[Show abstract][Hide abstract] 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.
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.
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.
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
[Show abstract][Hide abstract] 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
= 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
[Show abstract][Hide abstract] 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.
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.
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.
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
[Show abstract][Hide abstract] 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.
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.
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.
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.
[Show abstract][Hide abstract] 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
[Show abstract][Hide abstract] 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.
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).
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.
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
[Show abstract][Hide abstract] 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.
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.
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.
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
[Show abstract][Hide abstract] 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.
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.
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.
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).
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
[Show abstract][Hide abstract] 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
[Show abstract][Hide abstract] 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.
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.
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.
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
[Show abstract][Hide abstract] 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
[Show abstract][Hide abstract] 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