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Background: Identification of risk factors and causes of stroke is key to optimize treatment and prevent recurrence. Up to one-third of young patients with stroke have a cryptogenic stroke according to current classification systems (Trial of ORG 10172 in Acute Stroke Treatment [TOAST] and atherosclerosis, small vessel disease, cardiac pathology, other causes, dissection [ASCOD]). The aim was to identify risk factors and leads for (new) causes of cryptogenic ischemic stroke in young adults, using the pediatric classification system from the IPSS study (International Pediatric Stroke Study). Methods: This is a multicenter prospective cohort study conducted in 17 hospitals in the Netherlands, consisting of 1322 patients aged 18 to 49 years with first-ever, imaging confirmed, ischemic stroke between 2013 and 2021. The main outcome was distribution of risk factors according to IPSS classification in patients with cryptogenic and noncryptogenic stroke according to the TOAST and ASCOD classification. Results: The median age was 44.2 years, and 697 (52.7%) were men. Of these 1322 patients, 333 (25.2%) had a cryptogenic stroke according to the TOAST classification. Additional classification using the ASCOD criteria reduced the number patients with cryptogenic stroke from 333 to 260 (19.7%). When risk factors according to the IPSS were taken into account, the number of patients with no potential cause or risk factor for stroke reduced to 10 (0.8%). Conclusions: Among young adults aged 18 to 49 years with a cryptogenic ischemic stroke according to the TOAST classification, risk factors for stroke are highly prevalent. Using a pediatric classification system provides new leads for the possible causes in cryptogenic stroke, and could potentially lead to more tailored treatment for young individuals with stroke.

Background and ObjectivesCauses of stroke in young adults differ from those in the elderly individuals, and in a larger percentage, no cause can be determined. To gain more insight into the etiology of (cryptogenic) stroke in the young population, we investigated whether trigger factors, such as short-lasting exposure to toxins or infection, may play a role.MethodsPatients aged 18–49 years with a first-ever ischemic stroke or intracerebral hemorrhage (ICH) in 17 participating centers in the Netherlands completed a questionnaire about exposure to 9 potential trigger factors in hazard periods and on a regular yearly basis. A case-crossover design was used to assess relative risks (RRs) with 95% confidence intervals (95% CIs) by the Mantel-Haenszel case-crossover method, for any stroke (ischemic stroke and ICH combined) and for different etiologic subgroups of ischemic stroke.ResultsOne thousand one hundred forty-six patients completed the questionnaire (1,043 patients with an ischemic stroke and 103 with an ICH, median age 44.0 years, 52.6% men). For any stroke, an increased risk emerged within 1 hour of cola consumption (RR 2.0, 95% CI 1.5–2.8) and vigorous physical exercise (RR 2.6, 95% CI 2.2–3.0), within 2 hours after sexual activity (RR 2.4, 95% CI 1.6–3.5), within 4 hours after illicit drug use (RR 2.8, 95% CI 1.7–4.9), and within 24 hours after fever or flu-like disease (RR 14.1, 95% CI 10.5–31.2; RR 13.9, 95% CI 8.9–21.9). Four trigger factors increased the risk of other determined and cryptogenic ischemic stroke, 3 that of cardioembolic stroke, 2 that of large vessel atherosclerosis and likely atherothrombotic stroke combined and stroke with multiple causes, and none that of stroke due to small vessel disease.DiscussionWe identified cola consumption, vigorous physical exercise, sexual activity, illicit drug use, fever, and flu-like disease as potential trigger factors for stroke in the young population and found differences in the type and number of trigger factors associated with different etiologic subgroups of ischemic stroke. These findings might help in better understanding the pathophysiologic mechanisms of (cryptogenic) stroke in the young population.

Background and Purpose: The frequency of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) varies in the current literature, and risk factors are unknown. We assessed the incidence, risk factors, and outcomes of acute ischemic stroke in hospitalized patients with COVID-19. Methods: We included patients with a laboratory-confirmed SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) infection admitted in 16 Dutch hospitals participating in the international CAPACITY-COVID registry between March 1 and August 1, 2020. Patients were screened for the occurrence of acute ischemic stroke. We calculated the cumulative incidence of ischemic stroke and compared risk factors, cardiovascular complications, and in-hospital mortality in patients with and without ischemic stroke. Results: We included 2147 patients with COVID-19, of whom 586 (27.3%) needed treatment at an intensive care unit. Thirty-eight patients (1.8%) had an ischemic stroke. Patients with stroke were older but did not differ in sex or cardiovascular risk factors. Median time between the onset of COVID-19 symptoms and diagnosis of stroke was 2 weeks. The incidence of ischemic stroke was higher among patients who were treated at an intensive care unit (16/586; 2.7% versus nonintensive care unit, 22/1561; 1.4%; P =0.039). Pulmonary embolism was more common in patients with (8/38; 21.1%) than in those without stroke (160/2109; 7.6%; adjusted risk ratio, 2.08 [95% CI, 1.52–2.84]). Twenty-seven patients with ischemic stroke (71.1%) died during admission or were functionally dependent at discharge. Patients with ischemic stroke were at a higher risk of in-hospital mortality (adjusted risk ratio, 1.56 [95% CI, 1.13–2.15]) than patients without stroke. Conclusions: In this multicenter cohort study, the cumulative incidence of acute ischemic stroke in hospitalized patients with COVID-19 was ≈2%, with a higher risk in patients treated at an intensive care unit. The majority of stroke patients had a poor outcome. The association between ischemic stroke and pulmonary embolism warrants further investigation.

