Incident Cerebral Microbleeds Research Articles

Abstract MP90: Carotid Arterial Stiffness is Associated with An Increased Risk of Incident Cerebral Microbleeds in Older People: the Age, Gene/Environment Susceptibility-Reykjavik Study

Introduction: Cerebral microbleeds (CMBs) resulting from cerebral amyloid angiopathy are predominantly located in lobar regions, whereas those from hypertension are in deep and infratentorial regions. Although age and high blood pressure are major risk factors for CMBs, the underlying mechanisms remain unclear; arterial stiffness may be important. Hypothesis: We hypothesized that carotid arterial stiffness, would be associated with incident CMBs. Given the spatial distributions of the underlying arteriopathies in which hypertensive arteriopathy typically affects the small perforating end-arteries of the deep structures, we further hypothesized that the associations would be more robust for deep CMBs attributed to hypertensive arteriopathy. Methods: In the prospective, population-based Age, Gene/Environment Susceptibility-Reykjavik Study, 2,512 participants aged 66-97 years underwent a baseline brain MRI examination and carotid ultrasound in 2002-2006, and returned for a repeat brain MRI in 2007-2011. Common carotid arterial stiffness was assessed using a standardized protocol and expressed as carotid arterial strain (CAS), distensibility coefficient (DC) and Young’s elastic modulus (YEM). Log-binomial regression was applied to relate carotid arterial stiffness parameters to CMBs incidence. Results: During a mean follow-up of 5.2 years, 463 people (18.4%) developed new CMBs, of whom 292 had CMBs restricted to lobar regions and 171 had CMBs in a deep or infratentorial region. After adjusting for age, sex and brain MRI interval, all arterial stiffness parameters were each significantly associated with incident CMBs (Risk ratio [RR] per SD decrease in CAS, 1.11 [95%CI, 1.02-1.21]; RR per SD decrease in natural log-transformed DC, 1.14[1.05-1.23]; RR per SD decrease in natural log-transformed YEM, 1.13[1.04-1.22]) and deep CMBs (RR, 1.17[1.00-1.36]; 1.24[1.07-1.43]; 1.22[1.06-1.41] respectively) but not with lobar CMBs. When further adjusted for baseline vascular risk factors including blood pressure and use of blood pressure lowering drugs, the presence of carotid plaque, prevalent CMBs, subcortical infarcts and white matter hyperintensities, the associations persisted. Conclusion: Our findings support the hypothesis that localized increases in carotid arterial stiffness may contribute to the development of CMBs, especially those occuring in a deep location.

Cerebral Microbleeds Are Associated with the Progression of Ischemic Vascular Lesions

Background: Despite their different appearance on imaging, hemorrhagic and ischemic vascular lesions frequently co-occur in the brain and are hypothesized to progress concurrently. Although silent hemorrhagic and ischemic vascular brain lesions are highly prevalent in the general population, the concomitant progression of these lesions has only been studied to a limited extent in this population. We therefore aimed to investigate whether pre-existing and incident cerebral microbleeds (CMBs) are related to the progression of ischemic lesions in the general population. Methods: In the prospective population-based Rotterdam Scan Study, 803 individuals aged ≥60 years underwent magnetic resonance imaging at baseline and after an average interval of 3.4 years. The presence of microbleeds and lacunes was visually rated by trained research physicians, and white matter lesions (WMLs) were automatically segmented at both time points. Logistic regression was used to investigate the association of microbleeds with incident lacunes, and linear regression was used to investigate the relation between microbleeds and progression of WML volume. All analyses were adjusted for age, sex and the time interval between baseline and follow-up scanning. The analyses were repeated after additional adjustments for cardiovascular risk factors: blood pressures; total and high-density lipoprotein cholesterol; smoking; diabetes mellitus; lipid lowering, antihypertensive and antiplatelet medications, and apolipoprotein E ε4. The analyses involving WMLs were also adjusted for intracranial volume. Results: We found that pre-existing microbleeds in any location of the brain were related to a higher incidence of lacunes (odds ratio [OR] adjusted for age, sex and scan interval: 4.67; 95% confidence interval [CI]: 1.84-11.85). Pre-existing microbleeds were not related to progression of WML volume (mean difference in WML volume increase: -0.03; 95% CI: -0.15 to 0.09). Additional adjustments for cardiovascular risk factors did not change the results considerably. Incident microbleeds in any location of the brain were associated with a higher incidence of lacunes (OR: 9.18; 95% CI: 3.61-23.35), whereas only incident microbleeds located in cortico-subcortical regions were related to progression of WML volume (mean difference in WML volume increase: 0.41; 95% CI: 0.21-0.62). Again, adjustments for cardiovascular risk factors did not change the results significantly. Conclusions: Our findings suggest that in the general population, CMBs serve as a predictor of ischemic brain lesions and may represent an imaging marker of active vasculopathy. These results support the hypothesis of a common underlying pathway in the development of ischemic and hemorrhagic brain lesions.

Pre-Existing and Incident Cerebral Microbleeds Are Associated with Progression of Ischemic Vascular Lesions (S62.006)

Pre-Existing and Incident Cerebral Microbleeds Are Associated with Progression of Ischemic Vascular Lesions (S62.006)

Chronic Obstructive Pulmonary Disease and Cerebral Microbleeds. The Rotterdam Study

Chronic obstructive pulmonary disease (COPD) is a common, complex multisystem disease in the elderly with multiple comorbidities that significantly impact morbidity and mortality. Although cerebral small-vessel disease is an important cause of cognitive decline and age-related disability, it is a poorly investigated potential systemic manifestation of patients with COPD. To examine whether COPD relates to the development and location of cerebral microbleeds, a novel marker of cerebral small-vessel disease. Cross-sectional and longitudinal analyses were part of the Rotterdam Study, a prospective population-based cohort study in subjects aged greater than or equal to 55 years. Diagnosis of COPD was confirmed by spirometry. Cerebral microbleeds were detected using high-resolution magnetic resonance imaging (MRI). Subjects with COPD (n = 165) had a higher prevalence of cerebral microbleeds compared with subjects with normal lung function (n = 645) independent of age, sex, smoking status, atherosclerotic macroangiopathy, antithrombotic use, total cholesterol, triglycerides, and serum creatinin (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.15-2.47; P = 0.007). Regarding the specific microbleed location, subjects with COPD had a significantly higher prevalence of microbleeds in deep or infratentorial locations (OR, 3.3; 95% CI, 1.97-5.53; P < 0.001), which increased with severity of airflow limitation and are suggestive of hypertensive or arteriolosclerotic microangiopathy. Furthermore, in longitudinal analysis restricted to subjects without microbleed at baseline, COPD was an independent predictor of incident cerebral microbleeds in deep or infratentorial locations (OR, 7.1; 95% CI, 2.1-24.5; P = 0.002). Our findings are compatible with COPD causing an increased risk of the development of cerebral microbleeds in deep or infratentorial locations.