M Arfan Ikram

Erasmus MC, Rotterdam, South Holland, Netherlands

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Publications (182)1716.94 Total impact

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    ABSTRACT: Background and purposeAmino-terminal pro-B-type natriuretic peptide (NT-proBNP) is a predictor of heart disease. It has also been related to stroke, but its association with transient ischaemic attacks (TIAs) is unclear. Moreover, it is unknown how clinical heart disease influences this relation. Within the prospective population-based Rotterdam Study, the association of NT-proBNP with stroke and TIA was examined and the role of heart disease on this association was investigated.MethodsNT-proBNP was measured in 1997–2001 in 5611 participants (mean age 68.7 years; 57.7% women) without a history of stroke, TIA or heart failure. Follow-up for stroke and TIA finished in 2012. Models were adjusted for age and cardiovascular risk factors, and were stratified by sex.ResultsDuring 22 058 person-years 195 men suffered a stroke and 118 a TIA. During 31 825 person-years 230 women suffered a stroke and 187 a TIA. Higher NT-proBNP was associated with a higher risk of stroke in men [hazard ratio (HR) per SD increase 1.50; 95% confidence interval (CI) 1.29–1.76] and in women (HR 1.24; 95% CI 1.05–1.46). Associations with TIA were only present in women (HR 1.51; 95% CI 1.26–1.82) but not in men (HR 1.02; 95% CI 0.83–1.26). Excluding persons with a history of clinical coronary heart disease, heart failure or atrial fibrillation and censoring for clinical heart disease during follow-up did not change the associations.Conclusions Higher NT-proBNP is associated with incident stroke in men and women and with incident TIA only in women. These associations are independent of clinical heart disease preceding cerebrovascular disease.
    European Journal of Neurology 01/2015; · 3.85 Impact Factor
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    ABSTRACT: Background The greatest potential to reduce the burden of stroke is by primary prevention of first-ever stroke, which constitutes three quarters of all stroke. In addition to population-wide prevention strategies (the ‘mass’ approach), the ‘high risk’ approach aims to identify individuals at risk of stroke and to modify their risk factors, and risk, accordingly. Current methods of assessing and modifying stroke risk are difficult to access and implement by the general population, amongst whom most future strokes will arise. To help reduce the burden of stroke on individuals and the population a new app, the Stroke RiskometerTM, has been developed. We aim to explore the validity of the app for predicting the risk of stroke compared with current best methods. Methods 752 stroke outcomes from a sample of 9501 individuals across three countries (New Zealand, Russia and the Netherlands) were utilized to investigate the performance of a novel stroke risk prediction tool algorithm (Stroke RiskometerTM) compared with two established stroke risk score prediction algorithms (Framingham Stroke Risk Score [FSRS] and QStroke). We calculated the receiver operating characteristics (ROC) curves and area under the ROC curve (AUROC) with 95% confidence intervals, Harrels C-statistic and D-statistics for measure of discrimination, R2 statistics to indicate level of variability accounted for by each prediction algorithm, the Hosmer-Lemeshow statistic for calibration, and the sensitivity and specificity of each algorithm. Results The Stroke RiskometerTM performed well against the FSRS five-year AUROC for both males (FSRS = 75·0% (95% CI 72·3%–77·6%), Stroke RiskometerTM = 74·0(95% CI 71·3%–76·7%) and females [FSRS = 70·3% (95% CI 67·9%–72·8%, Stroke RiskometerTM = 71·5% (95% CI 69·0%–73·9%)], and better than QStroke [males – 59·7% (95% CI 57·3%–62·0%) and comparable to females = 71·1% (95% CI 69·0%–73·1%)]. Discriminative ability of all algorithms was low (C-statistic ranging from 0·51–0·56, D-statistic ranging from 0·01–0·12). Hosmer-Lemeshow illustrated that all of the predicted risk scores were not well calibrated with the observed event data (P < 0·006). Conclusions The Stroke RiskometerTM is comparable in performance for stroke prediction with FSRS and QStroke. All three algorithms performed equally poorly in predicting stroke events. The Stroke RiskometerTM will be continually developed and validated to address the need to improve the current stroke risk scoring systems to more accurately predict stroke, particularly by identifying robust ethnic/race ethnicity group and country specific risk factors.
