M Arfan Ikram

Erasmus Universiteit Rotterdam, Rotterdam, South Holland, Netherlands

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Publications (290)2621.52 Total impact

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    ABSTRACT: Background Cardiovascular factors and low education are important risk factors of dementia. We provide contemporary estimates of the proportion of dementia cases that could be prevented if modifiable risk factors were eliminated, i.e., population attributable risk (PAR). Furthermore, we studied whether the PAR has changed across the last two decades. Methods We included 7,003 participants of the original cohort (starting in 1990) and 2,953 participants of the extended cohort (starting in 2000) of the Rotterdam Study. Both cohorts were followed for dementia until ten years after baseline. We calculated the PAR of overweight, hypertension, diabetes mellitus, cholesterol, smoking, and education. Additionally, we assessed the PAR of stroke, coronary heart disease, heart failure, and atrial fibrillation. We calculated the PAR for each risk factor separately and the combined PAR taking into account the interaction of risk factors. Results During 57,996 person-years, 624 participants of the original cohort developed dementia, and during 26,177 person-years, 145 participants of the extended cohort developed dementia. The combined PAR in the original cohort was 0.23 (95 % CI, 0.05–0.62). The PAR in the extended cohort was slightly higher at 0.30 (95 % CI, 0.06–0.76). The combined PAR including cardiovascular diseases was 0.25 (95 % CI, 0.07–0.62) in the original cohort and 0.33 (95 % CI, 0.07–0.77) in the extended cohort. Conclusions A substantial part of dementia cases could be prevented if modifiable risk factors would be eliminated. Although prevention and treatment options of cardiovascular risk factors and diseases have improved, the preventive potential for dementia has not declined over the last two decades.
    BMC Medicine 12/2015; 13(1). DOI:10.1186/s12916-015-0377-5 · 7.25 Impact Factor
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    ABSTRACT: Structural brain magnetic resonance imaging (MRI) traits share part of their genetic variance with cognitive traits. Here, we use genetic association results from large meta-analytic studies of genome-wide association (GWA) for brain infarcts (BI), white matter hyperintensities, intracranial, hippocampal, and total brain volumes to estimate polygenic scores for these traits in three Scottish samples: Generation Scotland: Scottish Family Health Study (GS:SFHS), and the Lothian Birth Cohorts of 1936 (LBC1936) and 1921 (LBC1921). These five brain MRI trait polygenic scores were then used to: (1) predict corresponding MRI traits in the LBC1936 (numbers ranged 573 to 630 across traits), and (2) predict cognitive traits in all three cohorts (in 8,115–8,250 persons). In the LBC1936, all MRI phenotypic traits were correlated with at least one cognitive measure, and polygenic prediction of MRI traits was observed for intracranial volume. Meta-analysis of the correlations between MRI polygenic scores and cognitive traits revealed a significant negative correlation (maximal r = 0.08) between the HV polygenic score and measures of global cognitive ability collected in childhood and in old age in the Lothian Birth Cohorts. The lack of association to a related general cognitive measure when including the GS:SFHS points to either type 1 error or the importance of using prediction samples that closely match the demographics of the GWA samples from which prediction is based. Ideally, these analyses should be repeated in larger samples with data on both MRI and cognition, and using MRI GWA results from even larger meta-analysis studies.
    Twin Research and Human Genetics 10/2015; DOI:10.1017/thg.2015.71 · 2.30 Impact Factor
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    ABSTRACT: Rationale: Worldwide, chronic obstructive pulmonary disease (COPD) and stroke are leading causes of death. Increasing evidence suggests an association between both diseases, either caused by an increased atherosclerosis risk in patients with COPD, or as a consequence of shared risk factors between stroke and COPD. Objectives: To examine the associations between COPD and subtypes of stroke in the general population and to explore the role of cardiovascular risk factors and exacerbations on these associations. Methods: Within the prospective population-based Rotterdam Study, we followed 13115 participants without history of stroke for occurrence of stroke. Follow-up started in 1990-2008 and ended in 2012. COPD was related to stroke using a time-dependent Cox proportional hazard model. Measurements and main results: COPD was diagnosed in 1566 participants. During 126347 person-years, 1250 participants suffered a stroke, of which 701 were ischemic and 107 hemorrhagic. Adjusted for age, age2, and sex, COPD was significantly associated with all stroke (HR 1.20; 95%CI 1.00-1.43), ischemic stroke (HR 1.27; 1.02-1.59), and hemorrhagic stroke (HR 1.70; 1.01-2.84). Adjusting for cardiovascular risk factors gave similar effect sizes. In contrast, additional adjusting for smoking attenuated the effect sizes: HR 1.09 (0.91-1.31) for all stroke, HR 1.13 (0.91-1.42) for ischemic stroke, and HR 1.53 (0.91-2.59) for hemorrhagic stroke. Following an acute severe exacerbation subjects with COPD had a 6.66-fold (2.42-18.20) increased risk of stroke. Conclusion: Our cohort study demonstrated a higher risk of both ischemic and hemorrhagic stroke in subjects with COPD, and revealed the importance of smoking as a shared risk factor.
