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The COVID-19 pandemic and the related governmental restrictions have greatly impacted the lives of people worldwide and have been suggested to negatively impact mental health. We describe the trajectories of depressive and anxiety symptoms during the pandemic and their determinants in a large population-based sample of middle-aged and older adults. From April to June 2020, participants of the Rotterdam Study were asked to complete questionnaires including questions on depressive symptoms (Center of Epidemiological Studies Depression Scale, 10 item version) and anxiety symptoms (Hospital Anxiety and Depression Scale, anxiety subscale). We compared depressive and anxiety symptom scores to those before the pandemic and described its trajectories during the pandemic by demographic variables, chronic disease status and pre-pandemic clinically relevant depressive or anxiety symptoms. In total, 6241 participants responded to the questionnaires (mean age [standard deviation] 70.1 years [11.6]; 58% women). Participants more often reported clinically relevant depressive symptoms during than before the pandemic (19% vs. 12%, P < .001), which was similar for clinically relevant anxiety symptoms (17% vs. 12%, P < .001). During the pandemic, depressive symptoms persisted over time while anxiety symptoms improved. Depressive and anxiety symptoms were more common among women, persons living alone, with chronic diseases and with pre-pandemic clinically relevant symptoms, although the trajectories of these symptoms over time were broadly similar for the subgroups. Together, these results suggest that it is important to be aware of long-term depressive symptoms following the COVID-19 pandemic in the general population.

Background: The immune system is known to be involved in Parkinson’s disease (PD) pathogenesis, but the temporal relationship between peripheral immune responses and PD remains unknown. Objective: We determined the association between peripheral immune cell numbers, C-reactive protein (CRP), and prevalent as well as incident PD. Methods: This study was embedded in the population-based setting of the Rotterdam Study. We repeatedly measured peripheral immune cell numbers (differential leukocyte count and platelet count, granulocyte-to-lymphocyte ratio [GLR], platelet-to-lymphocyte ratio [PLR], and adapted systemic immune-inflammation index [adapted SII]) and CRP between 1990 and 2016. Participants were continuously followed-up for PD until 2018. We estimated the association of the markers with prevalent and incident PD using logistic regression models and joint models, respectively. Models were adjusted for age, sex, smoking, body mass index, and medication use. Odds ratios (OR) and hazard ratios (HR) are shown per doubling of the marker. Results: A total of 12,642 participants were included in this study. The mean age (standard deviation) was 65.1 (9.8) years and 57.5%were women. Participants with a higher lymphocyte count were less likely to have prevalent PD (adjusted OR: 0.34, 95%CI 0.17–0.68). Participants with a higher GLR, PLR, and adapted SII were more likely to have prevalent PD, but these effects were explained by the lymphocyte count. The peripheral immune cell numbers and CRP were not significantly associated with the risk of incident PD. Conclusion: We found participants with a higher lymphocyte count to be less likely to have prevalent PD, but we did not find an association between peripheral immune cell numbers nor CRP and the risk of incident PD.

