Showing papers by "Peter J. Koudstaal published in 2008"

Progression of Cerebral Small Vessel Disease in Relation to Risk Factors and Cognitive Consequences. Rotterdam Scan Study

Abstract: 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. Methods— Six hundred sixty-eight people, aged 60 to 90 years, underwent repeated MRI scanning and neuropsychological testing within 3-year follow-up. We rated incident lacunar infarcts and change in periventricular and subcortical white matter lesion severity with a semiquantitative scale. We assessed the relationships between age, sex, baseline lesion load, risk factors, lesion progression, and change in cognitive function by multivariate regression analyses and additional stratified analyses. Results— Baseline lesion load, higher age, high blood pressure, and current smoking were independently associated with progression of white matter lesions. Women...

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

Abstract: 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. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale. Volumetric assessment of the hippocampus and amygdala was performed using three-dimensional MRI. All subjects were followed for an average of 6 years for development of AD, diagnosed according to National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association criteria. Results: A total of 134 subjects (26.6%) reported a history of depression (88 reported an onset Conclusion: History of depression, and particularly an early onset, but not presence of depressive symptoms increased the risk for Alzheimer disease. This risk was not mediated by smaller hippocampal or amygdalar volumes.

Prestroke Cognitive Performance, Incident Stroke, and Risk of Dementia The Rotterdam Study

Abstract: Background and Purpose— Several studies indicate that stroke increases the risk of dementia. Most of these studies lacked the ability to take accurately assessed prestroke cognitive function into account. Whether the effects of stroke merely unravel an ongoing underlying dementing process or in fact cause the dementia has implications for the prevention of dementia in persons with cerebrovascular disease. We explored in a prospective cohort study whether stroke occurrence was related to a higher risk of subsequent dementia and whether this association was dependent on prestroke slope of cognitive function. Methods— Cox proportional hazard models were used to relate incident stroke as a time-varying exposure with the risk of dementia in 6724 participants of the Rotterdam Study without dementia or stroke at baseline (49 361 person years of follow-up). Subsequently Cox proportional hazard models were performed to assess whether this association was dependent on slope of prestroke cognitive performance and ot...

Inadequate Acoustical Temporal Bone Window in Patients with a Transient Ischemic Attack or Minor Stroke: Role of Skull Thickness and Bone Density

Abstract: Transcranial Doppler (TCD) ultrasonography may provide important diagnostic and prognostic information in patients with ischemic stroke or transient ischemic attack. TCD also enhances the effect of thrombolytic treatment in patients with acute stroke. In some patients, especially elderly women, TCD cannot be performed because of temporal bone window failure (WF). We investigated whether skull thickness or bone density on computed tomography scans predicts WF. In 182 patients with a transient ischemic attack or minor ischemic stroke, skull thickness and bone density measurements were made at the level of the temporal bone window. Multiple logistic regression analysis was used to relate independent variables to WF and to adjust the estimates for possible confounding factors. TCD signals were absent on the symptomatic side in 22 female and 11 male patients (18%). Both skull thickness and radiodensity at the level of the temporal bone window were strongly related to WF as well as age and female gender. After adjustment according to age and gender, skull thickness at the temporal bone window was an independent prognostic factor of WF (odds ratio [OR]: 2.3 per mm increase in skull thickness, 95% confidence interval [CI]: 1.4 to 3.8). Radiodensity of the temporal bone decreased with age in women (-52 HU per 10 y over 50 y of age, 95% CI: -73 to -30) but in men (-10 HU per 10 y over 50 y of age, 95% CI: -33 to 13), no statistically significant association was observed. We computed probabilities of WF for each patient individually. With a probability cut point of 50%, 33% of the patients with WF and 97% of the patient without WF were correctly identified. The area under the receiver operating characteristic (ROC) curve of this simple prediction model including age, gender and skull thickness was 0.88; the area under the ROC curve of a gender-stratified model including age, skull thickness and radiodensity was 0.90. This difference was not statistically or clinically significant p = 0.13). WF is more common in women because density of the temporal bone in elderly women is low. Absence of WF can be predicted by a combination of three simple parameters: skull thickness, age and gender. This may help to select patients with ischemic stroke for diagnostic TCD screening and to facilitate targeted delivery of ultrasound-enhanced thrombolysis.

