A new analysis from the Rotterdam Scan Study shows that cerebral microbleeds on
magnetic resonance imaging (MRI) are more prevalent in elderly subjects who use
platelet-aggregation inhibitors than in nonusers.

In particular, strictly lobar microbleeds ¡X which may indicate the presence of
cerebral amyloid angiopathy and possibly bleeding-prone microvessels ¡X were
more frequent among those who used aspirin vs users of carbasalate calcium, the
researchers report. The association between anticoagulant use and microbleeds
was not significant.

The researchers, with senior author Monique M. B. Breteler, MD, PhD, from
Erasmus MC University Medical Center, in Rotterdam, the Netherlands, caution
that the cross-sectional design of their study prevents determining whether
these microbleeds increase the risk for symptomatic hemorrhage and point out
that the benefits of antithrombotic therapy in patients with a history of
myocardial infarction and cerebrovascular disease have been shown to outweigh
the risks.

"Nevertheless, it may be that in selected persons (eg, those with signs of
cerebral amyloid angiopathy), this risk/benefit ratio may differ for certain
drugs (eg, aspirin), thus influencing treatment decisions," they conclude.

Their report, with first author Meike W. Vernooij, MD, also from Erasmus MC
University Medical Center, is published online April 13 and will appear in the
June issue of the Archives of Neurology.

New Markers of Small Vessel Disease

Cerebral microbleeds consist of deposits of hemosiderin in macrophages and can
be seen on T2-weighted gradient recalled echo (GRE) MRI as small areas of
hypointensity, the authors write. In the past decade, "these microbleeds have
become acknowledged as new markers of small vessel disease in the brain."

Microbleeds are thought to occur in the setting of either cerebral amyloid
angiopathy or arteriosclerotic microangiopathy, they note. Their location in the
brain is thought to reflect their underlying origin: microbleeds in the deep or
infratentorial locations, for example, are thought to relate to hypertensive or
arteriosclerotic microangiopathy, while those in the strictly lobar brain sites
result from cerebral amyloid angiopathy, a bleeding-prone state, they write.

Previous work has linked the use of platelet-aggregation inhibitors and
anticoagulants to increased risk for symptomatic hemorrhage in patients with
cerebral amyloid angiopathy, raising the question of whether asymptomatic
microbleeds might also be accelerated by use of these drugs.

"We hypothesized that microbleeds, especially those with strictly lobar
locations, occur more often in persons using antithrombotic drugs," they write.

To investigate this relationship, Dr. Breteler and colleagues used data from the
Rotterdam Scan Study, a large, population-based cross-sectional imaging study of
community-dwelling elderly in the Netherlands. A total of 1062 subjects who were
60 years of age or older and free of dementia underwent MRI imaging between
August 15, 2005 and November 22, 2006. Complete information on their use of
antithrombotic drugs was obtained from automated pharmacy records.

Of the 1062 subjects, 363 (34.2%) had used any antithrombotic agent. Of these,
245 (23.1%) took platelet-aggregation inhibitors, including 67 who used aspirin
and 141 taking carbasalate calcium.


Compared with nonusers, those taking platelet-aggregation inhibitors had a
significantly increased prevalence of cerebral microbleeds. The relationship
between microbleeds and anticoagulant use was not significant.

When they looked by type of antiplatelet medication, strictly lobar microbleeds
were more prevalent among users of aspirin than among those taking carbasalate
calcium.

The difference in risk for microbleeds was even more pronounced when they
compared those who were using similar doses of each drug, they note.

These findings justify further longitudinal research into this association, the
authors conclude. "Of particular clinical interest would be a study of whether
the presence of microbleeds increases the risk of symptomatic intracerebral
hemorrhage in persons using antithrombotic medication."

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; and the Municipality of Rotterdam. The study was further supported
by grants from the Netherlands Organization for Scientific Research. The authors
report no conflict of interest.

Arch Neurol. Published online April 13, 2009. Abstract