Background Orthostatic hypotension is common in patients with Parkinson's disease (PD). However, it remains unknown whether orthostatic hypotension is a marker of prodromal PD or more advanced disease. The objectives of this study were to assess whether orthostatic hypotension is a prodromal marker of PD in the general population. Methods This study was embedded in the Rotterdam Study, a large prospective population‐based cohort in the Netherlands. We measured orthostatic hypotension in 6910 participants. First, we determined the relation between prevalent PD and orthostatic hypotension using logistic regression. Second, we followed PD‐free participants for the occurrence of PD until 2016 and studied the association between orthostatic hypotension and the risk of PD using Cox proportional hazards models. All models were adjusted for age and sex. Results At baseline, the mean age ± standard deviation of the study population was 69.0 ± 8.8 years, and 59.1% were women. Orthostatic hypotension was present in 1245 participants (19.8%), and 62 participants (1.0%) had PD at the time of orthostatic hypotension measurement. Participants with PD were significantly more likely to have orthostatic hypotension (odds ratio, 1.88; 95% confidence interval, 1.09–3.24). During a median (interquartile range) follow‐up of 16.1 years (8.5–22.7 years), 122 participants were diagnosed with incident PD. Orthostatic hypotension at baseline was not associated with an increased risk of PD (hazard ratio, 0.97; 95% confidence interval, 0.59–1.58). Conclusions Our study suggests that orthostatic hypotension is common in patients with PD, but that orthostatic hypotension is not associated with an increased risk of PD and thus is not a prodromal marker of PD in the general population. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Clinical studies have shown that up to 90% of patients with idiopathic rapid eye movement sleep behavior disorder (RBD) will eventually be diagnosed with a clinical α-synucleinopathy. Because of this high conversion rate, screening for RBD is often performed to identify eligible participants for studies aimed at elucidating the prodromal phase of α-synucleinopathies. However, screening for RBD, especially in the general population, raises many ethical dilemmas. In light of the existing ethical literature and our experience in establishing a screening approach for RBD in the Rotterdam Study, we discuss ethical dilemmas when screening for RBD in population-based studies. We conclude that informing study participants about the reason for invitation and the possible trajectory that lies ahead when participating is essential. However, participants should not be troubled unnecessarily by giving them detailed information about possible diagnoses or associated disease risks. © 2020 International Parkinson and Movement Disorder Society.

The COVID-19 pandemic has introduced a myriad of challenges to the social life and care of people with Parkinson’s disease (PD), which could potentially worsen mental health problems. We used baseline data of the PRIME-NL study (N = 844) to examine whether the association between COVID-19 stressors and mental health is disproportionately large in specific subgroups of people with PD and to explore effects of hypothetical reductions in COVID-19 stressors on mental health and quality of life. The mean (SD) age of the study population was 70.3 (7.8) years and 321 (38.0%) were women. The linear regression effect estimate of the association of COVID-19 stressors with mental health was most pronounced in women, highly educated people, people with advanced PD and people prone to distancing or seeking social support. Smaller effect estimates were found in people scoring high on confrontive coping or planful problem solving. The parametric G-formula method was used to calculate the effects of hypothetical interventions on COVID-19 stressors. An intervention reducing stressors with 50% in people with above median MDS-UPDRS-II decreased the Beck Depression Inventory in this group from 14.7 to 10.6, the State-Trait Anxiety Inventory from 81.6 to 73.1 and the Parkinson’s Disease Quality of Life Questionnaire from 35.0 to 24.3. Insights from this cross-sectional study help to inform tailored care interventions to subgroups of people with PD most vulnerable to the impact of COVID-19 on mental health and quality of life.

The Mediterranean diet has been associated with the risk of Parkinson’s disease (PD), but limited research has been performed on other dietary patterns. We studied the relationship between overall diet quality and PD risk in the general population. We included 9414 participants from the Rotterdam Study, a prospective population-based study in the Netherlands. Diet was defined using a Dutch diet quality score, a Mediterranean diet score and data-driven dietary patterns constructed with principal component analysis (PCA). During an average follow-up of 14.1 years, PD was diagnosed in 129 participants. We identified a ‘Prudent’, ‘Unhealthy’ and ‘Traditional Dutch’ pattern from the PCA. We found a possible association between the Mediterranean diet (Hazard ratio (HR) per standard deviation (SD) 0.89 (95% confidence interval (CI) 0.74–1.07)), the ‘Prudent’ pattern (HR per SD 0.81 (95% CI 0.61–1.08)) and the risk of PD. However, no associations with PD risk were found for the Dutch diet quality score (HR per SD 0.93 (95% CI 0.77–1.12)), the ‘Unhealthy’ pattern (HR per SD 1.05 (95% CI 0.85–1.29)) or the ‘Traditional Dutch’ pattern (HR per SD 0.90 (95% CI 0.69–1.17)). In conclusion, our results corroborate previous findings of a possible protective effect of the Mediterranean diet. Further research is warranted to study the effect of other dietary patterns on PD risk.

