Variation in fibrinogen FGG and FGA genes and risk of stroke: the Rotterdam Study.

Haplotypes of the fibrinogen gamma and alpha (FGG and FGA) genes are associated with the structure of the fibrin network and may therefore influence the risk of stroke. We investigated the relationship between common variation in these genes with ischemic and haemorrhagic stroke. The study was based on 6,275 participants of the prospective population-based Rotterdam Study who at baseline (1990-1993) were aged 55 years or over, free from stroke, and had successful assessment of at least one FGG or FGA single nucleotide polymorphisms (SNP).

Progression of cerebral small vessel disease in relation to risk factors and cognitive consequences: Rotterdam Scan study.

Background And Purpose: Cerebral white matter lesions and lacunar infarcts are small vessel disease-related lesions, which are associated with cognitive decline and dementia. We aimed to assess the relationship between risk factors, effect modifiers, and progression of these lesions. Furthermore, we studied the cognitive consequences of lesion progression.

Ankle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: a meta-analysis.

Context: Prediction models to identify healthy individuals at high risk of cardiovascular disease have limited accuracy. A low ankle brachial index (ABI) is an indicator of atherosclerosis and has the potential to improve prediction.

Objective: To determine if the ABI provides information on the risk of cardiovascular events and mortality independently of the Framingham risk score (FRS) and can improve risk prediction.

Matrix metalloproteinase 3 haplotypes and plasma amyloid beta levels: the Rotterdam Study.

Experimental studies suggest that matrix metalloproteinases (MMPs) are involved in the degradation of amyloid beta (Abeta) protein which plays a key role in the pathogenesis of Alzheimer's disease. Whether MMPs are associated with changes in beta amyloid levels in humans remains unclear. We related common haplotypes within the gene encoding MMP-3 with plasma levels of Abeta(1-40) and Abeta(1-42) in 1621 non-demented participants of the population-based Rotterdam Study.

Total cerebral blood flow in relation to cognitive function: the Rotterdam Scan Study.

Cerebral hypoperfusion has been associated with worse cognitive function. We investigated the association between cerebral blood flow and cognition and whether this association is independent of brain volume. In 892 participants, aged 60 to 91 years, of the population-based Rotterdam Scan study, we measured total cerebral blood flow (tCBF) and brain volume using magnetic resonance imaging.

A benzodiazepine discontinuation programme does not increase the frequency of contacts with the family practice.

Objective: The efficacy of programmes to reduce long-term benzodiazepine use could be compromised by subsequent increases in contacts with the family practice. In this study the hypothesis was tested as to whether participation in a benzodiazepine discontinuation programme affects the frequency of contacts with the family practice.

Design: A controlled stepped-care intervention programme to decrease long-term benzodiazepine use.

Cyclooxygenase selectivity of nonsteroidal anti-inflammatory drugs and risk of stroke.

Background: In clinical trials, cyclooxygenase (COX)-2-selective nonsteroidal anti-inflammatory drugs (NSAIDs) were associated with an increased risk of thromboembolic events. We studied the association between NSAID use and risk of stroke in the prospective, population-based Rotterdam Study.

Methods: We followed 7636 persons free of stroke at baseline (1991-1993) for incident stroke until September 2004.

Brain tissue volumes in relation to cognitive function and risk of dementia.

We investigated in a population-based cohort study the association of global and lobar brain tissue volumes with specific cognitive domains and risk of dementia. Participants (n=490; 60-90 years) were non-demented at baseline (1995-1996). From baseline brain MRI-scans we obtained global and lobar volumes of CSF, GM, normal WM, white matter lesions and hippocampus.

Organic anion transporter 1B1: an important factor in hepatic thyroid hormone and estrogen transport and metabolism.

Sulfation is an important pathway in the metabolism of thyroid hormone and estrogens. Sulfation of estrogens is reversible by estrogen sulfatase, but sulfation of thyroid hormone accelerates its degradation by the type 1 deiodinase in liver. Organic anion transporters (OATPs) are capable of transporting iodothyronine sulfates such as T4 sulfate (T4S), T3S, and rT3S or estrogen sulfates like estrone sulfate (E1S), but the major hepatic transporter for these conjugates has not been identified.

Cerebral microbleeds: accelerated 3D T2*-weighted GRE MR imaging versus conventional 2D T2*-weighted GRE MR imaging for detection.

The purpose of this study was to prospectively compare high-spatial-resolution accelerated three-dimensional (3D) T2*-weighted gradient-recalled-echo (GRE) magnetic resonance (MR) images with conventional two-dimensional (2D) T2*-weighted GRE MR images for the depiction of cerebral microbleeds. After obtaining institutional review board approval and informed consent, 200 elderly participants (age range, 69.7-96.

Measuring cognitive function with age: the influence of selection by health and survival.

Background: Research into the pathophysiology of age-associated cognitive function and decline requires a valid estimate of cognitive function. However, this estimation can be grossly influenced by a selective loss to follow-up.

Methods: We investigated the influence of health selection on the estimated age-associated cognitive function and decline by studying the effect on this estimation of study design and of the handling of multiple and missing data.

History of depression, depressive symptoms, and medial temporal lobe atrophy and the risk of Alzheimer disease.

