Systemic Inflammatory Markers, Cognition and Brain Structure among Cognitively Normal Elderly (P02.061)

Abstract

Objective: To establish whether systemic inflammatory markers predict brain small vessel disease, brain volumes, and cognitive performance in cognitively normal elderly subjects. Background There is increasing evidence inflammation may be linked to dementia, and to the cognitive decline associated with aging. Higher concentrations of peripheral C-reactive protein (CRP) and interleukin 6 (IL-6) have been observed in dementia and AD patients compared to control subjects. Several studies have also shown that inflammatory markers are linked to lower brain volumes, white matter lesions (WMLs) and silent brain infarcts; however, these results have not been replicated. Design/Methods: We analyzed demographic, medical, biochemical, neuropsychological, and brain imaging data from 740 cognitively normal subjects from the Cardiovascular Health Cognition Study. CRP was measured at baseline and at visit 5, while IL-6 was only measured at baseline. On the other hand, the MRI and the cognition assessment were performed at visit 10. The grey matter (GM) volumes were analyzed using Voxel-Based Morphometry (VBM). Visual ratings of white matter lesions are used to determine the severity of brain SVD. Results: Baseline CRP levels predicted poorer cognitive performance in cognitively normal elderly a decade later. Baseline IL-6 levels predicted poorer cognitive performance 5 and 10 years later and also predicted increased white matter lesions and lower grey matter volume. This association between inflammatory markers and cognition or neuroimaging findings persisted after adjusting for sociodemographic variables and ApoE4 status, but disappeared when adjusted by vascular risk factors. Finally, the VBM analysis showed that baseline CRP levels predict GM volume loss in the inferior parietal lobule bilaterally. Conclusions: This highlights the effects of cumulative exposure to vascular risk factors on brain structure and cognition, and suggests that vascular risk factors mediate the association between inflammatory markers and cognitive performance or brain structural changes. Disclosure: Dr. Riverol has nothing to disclose. Dr. Becker has nothing to disclose. Dr. Lopez has received personal compensation for activities with Lundbeck and Johnson & Johnson as a consultant. Dr. Raji has nothing to disclose. Dr. Thompson has nothing to disclose. Dr. Carmichael has nothing to disclose. Dr. Gach has nothing to disclose. Dr. Longstreth has nothing to disclose. Dr. Fried has received personal compensation for activities with Pfizer Inc and Bayer Pharmaceuticals as a consultant. Dr. Fried has received personal compensation in an editorial capacity for ACP. Dr. Fried has received research support from Merck & Co., Inc. and Roche Diagnostics. Dr. Tracy has nothing to disclose. Dr. Kuller has nothing to disclose.