Background: In patients with atrial fibrillation who survive an anticoagulation-associated intracerebral haemorrhage, a decision must be made as to whether restarting or permanently avoiding anticoagulation is the best long-term strategy to prevent recurrent stroke and other vascular events. In APACHE-AF, we aimed to estimate the rates of non-fatal stroke or vascular death in such patients when treated with apixaban compared with when anticoagulation was avoided, to inform the design of a larger trial. Methods: APACHE-AF was a prospective, randomised, open-label, phase 2 trial with masked endpoint assessment, done at 16 hospitals in the Netherlands. Patients who survived intracerebral haemorrhage while treated with anticoagulation for atrial fibrillation were eligible for inclusion 7–90 days after the haemorrhage. Participants also had a CHA2DS2-VASc score of at least 2 and a score on the modified Rankin scale (mRS) of 4 or less. Participants were randomly assigned (1:1) to receive oral apixaban (5 mg twice daily or a reduced dose of 2·5 mg twice daily) or to avoid anticoagulation (oral antiplatelet agents could be prescribed at the discretion of the treating physician) by a central computerised randomisation system, stratified by the intention to start or withhold antiplatelet therapy in participants randomised to avoiding anticoagulation, and minimised for age and intracerebral haemorrhage location. The primary outcome was a composite of non-fatal stroke or vascular death, whichever came first, during a minimum follow-up of 6 months, analysed using Cox proportional hazards modelling in the intention-to-treat population. APACHE-AF is registered with ClinicalTrials.gov (NCT02565693) and the Netherlands Trial Register (NL4395), and the trial is closed to enrolment at all participating sites. Findings: Between Jan 15, 2015, and July 6, 2020, we recruited 101 patients (median age 78 years [IQR 73–83]; 55 [54%] were men and 46 [46%] were women; 100 [99%] were White and one [1%] was Black) a median of 46 days (IQR 21–74) after intracerebral haemorrhage. 50 were assigned to apixaban and 51 to avoid anticoagulation (of whom 26 [51%] started antiplatelet therapy). None were lost to follow-up. Over a median follow-up of 1·9 years (IQR 1·0–3·1; 222 person-years), non-fatal stroke or vascular death occurred in 13 (26%) participants allocated to apixaban (annual event rate 12·6% [95% CI 6·7–21·5]) and in 12 (24%) allocated to avoid anticoagulation (11·9% [95% CI 6·2–20·8]; adjusted hazard ratio 1·05 [95% CI 0·48–2·31]; p=0·90). Serious adverse events that were not outcome events occurred in 29 (58%) of 50 participants assigned to apixaban and 29 (57%) of 51 assigned to avoid anticoagulation. Interpretation: Patients with atrial fibrillation who had an intracerebral haemorrhage while taking anticoagulants have a high subsequent annual risk of non-fatal stroke or vascular death, whether allocated to apixaban or to avoid anticoagulation. Our data underline the need for randomised controlled trials large enough to allow identification of subgroups in whom restarting anticoagulation might be either beneficial or hazardous. Funding: Dutch Heart Foundation (grant 2012T077).

BACKGROUND: In patients with aneurysmal subarachnoid haemorrhage, short-term antifibrinolytic therapy with tranexamic acid has been shown to reduce the risk of rebleeding. However, whether this treatment improves clinical outcome is unclear. We investigated whether ultra-early, short-term treatment with tranexamic acid improves clinical outcome at 6 months.METHODS: In this multicentre prospective, randomised, controlled, open-label trial with masked outcome assessment, adult patients with spontaneous CT-proven subarachnoid haemorrhage in eight treatment centres and 16 referring hospitals in the Netherlands were randomly assigned to treatment with tranexamic acid in addition to care as usual (tranexamic acid group) or care as usual only (control group). Tranexamic acid was started immediately after diagnosis in the presenting hospital (1 g bolus, followed by continuous infusion of 1 g every 8 h, terminated immediately before aneurysm treatment, or 24 h after start of the medication, whichever came first). The primary endpoint was clinical outcome at 6 months, assessed by the modified Rankin Scale, dichotomised into a good (0-3) or poor (4-6) clinical outcome. Both primary and safety analyses were according to intention to treat. This trial is registered at ClinicalTrials.gov, NCT02684812.FINDINGS: Between July 24, 2013, and July 29, 2019, we enrolled 955 patients; 480 patients were randomly assigned to tranexamic acid and 475 patients to the control group. In the intention-to-treat analysis, good clinical outcome was observed in 287 (60%) of 475 patients in the tranexamic acid group, and 300 (64%) of 470 patients in the control group (treatment centre adjusted odds ratio 0·86, 95% CI 0·66-1·12). Rebleeding after randomisation and before aneurysm treatment occurred in 49 (10%) patients in the tranexamic acid and in 66 (14%) patients in the control group (odds ratio 0·71, 95% CI 0·48-1·04). Other serious adverse events were comparable between groups.INTERPRETATION: In patients with CT-proven subarachnoid haemorrhage, presumably caused by a ruptured aneurysm, ultra-early, short-term tranexamic acid treatment did not improve clinical outcome at 6 months, as measured by the modified Rankin Scale.FUNDING: Fonds NutsOhra.

Introduction We investigated the impact of the Corona Virus Disease 2019 (COVID-19) pandemic and the resulting lockdown on reperfusion treatments and door-to-treatment times during the first surge in Dutch comprehensive stroke centers. Furthermore, we studied the association between COVID-19-status and treatment times. Methods We included all patients receiving reperfusion treatment in 17 Dutch stroke centers from May 11th, 2017, until May 11th, 2020. We collected baseline characteristics, National Institutes of Health Stroke Scale (NIHSS) at admission, onset-to-door time (ODT), door-to-needle time (DNT), door-to-groin time (DGT) and COVID-19-status at admission. Parameters during the lockdown (March 15th, 2020 until May 11th, 2020) were compared with those in the same period in 2019, and between groups stratified by COVID-19-status. We used nationwide data and extrapolated our findings to the increasing trend of EVT numbers since May 2017. Results A decline of 14% was seen in reperfusion treatments during lockdown, with a decline in both IVT and EVT delivery. DGT increased by 12 min (50 to 62 min, p-value of Conclusions During the first surge of the COVID-19 pandemic, a decline in acute reperfusion treatments and a delay in DGT was seen, which indicates a target for attention. It also appeared that COVID-19-positive or -suspected patients had more severe neurologic symptoms, whereas their EVT-workflow was not affected.

Background: The noninjured, contralateral hemisphere is increasingly acknowledged in the process of recovery from acute ischemic stroke. We estimated the value of conventional electroencephalography (EEG) recordings for identifying contralateral hemisphere involvement in relation to functional recovery. Methods: We analyzed 2-min epochs from 21 electrode EEG registrations of 18 patients with acute hemispheric ischemic stroke and compared with 18 age-matched controls. Outcome was dichotomized as good (modified Rankin Scale [mRS] 0–2) or poor (mRS 3–5 or death) at 3 months. Effects of the infarct on the ipsi-and contralateral hemispheres were analyzed by the delta/alpha ratio (DAR) and 2 measures of functional connectivity (magnitude squared coherence [MSC] and weighted phase lag index [WPLI]). Results: DAR was higher in patients than in controls, both in the ipsilateral and in the contralateral hemisphere (median 4.5 ± 6.7 ipsilateral and 2.4 ± 2.0 contralateral vs. 0.5 ± 0.5 in the control group, p < 0.001), indicating robust EEG changes in both lesioned and non-lesioned hemisphere. MSC and WPLI in the alpha and beta frequency bands were lower in patients than in controls in both hemispheres, indicating clear disturbances of functional connectivity (p < 0.05). In the poor outcome group, contralateral MSC and WPLI were lower than in the good outcome group, although these differences did not reach statistical significance. Conclusions: Short conventional EEG measurements show robust changes of brain activity and functional connectivity in both ipsilateral and contralateral hemispheres of patients with acute ischemic stroke. Changes of remote functional connectivity tend to interact with functional recovery. Future studies should estimate predictive values for individual patients and interactions with plasticity enhancing treatments.

