SummaryBackgroundCerebral microbleeds are a potential neuroimaging biomarker of cerebral small vessel diseases that are prone to intracranial bleeding. We aimed to determine whether presence of cerebral microbleeds can identify patients at high risk of symptomatic intracranial haemorrhage when anticoagulated for atrial fibrillation after recent ischaemic stroke or transient ischaemic attack.MethodsOur observational, multicentre, prospective inception cohort study recruited adults aged 18 years or older from 79 hospitals in the UK and one in the Netherlands with atrial fibrillation and recent acute ischaemic stroke or transient ischaemic attack, treated with a vitamin K antagonist or direct oral anticoagulant, and followed up for 24 months using general practitioner and patient postal questionnaires, telephone interviews, hospital visits, and National Health Service digital data on hospital admissions or death. We excluded patients if they could not undergo MRI, had a definite contraindication to anticoagulation, or had previously received therapeutic anticoagulation. The primary outcome was symptomatic intracranial haemorrhage occurring at any time before the final follow-up at 24 months. The log-rank test was used to compare rates of intracranial haemorrhage between those with and without cerebral microbleeds. We developed two prediction models using Cox regression: first, including all predictors associated with intracranial haemorrhage at the 20% level in univariable analysis; and second, including cerebral microbleed presence and HAS-BLED score. We then compared these with the HAS-BLED score alone. This study is registered with ClinicalTrials.gov, number NCT02513316.FindingsBetween Aug 4, 2011, and July 31, 2015, we recruited 1490 participants of whom follow-up data were available for 1447 (97%), over a mean period of 850 days (SD 373; 3366 patient-years). The symptomatic intracranial haemorrhage rate in patients with cerebral microbleeds was 9·8 per 1000 patient-years (95% CI 4·0–20·3) compared with 2·6 per 1000 patient-years (95% CI 1·1–5·4) in those without cerebral microbleeds (adjusted hazard ratio 3·67, 95% CI 1·27–10·60). Compared with the HAS-BLED score alone (C-index 0·41, 95% CI 0·29–0·53), models including cerebral microbleeds and HAS-BLED (0·66, 0·53–0·80) and cerebral microbleeds, diabetes, anticoagulant type, and HAS-BLED (0·74, 0·60–0·88) predicted symptomatic intracranial haemorrhage significantly better (difference in C-index 0·25, 95% CI 0·07–0·43, p=0·0065; and 0·33, 0·14–0·51, p=0·00059, respectively).InterpretationIn patients with atrial fibrillation anticoagulated after recent ischaemic stroke or transient ischaemic attack, cerebral microbleed presence is independently associated with symptomatic intracranial haemorrhage risk and could be used to inform anticoagulation decisions. Large-scale collaborative observational cohort analyses are needed to refine and validate intracranial haemorrhage risk scores incorporating cerebral microbleeds to identify patients at risk of net harm from ora...

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V ascular dementia (VaD) comprises a group of syndromes caused by vascular lesions in the brain. Cognitive impairment may follow a single cortical or lacunar infarct in a strategic area of the brain, multiple infarcts, small-vessel disease (leukoaraiosis), intracerebral hemorrhage, or any of these conditions coexisting with Alzheimer dementia (so-called mixed dementia). Depending on case mix and the type of observational study, 10% of patients already have dementia before their first stroke, 10% develop it soon after their first stroke, and more than 33% have dementia after a recurrent stroke. 1 Typically, dementia develops at a rate of 3% per year after stroke, and it is the stroke, rather than its underlying risk factors, that appears to be the dominant cause of subsequent dementia. 1 See accompanying articles on pages 599 and 605Although VaD, including poststroke dementia, is associated with conventional risk factors, such as hypertension and hypercholesterolemia, 2,3 their relationship with hemostatic factors is less clear. This contrasts with the relationship between hemostatic factors and stroke, which is well established and involves both soluble (eg, fibrinogen 4 ) and cellular (eg, mean platelet volume 5 ) biomarkers. Several hemostatic factors, including fibrinogen and fibrin D-dimer levels, are associated with subsequent cognitive impairment and dementia in observational studies (Table). 6 -10 This issue of Arteriosclerosis, Thrombosis, and Vascular Biology expands on this relationship between "sticky blood" and cognition. 11 Two new studies are described.First, Stott and colleagues 12 report observational data from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER), which examined lipid lowering 13 : 5699 people (average age, 75 years) not taking warfarin had measurements of hemostatic factors at baseline and annual assessments of cognition over 3.2 years of follow-up. Cognitive measures included speed of information processing (Letter Digit Coding Test and Stroop test) and verbal memory (picture-word naming). The central finding was that increased levels of D-dimer and prothrombin fragment 1ϩ2 (ie, markers of thrombin generation) were associated independently with increased rates of cognitive decline and deterioration in activities of daily living (Table). 12 Interestingly, markers of endothelial dysfunction (eg, tissue plasminogen activator and von Willebrand factor) were not associated with cognitive decline.Second, Gallacher and colleagues 14 present data on 865 men free of vascular disease, with biomarker measurements, who were observed in the Caerphilly community cohort. Hemostasis factors were measured at the age of 45 to 59 years, and cognition and dementia were determined up to the age of 65 to 84 years. During 17 years of follow-up, 59 of the men developed dementia and 112 developed cognitive impairment/no dementia. Increased fibrinogen, factor VIII, and plasminogen activator inhibitor-1 levels were associated independently with VaD (Table). 14 In contrast, increased lev...