APOE and the risk of PD with or without dementia in a population-based study.

OBJECTIVE: To study the association between APOE genotype and PD with or without dementia. METHODS: The study formed part of the Rotterdam Study, a prospective, population-based cohort study on the frequency, etiology, and prognosis of chronic diseases. The cohort examined for PD consisted of 6,969 independently living or institutionalized i

Use of antidepressants and the risk of myocardial infarction in middle-aged and older adults: A matched case-control study

Purpose: Antidepressants, specifically selective serotonin reuptake-inhibiting antidepressants (SSRIs), decrease platelet activation and aggregation in in vitro experiments and could therefore decrease the risk of myocardial infarction (MI). However, prior studies addressing this hypothesis showed contradictory results. Our purpose was to investigate the association between the use of any antidepressant drug and incident MI among middle-aged and older adults. Methods: We embedded a case-control study in the prospective Rotterdam Study (1991-2011). Controls were matched to MI cases based on sex and age at the same calendar date, and confounding factors were taken into account as time-varying covariates. The relative risk of MI during current and past use of an antidepressant was analyzed with conditional logistic regression with never use of antidepressant dr

Clopidogrel use is associated with an increased prevalence of cerebral microbleeds in a stroke-free population: the Rotterdam study.

Although clopidogrel reduces the incidence of atherothrombotic events, its use is associated with an increased risk of major bleeding. Cerebral microbleeds (CMBs) are indicative of subclinical microangiopathy in the brain and may prelude symptomatic intracerebral hemorrhage. We examined the association between use of clopidogrel and CMBs in persons without a history of stroke. We performed a cross-sectional analysis using data from the Rotterdam Study, a prospective population-based cohort of persons aged 45 years and older. Among 4408 stroke-free individuals who underwent brain magnetic resonance imaging for the detection of CMBs, we identified 121 ever-users and 4287 never-users of clopidogrel before magnetic resonance imaging. We used multiple logistic regression to analyze the association between clopidogrel and CMBs with adjustment for age, sex, cardiovascular risk factors, and common cardiovascular medication. Users of clopidogrel had a higher prevalence of CMBs (odd ratio 1.55, 95% CI 1.01 to 2.37) than nonusers and more often had a high number (> 4) of CMBs (odds ratio 3.19, 95% CI 1.52 to 6.72). Clopidogrel use was associated with a significantly higher prevalence of deep or infratentorial CMBs (odd ratio 1.90, 95% CI 1.05 to 3.45). Among clopidogrel users, we were unable to demonstrate differences in the prevalence of CMBs by indication of prescription, history of coronary heart disease, or common genetic variants in CYP2C19. In stroke-free individuals, clopidogrel use was associated with a higher prevalence and higher number of CMBs. Whether this association is causal requires confirmation in prospective studies, especially given the small number of participants taking clopidogrel and the possibil

Maternal smoking during pregnancy and kidney volume in the offspring: the Generation R Study

An adverse fetal environment leads to smaller kidneys, with fewer nephrons, which might predispose an individual to the development of kidney disease and hypertension in adult life. In a prospective cohort study among 1,072 children followed from early fetal life onward, we examined whether maternal smoking during pregnancy, as a significant adverse fetal exposure, is associated with fetal (third trimester of pregnancy, n = 1,031) and infant kidney volume (2 years of age, n = 538) measured by ultrasound. Analyses were adjusted for various potential confounders. Among mothers who continued smoking, we observed dose-dependent associations between the number of cigarettes smoked during pregnancy and kidney volume in fetal life. Smoking less than five cigarettes per day was associated with larger fetal combined kidney volume, while smoking more than ten cigarettes per day tended to be associated with smaller fetal combined kidney volume (p for trend: 0.002). This pattern was not significant for kidney volume at the age of 2 years. Our results suggest that smoking during pregnancy might affect kidney development in fetal life with a dose-dependent relationship. Further studies are needed to assess the underlying mechanisms and whether these differences in fetal kidney volume have postnatal consequences for kidney function and blood pressure

Evaluating the impacts of a large-scale voluntary REDD+ project in Sierra Leone

Carbon offsets from the REDD+ (reducing emissions from deforestation and degradation) framework to protect forests are expected to see a 100-fold increase in market value by 2050. However, independent causal impact evaluations are scarce and only a few studies assess benefits to communities themselves, a core objective of REDD+. Following a pre-analysis plan, we use a before-after-control-intervention (BACI) framework to evaluate the impact of a large-scale voluntary REDD+ project in Sierra Leone—the Gola project. We use a panel of both satellite images and household surveys to provide causal evidence of the impact of the project on local deforestation rates and socioeconomic indicators over the first 5 yr of its implementation. We find that REDD+ slowed deforestation by 30% relative to control communities while not changing economic wellbeing and conservation attitudes. We find suggestive evidence that the programme increased the value of alternative income sources, by shifting labour away from forest-dependent farming activities. A cost-to-carbon calculation shows that REDD+ led to 340,000 tCO2 in avoided emissions per year, with an estimated cost of US$1.12 per averted tCO2. Our study contributes to developing an evidence base for voluntary REDD+ projects and offers a robust approach to carry out BACI assessments

Pulmonary function and diffusion capacity are associated with pulmonary arterial systolic pressure in the general population : the Rotterdam study

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Development of refractive errors - what can we learn from inherited retinal dystrophies?

