Archief Roodbont

Learning Objectives

Upon completion of this activity, participants will be able to:

1. Report whether overall calcification in the coronary arteries, aortic arch, extracranial carotid arteries, and intracranial carotid arteries identified on computed tomography scan is associated with cerebral infarcts, microbleeds, and white matter lesions on brain magnetic resonance imaging scan.
2. Describe whether separate calcification in the coronary arteries, aortic arch, extracranial carotid arteries, or intracranial carotid arteries identified on computed tomography scan is associated with cerebral infarcts, microbleeds, and white matter lesions on brain magnetic resonance imaging scan.

Calcification of the carotid artery noted on computed tomography (CT) scan might predict the risk for stroke, as reported by Nandalur and colleagues in the February 2006 issue of AJR. American Journal of Roentgenology. In the July 2010 issue of Lancet Neurology, Pantoni reported that white matter lesions (WMLs), cerebral infarcts, and cerebral microbleeds on magnetic resonance imaging (MRI) scan are important markers of cerebrovascular disease.

This study by Bos and colleagues, based on the prospective population-based cohort Rotterdam Study described by Hofman and colleagues in the 2009 issue of the European Journal of Epidemiology, assesses the relationship between calcification in major vessel beds identified by CT and MRI markers of vascular brain disease.

Study Synopsis and Perspective

Arterial calcification in major vessel beds outside the brain, as shown with MRI, is associated with vascular brain disease and may be linked to future risk for dementia and stroke, a new study shows.

"Most notably, larger intracranial carotid calcification load relates to larger WML volumes, and larger extracranial carotid calcification load relates to the presence of cerebral infarcts, independently of ultrasound carotid plaque score," the authors, led by Daniel Bos, MD, from Erasmus Medical Center, Rotterdam, the Netherlands, write. Such calcification "provides novel insights into the etiology of vascular brain disease," the authors note.

"The relationship between calcium in atherosclerotic plaque and brain changes exists on top of the effect of classic cardiovascular risk factors such as high blood pressure, smoking and diabetes," senior author Meike W. Vernooij, MD, PhD, also from Erasmus Medical Center, said in a statement.

The amount of calcified plaque outside the brain provided more information about the extent of brain changes than traditional ultrasound measures of plaque in the carotid artery, the authors add.

The findings were published online August 25 in Arteriosclerosis, Thrombosis and Vascular Biology.

The Rotterdam Study

The researchers studied 885 community-dwelling people (50.8% women), mean age 66.7 years, who were participants in the Rotterdam Study, a prospective, population-based cohort study on causes of disease in the elderly.

The authors used CT scans to measure calcification in the coronary arteries, aortic arch, and extracranial and intracranial carotid arteries. They also used brain MRI scans to assess cerebral infarcts, microbleeds, and WMLs, which are considered important markers of vascular brain disease.

The study found that higher CT calcification was associated with larger WML volume and the presence of cerebral infarcts, but not with presence of cerebral microbleeds.

The strongest associations were between intracranial carotid calcification and WML volume, and between extracranial carotid calcification and infarcts. Adjusting for cardiovascular risk factors or ultrasound carotid plaque scores did not change these results.

"The distinction between the impact of calcification in the extracranial and intracranial carotids adds to the current belief that [WMLs] mainly result from disease in smaller intracranial vessels, while brain infarctions are thought to be mainly caused by larger vessel disease," Dr. Vernooij said in a statement.

The authors note that using CT-calcification measurement on a large scale means exposing people to radiation and requires further research.

They add that they can speculate about the possibilities for using CT for such a purpose in the future and point out that at this time, CT is being used more frequently for both diagnostic and screening purposes.

"It is a long way from these results towards making meaningful inferences on what this means for screening individual subjects with CT. Primarily, this study provides novel insight into the link between atherosclerosis and vascular brain disease, which we will use for further studies on how atherosclerosis may affect brain function, and ultimately the risk to develop dementia," Dr. Vernooij told Medscape Medical News.

Dr. Vernooij added that this does not imply that screening for vessel calcification will be cost-effective.

"In the short term, a practical use of our findings in clinical practice could be found in the fact that cardiac CT scans are increasingly performed to assess the risk for coronary heart disease. For a clinician, it may be useful to understand that calcification in coronary arteries, though far away from the brain, may indicate presence of subclinical brain disease as well. However, at present this does not have, yet, implications for therapeutic management," Dr. Vernooij said.

Interesting, but no Clinical Effect at Present

In general, calcification is a marker for chronic and more extensive vascular disease, Joseph Broderick, MD, Albert Barnes Voorheis Chair of Neurology at University of Cincinnati, Ohio, told Medscape Medical News.

"This study of arterial calcification in 4 vascular beds by CT, and correlating this with brain parenchymal changes on MRI, has not been done before," Dr. Broderick, a spokesperson for the American Academy of Neurology, said. "However, it is not surprising that [intracranial carotid artery] calcification correlates better with MRI tissue changes than coronary or aortic arch calcification."

He added that he found it "interesting" that large-vessel calcification load was not associated with microbleeds. "However, these microbleeds have generally been associated with small-vessel, rather than large-vessel, disease. For instance, amyloid vascular disease in brain is small-vessel disease of the cortical vessels."

What Is Old Is New Again

The findings from this study are consistent with a growing body of knowledge, Patrick Lyden, MD, chairman of the Department of Neurology at Cedars-Sinai Medical Center, Los Angeles, California, told Medscape Medical News.

"These patients all had atherosclerosis; they had hardening of the arteries. That's all that calcium is telling you, that there's hardening of the arteries, so you see hardening of the arteries outside the brain, and that tells you there is something wrong in the brain."

Dr. Lyden noted that originally, Alzheimer's disease was thought to be caused by atherosclerosis in the brain.

"When Alzheimer published his very first paper in Germany, he said that Alzheimer's disease was really due to hardening of the arteries in the brain. Then, about 30 years ago, a very clever biochemist showed that no, it has nothing to do with hardening of the arteries. It's all about amyloid, it's all about plaques and tangles in the brain, and so the vascular part of the story was forgotten. But in the last 5 years, the vascular part of the story has been rediscovered, and doctors are paying attention to it again," he said.

Dr. Bos and Dr. Lyden have disclosed no relevant financial relationships. Dr. Vernooij was supported by an Alzheimer's Association Grant.

Arteriscler Thromb Vasc Biol. Published online August 25, 2011. Abstract