Transient ischemic attack (TIA) can be difficult to diagnose. Episodes of acute atypical or nonfocal neurological symptoms, referred to as transient neurological attack (TNA), are as prevalent as TIAs. Diffusion-weighted imaging (DWI) provides evidence of acute cerebral ischemia in a third of TIA patients. We now report that DWI shows acute ischemia in 23% of patients clinically diagnosed as TNA by experienced stroke neurologists. This questions the accuracy of clinically diagnosing TIA and suggests added value for early magnetic resonance imaging after an episode of acute onset atypical or nonfocal neurological symptoms.

Background and purpose We aimed to assess the safety, feasibility, and effects on glucose metabolism of treatment with metformin in patients with TIA or minor ischemic stroke and impaired glucose tolerance. Methods We performed a multicenter, randomized, controlled, open-label phase II trial with blinded outcome assessment. Patients with TIA or minor ischemic stroke in the previous six months and impaired glucose tolerance (2-hour post-load glucose levels of 7.8–11.0 mmol/l) were randomized to metformin, in a daily dose of 2 g, or no metformin, for three months. Primary outcome measures were safety and feasibility of metformin, and the adjusted difference in 2-hour post-load glucose levels at three months. This trial is registered as an International Standard Randomized Controlled Trial Number 54960762. Results Forty patients were enrolled; 19 patients were randomly assigned metformin. Nine patients in the metformin group had side effects, mostly gastrointestinal, leading to permanent discontinuation in four patients after 3–10 weeks. Treatment with metformin was associated with a significant reduction in 2-hour post-load glucose levels of 0·97 mmol/l (95% CI 0·11–1·83) in the on-treatment analysis, but not in the intention-to-treat analysis (0·71 mmol/l; 95% CI −0·36 to 1·78). Conclusions Treatment with metformin in patients with TIA or minor ischemic stroke and impaired glucose tolerance is safe, but leads to minor side effects. If tolerated, it may lead to a significant reduction in post-load glucose levels. This suggests that the role of metformin as potential therapeutic agent for secondary stroke prevention should be further explored.

Background and Purpose— Although by definition transient, both transient ischemic attack (TIA) and transient neurological attack (TNA) are associated with cognitive impairment. Determinants and course of cognitive function afterward are, however, unclear. We prospectively determined cognitive performance after TIA and TNA in relation to clinical diagnosis and diffusion-weighted imaging (DWI) results. Methods— TIA and TNA patients aged ≥45 years without prior stroke or dementia underwent comprehensive cognitive assessment and magnetic resonance imaging within 7 days after the qualifying event. Cognitive tests were repeated after 6 months. Domain-specific compound z scores based on the baseline mean and SD were calculated. Repeated-measures analysis was used to test for differences in domain-specific cognitive performance over time between DWI-positive and DWI-negative patients, as well as between TIA and TNA patients. Results— One hundred twenty-one patients were included (mean age (SD), 64.6 years (9.2 years), 60% TIA and 40% TNA) of whom 32 (26%) had a DWI lesion. Executive function performance decreased over time (mean change in compound score −0.23; P =0.01 adjusted for age, sex, education), whereas attention improved (0.11; P =0.02), and information processing speed and episodic memory remained unchanged. Patients with a DWI lesion had worse executive function at baseline than those without a DWI lesion (compound scores −0.26 versus 0.08; P =0.048), which persisted throughout the study period ( P =0.04). Clinical diagnosis (TIA or TNA) was not related to cognitive function over time. Conclusions— Executive function declines during the first 6 months after TIA or TNA. Patients with an initial DWI lesion have persisting worse executive function than those without.

Introduction. Subjective cognitive impairment (SCI), depressive symptoms, and fatigue are common after stroke and are associated with reduced quality of life. We prospectively investigated their prevalence and course after a transient ischemic attack (TIA) or nonfocal transient neurological attack (TNA) and the association with diffusion-weighted imaging (DWI) lesions. Methods. The Cognitive Failures Questionnaire, Hospital Anxiety and Depression Scale, and Subjective Fatigue subscale from the Checklist Individual Strength were used to assess subjective complaints shortly after TIA or TNA and six months later. With repeated measure analysis, the associations between DWI lesion presence or clinical diagnosis (TIA or TNA) and subjective complaints over time were determined. Results. We included 103 patients (28 DWI positive). At baseline, SCI and fatigue were less severe in DWI positive than in DWI negative patients, whereas at follow-up, there were no differences. SCI (p=0.02) and fatigue (p=0.01) increased in severity only in DWI positive patients. There were no differences between TIA and TNA. Conclusions. Subjective complaints are highly prevalent in TIA and TNA patients. The short-term prognosis is not different between DWI-positive and DWI negative patients, but SCI and fatigue increase in severity within six months after the event when an initial DWI lesion is present.

Introduction The non-injured, contralateral hemisphere is increasingly acknowledged in recovery from acute ischemic stroke. We estimate the value of conventional EEG recordings for identification of contralateral hemisphere involvement in relation to functional recovery. Methods We analyzed two-minute epochs from 21 electrode EEG registrations from 18 patients with acute hemispheric ischemic stroke and compared with 18 age-matched controls. Outcome was dichotomized as good (mRS 0–2) or poor (mRS 3–5 or death) at three months. Effects of the infarct on the ipsi- and contralateral hemispheres were analyzed by the delta/alpha ratio (DAR) and two measures of functional connectivity (magnitude squared coherence (MSC) and weighted phase lag index (WPLI)). Results DAR was higher in patients than in controls, both in the ipsilateral and in the contralateral hemisphere (median 4.5 ± 6.7 ipsilateral and 2.4 ± 2.0 contralateral vs. 0.5 ± 0.5 in the control group, P Conclusion Short conventional EEG measurements show robust changes of brain activity and functional connectivity in both ipsilateral and contralateral hemisphere of patients with acute ischemic stroke. Changes of remote functional connectivity tend to interact with functional recovery. Associations between contralateral functional connectivity measures and incidence of apathy and depression are currently analyzed and will be presented.

