Cerebral microbleeds are predictive of mortality in the elderly.
ABSTRACT To investigate the prognostic value of cerebral microbleeds (CMB) regarding overall, cardiovascular-related, and stroke-related mortality and to investigate possible differences based on a cerebral amyloid angiopathy-type and nonlobar distribution of microbleeds.
We included 435 subjects who were participants from the nested MRI substudy of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Cox proportional hazard models were applied to estimate the risk of overall, cardiovascular-related, and stroke-related death associated with microbleeds in general and microbleeds with a lobar distribution suggestive of the presence of cerebral amyloid angiopathy. The corresponding Kaplan-Meier survival curves were calculated.
Subjects with >1 CMB had a 6-fold risk of stroke-related death compared to subjects without CMB (hazard ratio, 5.97; 95% CI, 1.60-22.26; P=0.01). The diagnosis of nonlobar microbleeds was associated with >2-fold risk of cardiovascular death compared to subjects without microbleeds (hazard ratio, 2.67; 95% CI, 1.23-5.81; P=0.01). Subjects with probable cerebral amyloid angiopathy-type microbleeds had >7-fold risk of stroke-related death compared to subjects without CMB (hazard ratio, 7.20; 95% CI, 1.44-36.10; P=0.02).
This is the first study investigating the association between microbleeds and risk of overall, cardiovascular-related, and stroke-related mortality in an elderly population. Our findings indicate that the diagnosis of microbleeds is potentially of clinical relevance. Larger studies are needed to expand our observations and to address potential clinical implications and cost-benefits of such a policy.
- SourceAvailable from: Sergi Martinez-Ramirez[Show abstract] [Hide abstract]
ABSTRACT: Cerebral microbleeds (MBs) are small chronic brain hemorrhages which are likely caused by structural abnormalities of the small vessels of the brain. Owing to the paramagnetic properties of blood degradation products, MBs can be detected in vivo by using specific magnetic resonance imaging (MRI) sequences. Over the last decades, the implementation of these MRI sequences in both epidemiological and clinical studies has revealed MBs as a common finding in many different populations, including healthy individuals. Also, the topographic distribution of these MBs has been shown to be potentially associated with specific underlying vasculopathies. However, the clinical and prognostic significance of these small hemorrhages is still a matter of debate as well as a focus of extensive research. In this article, we aim to review the current knowledge on the pathophysiology and clinical implications of MBs, with special emphasis on the links between lobar MBs, cerebral amyloid angiopathy, and Alzheimer’s disease.Alzheimer's Research and Therapy 06/2014; 6(33). · 4.39 Impact Factor
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ABSTRACT: Cerebral microbleeds (microbleeds) are small, punctuate hypointense lesions seen in T2* Gradient-Recall Echo (GRE) and Susceptibility-Weighted (SWI) Magnetic Resonance Imaging (MRI) sequences, corresponding to areas of hemosiderin breakdown products from prior microscopic hemorrhages. They occur in the setting of impaired small vessel integrity, commonly due to either hypertensive vasculopathy or cerebral amyloid angiopathy. Microbleeds are more prevalent in individuals with Alzheimer's disease (AD) dementia and in those with both ischemic and hemorrhagic stroke. However they are also found in asymptomatic individuals, with increasing prevalence with age, particularly in carriers of the Apolipoprotein (APOE) ε4 allele. Other neuroimaging findings that have been linked with microbleeds include lacunar infarcts and white matter hyperintensities on MRI, and increased cerebral β-amyloid burden using (11)C-PiB Positron Emission Tomography. The presence of microbleeds has been suggested to confer increased risk of incident intracerebral hemorrhage - particularly in the setting of anticoagulation - and of complications of immunotherapy for AD. Prospective data regarding the natural history and sequelae of microbleeds are currently limited, however there is a growing evidence base that will serve to inform clinical decision-making in the future.Frontiers in Neurology 01/2014; 4:205.
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ABSTRACT: Brain microbleeds (BMBs) are common in hypertensive patients and are associated with higher blood pressure (BP) levels. Little is known about risk factors for progression of BMBs, in particular the contribution of ambulatory BP levels. We aimed to determine BMB progression and the association with BP levels in a cohort of essential hypertensive patients. At baseline and after 2 years of follow-up, 193 participants underwent brain magnetic resonance imaging (MRI) and 24-hour ambulatory BP measurement in addition to office BP measurement. The relation between BMB progression and baseline untreated BP characteristics was tested in logistic regression analyses. Progression of BMBs on follow-up MRI was seen in 12 (6%) participants. Patients with progression were significantly older, and the prevalence as well as total number of BMBs at baseline was greater. With correction for age and sex, baseline 24-hour systolic and diastolic BP and 24-hour pulse pressure significantly predicted progression. Similar results were seen for baseline awake and asleep BP. On additional adjustments for baseline presence of BMBs, the associations remained significant for 24-hour, awake, and asleep systolic BP, awake diastolic BP, and awake and asleep pulse pressure. Office systolic BP was also associated with progression of BMBs, whereas office diastolic BP was not. High ambulatory BP levels are important and possibly modifiable predictors for progression of BMBs. This warrants further study, with an adequately long follow-up period and early adequate treatment of hypertension.American Journal of Hypertension 03/2014; · 3.67 Impact Factor
Cerebral microbleeds are predictive of mortality in the elderly
I. Schneider1, S. Trompet1, A. J. de Craen1, A. C. van Es1, M. A. van Buchem1, and J. van der Grond1
1Leiden University Medical Center, Leiden, Netherlands
Cerebral microbleeds represent focal hemosiderin deposits (1) which result from minimal blood leakage from damaged small vessels and can be
detected on T2*-weighted MRI, which is highly sensitive for iron-containing compounds (2). In terms of etiology, cerebral microbleeds can be
divided into microbleeds probably associated with cerebral amyloid angiopathy (CAA) which are located in the cerebral lobes (3) and microbleeds
associated with hypertension and atherosclerosis which are located in the thalamus, basal ganglia, brain stem and cerebellum (4). Microbleeds are not
only common in patients with ischemic stroke (5), intracerebral hemorrhage (ICH) (6) and Alzheimer disease (7) but also in healthy aging (8).