    International Journal of Stroke 01/2015; · 4.03 Impact Factor
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    Jones L, Jean-Charles Lambert, Wang L, Choi S, Harold D, Vedernikov A, Escott-Price V, Stone T, Richards A, Bellenguez C, [......], Launer LJ, Farrer LA, van Duijn CM, Van Broeckhoven C, Ramirez A, Schellenberg GD, Seshadri S, Amouyel P, Williams J, Holmans PA
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    ABSTRACT: BACKGROUND: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. METHODS: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. RESULTS: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 × 10-12 after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 × 10-11), cholesterol transport (P = 2.96 × 10-9), and proteasome-ubiquitin activity (P = 1.34 × 10-6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). CONCLUSIONS: The immune response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
    Alzheimer's and Dementia 12/2014; · 17.47 Impact Factor
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    ABSTRACT: Body mass index (BMI) has been used to simplify cardiovascular risk prediction models by substituting total cholesterol and high-density lipoprotein cholesterol. In the elderly, the ability of BMI as a predictor of cardiovascular disease (CVD) declines. We aimed to find the most predictive anthropometric measure for CVD risk to construct a non-laboratory-based model and to compare it with the model including laboratory measurements. The study included 2675 women and 1902 men aged 55-79 years from the prospective population-based Rotterdam Study. We used Cox proportional hazard regression analysis to evaluate the association of BMI, waist circumference, waist-to-hip ratio and a body shape index (ABSI) with CVD, including coronary heart disease and stroke. The performance of the laboratory-based and non-laboratory-based models was evaluated by studying the discrimination, calibration, correlation and risk agreement. Among men, ABSI was the most informative measure associated with CVD, therefore ABSI was used to construct the non-laboratory-based model. Discrimination of the non-laboratory-based model was not different than laboratory-based model (c-statistic: 0.680-vs-0.683, p=0.71); both models were well calibrated (15.3% observed CVD risk vs 16.9% and 17.0% predicted CVD risks by the non-laboratory-based and laboratory-based models, respectively) and Spearman rank correlation and the agreement between non-laboratory-based and laboratory-based models were 0.89 and 91.7%, respectively. Among women, none of the anthropometric measures were independently associated with CVD. Among middle-aged and elderly where the ability of BMI to predict CVD declines, the non-laboratory-based model, based on ABSI, could predict CVD risk as accurately as the laboratory-based model among men. 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.
    Heart (British Cardiac Society) 12/2014; · 6.02 Impact Factor
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    ABSTRACT: Persons with cognitive impairment, as assessed by cognitive tests, are at a higher risk of stroke. Subjective memory complaints might be an earlier marker for stroke, especially in persons with higher education. Their cognitive reserve might mask their cognitive impairment during cognitive testing. In a population-based setting, we investigated the association between subjective memory complaints and stroke. We simultaneously investigated the association between Mini-Mental State Examination and stroke. We also assessed whether these associations varied with educational level. 9152 participants from the Rotterdam Study (baseline 1990-1993 or 2000-2001) completed the subjective memory complaints questionnaire and underwent Mini-Mental State Examination assessment. Subsequently, the entire cohort was followed for incident stroke until 2012. We used Cox proportional hazard models to estimate the associations between subjective memory complaints and Mini-Mental State Examination, with stroke. During a follow-up of 111 593 person years, 1134 strokes were identified, of which 663 were ischemic and 99 hemorrhagic. In the fully adjusted model, presence of subjective memory complaints was independently associated with a higher risk of stroke (hazard ratio, 1.20; 95% confidence interval, 1.04-1.39), but a higher Mini-Mental State Examination was not (hazard ratio per point increase, 0.99; 95% confidence interval, 0.95-1.02). The association between subjective memory complaints and risk of stroke was modified by educational level, with a higher risk of stroke in persons with a higher level of education (hazard ratio, 1.39; 95% confidence interval, 1.07-1.81). Subjective memory complaints might be an early indicator of stroke risk, especially in highly educated individuals. © 2014 American Heart Association, Inc.
