Abstract
Low-grade inflammation is implicated in the pathogenesis of atherosclerosis, metabolic syndrome, and apathy as a form of vascular depression. We analyzed the brain magnetic resonance imaging findings in 259 community-dwelling older adults (122 men and 137 women, with a mean age of 68.4 years). The serum concentrations of high-sensitivity C-reactive protein (hsCRP) were measured by a quantitative enzyme-linked immunosorbent assay. Logistic regression analysis revealed that the log10 hsCRP value and the presence of a metabolic syndrome were independently associated with confluent but not punctate deep white matter lesions (DWMLs). Path analysis based on structural equation modeling (SEM) indicated that the direct path from the log10 hsCRP to the DWMLs was significant (β = 0.119, p = 0.039). The direct paths from the metabolic syndrome to the log10 hsCRP and to the DWMLs were also significant. The direct path from the DWMLs to apathy (β = −0.165, p = 0.007) was significant, but the direct path from the log10 hsCRP to apathy was not significant. Inflammation (i.e., elevated serum hsCRP levels) was associated with DWMLs independent of common vascular risk factors, while DWMLs were associated with apathy. The present analysis with SEM revealed the more realistic scheme that low-grade inflammation was associated with apathy indirectly via DWMLs in community-dwelling older adults.
Highlights
Low-grade inflammation, which is typically determined by increased levels of high-sensitivity C-reactive protein, has been recognized in several studies as a risk factor for ischemic stroke, independent of other cardiovascular risk factors [1,2,3,4]
An earlier study reported that higher levels of both CRP and IL-6 were associated with silent brain infarction even when adjusted with traditional vascular risk factors [8], whereas higher CRP levels were associated with the presence and progression of deep white matter lesions (DWMLs) [9,10] or white matter integrity [11] rather than lacunar infarcts
In the present cross-sectional study, we observed that the presence of confluent but not punctate DWMLs was associated with metabolic syndrome and low-grade inflammation
Summary
Low-grade inflammation, which is typically determined by increased levels of high-sensitivity C-reactive protein (hsCRP), has been recognized in several studies as a risk factor for ischemic stroke, independent of other cardiovascular risk factors [1,2,3,4]. An earlier study reported that higher levels of both CRP and IL-6 were associated with silent brain infarction even when adjusted with traditional vascular risk factors [8], whereas higher CRP levels were associated with the presence and progression of deep white matter lesions (DWMLs) [9,10] or white matter integrity [11] rather than lacunar infarcts. Recent meta-analyses revealed that elevated levels of inflammation markers were found to be associated with an increased risk of depression in the general population [15,16]. This association could be confounded by the symptoms of apathy, that is, apathy and depression might be confused due to overlapping clinical features. We hypothesized that apathy would be associated with systemic inflammation indirectly via DWMLs
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