Item does not contain fulltext OBJECTIVE AND METHODS: In the diagnostic work-up of patients suspected of a dural arteriovenous fistula (dAVF), imaging has a key role in order to diagnose the dAVF, assess its bleeding risk and choose optimal treatment strategy. Digital subtraction angiography (DSA) is the gold standard for the most detailed image of a dAVF. Nowadays four-dimensional CT angiography (4D-CTA) could possibly be an additional first-line tool in the work-up of a patient suspected of a dAVF. We describe three cases clinically suspected of a dAVF which had a diagnostic work-up with 4D-CTA as well as DSA. We evaluated the angioarchitecture of the dAVF both on 4D-CTA and DSA, with emphasis on the patterns of venous drainage as this is important in assessing the bleeding risk of a dAVF. RESULTS AND CONCLUSION: 4D-CTA identified the dAVF, revealed its angioarchitecture and correctly differentiated different patterns of venous drainage (Borden type I, II and III) as confirmed on DSA. Although DSA has the advantage of higher spatial and temporal resolution, 4D-CTA seems to be a new useful non-invasive tool in the diagnostic work-up of a patient suspected of a dAVF.

As the availability and quality of imaging techniques improve, doctors are identifying more patients with no history of transient ischaemic attack or stroke in whom imaging shows brain infarcts. Until recently, little was known about the relevance of these lesions. In this systematic review, we give an overview of the frequency, causes, and consequences of MRI-defined silent brain infarcts, which are detected in 20% of healthy elderly people and up to 50% of patients in selected series. Most infarcts are lacunes, of which hypertensive small-vessel disease is thought to be the main cause. Although silent infarcts, by definition, lack clinically overt stroke-like symptoms, they are associated with subtle deficits in physical and cognitive function that commonly go unnoticed. Moreover, the presence of silent infarcts more than doubles the risk of subsequent stroke and dementia. Future studies will have to show whether screening and treating high-risk patients can effectively reduce the risk of further infarcts, stroke, and dementia.

Transient ischemic attack (TIA) can be difficult to diagnose. Episodes of acute atypical or nonfocal neurological symptoms, referred to as transient neurological attack (TNA), are as prevalent as TIAs. Diffusion-weighted imaging (DWI) provides evidence of acute cerebral ischemia in a third of TIA patients. We now report that DWI shows acute ischemia in 23% of patients clinically diagnosed as TNA by experienced stroke neurologists. This questions the accuracy of clinically diagnosing TIA and suggests added value for early magnetic resonance imaging after an episode of acute onset atypical or nonfocal neurological symptoms.

Contains fulltext : 144629.pdf (Publisher’s version ) (Open Access) BACKGROUND: Transient ischemic attacks (TIA) are characterized by acute onset focal neurological symptoms and complete recovery within 24 hours. Attacks of nonfocal symptoms not fulfilling the criteria for TIA but lacking a clear alternative diagnosis are called transient neurological attacks (TNA). Although TIA symptoms are transient in nature, cognitive complaints may persist. In particular, attacks consisting of both focal and nonfocal symptoms (mixed TNA) have been found to be associated with an increased risk of dementia. We aim to study the prevalence, etiology and risk factors of cognitive impairment after TIA or TNA. METHODS/DESIGN: CONNECT is a prospective cohort study on cognitive function after TIA and TNA. In total, 150 patients aged >/=45 years with a recent (

Background and Purpose— Impaired glucose tolerance, an intermediate metabolic state between normal glucose and diabetes characterized by nonfasting glucose levels between 7.8 to 11.0 mmol/L, is associated with an increased stroke risk in patients with coronary heart disease. Whether impaired glucose tolerance increases the risk of stroke in patients with transient ischemic attack (TIA) or minor ischemic stroke is unknown. Methods— In total, 3127 patients with a TIA or minor ischemic stroke participated in the Dutch TIA Trial, testing 2 different doses of aspirin and atenolol versus placebo. We estimated the risk of stroke and the risk of myocardial infarction or cardiac death in relation to baseline nonfasting glucose levels (mean 6.0, SD 2.2 mmol/L) with Cox proportional hazards regression analysis, adjusted for cardiovascular risk factors. Results— During 2.6 years follow-up, 272 patients (9%) experienced a stroke and 200 (6%) a myocardial infarction or cardiac death. We found a J-shaped relationship between baseline nonfasting glucose levels and stroke risk. Stroke risk was nearly doubled in patients with impaired glucose tolerance (glucose 7.8 to 11.0 mmol/L) compared with those with normal glucose levels (hazard ratio [HR] 1.8, 95% CI, 1.1 to 3.0) and nearly tripled in diabetic patients (glucose ≥11.1 mmol/L; HR 2.8, 95% CI, 1.9 to 4.1). Patients with low glucose levels ( Conclusion— Impaired glucose tolerance is an independent risk factor for future stroke in nondiabetic patients with TIA or minor ischemic stroke.

Background: Blood pressure level is associated with the risk of clinical Alzheimer disease (AD), yet the underlying mechanisms are unclear. High blood pressure levels may cause cerebral small-vessel pathology, which contributes to cognitive decline in patients with AD. Alternatively, in persons with high blood pressure, increased numbers of neurofibrillary tangles and amyloid plaques at autopsy have also been observed, suggesting direct links between blood pressure and AD. Objective: To investigate the association of blood pressure and markers of small-vessel disease (white matter lesions [WMLs] on MRI) with hippocampal and amygdalar atrophy on MRI—potential in vivo indicators of Alzheimer pathology. Methods: In 1995 to 1996, 511 nondemented elderly subjects (age 60 to 90) underwent MRI. The extent of WMLs was assessed, and volumes of the hippocampus and amygdala were measured. Blood pressure levels were assessed at the time of MRI and 5 years before the MRI. Results: Higher diastolic blood pressure 5 years before MRI predicted more hippocampal atrophy in persons untreated for hypertension (per SD increase −0.10 mL [95% CI −0.19 to −0.02, p = 0.02]). Conversely, in persons treated for hypertension, a low diastolic blood pressure was associated with more severe atrophy. Persons with more WMLs on MRI more often had severe atrophy of the hippocampus and amygdala. Conclusion: Blood pressure and indicators of small-vessel disease in the brain may be associated with atrophy of structures affected by Alzheimer pathology.

