Prevalence and risk factors of cerebral microbleeds - The Rotterdam Scan Study

Department of Epidemiology and Biostatistics, Erasmus MC University Medical Center, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands.
Neurology (Impact Factor: 8.29). 05/2008; 70(14):1208-14. DOI: 10.1212/01.wnl.0000307750.41970.d9
Source: PubMed


Cerebral microbleeds are focal deposits of hemosiderin that can be visualized with MRI. Little is known on their prevalence in the general population and on their etiology. It has been suggested that, in analogy to spontaneous intracranial hemorrhage, the etiology of microbleeds differs according to their location in the brain, with lobar microbleeds being caused by cerebral amyloid angiopathy and deep or infratentorial microbleeds resulting from hypertension and atherosclerosis. We investigated the prevalence of and risk factors for microbleeds in the general population aged 60 years and older.
This study is based on 1,062 persons (mean age 69.6 years) from the population-based Rotterdam Scan Study. MRI was performed at 1.5 T and included a sequence optimized to increase the conspicuity of microbleeds. We assessed the relation of APOE genotype, cardiovascular risk factors, and markers of small vessel disease to the presence and location of microbleeds with multiple logistic regression.
Overall prevalence of cerebral microbleeds was high and increased with age from 17.8% in persons aged 60-69 years to 38.3% in those over 80 years. APOE epsilon 4 carriers had significantly more often strictly lobar microbleeds than noncarriers. In contrast, cardiovascular risk factors and presence of lacunar infarcts and white matter lesions were associated with microbleeds in a deep or infratentorial location but not in a lobar location.
The prevalence of cerebral microbleeds is high. Our data support the hypothesis that strictly lobar microbleeds are related to cerebral amyloid angiopathy, whereas microbleeds in a deep or infratentorial location result from hypertensive or atherosclerotic microangiopathy.

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    • "This finding is somewhat unexpected, given several indirect sources of evidence linking strictly lobar MBs to CAA. First, previous community-based studies show that strictly lobar MBs are associated with the apoplipoprotein epsilon 4 (ε4) allele, which is known to be strongly associated with CAA [5] [6]; second, the population-based Rotterdam study found that strictly lobar MBs (with or without cerebellar MBs) were associated with future ICH risk [7]; and third, a previous hospital study in patients with apparently incidental strictly lobar MBs (without ICH) had a similar rate of subsequent ICH to patients with CAA-related ICH [8]. However, these findings provide only indirect support for a link between strictly lobar MBs and CAA; the ε4 allele is also prevalent in other non– CAA-related conditions [9], and pathologic validation of CAA pathology in observational cohort studies remains scarce. "

    Alzheimer's & dementia: the journal of the Alzheimer's Association 10/2015; DOI:10.1016/j.jalz.2015.09.004 · 12.41 Impact Factor
    • "In the current study none of the DLB patients had CMBs in the deep or infratentorial regions. While this could be due to the limitations of our sample size, CMBs located in the deep or infratentorial regions were associated with cardiovascular risk factors, presence of lacunar infarcts and white matter hyperintensities suggesting hypertensive and atherosclerotic microangiopathy is the underlying etiology [18]. Based on the absence of deep or infratentorial CMBs in the current study, hypertensive and atherosclerotic microangiopathy is less likely to be contributing to CMB pathophysiology in DLB than in AD. "
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    ABSTRACT: To determine the frequency and topographic distribution of cerebral microbleeds (CMBs) in dementia with Lewy bodies (DLB) in comparison to CMBs in Alzheimer disease dementia (AD). Consecutive probable DLB (n = 23) patients who underwent 3-T T2* weighted gradient-recalled-echo MRI, and age and gender matched probable Alzheimer's disease patients (n = 46) were compared for the frequency and location of CMBs. The frequency of one or more CMBs was similar among patients with DLB (30%) and AD (24%). Highest densities of CMBs were found in the occipital lobes of patients with both DLB and AD. Patients with AD had greater densities of CMBs in the parietal, temporal lobes and infratentorial regions compared to DLB (p < 0.05). CMBs are as common in patients with DLB as in patients with AD, with highest densities observed in the occipital lobes, suggesting common pathophysiologic mechanisms underlying CMBs in both diseases. Copyright © 2015. Published by Elsevier Ltd.
    Parkinsonism & Related Disorders 07/2015; 21(9). DOI:10.1016/j.parkreldis.2015.07.008 · 3.97 Impact Factor
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    • "At a community level, the Rotterdam and Framingham studies have shown that healthy elderly individuals with strictly lobar MBs have an increased frequency of the APOE-ε4 allele (compared with patients with MBs not strictly confined to lobar regions) [11] [15], which is in agreement with increased APOE-ε4 frequencies seen in patients with " probable CAA " [16]. Also, strictly lobar MBs do not correlate with classic vascular risk factors [11] [15], which further reinforces their possible association with CAA. However, pathological data supporting the suspected link between lobar MBs and CAA in individuals without lobar ICH are currently lacking. "
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    ABSTRACT: The Boston criteria are the basis for a noninvasive diagnosis of cerebral amyloid angiopathy (CAA) in the setting of lobar intracerebral hemorrhage (ICH). We assessed the accuracy of these criteria in individuals with lobar microbleeds (MBs) without ICH. We identified individuals aged >55 years having brain magnetic resonance imaging (MRI) and pathologic assessment of CAA in a single academic hospital and a community-based population (Framingham Heart Study [FHS]). We determined the positive predictive value (PPV) of the Boston criteria for CAA in both cohorts, using lobar MBs as the only hemorrhagic lesion to fulfill the criteria. We included 102 individuals: 55 from the hospital-based cohort and 47 from FHS (mean age at MRI 74.7 ± 8.5 and 83.4 ± 10.9 years; CAA prevalence 60% and 46.8%; cases with any lobar MB 49% and 21.3%; and cases with ≥2 strictly lobar MBs 29.1% and 8.5%, respectively). PPV of "probable CAA" (≥2 strictly lobar MBs) was 87.5 (95% confidence interval [CI], 60.4-97.8) and 25 (95% CI, 13.2-78) in hospital and general populations, respectively. Strictly lobar MBs strongly predict CAA in non-ICH individuals when found in a hospital context. However, their diagnostic accuracy in the general population appears limited. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 06/2015; 128. DOI:10.1016/j.jalz.2015.04.009 · 12.41 Impact Factor
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