    American Journal of Respiratory and Critical Care Medicine 09/2015; DOI:10.1164/rccm.201505-0962OC · 13.00 Impact Factor
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    ABSTRACT: Importance: Atrial fibrillation (AF) has been suggested as a risk factor for dementia since it may lead to chronic cerebral hypoperfusion and stroke. However, longitudinal studies assessing the association between AF and dementia have shown inconsistent results. Objective: To determine the effect of AF on the risk of developing dementia during 20 years of follow-up. Design, setting, and participants: The association of prevalent and incident AF with incident dementia was assessed from July 6, 1989, to February 4, 2010, in 6514 dementia-free participants in the prospective population-based Rotterdam Study. Data analysis was conducted from September 18, 2014, to April 17, 2015. Cox proportional hazards regression models adjusting for age, sex, and cardiovascular risk factors; censored for stroke; and stratified by median age were used. In addition, we investigated whether the association between incident AF and dementia varied according to the duration of exposure, categorized in 6-year time bands. Exposures: Prevalent and incident AF. Main outcomes and measures: Incident dementia, determined according to the Diagnostic and Statistical Manual of Mental Disorders (Third Edition Revised) and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria. Results: At baseline, 318 of 6514 participants (4.9%) had prevalent AF, and during 81 483 person-years of follow-up, 994 participants (15.3%) developed incident dementia. With findings presented as adjusted hazard ratio (95% CI), prevalent AF was related to an increased risk of dementia (1.33; 1.02-1.73). Among 6196 participants without prevalent AF during 79 003 person-years of follow-up, 723 participants (11.7%) developed incident AF and 932 individuals (15.0%) developed incident dementia. Incident AF was associated with an increased risk of dementia in younger participants (<67 years: 1.81; 1.11-2.94 vs ≥67 years: 1.12; 0.85-1.46; P = .02 for interaction). The risk of dementia was strongly associated with duration of exposure to AF in the younger participants (in the highest stratum: 3.30; 1.16-9.38; P = .003 for trend) but not in the elder participants (0.25; 0.04-1.86; P = .94 for trend). Conclusions and relevance: Atrial fibrillation is associated with an increased risk of dementia, independent of clinical stroke. This association was strongest for younger participants with the longest duration of AF. Future studies should investigate whether optimal treatment of AF can prevent or postpone dementia.
    09/2015; DOI:10.1001/jamaneurol.2015.2161
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    ABSTRACT: The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city of Rotterdam in The Netherlands. The study targets cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, otolaryngological, locomotor, and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. The findings of the Rotterdam Study have been presented in over 1200 research articles and reports (see www.erasmus-epidemiology.nl/rotterdamstudy ). This article gives the rationale of the study and its design. It also presents a summary of the major findings and an update of the objectives and methods.
