NMDAR antibodies [OR = 42.48 (11.39; 158.52), p < 0.001] were associated with atypical dementia, but neither were associated with all-cause dementia. DISCUSSION: In the first meta-analysis to explore this literature, serum IgG and IgA/IgM NMDAR antibodies were significantly more common in atypical dementias. However, methodological issues and small-sample sizes necessitate caution interpreting this result. Further studies measuring both serum and CSF antibodies are needed to investigate the role of neuronal antibodies in dementia, since evidence of pathogenicity in even a subset of patients could pave the way for novel treatment options.

G-CSF mediated neutrophil augmentation in a unique case of comorbid idiopathic Parkinson's disease and treatment-resistant schizophrenia on clozapine.

Treatment of psychosis in Parkinson's disease (PD) is challenging; pharmacological options are limited, with clozapine considered most effective. The risk of agranulocytosis restricts the use of clozapine, but, where this occurs, cautious re-challenge with granulocyte stimulating factor can be successful. We present a unique case of a patient who developed early-onset PD on a background of antecedent treatment-resistant schizophrenia, who had been treated effectively with clozapine for over 15 years with no adverse events. However, during a hospital admission intended to optimise her Parkinsonian medications, she developed persistent neutropenia necessitating clozapine discontinuation. Numerous attempts to re-challenge with clozapine failed until augmentation with lithium and G-CSF was trialled. Two doses of G-CSF led to a sustained increase in the neutrophil count, allowing the continuation of clozapine therapy in the 1 year of follow up. This illustrates the potential for G-CSF to be used to facilitate clozapine use in a patient population not described previously. Neutrophil augmentation allowed the sustained continuation of this effective therapy, treating her psychotic symptoms without detriment to her movement disorder. We suggest that G-CSF might be considered as a treatment option in other cases where clozapine-associated neutropenia obstructs its use.

The Psychiatric Phenotype of Anti-NMDA Receptor Encephalitis.

In its early stages, anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is often characterized by prominent psychiatric manifestations that can lead to delays in diagnosis and treatment. The authors aimed to address this problem by providing a detailed description of the psychiatric phenotype and demographic features that may influence presentation. Eighty-six patients with positive serum NMDAR antibodies were identified, 22 of whom met diagnostic criteria for anti-NMDAR encephalitis. Medical notes were reviewed retrospectively to rate psychiatric symptoms using standardized scales. Clinical and demographic characteristics were compared for patients with and without psychosis. Patients with psychosis exhibited severe psychopathology with a characteristic phenotype: severe and disproportionate cognitive disturbance (p<0.005) with high negative symptom scores and excitability. Those presenting with psychotic symptoms were significantly younger than those without (p<0.005). Patients with anti-NMDAR encephalitis present with a somewhat distinct cluster of psychiatric symptoms not commonly seen in functional psychoses. When encountered, this atypical pattern should warrant further investigation and a high index of suspicion for anti-NMDAR encephalitis. The more prominent psychotic features in younger adults may reflect greater susceptibility of the young brain to exogenous psychosis.

Systematic review of the impact of arts for health activities on health, wellbeing and quality of life of older people living in care homes.

Care home populations frequently feature older people who often experience poor physical health and cognitive difficulties, along with vulnerability to psychological and social stressors. To date there has been no systematic review which focuses on the impact of arts for health activities to the care home population. Evidence was sourced from several databases and 71 studies were deemed eligible for inclusion in this review. These studies underwent data extraction and quality appraisal and the findings associated with health, wellbeing and quality of life are presented within this paper.

Key personality traits of sales managers.

BACKGROUND: Sales managers are crucial for producing positive sales outcomes for companies. However, there has been a relative dearth of scholarly investigations into the personal attributes of sales managers. Such information could prove important in the recruitment, selection, training needs identification, career planning, counseling, and development of sales managers. OBJECTIVE: Drawing on Holland's vocational theory, we sought to identify key personality traits that distinguish sales managers from other occupations and are related to their career satisfaction. PARTICIPANTS: The main sample was comprised of a total of 978 sales managers employed in a large number of companies across the United States (along with a comparison sample drawn from 79,512 individuals from other professional occupations). METHODS: Participants completed an online version of Resource Associates' Personal Style Inventory as well a measure of career satisfaction. RESULTS: Our sample of 978 sales managers had higher levels of Assertiveness, Customer Service Orientation, Extraversion, Image Management, Optimism, and Visionary Style; and lower levels of Conscientiousness, Agreeableness, Intrinsic Motivation, Openness, and Tough-Mindedness than a sample of 79,512 individuals in a variety of other occupations. Nine of these traits were significantly correlated with sales managers' career satisfaction. CONCLUSION: Based on the results, a psychological profile of sales managers was presented as were implications for their recruitment, selection, training, development, and mentoring.

Personality correlates of self-employed small business owners' success.

OBJECTIVE: Drawing on prior occupational choice research on entrepreneurs and self-employed business owners, we examined personality predictors of their occupational business success and work satisfaction. PARTICIPANTS AND PROCEDURES: A sample of 147 small business owners completed a web-based assessment of 14 work-related personality traits--adaptability, autonomy, competitiveness, dependability, emotional resilience, goal-setting, optimism, persistence, risk tolerance, self-promotion, networking, and tolerance for financial insecurity, work-based locus of control, and work drive--and three self-reported indices of business success--revenue growth, profit growth, and income growth--as well as multiple facets of individual satisfaction. Criterion variables included composite business success and overall satisfaction. RESULTS: Ten traits correlated with business success. The top four personality predictors of success--goal-setting, social networking, emotional resilience, and work drive--together accounted for 16% of the variance. Similarly, 12 of 14 personality traits were positively related to overall satisfaction. The top three personality predictors of satisfaction--optimism, work-based locus of control, and work drive--accounted for 29% of the variability in satisfaction. An expectancy analysis revealed that the percent of participants who reported at least a 20% increase in sales and profits the preceding year was 26% versus 54% for individual scoring in the lower and upper third of a personality composite measure. CONCLUSIONS: Results carry implications for future research, and have direct, practical applications for prospective and current entrepreneurs and self-employed owners of small businesses.

Personality traits and career satisfaction of health care professionals.

Based on Holland's theorizing that vocational satisfaction arises from a good match between one's personality and career choice, one purpose of the study was to examine broad and narrow personality traits that characterize health care workers in comparison with professionals from other occupations. Also investigated were ways in which characteristic traits of health care workers were related to career satisfaction. Professionals utilizing the services of eCareerfit.com responded to online surveys that have been demonstrated to produce reliable and valid measures of broad and narrow personality traits and levels of career satisfaction. An independent sample t test was used to compare means of health care workers with those from other occupations. Pearson product-moment correlations were then computed to assess relationships between the traits and career satisfaction of health care professionals. Two traits that were particularly strong among health care workers were also significantly correlated with career satisfaction: work drive and conscientiousness. Other traits were found to be significantly related to career satisfaction in health care but were not uniquely high in the sample of health care professionals. To increase career satisfaction of health care professionals and thus to improve retention rates, administrators should consider focusing on recruiting and selecting individuals with higher levels of key personality traits.