Cerebral small-vessel disease is common in older people and may contribute to the development of dementia. The objective of the present study was to evaluate the relationship between measures of cerebral small-vessel disease on MRI and the rate of decline in specific cognitive domains in participants from the prospective, population-based Rotterdam Scan Study. Participants were 60-90 years of age and free from dementia at baseline in 1995-1996. White matter lesions (WML), cerebral infarcts and generalized brain atrophy were assessed on the baseline MRI. We performed neuropsychological testing at baseline and repeatedly in 1999-2000 and in 2001-2003. We used random-effects models for repeated measures to examine the association between quantitative MRI measures and rate of decline in measures of global cognitive function, information processing speed, executive function and memory. There were a total of 2266 assessments for the 832 participants in the study, with an average time from the initial to last assessment of 5.2 years. Increasing severity of periventricular WML and generalized brain atrophy and the presence of brain infarcts on MRI were associated with a steeper decline in cognitive function. These structural brain changes were specifically associated with decline in information processing speed and executive function. The associations between MRI measures of cerebral small-vessel disease and cognitive decline did not change after additional adjustment for vascular risk factors or depressed mood. After exclusion of participants with an incident stroke, some of the associations of periventricular WML, brain infarcts and generalized brain atrophy with measures of information processing speed and executive function were no longer significant. This may indicate that stroke plays an intermediate role in the relationship between cerebral small-vessel disease and cognitive decline. Our results suggest that in older people cerebral small-vessel disease may contribute to cognitive decline by affecting information processing speed and executive function.

Objective: To study whether lower arterial oxygen saturation (SaO2) and chronic obstructive pulmonary disease (COPD) are associated with cerebral white matter lesions and lacunar infarcts. Methods: We measured SaO2 twice with a pulse oximeter, assessed the presence of COPD, and performed MRI in 1077 non-demented people from a general population (aged 60–90 years). We rated periventricular white matter lesions (on a scale of 0–9) and approximated a total subcortical white matter lesion volume (range 0–29.5 ml). All analyses were adjusted for age and sex and additionally for hypertension, diabetes, body mass index, pack years smoked, cholesterol, haemoglobin, myocardial infarction, and left ventricular hypertrophy. Results: Lower SaO2 was independent of potential confounders associated with more severe periventricular white matter lesions (score increased by 0.12 per 1% decrease in SaO2 (95% confidence interval 0.01 to 0.23)). Participants with COPD had more severe periventricular white matter lesions than those without (adjusted mean difference in score 0.70 (95% confidence interval 0.23 to 1.16)). Lower SaO2 and COPD were not associated with subcortical white matter lesions or lacunar infarcts. Conclusion: Lower SaO2 and COPD are associated with more severe periventricular white matter lesions.

Background and Purpose— Silent brain infarcts and white matter lesions are associated with an increased risk of subsequent stroke in minor stroke patients. In healthy elderly people, silent brain infarcts and white matter lesions are common, but little is known about their relevance. We examined the risk of stroke associated with these lesions in the general population. Methods— The Rotterdam Scan Study is a population-based prospective cohort study among 1077 elderly people. The presence of silent brain infarcts and white matter lesions was scored on cerebral MRI scans obtained from 1995 to 1996. Participants were followed for stroke for on average 4.2 years. We estimated the risk of stroke in relation to presence of brain lesions with Cox proportional hazards regression analysis. Results— Fifty-seven participants (6%) experienced a stroke during follow-up. Participants with silent brain infarcts had a 5 times higher stroke incidence than those without. The presence of silent brain infarcts increased the risk of stroke >3-fold, independently of other stroke risk factors (adjusted hazard ratio 3.9, 95% CI 2.3 to 6.8). People in the upper tertile of the white matter lesion distribution had an increased stroke risk compared with those in the lowest tertile (adjusted hazard ratio for periventricular lesions 4.7, 95% CI 2.0 to 11.2 and for subcortical lesions 3.6, 95% CI 1.4 to 9.2). Silent brain infarcts and severe white matter lesions increased the stroke risk independently of each other. Conclusion— Elderly people with silent brain infarcts and white matter lesions are at a strongly increased risk of stroke, which could not be explained by the major stroke risk factors.

Patients with Alzheimer's disease have higher plasma homocysteine levels than controls, but it is uncertain whether higher plasma homocysteine levels are involved in the early pathogenesis of the disease. Hippocampal, amygdalar and global brain atrophy on brain MRI have been proposed as early markers of Alzheimer's disease. In the Rotterdam Scan Study, a population-based study of age-related brain changes in 1077 non-demented people aged 60-90 years, we investigated the association between plasma homocysteine levels and severity of hippocampal, amygdalar and global brain atrophy on MRI. We used axial T(1)-weighted MRIs to visualize global cortical brain atrophy (measured semi-quantitatively; range 0-15) and a 3D HASTE (half-Fourier acquisition single-shot turbo spin echo) sequence in 511 participants to measure hippocampal and amygdalar volumes. We had non-fasting plasma homocysteine levels in 1031 of the participants and in 505 of the participants with hippocampal and amygdalar volumes. Individuals with higher plasma homocysteine levels had, on average, more cortical atrophy [0.23 units (95% CI 0.07-0.38 units) per standard deviation increase in plasma homocysteine levels] and more hippocampal atrophy [difference in left hippocampal volume -0.05 ml (95% CI -0.09 to -0.01) and in right hippocampal volume -0.03 ml (95% CI -0.07 to 0.01) per standard deviation increase in plasma homocysteine levels]. No association was observed between plasma homocysteine levels and amygdalar atrophy. These results support the hypothesis that higher plasma homocysteine levels are associated with more atrophy of the hippocampus and cortical regions in elderly at risk of Alzheimer's disease.

