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C-Reactive Protein May Predict Brain Changes
  MedPage Today
Published: March 29, 2010
Action Points
- Explain to interested patients that in this study, elevated levels of high-sensitivity C-reactive protein (CRP) were associated with cognitive impairment and white matter damage.
- But note that this cross-sectional study could not establish a causal relationship between CRP levels and either cognitive function or white matter microstructure.
Elevated levels of high-sensitivity C-reactive protein (CRP) are associated with cognitive impairment and white matter damage, a cross-sectional German study showed.
Stroke-free adults with higher levels of CRP had worse performance on tests of executive function than those with lower CRP levels (P=0.02), Heike Wersching, MD, of the University of Mčnster, and colleagues reported in the March 30 issue of Neurology.
Increased levels of CRP, which had been linked to a greater dementia risk in previous studies, were also associated with MRI markers of microstructural white matter damage.
Lowering CRP has been shown to reduce cardiovascular events, Wersching and her colleagues noted, but "whether lowering of CRP can also prevent cognitive decline and/or microstructural white matter alterations needs to be addressed in upcoming clinical trials."
The researchers looked at data from 447 adults ages 40 to 85 (mean 63.3) from the Systematic Evaluation and Alteration of Risk Factors for Cognitive Health (SEARCH) Health Study. All lived in the Mčnster area.
The mean serum CRP level at baseline was 0.12 mg/dL. Scores on neuropsychological tests were within normal ranges.
Higher levels of CRP were associated with worse scores on tests of executive function after adjustment for age, gender, education, and cardiovascular risk factors.
Compared with individuals who had a CRP level of less than 0.1 mg/dL, it took five to six seconds longer to complete the Trail-Making Test Part B for those with levels from 0.1 to 0.3 mg/dL and 12 seconds longer for those with levels greater than 0.3 mg/dL. Overall, the mean completion time was 85.32 seconds.
This association was significant among the younger subgroup only (ages 41 to 64).
High-field brain MRI with diffusion tensor imaging to evaluate white matter microstructure was performed in 321 of the participants.
Those with higher CRP levels had reduced whole-brain fractional anisotropy and regional fractional anisotropy of the frontal lobes, corticospinal tract, corona radiata, and corpus callosum, particularly in the genu (P▓0.016 for all).
Compared with the lowest tertile of CRP, the middle tertile was associated with a decrease in frontal fractional anisotropy equal to six years of aging, and the highest tertile was associated with a reduction equal to 12 years of aging.
According to Wersching and her colleagues, lower fractional anisotropy has been shown in postmortem studies of humans to reflect the extent of astrogliosis and loss of myelin and axons.
The inverse relationship between CRP levels and fractional anisotropy suggests "a microvascular damage of white matter projections in frontal-subcortical pathways, leading to executive dysfunction," they wrote.
The association between CRP and global and frontal fractional anisotropy was significant in adults with no or mild white matter disease, but not in those with more severe disease.
"These findings suggest the role of CRP as a very sensitive and early marker of cerebral small-vessel disease, maybe losing its predictive power in advanced cerebrovascular disease," the researchers wrote.
In an accompanying editorial, Ronald Killiany, PhD, of Boston University, wrote, "The findings ... offer the prospect that a combination of measurements of systemic inflammation (C-reactive protein) and sensitive imaging modalities (diffusion tensor imaging) might some day provide an assay for brain microvascular disease and provide a means for intervention."
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