ObjectiveAlthough knowledge on poststroke cognitive and functional decline is increasing, little is known about the possible decline of these functions before stroke. We determined the long-term trajectories of cognition and daily functioning before and after stroke.MethodsBetween 1990 and 2016, we repeatedly assessed cognition (Mini-Mental State Examination (MMSE), 15-Word Learning, Letter–Digit Substitution, Stroop, Verbal Fluency, Purdue Pegboard) and basic and instrumental activities of daily living (BADL and IADL) in 14 712 participants within the population-based Rotterdam Study. Incident stroke was assessed through continuous monitoring of medical records until 2018. We matched participants with incident stroke to stroke-free participants (1:3) based on sex and birth year. Trajectories of cognition and daily functioning of patients who had a stroke 10 years before and 10 years after stroke and the corresponding trajectories of stroke-free individuals were constructed using adjusted linear mixed effects models.ResultsDuring a mean follow-up of 12.5±6.8 years, a total of 1662 participants suffered a first-ever stroke. Patients who had a stroke deviated from stroke-free controls up to 10 years before stroke diagnosis in cognition and daily functioning. Significant deviations before stroke were seen in scores of MMSE (6.4 years), Stroop (5.7 years), Purdue Pegboard (3.8 years) and BADL and IADL (2.2 and 3.0 years, respectively).ConclusionPatients who had a stroke have steeper declines in cognition and daily functioning up to 10 years before their first-ever stroke compared with stroke-free individuals. Our findings suggest that accumulating intracerebral pathology already has a clinical impact before stroke.

textabstractPurpose: Aortic stiffness (AS) is associated with cardiovascular events and all-cause mortality in the older population. AS might also influence the health-related quality of life (HRQOL) as a result of the negative effects of AS on cognitive and physical morbidity. We aimed to investigate the possible association between AS and HRQOL in people aged 75 years and over. Patients and Methods: This cross-sectional study was part of the SCOPE study, an international multicenter cohort observational study. The indicators for AS were aortic pulse wave velocity (aPWV) and central pulse pressure (cPP). HRQOL was assessed using the EQ-5D index and the EQ-5D visual analog scale (VAS). ANCOVA and multivariate regression models were used to investigate possible associations. Results: We included 280 Dutch participants of the SCOPE study. Median age was 79 years (IQR 76–83) and 42.1% were women. Participants reporting any problem on the EQ-5D index (n=214) had higher values of aPWV (12.6 vs 12.2 m/s, p = 0.024) than participants not experiencing any problem (n=66) and comparable values of cPP (44.4 vs 42.0 mmHg, p = 0.119). Estimates only slightly changed after adjustments. No association was found between indicators of AS and EQ-5D VAS. Conclusion: Aortic stiffness was associated with impaired quality of late life. This association could be mediated by subclinical vascular pathology affecting mental and physical health.

Several lifestyle factors have been linked to risk for heart failure (HF) and premature mortality. The aim of this study was to estimate the impact of a healthy lifestyle on life expectancy with and without HF among men and women from a general population. This study was performed among 6113 participants (mean age 65.8 ± 9.7 years; 58.9% women) from the Rotterdam Study, a large prospective population-based cohort study. A continuous lifestyle score was created based on five lifestyle factors: smoking status, alcohol consumption, diet quality, physical activity and weight status (assessed 1995–2008). The lifestyle score was categorized into three levels: unhealthy (reference), intermediate and healthy. Gompertz regression and multistate life tables were used to estimate the effects of lifestyle on life expectancy with and without HF in men and women separately at ages 45, 65 and 85 years (follow-up until 2016). During an average follow-up of 11.3 years, 699 incident HF events and 2146 deaths occurred. At the age of 45 years, men in the healthy lifestyle category had a 4.4 (95% CI: 4.1–4.7) years longer total life expectancy than men in the unhealthy lifestyle category, and a 4.8 (95% CI: 4.4–5.1) years longer life expectancy free of HF. Among women, the difference in total life-expectancy at the age of 45 years was 3.4 (95% CI: 3.2–3.5) years and was 3.4 (95% CI: 3.3–3.6) years longer for life expectancy without HF. This effect persisted also at older ages. An overall healthy lifestyle can have a positive impact on total life expectancy and life expectancy free of HF.