    European Journal of Epidemiology 09/2015; 28(11). DOI:10.1007/s10654-015-0082-x · 5.34 Impact Factor
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    ABSTRACT: Introduction: Although preclinical dementia is characterized by decline in cognition and daily functioning, little is known on their temporal sequence. We investigated trajectories of cognition and daily functioning in preclinical dementia, during 18 years of follow-up. Methods: In 856 dementia cases and 1712 controls, we repetitively assessed cognition and daily functioning with memory complaints, mini-mental state examination (MMSE), instrumental activities of daily living (IADL), and basic activities of daily living (BADL). Results: Dementia cases first reported memory complaints 16 years before diagnosis, followed by decline in MMSE, IADL, and finally BADL. Vascular dementia related to earlier decline in daily functioning but later in cognition, compared with Alzheimer's disease. Higher education related to larger preclinical cognitive decline, whereas APOE-ε4 carriers declined less in daily functioning. Discussion: These results emphasize the long hierarchical preclinical trajectory of functional decline in dementia. Furthermore, they show that various pathologic, environmental, and genetic factors may influence these trajectories of decline.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 09/2015; DOI:10.1016/j.jalz.2015.08.001 · 12.41 Impact Factor
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    ABSTRACT: Background: Despite frailty being an important geriatric syndrome, its prevalence and associated mortality risk in older patients with chronic obstructive pulmonary disease (COPD) are unknown. Methods: We examined the relationship between COPD confirmed by spirometry, COPD severity, and frailty defined by the Fried criteria within 2,142 participants (aged 74.7±5.6 years) of the Rotterdam Study, a prospective population-based cohort study. Results: The frailty prevalence was significantly higher (p < .001) in participants with COPD (10.2%, 95% CI: 7.6%-13.5%) compared with participants without COPD (3.4%, 95% CI: 2.6%-4.4%). Adjusted for age, sex, smoking, corticosteroids, and other confounders, participants with COPD had a more than twofold increased prevalence of frailty (odds ratio 2.2, 95% CI: 1.34-3.54, p = .002). The prevalence was highest when severe airflow limitation, dyspnea, and frequent exacerbations were present. Participants with mild airflow limitation were more frequently prefrail. COPD elderly who were frail had significant worse survival. Conclusions: This population-based cohort study in elderly demonstrates that COPD is associated with frailty even after adjusting for shared risk factors. Our findings suggest that frailty-in addition to COPD severity and comorbidities-identifies those COPD participants at high risk of mortality.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 09/2015; DOI:10.1093/gerona/glv154 · 5.42 Impact Factor
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    ABSTRACT: Background: Cardiovascular disease (CVD) represents a leading cause of mortality worldwide, especially in the elderly. Lowering the number of CVD deaths requires preventive strategies targeted on the elderly. Objective: The objective was to generate evidence on the association between WHO dietary recommendations and mortality from CVD, coronary artery disease (CAD), and stroke in the elderly aged ≥60 y. Design: We analyzed data from 10 prospective cohort studies from Europe and the United States comprising a total sample of 281,874 men and women free from chronic diseases at baseline. Components of the Healthy Diet Indicator (HDI) included saturated fatty acids, polyunsaturated fatty acids, mono- and disaccharides, protein, cholesterol, dietary fiber, and fruit and vegetables. Cohort-specific HRs adjusted for sex, education, smoking, physical activity, and energy and alcohol intakes were pooled by using a random-effects model. Results: During 3,322,768 person-years of follow-up, 12,492 people died of CVD. An increase of 10 HDI points (complete adherence to an additional WHO guideline) was, on average, not associated with CVD mortality (HR: 0.94; 95% CI: 0.86, 1.03), CAD mortality (HR: 0.99; 95% CI: 0.85, 1.14), or stroke mortality (HR: 0.95; 95% CI: 0.88, 1.03). However, after stratification of the data by geographic region, adherence to the HDI was associated with reduced CVD mortality in the southern European cohorts (HR: 0.87; 95% CI: 0.79, 0.96; I(2) = 0%) and in the US cohort (HR: 0.85; 95% CI: 0.83, 0.87; I(2) = not applicable). Conclusion: Overall, greater adherence to the WHO dietary guidelines was not significantly associated with CVD mortality, but the results varied across regions. Clear inverse associations were observed in elderly populations in southern Europe and the United States.