Recently Hennemann et al. have shown that microbleeds are the strongest predictor of all-cause mortality within a group of MRI biomarkers of
vascular damage and atrophy in a memory clinic population (9). To our knowledge it is not known whether microbleeds or distributive patterns of
microbleeds are also predictive of mortality in the general population. Therefore, we investigated the prognostic value of microbleeds in terms of all-
cause mortality and cardiovascular mortality in a population suffering from vascular disease or at high risk for developing this condition.
Patients were included from the nested MRI substudy of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) who were recruited
from the general population. Inclusion and exclusion criteria have been described in detail elsewhere (10). A susceptibility-weighted scan for
microbleed score was available for 435 women and men aged between 70 and 82 years. All imaging was performed on an MR system operating at a
field strength of 1.5 T (Philips Medical Systems, Best, The Netherlands). Dual fast spin echo [repetition time (TR) = 3,000 ms; echo time (TE) =
27/120 ms; slice thickness = 3 mm; 48 slices; no interslice gap; field of view (FOV) = 220 x 220 mm; matrix = 256 x 204], FLAIR (TR = 8,000 ms;
TE = 100 ms; slice thickness = 3 mm; 48 slices; no interslice gap; FOV = 220 x 176 mm; matrix = 256 x 153) and susceptibility-weighted images
(multislice gradient echo sequence; TR = 2593 ms; TE = 48 ms; slice thickness = 6 mm; 22 slices; interslice gap = 0.6 mm; whole brain coverage;
FOV = 220 x 198 mm; matrix = 256 x 176) were obtained from all subjects.. All MRI scans were read in consensus by 2 experienced raters, who
were blinded to the clinical history. Microbleeds were defined as focal areas of signal loss on T2-weighted images that increased in size on the T2-
weighted gradient echo planar images (‘blooming effect’) (Figure 1) (11). In this way, microbleeds were differentiated from areas of signal loss based
on vascular flow void. Areas of symmetric hypointensity in the basal ganglia likely to represent calcification or nonhemorrhagic iron deposits were
disregarded. The location, number, and size of microbleeds were recorded (12). In a first analysis, we dichotomized subjects into a group having at
most 1 microbleed and into a group having two or more microbleeds. Subsequently, we applied the so-called Boston criteria for cerebral amyloid
angiopathy (CAA) in all subjects. The Boston criteria are designed to estimate the likelihood of the presence of CAA during life by means of location
and number of intracerbral hemorrhages (13, 14). Mean follow-up time of all-cause mortality was 6.4 (± 1.8) years. Mean follow-up time of
cardiovascular mortality was
5.7 (± 1.5) years.
Figure 2 shows Kaplan Meier
survival curves for
microbleeds for all-cause
mortality. Cox proportional
hazard models show that
subjects with two or more
microbleeds had a statistical
significant increased risk of
death compared to persons
with no or 1 microbleed (HR
1.75, 95% CI 1.07-2.87, p = 0.027). In terms of cardiovascular mortality Kaplan Meier survival curves show the same trend although reaching no
statistical significance (HR 2.12, 95% CI 0.95-4.72, p = 0.07). Figure 3 shows Kaplan Meier survival curves for microbleeds for cardiovascular
mortality during follow-up period II with microbleeds scored according to the Boston criteria. Cox proportional hazard models show that non-CAA
had a strong predictive effect. Persons diagnosed with non-CAA had a more than 4 fold risk of death compared to persons with at most 1 microbleed
(HR 4.21, 95% CI 1.85-9.58, p = 0.001). In terms of all-cause mortality Cox proportional hazard models show that probable CAA and non-CAA had
a predictive effect although reaching no statistical significance (HR 1.65, 95% CI 0.89-3.08, p = 0.11 and HR 1.73, 95% CI 0.92-3.23, p = 0.09
In this population-based study we found that the presence of two or more microbleeds implicates an increased risk of overall death. Furthermore, only
“non-CAA” type microbleeds were associated with increased risk of cardiovascular death, which is in line with the assumption that these microbleeds
are associated with hypertension and atherosclerosis. Therefore, CAA type small vessel disease cannot be considered as risk factor for
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