Integrated and patient-centred management of Parkinson’s disease:a network model for reshaping chronic neurological care

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Age and gender differences in non-motor symptoms in people with Parkinson’s disease

BackgroundNon-motor symptoms of Parkinson’s disease (PD) are highly prevalent and heterogenic. Previous studies aimed to gain more insight on this heterogeneity by investigating age and gender differences in non-motor symptom severity, but findings were inconsistent. Furthermore, besides examining the single effects of age and gender, the interaction between them in relation to non-motor functioning has -as far as we know- not been investigated before.ObjectivesTo investigate the association of age and gender identity -as well as the interaction between age and gender identity- with non-motor symptoms and their impact on quality of life.MethodsWe combined three large and independent studies. This approach resulted in a total number of unique participants of 1,509. We used linear regression models to assess the association of age and gender identity, and their interaction, with non-motor symptoms and their impact on quality of life.ResultsOlder people with PD generally had worse cognitive functioning, worse autonomic functioning and worse quality of life. Women with PD generally experienced more anxiety, worse autonomic functioning and worse quality of life compared to men with PD, whereas men with PD generally had worse cognitive functioning. In interaction analyses by age and gender identity, depressive symptoms and anxiety were disproportionally worse with increasing age in women compared to men.ConclusionOur findings indicate that both age and gender -as well as their interaction- are differentially associated with non-motor symptoms of PD. Both research and clinical practice should pay more attention to demographic subgroups differences and possible different treatment approaches with respect to age and gender. We showed how combining datasets is of added value in this kind of analyses and encourage others to use similar approaches

Lipopolysaccharide-binding protein and future Parkinson's disease risk: a European prospective cohort

INTRODUCTION: Lipopolysaccharide (LPS) is the outer membrane component of Gram-negative bacteria. LPS-binding protein (LBP) is an acute-phase reactant that mediates immune responses triggered by LPS and has been used as a blood marker for LPS. LBP has recently been indicated to be associated with Parkinson's disease (PD) in small-scale retrospective case-control studies. We aimed to investigate the association between LBP blood levels with PD risk in a nested case-control study within a large European prospective cohort. METHODS: A total of 352 incident PD cases (55% males) were identified and one control per case was selected, matched by age at recruitment, sex and study center. LBP levels in plasma collected at recruitment, which was on average 7.8 years before diagnosis of the cases, were analyzed by enzyme linked immunosorbent assay. Odds ratios (ORs) were estimated for one unit increase of the natural log of LBP levels and PD incidence by conditional logistic regression. RESULTS: Plasma LBP levels were higher in prospective PD cases compared to controls (median (interquartile range) 26.9 (18.1-41.0) vs. 24.7 (16.6-38.4) µg/ml). The OR for PD incidence per one unit increase of log LBP was elevated (1.46, 95% CI 0.98-2.19). This association was more pronounced among women (OR 2.68, 95% CI 1.40-5.13) and overweight/obese subjects (OR 1.54, 95% CI 1.09-2.18). CONCLUSION: The findings suggest that higher plasma LBP levels may be associated with an increased risk of PD and may thus pinpoint to a potential role of endotoxemia in the pathogenesis of PD, particularly in women and overweight/obese individuals

Trends in the incidence of dementia: design and methods in the Alzheimer Cohorts Consortium

Several studies have reported a decline in incidence of dementia which may have large implications for the projected burden of disease, and provide important guidance to preventive efforts. However, reports are conflicting or inconclusive with regard to the impact of gender and education with underlying causes of a presumed declining trend remaining largely unidentified. The Alzheimer Cohorts Consortium aggregates data from nine international population-based cohorts to determine changes in the incidence of dementia since 1990. We will employ Poisson regression models to calculate incidence rates in each cohort and Cox proportional hazard regression to compare 5-year cumulative hazards across study-specific epochs. Finally, we will meta-analyse changes per decade across cohorts, and repeat all analysis stratified by sex, education and APOE genotype. In all cohorts combined, there are data on almost 69,000 people at risk of dementia with the range of follow-up years between 2 and 27. The average age at baseline is similar across cohorts ranging between 72 and 77. Uniting a wide range of disease-specific and methodological expertise in research teams, the first analyses within the Alzheimer Cohorts Consortium are underway to tackle outstanding challenges in the assessment of time-trends in dementia occurrence

Twenty-seven-year time trends in dementia incidence in Europe and the United States: The Alzheimer Cohorts Consortium