Unrecognized Myocardial Infarction in Relation to Risk of Dementia and Cerebral Small Vessel Disease

Abstract: 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 In the Rotterdam Scan Study, 436 nondemented persons were similarly classified based on electrocardiography and interview and underwent brain MRI for the assessment of white matter lesions and brain infarction RESULTS: In men, unrecognized MI was associated with an increased risk of dementia (compared with men without MI hazard ratio, 214; 95% CI, 137 to 335) and with more white matter lesions and more often brain infarction on MRI In women, no associations were found with unrecognized MI Recognized MI was not associated with the risk of dementia in either sex Men, but not women, with recognized MI had more often any brain infarction or asymptomatic brain infarction, especially if they had Q-wave MI No consistent associations were found between recognized Q-wave or non-Q-wave MI and severity of white matter lesions Additional adjustment for cardiovascular risk factors did not change the results CONCLUSIONS: Men with unrecognized MI have an increased risk of dementia and more cerebral small vessel disease

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

Abstract: 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. Data on all filled prescriptions came from pharmacy records. With Cox regression models, we calculated crude and adjusted hazard ratios (HRs) of stroke for time-dependent current use, compared with never use, of NSAIDs grouped according to COX selectivity (COX-1 selective, nonselective, and COX-2 selective) and individual NSAIDs. Results: At baseline, the mean age of the study sample was 70.2 years, and 61.3% were female. During 70 063 person-years of follow-up (mean, 9.2 years), 807 persons developed a stroke (460 ischemic, 74 hemorrhagic, and 273 unspecified). Current users of nonselective (HR, 1.72; 95% confidence interval [CI], 1.22-2.44) and COX-2-selective (HR, 2.75; 95% CI, 1.28-5.95) NSAIDs had a greater risk of stroke, but not users of COX-1-selective NSAIDs (HR, 1.10; 95% CI, 0.41-2.97). Hazard ratios (95% CIs) for ischemic stroke were 1.68 (1.05-2.69) for nonselective and 4.54 (2.06-9.98) for COX-2-selective NSAIDs. For individual NSAIDs, current use of the nonselective naproxen (HR, 2.63; 95% CI, 1.47-4.72) and the COX-2-selective rofecoxib (HR, 3.38; 95% CI, 1.48-7.74) was associated with a greater risk of stroke. Hazard ratios (95% CIs) for diclofenac (1.60 [1.00-2.57]), ibuprofen (1.47 [0.73-3.00]), and celecoxib (3.79 [0.52-27.6]) were greater than 1.00 but were not statistically significant. Conclusions: In the general population, we found a greater risk of stroke with current use of nonselective and COX-2-selective NSAIDs. The risk of stroke was not limited to the use of COX-2-selective NSAIDs.

Depressive Symptoms and Risk of Stroke: The Rotterdam Study

Abstract: 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. Methods: This prospective population based cohort study included 4424 participants from the third Rotterdam Study Survey (1997–1999) who, at that time, were >61 years of age and free from stroke. Depressive symptoms were assessed using the Centre for Epidemiological Studies Depression Scale (CESD) and considered present if the CESD score was >16. Participants with depressive symptoms had a diagnostic interview for depressive disorder. Follow-up was complete until 1 January 2005. Data were analysed using Cox proportional hazards models with adjustment for relevant confounders. Results: Men with depressive symptoms (n = 73) were at increased risk of stroke (adjusted hazard ratio (HR) 2.17; 95% CI 1.11 to 4.23) and ischaemic stroke (adjusted HR 3.21; 95% CI 1.62 to 6.38). These associations were at least partly attributable to men who reported depressive symptoms but who did not fulfil Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV diagnostic criteria for depressive disorder (n = 32): they had a very high risk of stroke (adjusted HR 2.70; 95% CI 1.15 to 6.33) and ischaemic stroke (adjusted HR 4.01; 95% CI 1.68 to 9.57). In women there was no association between presence of depressive symptoms and risk of stroke. Conclusions: Presence of depressive symptoms is a strong risk factor for stroke in men but not in women. It was noted in the early 1970s that elderly patients with depressive disorder had a higher vascular disease burden than those without depressive disorder. 1 This observation evolved into the vascular depression hypothesis, which assumes that depressive disorder can be caused by otherwise subclinical cerebrovascular disease.

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

Abstract: Background and Purpose— Variations in the −397T>C (rs2234693) and −351A>G (rs9340799) single nucleotide polymorphisms of the estrogen α 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. Methods— This prospective population-based study was based on 6229 Rotterdam Study participants who at baseline (1990–1993) were aged 55 years or older, free from stroke, and had assessment of the ESR1 rs2234693 and rs9340799 single nucleotide polymorphisms. Follow-up for incident stroke was complete until January 1, 2005. Data were analyzed with Cox proportional hazards models for men and women separately with adjustment for age. Results— During an average follow-up time of 10.1 years, 659 strokes occurred, of which 386 were ischemic. Three common haplotypes we...