Background and Purpose— The prevalence of silent brain infarcts in healthy elderly people is high, and these lesions are associated with an increased risk of stroke. The incidence of silent brain infarcts is unknown. We investigated the incidence and cardiovascular risk factors for silent brain infarcts. Methods— The Rotterdam Scan Study is a prospective, population-based cohort study of 1077 participants 60 to 90 years of age. All participants underwent cranial MRI in 1995 to 1996, and 668 participants had a second MRI in 1999 to 2000 (response rate, 70%) with a mean interval of 3.4 years. We assessed cardiovascular risk factors by interview and physical examination at baseline. Associations between risk factors and incident silent infarcts were analyzed by multiple logistic regression. Results— Ninety-three participants (14%) had ≥1 new infarcts on the second MRI; of these, 81 had only silent and 12 had symptomatic infarcts. The incidence of silent brain infarcts strongly increased with age and was 5 times higher than that of symptomatic stroke. A prevalent silent brain infarct strongly predicted a new silent infarct on the second MRI (age- and sex-adjusted odds ratio, 2.9; 95% confidence interval, 1.7 to 5.0). Age, blood pressure, diabetes mellitus, cholesterol and homocysteine levels, intima-media thickness, carotid plaques, and smoking were associated with new silent brain infarcts in participants without prevalent infarcts. Conclusions— The incidence of silent brain infarcts on MRI in the general elderly population strongly increases with age. The cardiovascular risk factors for silent brain infarcts are similar to those for stroke.

Silent brain infarcts and white matter lesions are frequently seen on magnetic resonance imaging in healthy elderly people and both are associated with an increased risk of stroke and dementia. Plasma total homocysteine may be a potentially modifiable risk factor for stroke and dementia. We examined whether elevated total homocysteine levels are associated with silent brain infarcts and white matter lesions. The Rotterdam Scan Study is a population-based study of 1,077 people aged 60 to 90 years who had cerebral magnetic resonance imaging. The cross-sectional relation of total homocysteine with silent infarcts and white matter lesions was analyzed with adjustment for cardiovascular risk factors. The mean plasma total homocysteine level was 11.5mumol/1 (standard deviation 4.1). The risk of silent brain infarcts increased with increasing total homocysteine levels (odds ratio 1.24/standard deviation increase, 95% confidence interval 1.06-1.45). The severity of periventricular white matter lesions and extent of subcortical white matter lesions were also significantly associated with total homocysteine levels, even after excluding those with silent brain infarcts. The overall risk of having either a silent brain infarct or severe white matter lesions was strongly associated with total homocysteine levels (odds ratio 1.35/standard deviation increase, 95% confidence interval 1.16-1.58). We concluded that total homocysteine levels are associated with silent brain infarcts and white matter lesions independent of each other and of other cardiovascular risk factors.

Background and Purpose — Silent brain infarcts are commonly seen on magnetic resonance imaging (MRI) both in patients with a first stroke and in healthy elderly persons. These infarcts seem associated with an increased risk of stroke. It is unclear whether risk factors for silent infarcts differ from those for symptomatic stroke. We investigated the prevalence of, and cardiovascular risk factors for, silent brain infarcts. Methods — The Rotterdam Scan Study is a population-based cohort study among 1077 participants 60 to 90 years of age. Participants underwent cerebral MRI. We assessed cardiovascular risk factors by interview and physical examination. Associations between risk factors and presence of infarcts were analyzed by logistic regression and adjusted for age, sex, and relevant confounders. Results — For 259 participants (24%) 1 or more infarcts on MRI were seen; 217 persons had only silent and 42 had symptomatic infarcts. The prevalence odds ratio (OR) of both silent and symptomatic infarcts increased with age by 8% per year (95% CI, 1.06 to 1.10 and 1.04 to 1.13, respectively). Silent infarcts were more frequent in women (age-adjusted OR, 1.4; 95% CI, 1.0 to 1.8). Hypertension was associated with silent infarcts (age- and sex-adjusted OR, 2.4; 95% CI, 1.7 to 3.3), but diabetes mellitus and smoking were not. Conclusions — Silent brain infarcts are 5 times as prevalent as symptomatic brain infarcts in the general population. Their prevalence increases with age and seems higher in women. Hypertension is associated with silent infarcts, but other cardiovascular risk factors are not.

Background The proportion of strokes occurring in younger adults has been rising over the past decade. Due to the far longer life expectancy in the young, stroke in this group has an even larger socio-economic impact. However, information on etiology and prognosis remains scarce. Methods/design ODYSSEY is a multicentre prospective cohort study on the prognosis and risk factors of patients with a first-ever TIA, ischemic stroke or intracerebral hemorrhage aged 18 to 49 years. Our aim is to include 1500 patients. Primary outcome will be all cause mortality and risk of recurrent vascular events. Secondary outcome will be the risk of post-stroke epilepsy and cognitive impairment. Patients will complete structured questionnaires on outcome measures and risk factors. Both well-documented and less well-documented risk factors and potentially acute trigger factors will be investigated. Patients will be followed every 6 months for at least 3 years. In addition, an extensive neuropsychological assessment will be administered both at baseline and 1 year after the stroke/TIA. Furthermore we will include 250 stroke-free controls, who will complete baseline assessment and one neuropsychological assessment. Discussion ODYSSEY is designed to prospectively determine prognosis after a young stroke and get more insight into etiology of patients with a TIA, ischemic stroke and intracerebral hemorrhage in patients aged 18 to 49 years old in a large sample size.

In patients with TIA or stroke of arterial origin various antiplatelet agents, or combinations of these, have been found to be effective to reduce the risk of new vascular complications. International guidelines currently recommend three treatment strategies with antiplatelet agents after TIA or stroke: acetylsalicylic acid in combination with dipyridamole, clopidogrel monotherapy, or alternatively acetylsalicylic acid monotherapy. In the Netherlands, current standard antiplatelet therapy after a TIA or stroke is a combination of acetylsalicylic acid and dipyridamole. Clopidogrel monotherapy is probably equally as effective as the combination of acetylsalicylic acid and dipyridamole. Clopidogrel monotherapy is easier to use, has fewer side effects and has recently become cheaper than the combination of acetylsalicylic acid and dipyridamole. For secondary prevention in the Netherlands we advise following the international guidelines on thromboprophylaxis after TIA or stroke. Clopidogrel could be considered as an alternative treatment to the combination of acetylsalicylic acid and dipyridamole.