    American Journal of Clinical Nutrition 09/2015; DOI:10.3945/ajcn.114.095117 · 6.77 Impact Factor
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    ABSTRACT: Genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) for intracranial aneurysms in clinical samples. In addition, SNPs have been discovered for blood pressure, one of the strongest risk factors for intracranial aneurysms. We studied the role of these genetic variants on occurrence and size of unruptured intracranial aneurysms, discovered incidentally in a general community-dwelling population. In 4890 asymptomatic participants from the Rotterdam Study, 120 intracranial aneurysms were identified on brain imaging and segmented for maximum diameter and volume. Genetic risk scores (GRS) were calculated for intracranial aneurysms (10 SNPs), systolic blood pressure (33 SNPs), and diastolic blood pressure (41 SNPs). The GRS for intracranial aneurysms was not statistically significantly associated with presence of aneurysms in this population (OR, 1.16; 95% CI, 0.96-1.40; P=0.119), but showed a significant association with both maximum diameter (difference in log-transformed mm per SD increase of GRS, 0.10; 95% CI, 0.02-0.19; P=0.018) and volume (difference in log-transformed µL per SD increase of GRS, 0.21; 95% CI, 0.01-0.41; P=0.040) of aneurysms. GRSs for blood pressures were associated with neither presence nor size of aneurysms. Genetic variants previously identified for intracranial aneurysms in clinical studies relate to the size rather than the presence of incidentally discovered, unruptured intracranial aneurysms in the general population. © 2015 American Heart Association, Inc.
    Stroke 08/2015; DOI:10.1161/STROKEAHA.115.010414 · 5.72 Impact Factor
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    ABSTRACT: CKD is linked with various brain disorders. Whereas brain integrity is dependent on cerebral perfusion, the association between kidney function and cerebral blood flow has yet to be determined. This study was performed in the framework of the population-based Rotterdam Study and included 2645 participants with mean age of 56.6 years (45% men). We used eGFR and albumin-to-creatinine ratio to assess kidney function and performed phase-contrast magnetic resonance imaging of basilar and carotid arteries to measure cerebral blood flow. Participants had an average (SD) eGFR of 86.3 (13.4) ml/min per 1.73 m(2) and a median (interquartile range) albumin-to-creatinine ratio of 3.4 (2.2-6.1) mg/g. In age- and sex-adjusted models, a higher albumin-to-creatinine ratio was associated with lower cerebral blood flow level (difference in cerebral blood flow [milliliters per minute per 100 ml] per doubling of the albumin-to-creatinine ratio, -0.31; 95% confidence interval, -0.58 to -0.03). The association was not present after adjustment for cardiovascular risk factors (P=0.10). Each 1 SD lower eGFR was associated with 0.42 ml/min per 100 ml lower cerebral blood flow (95% confidence interval, 0.01 to 0.83) adjusted for cardiovascular risk factors. Thus, in this population-based study, we observed that lower eGFR is independently associated with lower cerebral blood flow. Copyright © 2015 by the American Society of Nephrology.
    Journal of the American Society of Nephrology 08/2015; DOI:10.1681/ASN.2014111118 · 9.34 Impact Factor
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    ABSTRACT: Human gait is a complex neurological and musculoskeletal function, of which the genetic basis remains largely unknown. To determine the influence of common genetic variants on gait parameters, we studied 2,946 participants of the Rotterdam Study, a population-based cohort of unrelated elderly individuals. We assessed 30 gait parameters using an electronic walkway, which yielded seven independent gait domains after principal component analysis. Genotypes of participants were imputed to the 1,000 Genomes reference panel for generating genetic relationship matrices to estimate heritability of gait parameters, and for subsequent genome-wide association scans (GWASs) to identify specific variants. Gait domains with the highest age- and sex-adjusted heritability were Variability (h (2) = 61%), Rhythm (37%), and Tandem (32%). For other gait domains, heritability estimates attenuated after adjustment for height and weight. Genome-wide association scans identified a variant on 1p22.3 that was significantly associated with single support time, a variable from the Rhythm domain (rs72953990; N = 2,946; β [SE] = 0.0069 (0.0012), p = 2.30×10(-8)). This variant did not replicate in an independent sample (N = 362; p = .78). In conclusion, human gait has highly heritable components that are explained by common genetic variation, which are partly attributed to height and weight. Collaborative efforts are needed to identify robust single variant associations for the heritable parameters.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 07/2015; DOI:10.1093/gerona/glv081 · 5.42 Impact Factor
