Cerebral Microbleeds Unexpectedly High In Older Individuals

By Judith Groch
ROTTERDAM, The Netherlands, March 31 -- Among persons 60 and older, the prevalence of cerebral microbleeds increased with age, and was higher than previously thought, according to a population-based study.
Extremely sensitive MRI technology produced a three- to four-fold higher overall prevalence of cerebral microbleeds compared with other studies, Monique Breteler, M.D., Ph.D., of ErasmusMC University Medical Center here, and colleagues reported in the April 1 issue of Neurology.
These findings are of major importance, Dr. Breteler said, because the location of these bleeds may reflect cerebrovascular pathology and may be associated with an increased risk of different disorders.
Little is known about the prevalence of microbleeds in the general population and their exact etiology, the researchers said.
It's been suggested that the etiology differs according to the location of the bleed, leading to a difference in risk factors and outcomes, a hypothesis supported by the results of this study.
The researchers analyzed 1,062 scans from randomly selected participants (mean age 69.6 years; 51% women) of the population-based Rotterdam Scan Study, a prospective brain MRI study.
The researchers used a multisequence MRI protocol on a 1.5-T scanner.
For microbleed detection, they used a custom-made accelerated three-dimensional T2*-weighted, gradient-recalled echo sequence with high spatial resolution and long echo time. The device had been previously shown to detect microbleeds nearly twice as often as conventional imaging.
The other sequences in the imaging protocol consisted of three high-resolution axial scans.
Using multiple logistic regression analysis, the researchers looked at the relation of APOE genotype, cardiovascular risk factors, and markers of small-vessel disease according to the presence and location of microbleeds.
The overall prevalence of cerebral microbleeds was high and increased with age from 17.8% in persons from 60 to 69 to 38.3% in those over 80.
Of 250 participants with microbleeds, 146 (58.4%) had bleeds in a strictly lobar location, 44 of them with multiple strictly lobar bleeds.
Carriers of APOE ε4, an allele known to increase the risk of Alzheimer's disease and cerebral amyloid angiopathy, had significantly more strictly lobar microbleeds than non-carriers.
In contrast, cardiovascular risk factors and the presence of lacunar infarcts and white matter lesions were associated with microbleeds in a deep or infratentorial location but not in a lobar location.
After analysis of these microbleeds, excluding those with additional lobar bleeds, the results did not markedly change.
APOE genotype was not related to deep or infratentorial microbleeds.
Rather these bleeds were associated with cardiovascular risk factors such a high systolic blood pressure, high pulse pressure, and smoking.
These microbleeds were also strongly related to lacunar infarcts and white matter lesions, both classic markers of ischemic cerebral small-vessel disease.
These findings suggest that microbleeds in deep or infratentorial locations are etiologically different from those that are strictly lobar in location, and that they may be caused by hypertensive or atherosclerotic microangiopathy, the researchers said.
Their results have major importance in view of previous reports from small clinical series suggesting that microbleeds may reflect an increased risk of recurrence of stroke and hemorrhagic transformation of ischemic stroke, the investigators wrote.
The relationship between microbleeds and therapy-induced bleeding has not been uniformly confirmed. However, the researchers said, it is important to determine whether the choice for thrombolytic treatment in persons with ischemic vascular disease or the use of antiplatelet therapy as primary prevention in asymptomatic persons is affected by the coexistence of cerebral microbleeds in certain locations.
In addition, they said, a potential relationship between microbleeds and impaired cognition or with the severity of small vessel disease suggests clinical relevance for these lesions.
As such, "this study offers new insights into risk factors for microbleeds and warrants further investigation into the prognosis of microbleeds in the general population, focusing on strictly lobar and deep or infratentorial microbleeds separately," the researchers concluded.
The Rotterdam Study is supported by the Erasmus MC University Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development; the Research Institute for Diseases in the Elderly; the Ministry of Education, Culture, and Science; the Ministry of Health, Welfare, and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. This study was further supported by the Netherlands Organization for Scientific Research.
The authors reported no conflicts of interest.
Primary source: NeurologySource reference:Vernooij, MW, et al "Prevalence and risk factors of cerebral microbleeds: The Rotterdam Scan Study" Neurology 2008; 70: 1208-1214.