Background— Inflammatory processes are involved in the development and consequences of atherosclerosis. Whether these processes are also involved in cerebral small-vessel disease is unknown. Cerebral white matter lesions and lacunar brain infarcts are caused by small-vessel disease and are commonly observed on MRI scans in elderly people. These lesions are associated with an increased risk of stroke and dementia. We assessed whether higher C-reactive protein (CRP) levels were related to white matter lesion and lacunar infarcts. Methods and Results— We based our study on 1033 participants of the population-based Rotterdam Scan Study for whom complete data on CRP levels were available and who underwent brain MRI scanning. Subjects were 60 to 90 years of age and free of dementia at baseline. Six hundred thirty-six subjects had a second MRI scan on average 3.3 years later. We used multivariate regression models to assess the associations between CRP levels and markers of small-vessel disease. Higher CRP levels were associated with presence and progression of white matter lesions, particularly with marked lesion progression (ORs for highest versus lowest quartile of CRP 3.1 [95% CI 1.3 to 7.2] and 2.5 [95% CI 1.1 to 5.6] for periventricular and subcortical white matter lesion progression, respectively). These associations persisted after adjustment for cardiovascular risk factors and carotid atherosclerosis. Persons with higher CRP levels tended to have more prevalent and incident lacunar infarcts. Conclusions— Inflammatory processes may be involved in the pathogenesis of cerebral small-vessel disease, in particular, the development of white matter lesions.

Objective To study the association between white matter lesions (WML) in specific locations and the risk of dementia. Design The Rotterdam Scan Study, a prospective population-based cohort study. We scored periventricular and subcortical WML on magnetic resonance imaging and observed participants until January 2002 for incident dementia. Setting General population. Participants We included 1077 people aged 60 to 90 years who did not have dementia at baseline. Main Outcome Measure Incident dementia by Diagnostic and Statistical Manual of Mental Disorders, Third Edition ( DSM III-R ) criteria. Results During a mean follow-up of 5.2 years, 45 participants developed dementia. Higher severity of periventricular WML increased the risk of dementia, whereas the association between subcortical WML and dementia was less prominent. The adjusted hazard ratio of dementia for each standard deviation increase in periventricular WML severity was 1.67 (95% confidence interval, 1.25-2.24). This increased risk was independent of other risk factors for dementia and partly independent of other structural brain changes on magnetic resonance imaging. Conclusion White matter lesions, especially in the periventricular region, increase the risk of dementia in elderly people.

Background: Consumers of light-to-moderate amounts of alcohol have a lower risk of dementia and, possibly, Alzheimer disease than do abstainers. Because vascular disease may contribute to symptoms of Alzheimer disease, reduction of cerebrovascular disease in consumers of light amounts of alcohol could account for that observation. However, a low concentration of alcohol may also have direct effects on the hippocampus, a brain structure highly affected by Alzheimer disease. Objective: We investigated alcohol intake in relation to brain magnetic resonance imaging (MRI) findings of presumed vascular origin (ie, white matter lesions and infarcts) and findings more specifically found in early Alzheimer disease (ie, hippocampal and amygdalar atrophy). Design: In a population-based sample of 1074 older persons without dementia (aged 60 –90 y), we made brain MRIs from which we rated white matter lesions and brain infarcts. In a subset of 509 people, hippocampal and amygdalar volumes on MRI were measured. Alcohol intake was assessed by using a structured questionnaire. We categorized alcohol intake as lifetime abstention and very light (1 drink/wk), light (1 drink/wk to1 drink/d), moderate (1 drink/d to 4 drinks/d), and heavy (4 drinks/d) intakes. Results: Persons whose alcohol consumption was light to moderate had less severe white matter lesions and brain infarcts on MRI than did abstainers or heavy drinkers. Abstainers and very light drinkers had smaller hippocampal and amygdalar volumes on MRI than did light-to-moderate drinkers, but only if the former carried an apolipoprotein (APOE) 4 allele. Conclusion: Light-to-moderate alcohol intake is associated with a lower prevalence of vascular brain findings and, in APOE4 carriers, hippocampal and amygdalar atrophy on MRI. Am J Clin Nutr 2004;80:992–7.

Lacunar brain infarcts and cerebral white matter lesions are frequently observed on magnetic resonance imaging scans in elderly subjects. These lesions are also frequent in patient with cerebral amyloid angiopathy. We examined whether plasma amyloid beta peptide (Abeta) levels are associated with lacunar infarcts and white matter lesions in the general population, and whether the apolipoprotein E (APOE) genotype modifies these associations. We studied 1,077 participants within the population-based Rotterdam Scan Study, who were 60 to 90 years of age and free of dementia. Cross-sectional associations were analyzed by regression models with adjustments for age, sex, creatinine levels, and hypertension. In APOE epsilon4 carriers, plasma Abeta levels were positively associated with lacunar infarcts and white matter lesions, whereas in noncarriers no associations were observed. Per standard deviation increase in Abeta(1-40) and Abeta(1-42) levels the odds ratios for lacunar infarcts were 1.72 (95% confidence interval [CI] = 1.22-2.43) and 1.93 (95% CI = 1.31-2.85), the periventricular white matter lesion grade increased by 0.32 (95% CI = 0.08-0.57) and 0.29 (95% CI = 0.00-0.57), and the subcortical white matter lesion volume increased by 0.48 ml (95% CI = 0.04-0.91) and 0.24 ml (95% CI = -0.27-0.75). Higher Abeta levels are associated with more lacunar infarcts and white matter lesions in elderly subjects who carry an APOE epsilon4 allele.

To assess the effect of aging on the proportions of choline (Cho), creatine, and N-acetylaspartate (NAA) in the brains of elderly women and men.A transverse plane above the ventricle of the brain was mapped with magnetic resonance spectroscopy. Examinations were performed in 1995-1996 with 271 healthy subjects (age range, 60-90 years; mean age, 73 years) and were repeated 4 years later (1999-2000). Student t tests were used for statistical analysis.Difference analysis of the changes in 4 years (paired data) reproduced the decrease in Cho in women only (2.9% per year, P.001) that had been indicated with intersubject correlation analyses. Decreases in NAA, though significant in both men and women according to age correlation analyses (P.01 for both), did not reach significance. The resulting sex difference in the Cho/NAA ratio at a mean age of 77 years, while not yet significant at a mean age of 73 years, was especially manifest in the posterior half of the plane analyzed.Increasing sex differences in Cho/NAA ratios in a supraventricular plane indicate that brain metabolite levels differ between women and men at advanced age.

