Plasma IL‐6 levels are Negatively Associated with MRI‐Based Water Exchange Rate Across the Blood‐Brain Barrier

Abstract

AbstractBackgroundChanges in blood‐brain barrier (BBB) integrity are associated with cognitive decline in aging. Inflammatory processes are thought to contribute to BBB dysfunction but this link has been difficult to measure in humans using non‐invasive, in‐vivo methods. Recently, a novel magnetic resonance imaging (MRI) technique, diffusion‐prepared arterial spin labeling (DP‐ASL), has been shown to provide a means to test the water exchange rate across the BBB (kw) as well as arterial transit time (ATT) and cerebral blood flow (CBF). Here, we tested the association between these DP‐ASL measures and a specific plasma marker of inflammation, IL‐6, in older adults without dementia.MethodWe tested the association between kw, ATT, and CBF and a marker of peripheral inflammation in a sample of 58 older adults without dementia. Regions of interest (ROIs) included the putamen, caudate, and pallidum. Plasma IL‐6 levels were assessed using Simoa assays. IL‐6 was natural log transformed and data collected ≤ 1 year from the MRI visit were used for subsequent analyses. Multiple linear regression models, controlling for age, sex, and ROI size, tested the impact of plasma IL‐6 on kw, ATT, and CBF metrics. Both linear and quadratic effects of IL‐6 on the outcomes of interest were examined.ResultThere was a negative linear association between IL‐6 and kw in the putamen. As plasma IL‐6 levels increased, kw values decreased. In contrast, no relationships were observed between plasma IL‐6 and ATT or CBF in any of the ROIs tested.ConclusionOur results suggest that the water exchange rate across the BBB in the putamen was most uniquely associated with the peripheral proinflammatory cytokine, IL‐6. These findings could be indicative of the involvement of peripheral inflammation in reducing glymphatic clearance which would manifest as reduced water exchange rate across the BBB. The lack of association with ATT and CBF suggest that peripheral cytokines could act on a mechanism more closely related to water channel function rather than overall brain perfusion.