Long-term occurrence of death and cardiovascular events in patients with transient ischaemic attack or minor ischaemic stroke: comparison between arterial and cardiac source of the index event

Abstract: Background and aim: Published data suggest that patients with cerebral ischaemia and atrial fibrillation (CIAF) have higher inhospital mortality than patients with cerebral ischaemia of arterial origin (CIAO). Data on long term risks are scarce. We compared the long term risks of death and vascular events (VE) between these groups. Methods: We extended the follow-up of 2473 patients from the Dutch TIA Trial (recruitment March 1986 to March 1989, all treated with aspirin; CIAO) and 186 Dutch participants of the European Atrial Fibrillation Trial (recruitment June 1988 to May 1992, 26% on anticoagulants during the trial; CIAF). Hazard ratios (HRs) for death and VE of CIAF versus CIAO were analysed by means of Cox regression analysis and adjusted for age, sex and several cardiovascular risk factors. Results: After a mean follow-up of 10.1 years, 1484 patients with CIAO had died and 1336 had suffered at least one VE (377 cardiac, 455 stroke). Mean follow-up of the CIAF patients was 6.8 years; 150 patients had died and 136 had suffered at least one VE (41 cardiac, 63 stroke). Adjusted HRs (CIAF vs CIAO) were 1.46 (95% CI 1.22 to 1.74) for death, 1.49 (1.24 to 1.79) for first VE, 1.94 (1.47 to 2.55) for first stroke and 1.41 (1.01 to 1.96) for first cardiac event. These HRs were essentially the same as those for the duration of the trials. Conclusion: Our study shows that the long term risk of death or vascular events is 1.5 times higher in patients with CIAF than in those with CIAO, after adjustment for differences between the groups.

Risk indicators for development of headache during dipyridamole treatment after cerebral Ischaemia of arterial origin

Abstract: A considerable proportion of patients discontinue dipyridamole therapy because of headache. Risk indicators for the development of dipyridamole induced headache were identified by means of an exploratory analysis of data from the European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) and the Second European Stroke Prevention Study (ESPS 2). In ESPRIT, dipyridamole induced headache was significantly associated with female sex, absence of hypertension and non-smoking (area under the receiver operator characteristic (ROC) curve 0.63 (95% CI 0.58 to 0.68)) and in ESPS 2 with female sex and absence of ischaemic lesions on imaging (area under the ROC curve 0.64 (95% CI 0.59 to 0.69)).

Haplotypes of the fibrinogen gene and cerebral small vessel disease: the Rotterdam scan study

Abstract: Objective: Fibrinogen levels and fibrinogen clot structure have been implicated in the pathogenesis of vascular disease. We examined fibrinogen levels and variation in fibrinogen genes (fibrinogen γ (FGG), α (FGA) and β (FGB)), which have been associated with fibrin clot structure and fibrinogen levels, in relation to cerebral small vessel disease (SVD). Methods and results: This study was performed as part of the Rotterdam Scan Study, a population based study in 1077 elderly patients undergoing cerebral MRI. Plasma fibrinogen levels and haplotypes were determined. We examined the association between fibrinogen levels and haplotype with silent brain infarcts and white matter lesions using logistic regression models. We constructed seven haplotypes (frequency >0.01) that describe the total common variation in the FGG and FGA genes. Haplotype 2 (G A T A GT G ) was associated with the presence of silent brain infarcts compared with the most frequent haplotype (GGTGGTA) (OR 1.41, 95% CI 1.03 to 1.94). Haplotype 3 (GG C G A TA) was associated with periventricular white matter lesions in the highest tertile of the distribution (OR 1.40, 95% CI 1.01 to 1.92). No association was found between plasma fibrinogen levels and SVD. Conclusions: Our study provides evidence for an association of common variation in the FGG and FGA genes with cerebral SVD. It is possible that the structure of the fibrin clot rather than plasma fibrinogen levels plays a role in the pathogenesis of cerebral SVD.

Relation Between Aspirin Dose, All-Cause Mortality, and Bleeding in Patients With Recent Cerebrovascular or Coronary Ischemic Events (from the BRAVO Trial)

Abstract: Despite aspirin's established role in the treatment of atherosclerotic vascular disease, considerable controversy exists regarding its most effective dosing strategy. In a retrospective observational study, we examined the relation between prescribed aspirin dose (

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

Abstract: 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). Common haplotypes were estimated using seven tagging SNPs across a 30 kb region containing the FGG and FGA genes. Follow-up for incident stroke was complete until January 1, 2005. Associations between constructed haplotypes and risk of stroke were estimated with an age- and sex-adjusted logistic regression model. We observed 668 strokes, of which 393 were ischemic and 62 haemorrhagic, during a median follow-up time of 10.1 years. FGG+FGA haplotype 3 (H3) was associated with an increased risk of ischemic stroke (odds ratio [OR] 1.36, 95% confidence interval [CI] 1.09–1.69) and the risk estimate for hemorrhagic stroke was 0.71 (95% CI 0.46–1.09) compared to the most frequent H1. The FGG and FGA genes were not associated with stroke or its subtypes when analyzed separately. In conclusion, risk of ischemic stroke was higher in FGG+FGA H3 than in H1. The results suggested that an opposite association may exist for haemorrhagic stroke.