Aim/hypothesis. Type 2 diabetes increases the risk not only of vascular dementia but also of Alzheimer's disease. The question remains whether diabetes increases the risk of Alzheimer's disease by diabetic vasculopathy or whether diabetes influences directly the development of Alzheimer neuropathology. In vivo, hippocampal and amygdalar atrophy on brain MRI are good, early markers of the degree of Alzheimer neuropathology. We investigated the association between diabetes mellitus, insulin resistance and the degree of hippocampal and amygdalar atrophy on magnetic resonance imaging (MRI) accounting for vascular pathology. Methods. Data was obtained in a population-based study of elderly subjects without dementia between 60 to 90 years of age. The presence of diabetes mellitus and, in non-diabetic subjects, insulin resistance was assessed for 506 participants in whom hippocampal and amygdalar volumes on MRI were measured. We assessed the degree of vascular morbidity by rating carotid atherosclerosis, and brain white matter lesions and infarcts on MRI. Results. Subjects with diabetes mellitus had more hippocampal and amygdalar atrophy on MRI compared to subjects without diabetes mellitus. Furthermore, increasing insulin resistance was associated with more amygdalar atrophy on MRI. The associations were not due to vascular morbidity being more pronounced in persons with diabetes mellitus. Conclusions/interpretation. Type 2 diabetes is associated with hippocampal and amygdalar atrophy, regardless of vascular pathology. This could suggest that Type 2 diabetes directly influences the development of Alzheimer neuropathology.

White matter lesions and silent lacunar infarcts are related to andmay result from cerebral small vessel disease. Reported frequencies of theselesions vary largely among studies. Differences in imaging techniques, ratingscales, cut-off points in lesion severity grading and study populations contribute to the variation, in addition to differences in risk factor profiles acrossstudies.

Background: Little is known about the long-term outcome for patients who recover from a primary intracerebral hemorrhage. The authors examined the rate of recurrence, vascular events, and death in survivors of a primary intracerebral hemorrhage and the factors related to the long-term prognosis.Methods: All 243 patients admitted to one of three hospitals with a primary intracerebral hemorrhage who regained independence were interviewed about vascular events after the index hemorrhage. The authors used the Kaplan–Meier method to estimate the event-free survival and Cox proportional hazards regression analysis to identify predictors of recurrence, any vascular event, or death.Results: During a mean follow-up of 5.5 years, the annual rates of recurrent primary intracerebral hemorrhage, vascular events, and vascular death were 2.1% (95% CI, 1.4 to 3.3%), 5.9% (95% CI, 4.5 to 7.7%), and 3.2% (95% CI, 2.2 to 4.5%). Age of 65 years or older was the only predictor of a recurrence (hazard ratio [HR], 2.8; 95% CI, 1.3 to 6.1) and vascular death (HR, 3.7; 95% CI, 2.0 to 7.0). In addition to age, male sex predicted the occurrence of vascular events (HR, 1.8; 95% CI, 1.1 to 3.0). Use of anticoagulation after the index bleeding tripled the risk of hemorrhagic events (HR, 3.0; 95% CI, 1.3 to 7.2).Conclusion: Patients who recovered from a primary intracerebral hemorrhage had a 2.1% to 5.9% annual rate of recurrence, vascular death, or vascular events. Age of 65 years or older more than doubled the risk of recurrence, vascular event, or death. The risk of vascular events in men was increased twofold.

The devastating effects of stroke have been recognized since antiquity. As the name stroke implies, this clinical event is characterized by the sudden onset of neurologic deficits related to vascular disease. An initial hint that vascular disease of the brain was far more pervasive than suggested by the occurrence of strokes due to overt brain infarcts came from pathologic studies showing that small subcortical brain infarcts were common in elderly patients who had no history of a stroke.1 With the advent of sophisticated brain imaging, especially MRI, the frequency of brain infarcts could be quantified initially in groups of select patients and eventually in populations of healthy people. These brain infarcts are common and, although often labeled benign and silent, have been associated with an increased risk of subsequent cognitive impairment, dementia, and stroke.2–6 The descriptor covert was suggested to convey the potentially ominous clinical course in patients harboring these MRI-defined brain …

Background and Purpose Several studies have found a morning peak in onset of stroke. A similar peak has been suggested for subarachnoid hemorrhage (SAH), which seems in contradiction with the physical activities associated with aneurysmal rupture. Most studies included only a few patients with SAH. We analyzed time of onset of aneurysmal SAH in our patients and in data pooled from previous studies. We also studied time of onset in patients with perimesencephalic hemorrhage, which is believed to have a nonaneurysmal venous origin. Methods Of all 468 patients registered from 1989 through 1995, 385 fulfilled the criteria for aneurysmal SAH and 37 the criteria for perimesencephalic hemorrhage. Time of onset was categorized in 2-hour and 6-hour intervals. We did a Medline search to find previous studies on time of onset of SAH and pooled the data in 2-hour, 3-hour, and 6-hour intervals. Analysis of all intervals was performed by calculating rate ratios with 95% confidence intervals by means of Poisson methods. Results The risk of aneurysmal rupture was lower at night (from 12 pm to 6 am ) in our series and in the pooled-data series. Risk remained high throughout the day and evening, with a nadir around noon. For perimesencephalic hemorrhage, we found the same fluctuation in onset but without a nadir around noon. Conclusions The risk of aneurysmal SAH is low during the night and at noon and high during working hours. This circadian fluctuation parallels that of blood pressure and suggests that an increase in blood pressure is a risk factor for aneurysmal rupture.

P137 Background Silent brain infarcts are commonly seen on MRI in patients with a first stroke, and in healthy elderly as well. They seem to be associated with an increased risk of stroke. It is unclear whether risk factors for silent infarcts are identical to those for symptomatic stroke. We investigated the prevalence of and cardiovascular risk factors for silent brain infarcts. Methods The Rotterdam Scan Study is a population based cohort study among 1077 participants, aged 60–90 years. All participants underwent cerebral MRI. Infarcts were scored blind to history of stroke and TIA. We assessed cardiovascular risk factors by interview and physical examination. We analysed the associations between risk factors and presence of infarcts by logistic regression, adjusted for age, sex and relevant confounders. Results In 262 participants (24%) infarcts showed on MRI. Of them, 216 persons had silent and 46 symptomatic infarcts. Prevalence of both silent and symptomatic infarcts increased with age (OR 1.08 per year (95%CI 1.06–1.10) and 1.08 (1.03–1.12), respectively). Silent infarcts were more frequent in women than men (OR 1.4 (1.0–1.9)). We found no sex difference for symptomatic infarcts. Hypertension was associated with silent infarcts (OR 2.3 (1.6–3.2)), as was pulse pressure (OR 1.2 per 10 mm Hg increase (1.1–1.3)). Diabetes mellitus, smoking and myocardial infarction tripled the odds only of symptomatic infarcts. Conclusions Prevalence of silent brain infarcts is higher with increasing age and in women. Hypertension and high pulse pressure are associated with silent infarcts. Other cardiovascular risk factors are related only to symptomatic infarcts.