Background: Depression may increase risk for Alzheimer disease (AD), but it is not clear whether this risk is mediated by structural brain changes. We determined whether history of depressive episodes and presence of depressive symptoms were associated with smaller hippocampal and amygdalar volumes and with increased risk for incident AD.

Methods: Within the Rotterdam Scan Study 503 persons, aged 60-90 years at baseline and without dementia, reported their history of depressive episodes.

Prevalence and risk factors of cerebral microbleeds: the Rotterdam Scan Study.

Background: Cerebral microbleeds are focal deposits of hemosiderin that can be visualized with MRI. Little is known on their prevalence in the general population and on their etiology. It has been suggested that, in analogy to spontaneous intracranial hemorrhage, the etiology of microbleeds differs according to their location in the brain, with lobar microbleeds being caused by cerebral amyloid angiopathy and deep or infratentorial microbleeds resulting from hypertension and atherosclerosis.

Cyclin-dependent kinase 5 is associated with risk for Alzheimer's disease in a Dutch population-based study.

Although the role of the Cdk5 protein in Alzheimer's disease (AD) is well recognized, there have been relatively few studies investigating genetic variants in the CDK5 gene in AD. In this study, we assessed the association between five previously described single nucleotide polymorphisms (SNPs) in the CDK5 gene and late onset AD by means of logistic regression and haplotype association analyses. Including all prevalent and incident AD cases, we found a significantly increased risk of AD for carriers of the GG genotype of SNP rs2069442 (OR = 1.

Interaction between polymorphisms in the renin-angiotensin-system and angiotensin-converting enzyme inhibitor or beta-blocker use and the risk of myocardial infarction and stroke.

This study investigates whether the interaction between angiotensin-converting enzyme (ACE) inhibitors or beta-blockers and the ACE insertion/deletion (I/D) polymorphism or angiotensin receptor II type 1 (AGTR1) 573C/T polymorphism modifies the risk of myocardial infarction (MI) or stroke. In total, 4097 subjects with hypertension were included in this study. The drug-gene interaction on the risk of MI or stroke was determined with a Cox proportional hazard model.

Unrecognized myocardial infarction in relation to risk of dementia and cerebral small vessel disease.

Background And Purpose: Men, but not women, with unrecognized myocardial infarction (MI) have an increased risk of cardiac events and stroke compared with those without MI or with recognized MI. We investigated whether unrecognized MI is also a risk factor for dementia and cerebral small vessel disease (white matter lesions and brain infarction) in 2 population-based cohort studies.

Methods: In the Rotterdam Study, 6347 participants were classified at baseline (1990 to 1993) into those with recognized MI (subdivided into Q-wave and non-Q-wave MI), with unrecognized MI, and without MI based on electrocardiography and interview and were followed for incident dementia (n=613) until January 1, 2005.

Variation in the estrogen receptor alpha gene and risk of stroke: the Rotterdam Study.

Background And Purpose: Variations in the -397T>C (rs2234693) and -351A>G (rs9340799) single nucleotide polymorphisms of the estrogen alpha receptor (ESR1) gene were found to be strongly associated with risk of ischemic heart disease, although not all studies could replicate this finding. One study also reported an association with stroke. We assessed whether variations in the ESR1 gene are associated with the risk of stroke in the general population.

Depressive symptoms and risk of stroke: the Rotterdam Study.

Background: Previous studies that have assessed whether the presence of depressive symptoms predisposes to stroke in the general elderly population have been contradictory. Moreover, they did not distinguish between men and women and did not perform psychiatric workups in those with depressive symptoms. This study examines the association between depressive symptoms, depressive disorder and the risk of stroke in the general population.

The role of craving in relapse after discontinuation of long-term benzodiazepine use.

Objective: Craving for benzodiazepines has never been examined as a factor of relapse after successful benzodiazepine discontinuation. In this study, we examined the predictive value of craving on benzodiazepine relapse.

Method: A stepped-care intervention trial aimed to discontinue long-term benzodiazepine use in general practice.

Incidence and prognosis of transient neurological attacks.

Context: Transient neurological attacks (TNAs) are attacks with temporary (<24 hours) neurological symptoms. These symptoms can be focal, nonfocal, or a mixture of both. The prognostic significance of TNAs with focal symptoms (better known as transient ischemic attacks [TIAs]) is well understood.

Arteriolar oxygen saturation, cerebral blood flow, and retinal vessel diameters. The Rotterdam Study.

Objective: Retinal vessel diameters, in particular larger venular diameters, have been associated with cerebrovascular disease. Larger retinal venular diameters may reflect cerebral ischemia. The authors investigated whether arteriolar oxygen saturation (SaO2) and total cerebral blood flow (CBF), indicators of cerebral oxygen supply, are associated with retinal arteriolar or venular diameters.

Kidney function is related to cerebral small vessel disease.

Background And Purpose: Poor kidney function, as measured by glomerular filtration rate (GFR), is closely associated with presence of glomerular small vessel disease. Given the hemodynamic similarities between the vascular beds of the kidney and the brain, we hypothesized an association between kidney function and markers of cerebral small vessel disease on MRI. We investigated this association in a population-based study of elderly persons.