Gait is a complex process involving various cortical and subcortical brain regions. An acute stroke or transient ischemic attack (TIA) may disrupt white and gray matter integrity and, therefore, affect gait in patients without evident neurological signs. We determined whether patients with stroke and TIA experience subtle changes in global gait and several independent gait domains.In the population-based Rotterdam Study, 4456 participants (median age, 65 years; 55% women) underwent detailed quantitative gait assessment (GAITRite) between 2009 and 2016. We summarized 30 gait parameters into a global gait score and 7 mutually independent gait domains. First, we assessed the association between prior stroke or TIA and global and domain-specific gait using linear regression models adjusted for age, sex, vascular risk factors, and cognition. Subsequently, we repeated the analysis stratified by the presence of different neurological symptoms in a subgroup of participants with ischemic stroke after study entry.Compared with participants without prior stroke, patients with stroke had a worse global gait (SD, -0.49 [95% CI, -0.64 to -0.34]), especially in the gait domains Pace, Phases, and Turning. The detrimental effect of stroke on gait was amplified in participants with worse cognition. No gait differences were found between participants with and without prior TIA. Ischemic stroke patients without lower limb weakness, loss of coordination, or visuospatial problems still had a worse gait compared with participants without stroke. Stratification by different stroke symptoms showed that different gait domains were affected in each group.Prior stroke without neurological signs that affect gait is still associated with gait difficulties compared with individuals without stroke. Our study suggests that stroke not only has a direct impact on gait through neurological impairments but also includes an indirect effect possibly through disruption of gray and white matter integrity and accelerated neurodegeneration.

Background: Gait speed is a simple, inexpensive and clinically useful marker of physical function in older adults. We aimed to establish gait speed reference values for community-dwelling older adults. To this end, we further explored the association of age, sex and height with gait speed.Methods: This study included community-dwelling participants aged 50 years and over enrolled in the Rotterdam Study. Participants completed the gait protocol between 2009 and 2016. The mean gait speed was calculated for age and height groups, stratified by sex. Reference values for gait speed were calculated using a quantile regression model adjusted for sex, the non-linear effects of age and height, as well as the interaction between age and sex plus the interaction between age and height.Results: The study population included 4656 Dutch participants with a mean (standard deviation) age of 67.7 (9.5) years, comprising 2569 (55.2%) women. The mean height of the participants was 1.69 (0.10) meters and the mean gait speed was 1.20 (0.20) m/s. Gait speed was lower with older age and greater with taller stature, but the effect of height disappeared above the age of 80 years. Sex did not affect gait speed after accounting for age and height. Age-, sex-, and height-specific reference values for gait speed are available for use at https://emcbios tatistics.shinyapps.io/GaitSpeedReferenceValues/.Conclusions: We found that height explains the commonly noted difference in usual gait speed between sexes and that neither height nor sex impacts gait speed in the very oldest adults. We developed reference values for usual gait speed in Western European community-dwelling older adults.