    Stroke 12/2014; 46(1). · 6.02 Impact Factor
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    ABSTRACT: Left-sided strokes are reported to be more common than right-sided strokes, but it is unknown whether they occur more often or are simply recognized more easily by clinicians. In a large unselected community-dwelling population, we examined the frequency of clinical left- and right-sided strokes and transient ischemic attacks (TIAs) and compared it with the frequency of left- and right-sided infarcts on MRI. This study was conducted within the population-based Rotterdam Study. Between 1990 and 2012, 13 894 participants were followed up for first-ever stroke and TIA. MRI scans were performed within a random subgroup of 5081 persons and were rated for the presence of supratentorial cortical and lacunar infarcts. We compared frequencies of left- and right-sided strokes, TIAs, or MRI infarcts using binomial and Fisher exact tests. After a mean follow-up of 9.6 (±6.0) years, 1252 patients had a stroke, of which 704 were ischemic, and 799 participants had a TIA. Within the subgroup with MRI, we identified 673 infarcts. Ischemic strokes were more frequently left-sided (57.7%; 95% confidence interval, 53.7-61.6) than right-sided, similar to TIAs (57.8% left-sided; 53.4-62.3). In contrast, we found no left-right difference in distribution of infarcts on MRI (51.9% left-sided; 48.1-55.6). Clinical ischemic strokes and TIAs are more frequently left-sided than right-sided, whereas this difference is not present for infarcts on MRI. This suggests that left-sided strokes and TIAs are more easily recognized. Consequently, there should be more attention for symptoms of right-sided strokes and TIAs. © 2014 American Heart Association, Inc.
    Stroke 12/2014; 46(1). · 6.02 Impact Factor
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    Renée Fag de Bruijn, M Arfan Ikram
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    ABSTRACT: Alzheimer's disease (AD) is the most common neurodegenerative disorder in elderly people, but there are still no curative options. Senile plaques and neurofibrillary tangles are considered hallmarks of AD, but cerebrovascular pathology is also common. In this review, we summarize findings on cardiovascular disease (CVD) and risk factors in the etiology of AD. Firstly, we discuss the association of clinical CVD (such as stroke and heart disease) and AD. Secondly, we summarize the relation between imaging makers of pre-clinical vascular disease and AD. Lastly, we discuss the association of cardiovascular risk factors and AD. We discuss both established cardiovascular risk factors and emerging putative risk factors, which exert their effect partly via CVD.
    BMC Medicine 12/2014; 12(1):130. · 7.28 Impact Factor
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    ABSTRACT: Objectives Anxiety and depression frequently co-occur in the elderly and in patients with dementia. Prior research has shown that depression is related to the risk of dementia, but the effect of anxiety on dementia remains unclear. We studied whether anxiety symptoms and anxiety disorders are associated with the risk of dementia and cognition. Design: prospective cohort study. Setting: population-based Rotterdam Study. Participants 2,708 non-demented participants who underwent the Hospital Anxiety and Depression Scale (HADS) (sample I, baseline 1993-1995) and 3,069 non-demented participants who underwent screening for anxiety disorders (sample II, baseline 2002-2004). Measure ments: In 1993-1995, anxiety symptoms were assessed using the HADS. In 2002-2004, anxiety disorders were assessed using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. In both study samples, participants were continuously monitored for dementia until January 1, 2011. Cognition was tested in 2002-2004 and at a follow-up visit in 2009-2011 in sample II only. Results In sample I, 358 persons developed dementia and in sample II, 248 persons developed dementia. We did not find an association with the risk of dementia for anxiety symptoms (hazard ratio (HR) 1.05, 95%-confidence interval (CI) 0.77; 1.43, Wald-statistic 0.08, p-value 0.77, degrees of freedom (df) 1) or for anxiety disorders (HR 0.92, 95%-CI 0.58; 1.45, Wald-statistic 0.14, p-value 0.71, df 1). We could demonstrate an association of anxiety disorders with poor cognition cross-sectionally, but this attenuated after additional adjustments. Conclusions Our findings do not offer evidence for an association between anxiety symptoms or anxiety disorders with the risk of dementia or with cognition. This suggests that anxiety is not a risk factor nor a prodrome of dementia in an elderly, community-dwelling population.
