warfarin and Cerebral-Amyloid-Angiopathy

Recent studies have revealed that atrial fibrillation (AF) patients have a high risk of developing cognitive impairment, vascular dementia, and Alzheimer's disease (AD). Some reports suggest that the application of oral anticoagulant with an appropriate dose may have a preventive effect on AD. However, which oral anticoagulant drug is more appropriate for preventing AD and the underlying mechanism(s) is still unknown.. The aim of the present study was to assess the treatment effect of rivaroxaban administration as well as investigate the roles of PAR-1 and PAR-2 in the AD + CAA mice model.. In the present study, we compared a traditional oral anticoagulant, warfarin, and a direct oral anticoagulant (DOAC), rivaroxaban, via long-term administration to an AD with cerebral amyloid angiopathy (CAA) mice model.. Rivaroxaban treatment attenuated neuroinflammation, blood-brain barrier dysfunction, memory deficits, and amyloid-β deposition through PAR-1/PAR-2 inhibition in the AD + CAA mice model compared with warfarin and no-treatment groups.. The present study demonstrates that rivaroxaban can attenuate AD progress and can be a potential choice to prevent AD.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Anticoagulants; Cerebral Amyloid Angiopathy; Disease Models, Animal; Humans; Mice; Neuroinflammatory Diseases; Rivaroxaban; Warfarin

Brain microbleeds are small dot-like lesions appearing as hyposignal on gradient echo T2* MR sequences. They represent microscopic areas of old haemosiderin deposits. They are frequent in the setting of symptomatic cerebrovascular disease and also in older healthy people, suggesting a link with cerebral amyloid angiopathy. Their use as diagnostic or prognostic biomarkers remains uncertain. More recently, they have been highlighted as a potential key factor in the pathogenesis of Alzheimer's disease, connecting the main pathological contributors of amyloid accumulation and cerebrovascular damage. The increasing use of MRI in clinical practice and research has brought brain microbleeds very much to our attention, raising many clinical dilemmas, such as-what do they mean? Should I treat a patient with antithrombotic drugs or thrombolysis? And many others.

Topics: Alzheimer Disease; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Brain; Cerebral Amyloid Angiopathy; Humans; Intracranial Hemorrhages; Magnetic Resonance Imaging; Warfarin

To identify and compare clinical and neuroimaging predictors of primary lobar intracerebral hemorrhage (ICH) recurrence, assessing their relative contributions to recurrent ICH.. Subjects were consecutive survivors of primary ICH drawn from a single-center prospective cohort study. Baseline clinical, imaging, and laboratory data were collected. Survivors were followed prospectively for recurrent ICH and intercurrent aspirin and warfarin use, including duration of exposure. Cox proportional hazards models were used to identify predictors of recurrence stratified by ICH location, with aspirin and warfarin exposures as time-dependent variables adjusting for potential confounders.. A total of 104 primary lobar ICH survivors were enrolled. Recurrence of lobar ICH was associated with previous ICH before index event (hazard ratio [HR] 7.7, 95% confidence interval [CI] 1.4-15.7), number of lobar microbleeds (HR 2.93 with 2-4 microbleeds present, 95% CI 1.3-4.0; HR = 4.12 when >or=5 microbleeds present, 95% CI 1.6-9.3), and presence of CT-defined white matter hypodensity in the posterior region (HR 4.11, 95% CI 1.01-12.2). Although aspirin after ICH was not associated with lobar ICH recurrence in univariate analyses, in multivariate analyses adjusting for baseline clinical predictors, it independently increased the risk of ICH recurrence (HR 3.95, 95% CI 1.6-8.3, p = 0.021).. Recurrence of lobar ICH is associated with previous microbleeds or macrobleeds and posterior CT white matter hypodensity, which may be markers of severity for underlying cerebral amyloid angiopathy. Use of an antiplatelet agent following lobar ICH may also increase recurrence risk.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Cerebral Amyloid Angiopathy; Cerebral Hemorrhage; Cohort Studies; Female; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Prospective Studies; Secondary Prevention; Warfarin

Intracerebral hemorrhage (ICH) is the most feared complication of warfarin therapy. The pathogenesis of this often-fatal complication remains obscure. Cerebral amyloid angiopathy (CAA) is a major cause of spontaneous lobar hemorrhage in the elderly and is associated with specific alleles of the APOE gene.. To assess the role of CAA in warfarin-associated ICH.. Clinical characteristics and APOE genotype were compared between 41 patients with warfarin-related ICH (from a cohort of 59 consecutive patients aged > or = 65 years with supratentorial ICH on warfarin) and 66 randomly selected individuals aged > or = 65 years without ICH taking warfarin. In addition, all neuropathologic specimens from ICH patients were reviewed for the presence and severity of CAA.. Hemorrhages tended to be in the lobar regions of the brain, and most (76%) occurred with an international normalized ratio of < or = 3.0. The APOE epsilon2 allele was overrepresented among patients with warfarin-associated lobar hemorrhage (allele frequency 0.13 versus 0.04 in control subjects; p = 0.031). After controlling for other variables associated with ICH, carriers of the epsilon2 allele had an OR of 3.8 (95% CI, 1.0 to 14.6) for lobar ICH. CAA was pathologically diagnosed as the cause of lobar hemorrhage in 7 of 11 patients with available tissue samples.. CAA is an important cause of warfarin-associated lobar ICH in the elderly. Although diagnosis of CAA before hemorrhage is not yet possible, these data offer hope that future patients at high risk for hemorrhage may be identified before initiation of warfarin therapy.

Topics: Aged; Aged, 80 and over; Alleles; Apolipoproteins E; Cerebral Amyloid Angiopathy; Cerebral Hemorrhage; Female; Genotype; Humans; Male; Prospective Studies; Warfarin

Topics: Aged; Cerebral Amyloid Angiopathy; Cerebral Hemorrhage; Diagnosis, Differential; Fatal Outcome; Female; Humans; Radiography; Warfarin