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    ABSTRACT: Background/objectives: Gait is an important health indicator, relating strongly to the risk of falling, morbidity and mortality. In a community-dwelling population, we investigated associations of alcohol, coffee and tobacco consumption with gait. Subjects/methods: Two thousand forty-six non-demented participants from the Rotterdam Study underwent gait assessment by electronic walkway. We measured gait velocity and Global Gait, which is the average of seven gait domains: Rhythm, Phases, Variability, Pace, Tandem, Turning and Base of Support. Alcohol, coffee and tobacco consumption was assessed by questionnaires. With analysis of covariance, we investigated associations of consumption of alcoholic beverages, coffee consumption and smoking with Global Gait, gait velocity and the seven individual gait domains. Results: In all, 81.9% of participants drank alcohol, 92.4% drank coffee, 17.3% were current smokers and 50.9% were past smokers. Moderate alcohol consumption (1-3 glasses per day) associated with better gait, as measured by Global Gait (0.20 standard deviations (s.d.) (95% confidence interval: 0.10; 0.31)), gait velocity (2.65 cm/s (0.80; 4.50)), Rhythm and Variability. Consuming high amounts of coffee (>3 cups per day) associated with better Global Gait (0.18 s.d. (0.08; 0.28)), gait velocity (2.63 cm/s (0.80; 4.45)), Pace, Turning and Variability. Current smoking associated with worse Global Gait (-0.11 s.d. (-0.21; 0.00)), gait velocity (-3.47 cm/s (-5.33; -1.60)), Rhythm and Pace, compared with non-smokers. Conclusions: In a community-dwelling population, consuming >1 cup of coffee and 1-3 glasses of alcohol relate to better gait, whereas smoking is related to worse gait. Further studies are required to evaluate whether interventions targeting substance consumption may aid to prevent or reduce gait deterioration and thereby related health problems.European Journal of Clinical Nutrition advance online publication, 29 July 2015; doi:10.1038/ejcn.2015.120.
    European journal of clinical nutrition 07/2015; DOI:10.1038/ejcn.2015.120 · 2.71 Impact Factor
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    ABSTRACT: Along with the aging population, the public health burden of cerebrovascular disease is increasing. Cerebral small vessel disease and accumulation of brain pathology associate with cognitive decline and can lead to clinical outcomes, such as stroke and dementia. Chronic Obstructive Pulmonary Disease (COPD) is a common respiratory disease among elderly. The quality of life and prognosis of patients with COPD is greatly determined by the presence of comorbidities including stroke and cognitive impairment. Despite the clinical relevance of cerebral small vessel disease, stroke and (vascular) cognitive impairment in patients with COPD, literature is scarce and underlying mechanisms are unknown. The aim of the present review is therefore to summarize current scientific knowledge, to provide a better understanding of the interplay between COPD and the aging brain and to define remaining knowledge gaps. This narrative review article 1) overviews the epidemiology of cerebral small vessel disease, stroke and cognitive impairment in patients with COPD; 2) discusses potential underlying mechanisms including aging, smoking, systemic inflammation, vasculopathy, hypoxia and genetic susceptibility; and 3) highlights areas requiring further research. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Respiratory medicine 07/2015; DOI:10.1016/j.rmed.2015.07.014 · 3.09 Impact Factor
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    ABSTRACT: Cerebral small vessel disease is common in elderly persons. Patients with dementia or stroke frequently have cerebral small vessel disease and often experience disturbances in the sleep-wake rhythm. It is unknown whether cerebral small vessel disease is related to disturbances in sleep and 24-h activity rhythms. This study was conducted in the Rotterdam Study. A total of 970 community-dwelling persons (mean age 59.2 years) underwent brain magnetic resonance imaging and actigraphy. Cerebral small vessel disease was defined as white matter lesions (total volume in millilitres) and the presence of cerebral microbleeds and lacunar infarcts. Twenty-four hour activity rhythms and sleep were measured with actigraphy by estimating the instability and fragmentation of the activity rhythm and total sleep time. Sleep quality was assessed with the Pittsburgh Sleep Quality Index. White matter lesions, instability, fragmentation and sleep quality were standardized for analyses. Higher white matter lesion volume (B = 0.09 per SD, 95% confidence interval 0.02; 0.15) and cerebral microbleeds (B = 0.19 per SD, 95% confidence interval 0.02; 0.37) were significantly related to more fragmented 24-h activity rhythms. None of the small vessel disease markers was related to total sleep time or sleep quality. White matter lesion volume and the presence of cerebral microbleeds are related to disturbed activity rhythms. This suggests that subclinical brain damage affects the 24-h activity rhythm. © 2015 EAN.