Assessment of feasibility of endovascular treatment of ruptured intracranial aneurysms with 16-detector row CT angiography.

Abstract: Background: It is unclear whether 16-detector row CT angiography (CTA) can replace digital subtraction angiography (DSA) to assess the feasibility of endovascular treatment (EVT) in

Methodological Quality and Publication Bias in Observational Studies on Risk of Rupture of Unruptured Intracranial Aneurysms

Abstract: To the Editor: We would like to comment on some aspects of the very interesting updated meta-analysis on risk of rupture of unruptured intracranial aneurysms by Wermer and colleagues.1 First, with regard to the assessment of methodological quality of the included studies, the authors have rated studies as “good” when they fulfilled 3 criteria with regard to design, completeness of follow-up and certainty of diagnosis of subarachnoid hemorrhage. Several other studies have stressed that accounting for confounders …

Depressive symptoms and risk of stroke : the Rotterdam Study. Commentary

Abstract: 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. Methods: This prospective population based cohort study included 4424 participants from the third Rotterdam Study Survey (1997-1999) who, at that time, were ≥61 years of age and free from stroke. Depressive symptoms were assessed using the Centre for Epidemiological Studies Depression Scale (CESD) and considered present if the CESD score was ≥16. Participants with depressive symptoms had a diagnostic interview for depressive disorder. Follow-up was complete until 1 January 2005. Data were analysed using Cox proportional hazards models with adjustment for relevant confounders. Results: Men with depressive symptoms (n = 73) were at increased risk of stroke (adjusted hazard ratio (HR) 2.17; 95% Cl 1.11 to 4.23) and ischaemic stroke (adjusted HR 3.21; 95% Cl 1.62 to 6.38). These associations were at least partly attributable to men who reported depressive symptoms but who did not fulfil Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV diagnostic criteria for depressive disorder (n = 32): they had a very high risk of stroke (adjusted HR 2.70; 95% Cl 1.15 to 6.33) and ischaemic stroke (adjusted HR 4.01; 95% Cl 1.68 to 9.57). In women there was no association between presence of depressive symptoms and risk of stroke. Conclusions: Presence of depressive symptoms is a strong risk factor for stroke in men but not in women.

Response to Letter by Markoula et al

Abstract: Response: We have read with interest the results presented in Lazaros et al1 and discussed by Markoula et al2 on the relationship between risk of stroke and the genetic variations in the estrogen receptor α (ESR1), commonly known as the PvuII (−397T>C; rs2234693) and XbaI (−351A>G; rs9340799) polymorphisms. In correspondence with our findings3 they observed no such relationship in their primary analysis of 130 ischemic stroke patients versus 240 healthy age-matched controls. However, on additional analysis in smaller subgroups the authors report an association between the −351 (XbaI) A variant and earlier age at onset of stroke in males, and the …

Interpretation of ESPRIT in the FASTER trial.

Abstract: 198 http://neurology.thelancet.com Vol 7 March 2008 The Fast Assessment of Stroke and Transient Ischaemic Attack to Prevent Early Recurrence (FASTER) investigators should be commended for their attempt to assign patients to treatment fast after a transient ischaemic attack or minor ischaemic stroke. However, the trial had to be halted early because recruitment at the prespecifi ed speed seemed unfeasible. In their discussion, the investigators contrast the presumably fast eff ect of the combination of aspirin plus clopidogrel with that of aspirin plus dipyridamole, “which in the ESPRIT trial required 2 years of treatment before the treatment curves diverged”. We think this is an erroneous interpretation of data from the European/ Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) because the presumed lack of divergence would be due to a deceleration of the hazard after about 2 years in the aspirin-only curve, whereas such decelerations have not been reported in secondary stroke prevention trials that studied the eff ects of aspirin. Moreover, the hazard rate in the aspirin plus dipyridamole group is more or less constant. These factors together suggest that the eff ects of aspirin plus Interpretation of ESPRIT in the FASTER trial throughout the body, including the diaphragm and the heart. Such a delivery method and the large quantities of antisense oligonucleotides that will need to be administered pose challenges for safety and increase the risks of adverse events. Equally important is the problem that antisense oligonucleotides are gradually degraded; functional dystrophin protein is only produced in their presence. Therefore, it will be necessary either to give antisense nucleotides on a regular basis, perhaps even several times per year, or to develop viral vectors that will support the continued production of therapeutic oligonucleotides within muscle cells. Of course, this would then introduce the additional challenges associated with the use of viruses for gene therapy. Antisense oligonucleotide therapy is also likely to face new regulatory hurdles, particularly when patients require custom-designed vectors for their specifi c mutations. Nevertheless, the success of this trial in terms of safety and initial effi cacy measures is an important step towards new treatments that are based on emerging technologies, and will usher in a new era of genetic and cellular therapies.