    The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 12/2014; · 3.35 Impact Factor
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    ABSTRACT: Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/100,000 per year)1. Minor cervical traumas, infection, migraine and hypertension are putative risk factors1, 2, 3, and inverse associations with obesity and hypercholesterolemia are described3, 4. No confirmed genetic susceptibility factors have been identified using candidate gene approaches5. We performed genome-wide association studies (GWAS) in 1,393 CeAD cases and 14,416 controls. The rs9349379[G] allele (PHACTR1) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69–0.82; P = 4.46 × 10−10), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 × 10−3; combined P = 1.00 × 10−11). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction6, 7, 8, 9. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions.
    Nature Genetics 11/2014; · 29.65 Impact Factor
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    ABSTRACT: Large-scale epidemiological evidence on the role of inflammation in early atherosclerosis, assessed by carotid ultrasound, is lacking. We aimed to quantify cross-sectional and longitudinal associations of inflammatory markers with common-carotid-artery intima-media thickness (CCA-IMT) in the general population. Information on high-sensitivity C-reactive protein, fibrinogen, leucocyte count and CCA-IMT was available in 20 prospective cohort studies of the PROG-IMT collaboration involving 49,097 participants free of pre-existing cardiovascular disease. Estimates of associations were calculated within each study and then combined using random-effects meta-analyses. Mean baseline CCA-IMT amounted to 0.74 mm (SD = 0.18) and mean CCA-IMT progression over a mean of 3.9 years to 0.011 mm/year (SD = 0.039). Cross-sectional analyses showed positive linear associations between inflammatory markers and baseline CCA-IMT. After adjustment for traditional cardiovascular risk factors, mean differences in baseline CCA-IMT per one-SD higher inflammatory marker were: 0.0082 mm for high-sensitivity C-reactive protein (p < 0.001); 0.0072 mm for fibrinogen (p < 0.001); and 0.0025 mm for leucocyte count (p = 0.033). 'Inflammatory load', defined as the number of elevated inflammatory markers (i.e. in upper two quintiles), showed a positive linear association with baseline CCA-IMT (p < 0.001). Longitudinal associations of baseline inflammatory markers and changes therein with CCA-IMT progression were null or at most weak. Participants with the highest 'inflammatory load' had a greater CCA-IMT progression (p = 0.015). Inflammation was independently associated with CCA-IMT cross-sectionally. The lack of clear associations with CCA-IMT progression may be explained by imprecision in its assessment within a limited time period. Our findings for 'inflammatory load' suggest important combined effects of the three inflammatory markers on early atherosclerosis. © The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
    European Journal of Preventive Cardiology 11/2014; · 2.68 Impact Factor
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    ABSTRACT: To evaluate differences in first manifestations of cardiovascular disease between men and women in a competing risks framework. Prospective population based cohort study. People living in the community in Rotterdam, the Netherlands. 8419 participants (60.9% women) aged ≥55 and free from cardiovascular disease at baseline. First diagnosis of coronary heart disease (myocardial infarction, revascularisation, and coronary death), cerebrovascular disease (stroke, transient ischaemic attack, and carotid revascularisation), heart failure, or other cardiovascular death; or death from non-cardiovascular causes. Data were used to calculate lifetime risks of cardiovascular disease and its first incident manifestations adjusted for competing non-cardiovascular death. During follow-up of up to 20.1 years, 2888 participants developed cardiovascular disease (826 coronary heart disease, 1198 cerebrovascular disease, 762 heart failure, and 102 other cardiovascular death). At age 55, overall lifetime risks of cardiovascular disease were 67.1% (95% confidence interval 64.7% to 69.5%) for men and 66.4% (64.2% to 68.7%) for women. Lifetime risks of first incident manifestations of cardiovascular disease in men were 27.2% (24.1% to 30.3%) for coronary heart disease, 22.8% (20.4% to 25.1%) for cerebrovascular disease, 14.9% (13.3% to 16.6%) for heart failure, and 2.3% (1.6% to 2.9%) for other deaths from cardiovascular disease. For women the figures