Background Slowness of walking is one of the very first signs of aging and is considered a marker for overall health that is strongly associated with mortality risk. In this study, we sought to disentangle the clinical drivers of the association between gait and mortality. Methods We included 4,490 participants of the Rotterdam Study who underwent a gait assessment between 2009 and 2015 and were followed-up for mortality until 2018. Gait was assessed with an electronic walkway and summarized into the domains Rhythm, Phases, Variability, Pace, Tandem, Turning, and Base of Support. Cox models adjusted for age, sex, and height were built and consecutively adjusted for six categories of health indicators (lifestyle, musculoskeletal, cardiovascular, pulmonary, metabolic, and neurological). Analyses were repeated in comorbidity-free individuals. Results Multiple gait domains were associated with an increased risk of mortality, including Pace (hazard ratio (HR) per SD worse gait, adjusted for other domains: 1.34 [1.19–1.50]), Rhythm (HR: 1.12 [1.02–1.23]) and Phases (HR: 1.12 [1.03–1.21]). Similarly, a 0.1 m/s decrease in gait speed was associated with a 1.21 (1.15–1.27) times higher hazard of mortality (HR fully adjusted: 1.14 [1.08–1.20]). In a comorbidity-free subsample, the HR per 0.1 m/s decrease in gait speed was 1.25 (1.09–1.44). Cause-specific mortality analyses revealed an association between gait speed and multiple causes of death. Conclusions Several gait domains were associated with mortality risk, including Pace which primarily represents gait speed. The association between gait speed and mortality persisted after an extensive adjustment for covariates, suggesting that gait is a marker for overall health.

Introduction: Detailed data on the life expectancy of patients with parkinsonism from the general population are largely lacking. This study aimed to determine the absolute life expectancy of patients newly-diagnosed with parkinsonism. Methods: This study was part of the Rotterdam Study, an ongoing, population-based cohort study in the Netherlands. We included 12,789 participants of 50 years and older, free of parkinsonism. Patients diagnosed with parkinsonism were matched to controls on sex, birth year, dementia status, cancer status, and coronary heart disease status. We used Gompertz regression and lifetables to estimate the remaining life expectancy per year of age. Results: The mean age of our study population was 65.0 (SD 9.7) years and 57.6% were women. During an average follow-up of 12 years, 297 participants were diagnosed with parkinsonism. The mean age at parkinsonism diagnosis was 78.6 (SD 8.1) years. Once diagnosed with parkinsonism, the life expectancy was lower than matched controls across a wide age range. At 65 years, the life expectancy of patients with parkinsonism was reduced with 6.7 [95% CI: 2.4;10.7] years compared to controls. At 85, the difference in life expectancy was 1.2 [95% CI: -2.2;4.5] years compared to controls. Conclusion: Patients diagnosed with parkinsonism have a reduced life expectancy compared to their peers in the general population. The absolute life expectancy is mainly reduced if parkinsonism is diagnosed before the age of 70.

Purpose Aortic stiffness (AS) is associated with cardiovascular events and all-cause mortality in the older population. AS might also influence the health-related quality of life (HRQOL) as a result of the negative effects of AS on cognitive and physical morbidity. We aimed to investigate the possible association between AS and HRQOL in people aged 75 years and over. Patients and Methods This cross-sectional study was part of the SCOPE study, an international multicenter cohort observational study. The indicators for AS were aortic pulse wave velocity (aPWV) and central pulse pressure (cPP). HRQOL was assessed using the EQ-5D index and the EQ-5D visual analog scale (VAS). ANCOVA and multivariate regression models were used to investigate possible associations. Results We included 280 Dutch participants of the SCOPE study. Median age was 79 years (IQR 76–83) and 42.1% were women. Participants reporting any problem on the EQ-5D index (n=214) had higher values of aPWV (12.6 vs 12.2 m/s, p = 0.024) than participants not experiencing any problem (n=66) and comparable values of cPP (44.4 vs 42.0 mmHg, p = 0.119). Estimates only slightly changed after adjustments. No association was found between indicators of AS and EQ-5D VAS. Conclusion Aortic stiffness was associated with impaired quality of late life. This association could be mediated by subclinical vascular pathology affecting mental and physical health.

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