VAS-COG: Brain Effects of Carotid Disease Emerge in Middle Age

SAN ANTONIO, July 13 -- Years before carotid artery disease poses a stroke risk, arterial thickening and early-stage atherosclerosis may cause deterioration in cognitive performance.

Early carotid disease was associated with lower total cerebral brain volume (P=0.04 with >25% stenosis) and an increased prevalence of white matter hyperintensity (P=0.001 with >25% stenosis) on MRI, indicative of brain ischemia and aging, investigators reported at the International Society of Vascular Behavioral and Cognitive Disorders meeting here.

Thickening of the internal carotid artery had the greatest impact, however, with MRI evidence of aging and decreased performance on multiple measures of cognitive function, said Jose Rafael Romero, M.D., of the University of Kansas Medical Center in Kansas City.

"The associations varied according to the carotid arterial site where atherosclerosis was evaluated," he said.

Vascular risk factors are associated with carotid stenosis, carotid intima-media thickness (IMT), and MRI signs of brain ischemia and aging, specifically white matter hyperintensity and reduced brain volume. MRI evidence of ischemia and aging has been linked to an increased risk of cognitive impairment, dementia, and stroke.

The Framingham Offspring Study afforded an opportunity to study associations among vascular risk factors, carotid disease, and MRI evidence of brain ischemia and aging, said Dr. Romero.

In particular, the Framingham database allowed Dr. Romero and colleagues to examine the effect of site-specific differences in carotid atherosclerosis on MRI brain volume and cognitive performance.

Their study involved 2,236 men and women whose mean age was 58. The participants had had a carotid ultrasound during the 1995 through 1998 Framingham examination cycle and brain MRI and neuropsychological testing during the 1999-2001 cycle. All of the patients were free of stroke, dementia, and neurologic disease at the time of the MRI scan.

Carotid ultrasound was by a standard protocol that consisted of two images at the common carotid, bifurcation, and proximal internal carotid arteries. Intima-media thickness was measured at three sites in both carotid arteries, and maximal thickness was the measure used for analysis.

Total cerebral brain volume was assessed by quantitative MRI, read by a radiologist blinded to the clinical data. Large areas of white matter hyperintensity also were examined.

Five aspects of neuropsychological functioning were included in the study: verbal memory, visual memory, new learning, executive function, and non-memory.

Dr. Romero reported that 14.6% of study participants had carotid stenosis in excess of 25%, and 1.8% had stenosis in excess of 50%. Total cerebral brain volume (parenchymal volume divided by intracranial volume) averaged 78%, and 13% of participants had large white matter hyperintensity.

In a multivariate analysis adjusted for age, sex, and stroke risk factors, carotid stenosis greater than 25% had a significant association with large white matter hyperintensity (P=0.001) and lower total cerebral brain volume (P=0.04). Stenosis exceeding 50% was associated with white matter hyperintensity (P=0.03) and impaired executive function (P=0.03).

A greater intima-media thickness in the internal carotid artery predicted larger white matter hyperintensity (P=0.02), reduced brain volume (P=0.02), impaired verbal memory (P=0.05), and nonmemory cognitive function (P=0.004).

Intima-media thickness of the common carotid arteries did not correlate with any of the outcome parameters.

Reviewing limitations of the study, Dr. Romero noted that the population was predominantly white, and the study was a cross-sectional analysis. However, the large sample size and the community-based environment lent credence to the results, he said.