were 16.9% (13.5% to 20.4%), 29.8% (27.7% to 31.9%), 17.5% (15.9% to 19.2%), and 2.1% (1.6% to 2.7%), respectively. Differences in the number of events that developed over the lifespan in women compared with men (per 1000) were -7 for any cardiovascular disease, -102 for coronary heart disease, 70 for cerebrovascular disease, 26 for heart failure, and -1 for other cardiovascular death; all outcomes manifested at a higher age in women. Patterns were similar when analyses were restricted to hard atherosclerotic cardiovascular disease outcomes, but absolute risk differences between men and women were attenuated for both coronary heart disease and stroke. At age 55, though men and women have similar lifetime risks of cardiovascular disease, there are considerable differences in the first manifestation. Men are more likely to develop coronary heart disease as a first event, while women are more likely to have cerebrovascular disease or heart failure as their first event, although these manifestations appear most often at older ages. © Leening et al 2014.
    BMJ Clinical Research 11/2014; 349:g5992. · 14.09 Impact Factor
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    ABSTRACT: The variation between images obtained with different scanners or different imaging protocols presents a major challenge in automatic segmentation of biomedical images. This variation especially hampers the application of otherwise successful supervised-learning techniques which, in order to perform well, often require a large amount of labeled training data that is exactly representative of the target data. We therefore propose to use transfer learning for image segmentation. Transfer-learning techniques can cope with differences in distributions between training and target data, and therefore may improve performance over supervised learning for segmentation across scanners and scan protocols. We present four transfer classifiers that can train a classification scheme with only a small amount of representative training data, in addition to a larger amount of other training data with slightly different characteristics. The performance of the four transfer classifiers was compared to that of standard supervised classification on two MRI brain-segmentation tasks with multi-site data: white matter, gray matter, and CSF segmentation; and white-matter- /MS-lesion segmentation. The experiments showed that when there is only a small amount of representative training data available, transfer learning can greatly outperform common supervised-learning approaches, minimizing classification errors by up to 60%.
    IEEE Transactions on Medical Imaging 11/2014; · 3.80 Impact Factor
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    ABSTRACT: Background. Several psychosocial risk factors for complicated grief have been described. However, the association of complicated grief with cognitive and biological risk factors is unclear. The present study examined whether complicated grief and normal grief are related to cognitive performance or structural brain volumes in a large population-based study. Method. The present research comprised cross-sectional analyses embedded in the Rotterdam Study. The study included 5501 non-demented persons. Participants were classified as experiencing no grief (n = 4731), normal grief (n = 615) or complicated grief (n = 155) as assessed with the Inventory of Complicated Grief. All persons underwent cognitive testing (Mini-Mental State Examination, Letter-Digit Substitution Test, Stroop Test, Word Fluency Task, word learning test - immediate and delayed recall), and magnetic resonance imaging to measure general brain parameters (white matter, gray matter), and white matter lesions. Total brain volume was defined as the sum of gray matter plus normal white matter and white matter lesion volume. Persons with depressive disorders were excluded and analyses were adjusted for depressive symptoms. Results. Compared with no-grief participants, participants with complicated grief had lower scores for the Letter-Digit Substitution Test [Z-score -0.16 v. 0.04, 95% confidence interval (CI) -0.36 to -0.04, p = 0.01] and Word Fluency Task (Z-score -0.15 v. 0.03, 95% CI -0.35 to -0.02, p = 0.02) and smaller total volumes of brain matter (933.53 ml v. 952.42 ml, 95% CI -37.6 to -0.10, p = 0.04). Conclusions. Participants with complicated grief performed poorly in cognitive tests and had a smaller total brain volume. Although the effect sizes were small, these findings suggest that there may be a neurological correlate of complicated grief, but not of normal grief, in the general population.