OBJECTIVE: To determine changes in the incidence of dementia between 1988 and 2015. METHODS: This analysis was performed in aggregated data from individuals >65 years of age in 7 population-based cohort studies in the United States and Europe from the Alzheimer Cohort Consortium. First, we calculated age- and sex-specific incidence rates for all-cause dementia, and then defined nonoverlapping 5-year epochs within each study to determine trends in incidence. Estimates of change per 10-year interval were pooled and results are presented combined and stratified by sex. RESULTS: Of 49,202 individuals, 4,253 (8.6%) developed dementia. The incidence rate of dementia increased with age, similarly for women and men, ranging from about 4 per 1,000 person-years in individuals aged 65-69 years to 65 per 1,000 person-years for those aged 85-89 years. The incidence rate of dementia declined by 13% per calendar decade (95% confidence interval [CI], 7%-19%), consistently across studies, and somewhat more pronouncedly in men than in women (24% [95% CI 14%-32%] vs 8% [0%-15%]). CONCLUSION: The incidence rate of dementia in Europe and North America has declined by 13% per decade over the past 25 years, consistently across studies. Incidence is similar for men and women, although declines were somewhat more profound in men. These observations call for sustained efforts to finding the causes for this decline, as well as determining their validity in geographically and ethnically diverse populations

Lifestyle Interventions for the Prevention of Parkinson Disease: A Recipe for Action

The prevalence of Parkinson disease (PD) is growing fast, amplifying the quest for disease-modifying therapies in early disease phases where pathology is still limited. Lifestyle interventions offer a promising avenue for preventing progression from prodromal to manifest PD. We illustrate this primarily for 1 specific lifestyle intervention, namely aerobic exercise because the case for the other main lifestyle factor (dietary interventions) to modify the course of prodromal PD is currently less persuasive. Various observations have hinted at the disease-modifying potential of exercise. First, studies in rodents with experimental parkinsonism showed that exercise elicits adaptive neuroplasticity in basal ganglia circuitries. Second, exercise is associated with a reduced risk of developing PD, suggesting a disease-modifying potential. Third, 2 large trials in persons with manifest PD indicate that exercise can help to stabilize motor parkinsonism, although this could also reflect a symptomatic effect. In addition, exercise seems to be a feasible intervention, given its minimal risk of side effects. Theoretical risks include an increase in fall incidents and cardiovascular complications, but these concerns seem to be acceptably low. Innovative approaches using gamification elements indicate that adequate long-term compliance with regular exercise programs can be achieved, although more work remains necessary to demonstrate enduring adherence for multiple years. Advances in digital technology can be used to deliver the exercise intervention in the participant's own living environment and also to measure the outcomes remotely, which will help to further boost long-term compliance. When delivering exercise to prodromal participants, outcome measures should focus not just on phenoconversion to manifest PD (which may well take many years to occur) but also on measurable intermediate outcomes, such as physical fitness or prodromal nonmotor symptoms. Taken together, there seems to be sufficient evidence to advocate the first judicious attempt of investigating exercise as a disease-modifying treatment in prodromal PD

Gender-aware Parkinson's care: a design-based study of patient perspectives on gender norms and gender-sensitive care

Göttgens I, Modderkolk L, Vermue P, Darweesh SKL, Bloem BR, Oertelt-Prigione S. Gender-aware Parkinson's care: a design-based study of patient perspectives on gender norms and gender-sensitive care. EClinicalMedicine . 2023;65: 102285.Background Gender dimensions are progressively recognised as a relevant social determinant of health in people with Parkinson's disease (PD). However, little is known about the impact of gender norms and stereotypes on illness experiences of men and women with PD and what they consider important focal points for gender-sensitive PD care.Methods We conducted two equity-centred design (ECD) sessions on December 7, 2022 and December 8, 2022, at the Radboud University Medical Centre in the Netherlands. This participatory multi-method approach includes patients in the research and design process and was used to explore the impact of gender norms and stereotypes in illness experiences and generate patient-driven recommendations for gender-aware Parkinson's care. Quantitative survey data and design-based data were descriptively analysed, and qualitative focus group discussions were thematically analysed.Findings This study included thirteen men and fifteen women with PD in the Netherlands. All participants were of Dutch descent, with a median age of 65.5 years and a median clinical disease duration of 4.2 years. The gendered stereotype that "people with PD are old men" affected both men's and women's perception of living with the disease and the perceptions of their social environment. Men described masculine stereotypes related to physical strength and provider roles, while women expressed those related to feminine physical appearance and caregiver roles, influencing their illness experiences. For some, these norms influenced personal behaviours, while for others, they affected experiences through societal attitudes.Interpretation Our findings suggested that several gender norms and stereotypes influence the illness experiences of men and women with PD, manifesting at ideological, interpersonal, and internalised levels. Some participants internalised these norms, affecting their coping behaviours, while others encountered them in broader ideological contexts that shaped societal attitudes and interpersonal relationships. To advance gender sensitive PD care, it's essential to explore the impact of gender roles and norms, especially regarding how they might impede coping strategies, care access and utilisation for individuals of diverse gender identities.Funding The Gatsby Foundation and co-funded by the PPP Allowance by Health similar to Holland. Travel reimbursements for participants were made available through a Parkinson's Foundation grant (PF-FBS-2026).Copyright (c) 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). 2023;65: Published October https://doi.org/10. 1016/j.eclinm.2023. 10228