Abstract WP204: Low-grade Inflammation is Associated With Apathy Indirectly Through Deep White Matter Lesions in Community-dwelling Older Adults

Abstract

Background: Low-grade inflammation is implicated in the pathogenesis of small vessel disease of the brain. Furthermore, systemic inflammation has been associated with apathy. Because our previous study showed the association between deep white matter lesions (DWMLs) and apathy, we investigated the association between inflammation, DWMLs, and apathy. Methods: We analyzed the brain magnetic resonance imaging (MRI) findings in 259 community-dwelling adults (122 men and 137 women) with a mean age of 64.8 years. Serum concentrations of high-sensitivity C-reactive protein (CRP) were measured by a quantitative enzyme-linked immunosorbent assay with a sensitivity of 22 ng/L. Each item of the Starkstein apathy scale was quantified on a visual analogue scale. The association between silent brain lesions and CRP was tested using the forward stepwise method of logistic regression analysis. We used structural equation modeling (SEM) to test the contribution of inflammation and silent brain lesions to the apathetic behavior. Results: Although CRP level distribution was highly skewed (median: 0.589 mg/L, interquartile range: 0.292-1.326 mg/L), log-transformed CRP values (log10 CRP) were normally distributed. Medium to high tertiles of CRP were associated with metabolic syndrome. Logistic regression analysis revealed that log10 CRP (odds ratio [OR]: 2.90; 95% confidence interval [95%CI]: 1.25-6.71) was independently associated with confluent but not total DWMLs. Metabolic syndrome and age were also associated with confluent DWMLs. Path analysis based on SEM indicated that the direct path from log10 CRP to DWMLs was significant (β = 0.12, P = 0.039). The direct paths from metabolic syndrome to log10 CRP and to DWMLs were also significant. The direct path from DWMLs to apathy was significant (β = –0.17, P = 0.007) as was the direct path from education to apathy (β = 0.18, P = 0.003). However, the direct path from log10 CRP to apathy was not significant. The measures of model fitness showed that the presented model reasonably fit the data. Conclusions: Independent of common vascular risk factors, elevated serum CRP levels were associated with confluent DWMLs. Although DWMLs were associated with apathy, direct association between inflammation and apathy was not shown.