    Psychological Medicine 11/2014; · 5.43 Impact Factor
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    ABSTRACT: Inflammation plays a key role in atherosclerosis. We hypothesized that novel inflammatory markers may predict the risk of coronary heart disease (CHD).
    Arteriosclerosis Thrombosis and Vascular Biology 10/2014; · 5.53 Impact Factor
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    ABSTRACT: It remains undetermined whether the use of coumarin anticoagulants associates with cerebral microbleeds in the general population. We investigated whether (1) coumarin use relates to higher prevalence and incidence of microbleeds, (2) microbleeds are more frequent in people with higher maximum international normalized ratios (INRs), and (3) among coumarin users, variability in INR associates with microbleed presence.
    Stroke 10/2014; 45(11). · 6.02 Impact Factor
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    ABSTRACT: We examined whether consumption of total dairy and dairy subgroups was related to incident stroke and coronary heart disease (CHD) in a general older Dutch population.
    European Journal of Nutrition 10/2014; · 3.84 Impact Factor
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    ABSTRACT: Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91 462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log10Bayes factor (BF)>5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P<5 × 10(-8)).Our genetic findings among European and African-American adults reinforce the role of caffeine in mediating habitual coffee consumption and may point to molecular mechanisms underlying inter-individual variability in pharmacological and health effects of coffee.Molecular Psychiatry advance online publication, 7 October 2014; doi:10.1038/mp.2014.107.
    Molecular Psychiatry 10/2014; · 15.15 Impact Factor
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    ABSTRACT: Observations that migraine increases risk of cardiovascular disease and ischemic brain changes may suggest sustained vascular differences between migraineurs and controls. In a population-based setting, we compared cerebral blood flow between migraineurs in the attack-free period and controls.
    Cephalalgia 10/2014; · 4.12 Impact Factor
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    ABSTRACT: Background Whether depression is a long-term risk factor for dementia or represents a dementia prodrome is unclear. Therefore, we examined the relationship between depressive symptoms and dementia during short and long follow-up in a population-based cohort. Methods In the Rotterdam Study, 4393 nondemented individuals were followed for incident dementia for 13.7 years by continuous monitoring. Cox proportional hazards models for different time intervals were used to estimate the risk of incident dementia. Results Five-hundred eighty-two participants developed dementia during 13.7 years. Persons with depressive symptoms had an 8% increased risk of dementia compared with those without depressive symptoms during the overall follow-up. The risk was highest in the short and intermediate follow-up, particularly in men. We did not find an association in the follow-up period beyond 10 years. Conclusion Our results suggest that late-life depressive symptoms are part of a dementia prodrome rather than an independent risk factor of dementia.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 10/2014; · 14.48 Impact Factor
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    ABSTRACT: In a population-based study of 1,912 community-dwelling persons of 45 years and older, we investigated the relation between age and fine motor skills using the Archimedes spiral-drawing test. Also, we studied the effect of brain volume on fine motor skills.
    Frontiers in Aging Neuroscience 09/2014; 6:259. · 2.84 Impact Factor

Publication Stats

4k Citations
1,716.94 Total Impact Points

Institutions

  • 2006–2014
    • Erasmus MC
      • • Department of Epidemiology
      • • Research Group for Public Health
      Rotterdam, South Holland, Netherlands
  • 2013
    • Delft University of Technology
      Delft, South Holland, Netherlands
    • Medical University of Graz
      • Institute of Molecular Biology and Biochemistry
      Gratz, Styria, Austria
  • 2011
    • Erasmus Universiteit Rotterdam
      • Department of Epidemiology
      Rotterdam, South Holland, Netherlands
  • 2010
    • University of Massachusetts Boston
      Boston, Massachusetts, United States