PURPOSE: It is unknown which retinal cells are involved in the retina-to-sclera signaling cascade causing myopia. As inherited retinal dystrophies (IRD) are characterized by dysfunction of a single retinal cell type and have a high risk of refractive errors, a study investigating the affected cell type, causal gene and refractive error in IRDs may provide insight herein. DESIGN: Case-control study. METHODS: _Study population:_ 302 patients with IRD from two ophthalmogenetic centers in the Netherlands. _Reference population:_ population-based Rotterdam Study-III and ERF Study (N=5,550). Distributions and mean spherical equivalent (SE) were calculated for main affected cell type and causal gene; and risks of myopia and hyperopia were evaluated using logistic regression. RESULTS: Bipolar cell related dystrophies were associated with the highest risk of SE high myopia 239.7; OR mild hyperopia 263.2, both P<0.0001; SE -6.86 D [SD 6.38]); followed by cone dominated dystrophies (OR high myopia 19.5, P<0.0001; OR high hyperopia 10.7, P=0.033; SE -3.10 D [SD 4.49]); rod dominated dystrophies (OR high myopia 10.1, P<0.0001; OR high hyperopia 9.7, P=0.001; SE -2.27 D [SD 4.65]); and RPE related dystrophies (OR low myopia 2.7; P=0.001; OR high hyperopia 5.8; P=0.025; SE -0.10 D [SD 3.09]). Mutations in RPGR (SE -7.63 D [SD 3.31]) and CACNA1F (SE -5.33 D [SD 3.10]) coincided with the highest degree of myopia; in CABP4 (SE 4.81 D [SD 0.35]) with the highest degree of hyperopia. CONCLUSIONS: Refractive errors, in particular myopia, are common in IRD. The bipolar synapse, and the inner and outer segments of the photoreceptor may serve as critical sites for myopia development

Plasma amyloid-β40 in relation to subclinical atherosclerosis and cardiovascular disease: A population-based study.

BACKGROUND AND AIMS We aimed to determine associations of plasma amyloid-β40 (Aβ40) with subclinical atherosclerosis and risk of atherosclerotic cardiovascular disease (ASCVD) in the general population. METHODS Between 2002 and 2005, plasma Aβ40 was measured by single molecule array (SiMoA®) in 3879 participants of the population-based Rotterdam Study (mean age: 71 years, 61% female). Subclinical atherosclerosis was quantified as computed tomography-assessed calcification volumes. We determined the association of Aβ40 with calcification volumes and clinical ASCVD event risk, and repeated the analyses for ASCVD in a replication cohort of 1467 individuals. RESULTS Higher levels of Aβ40 were associated with increased volumes of calcification in the coronary arteries and to a lesser extent extracranial carotid arteries, independent of traditional cardiovascular risk factors. Of all 3879 participants, 748 developed ASCVD during a median 9.7 years of follow-up. In age- and sex-adjusted models, higher Aβ40 predisposed to a minor increase in ASCVD risk (HR [95%CI]: 1.11[1.02-1.21] per 1-SD increase in Aβ40), driven by coronary heart disease (HR: 1.17[1.05-1.29]) rather than stroke (HR: 1.04[0.93-1.16]). However, excess risk of clinical outcomes was largely explained by baseline differences in cardiovascular risk factors and attenuated after further adjustment (for ASCVD- HR: 1.05[0.96-1.15] and for CHD- HR: 1.08[0.96-1.20]). Results were similar in the replication cohort, with highest risk estimates for CHD (HR: 1.24[1.04-1.48]) in age- and sex-adjusted models, attenuated after adjustment for cardiovascular risk factors (HR: 1.15[0.96-1.39]). CONCLUSIONS In this population-based study, higher plasma amyloid-β40 is associated with subclinical atherosclerosis, but not risk of first-ever ASCVD after accounting for traditional cardiovascular risk factors

Serum magnesium and the risk of death from coronary heart disease and sudden cardiac death

Background-Low serum magnesium has been implicated in cardiovascular mortality, but results are conflicting and the pathway is unclear. We studied the association of serum magnesium with coronary heart disease (CHD) mortality and sudden cardiac death (SCD) within the prospective population-based Rotterdam Study, with adjudicated end points and long-term follow-up. Methods and Results-Nine-thousand eight-hundred and twenty participants (mean age 65.1 years, 56.8% female) were included with a median follow-up of 8.7 years. We used multivariable Cox proportional hazard models and found that a 0.1 mmol/L increase in serum magnesium level was associated with a lower risk for CHD mortality (hazard ratio: 0.82, 95% CI 0.70-0.96). Furthermore, we divided serum magnesium in quartiles, with the second and third quartile combined as reference group (0.81-0.88 mmol/L). Low serum magnesium (=0.80 mmol/L) was associated with an increased risk of CHD mortality (N=431, hazard ratio: 1.36, 95% CI 1.09-1.69) and SCD (N=217, hazard ratio: 1.54, 95% CI 1.12-2.11). Low serum magnesium was associated with accelerated subclinical atherosclerosis (expressed as increased carotid intima-media thickness: +0.013 mm, 95% CI 0.005-0.020) and increased QT-interval, mainly through an effect on heart rate (RR-interval: -7.1 ms, 95% CI -13.5 to -0.8). Additional adjustments for carotid intima-media thickness and heart rate did not change the associations with CHD mortality and SCD. Conclusions-Low serum magnesium is associated with an increased risk of CHD mortality and SCD. Although low magnesium was associated with both carotid intima-media thickness and heart rate, this did not explain the relationship between serum magnesium and CHD mortality or SCD. Future studies should focus on why magnesium associates with CHD mortality and SCD and whether intervention reduces these risks