    European Journal of Neurology 07/2015; DOI:10.1111/ene.12775 · 4.06 Impact Factor
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    ABSTRACT: Carotid intima media thickness (CIMT) is a marker of subclinical organ damage and predicts cardiovascular disease (CVD) events in the general population. It has also been associated with vascular risk in people with diabetes. However, the association of CIMT change in repeated examinations with subsequent CVD events is uncertain, and its use as a surrogate end point in clinical trials is controversial. We aimed at determining the relation of CIMT change with CVD events in people with diabetes. In a comprehensive meta-analysis of individual participant data, we collated data from 3,902 adults (age 33-92 years) with type 2 diabetes from 21 population-based cohorts. We calculated the hazard ratio (HR) per standard deviation (SD) difference in mean common carotid artery intima media thickness (CCA-IMT) or in CCA-IMT progression, both calculated from two examinations on average 3.6 years apart, for each cohort, and combined the estimates with random-effects meta-analysis. Average mean CCA-IMT ranged from 0.72 to 0.97 mm across cohorts in people with diabetes. The HR of CVD events was 1.22 (95% CI 1.12-1.33) per SD difference in mean CCA-IMT, after adjustment for age, sex, and cardiometabolic risk factors. Average mean CCA-IMT progression in people with diabetes ranged between -0.09 and 0.04 mm/year. The HR per SD difference in mean CCA-IMT progression was 0.99 (0.91-1.08). Despite reproducing the association between CIMT level and vascular risk in subjects with diabetes, we did not find an association between CIMT change and vascular risk. These results do not support the use of CIMT progression as a surrogate end point in clinical trials in people with diabetes. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
    Diabetes care 07/2015; DOI:10.2337/dc14-2732 · 8.42 Impact Factor
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    ABSTRACT: Gait is an important indicator of health. Chronic lower body pain may impair gait and lead to morbidity and mortality. We investigated the associations between lower body pain and gait in community-dwelling individuals, independent from osteoarthritis (OA). This population based cohort study included 2304 Rotterdam Study participants who underwent electronic walkway gait assessment. Thirty different variables resulting from gait assessment were summarized into seven gait domains using principle components analysis: i.e. Rhythm, Variability, Phases, Pace, Tandem, Turning, and Base of Support. Chronic lower body pain was assessed using pain drawings. OA was defined as a Kellgren & Lawrence score of 2 or higher on radiographs of the hip and/or knee. Linear regression analysis was used to study associations. Participants with chronic pain in the leg and hip, had lower Rhythm, Phases, and Pace, independent from OA. Additionally, we found unilateral pain to associate with larger gait asymmetry. No associations were found between chronic pain and the other gait domains, including gait variability. However, within individuals with hip pain, gait variability was higher in individuals with radiographic OA compared to those without OA. This is the first population based study showing chronic lower body pain associates with gait differences independent from OA. Participants with pain were found to walk with slower and smaller steps, longer double support and more asymmetry. Proper care and treatment of chronic pain could be a way of reducing gait problems and thereby fall risk and associated mortality. In addition, gait assessment may help identifying individuals with OA from those having pain due to other causes. Copyright © 2015 Elsevier B.V. All rights reserved.
    Gait & posture 07/2015; DOI:10.1016/j.gaitpost.2015.06.193 · 2.75 Impact Factor
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    ABSTRACT: The association of body mass index (BMI) with mortality remains controversial among the middle-aged and elderly. Moreover, the contribution of other anthropometric measures to predict mortality is unclear. We assessed the association of BMI, waist circumference (WC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR) and a body shape index (ABSI=WC/(BMI(2/3)×height(1/2))) with total, cardiovascular and cancer mortality by using Cox proportion hazard models among 2626 men and 3740 women from the prospective population-based Rotterdam Study. Predictive performance was assessed through informativeness, c-statistic, integrated discrimination improvement (IDI), and continuous net reclassification improvement (cNRI). During 22 years of follow-up, 3675 deaths from all-causes, 1195 from cardiovascular disease, and 873 from cancer occurred. In the multivariable model, ABSI showed a stronger association with mortality compared with BMI, WC, WHtR and WHR. HRs and CIs (95% CIs) for total mortality per 1 SD increase in ABSI were 1.15 (1.09 to 1.21) for men and 1.09 (1.04 to 1.14) for women. For cardiovascular and cancer mortality, these HRs (95% CI) were 1.18 (1.08 to 1.29) and 1.10 (0.99 to 1.22) for men, 1.04 (0.96 to 1.12) and 1.18 (1.07 to 1.30) for women, respectively. The models including ABSI did not increase the c-statistics. Among men, in prediction of total mortality the model including ABSI was more informative (χ(2)=26.4) and provided improvement in risk stratification (IDI 0.003, 95% CI 0.001 to 0.005; cNRI 0.13, 95% CI 0.06 to 0.21). In our population-based study, among different anthropometric measures, ABSI showed a stronger association with total, cardiovascular and cancer mortality. However, the added predictive value of ABSI in prediction of mortality was limited. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Journal of epidemiology and community health 07/2015; DOI:10.1136/jech-2014-205257 · 3.50 Impact Factor
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    ABSTRACT: The question remains whether reduced cerebral blood flow (CBF) leads to brain atrophy or vice versa. We studied the longitudinal relation between CBF and brain volume in a community-dwelling population. In the Rotterdam Study, 3011 participants (mean age 59.6 years (s.d. 8.0)) underwent repeat brain magnetic resonance imaging to quantify brain volume and CBF at two time points. Adjusted linear regression models were used to investigate the bidirectional relation between CBF and brain volume. We found that smaller brain volume at baseline was associated with a steeper decrease in CBF in the whole population (standardized change per s.d. increase of total brain volume (TBV)=0.296 (95% confidence interval (CI) 0.200; 0.393)). Only in persons aged ⩾65 years, a lower CBF at baseline was associated with steeper decline of TBV (standardized change per s.d. increase of CBF=0.003 (95% CI -0.004; 0.010) in the whole population and 0.020 (95% CI 0.004; 0.036) in those aged ⩾65 years of age). Our results indicate that brain atrophy causes CBF to decrease over time, rather than vice versa. Only in persons aged >65 years of age did we find lower CBF to also relate to brain atrophy.Journal of Cerebral Blood Flow & Metabolism advance online publication, 8 July 2015; doi:10.1038/jcbfm.2015.157.
    Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 07/2015; DOI:10.1038/jcbfm.2015.157 · 5.41 Impact Factor
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    ABSTRACT: Many automatic segmentation methods are based on supervised machine learning. Such methods have proven to perform well, on the condition that they are trained on a sufficiently large manually labeled training set that is representative of the images to segment. However, due to differences between scanners, scanning parameters, and patients such a training set may be difficult to obtain. We present a transfer-learning approach to segmentation by multi-feature voxelwise classification. The presented method can be trained using a heterogeneous set of training images that may be obtained with different scanners than the target image. In our approach each training image is given a weight based on the distribution of its voxels in the feature space. These image weights are chosen as to minimize the difference between the weighted probability density function (PDF) of the voxels of the training images and the PDF of the voxels of the target image. The voxels and weights of the training images are then used to train a weighted classifier. We tested our method on three segmentation tasks: brain-tissue segmentation, skull stripping, and white-matter-lesion segmentation. For all three applications, the proposed weighted classifier significantly outperformed an unweighted classifier on all training images, reducing classification errors by up to 42%. For brain-tissue segmentation and skull stripping our method even significantly outperformed the traditional approach of training on representative training images from the same study as the target image. Copyright © 2015 Elsevier B.V. All rights reserved.
    Medical image analysis 07/2015; 24(1):245-254. DOI:10.1016/j.media.2015.06.010 · 3.65 Impact Factor

Publication Stats

7k Citations
2,621.52 Total Impact Points


  • 2006–2015
    • Erasmus Universiteit Rotterdam
      • Department of Epidemiology
      Rotterdam, South Holland, Netherlands
    • Erasmus MC
      • • Department of Neurology
      • • Department of Epidemiology
      Rotterdam, South Holland, Netherlands
  • 2014
    • Medical University of Graz
      • Institute of Molecular Biology and Biochemistry
      Gratz, Styria, Austria
  • 2012
    • University of California, Davis
      Davis, California, United States
    • St George's, University of London
      • Stroke and Dementia Research Centre
      Londinium, England, United Kingdom
    • University Pompeu Fabra
      • Department of Experimental and Health Sciences
      Barcino, Catalonia, Spain
  • 2011–2012
    • Leiden University Medical Centre
      Leyden, South Holland, Netherlands
  • 2010
    • University of Massachusetts Boston
      Boston, Massachusetts, United States