Peripheral inflammation is associated with structural brain atrophy and cognitive decline linked to mild cognitive impairment and Alzheimer’s disease

ABSTRACT Mounting evidence points towards inflammation as an important factor in Alzheimer’s disease (AD) pathogenesis. In this study, we investigated the relationship between a key marker of inflammation – glycoprotein acetyls (GlycA) – in blood and cognitive and brain structural changes in over 1500 participants enrolled into the Alzheimer’s Disease Neuroimaging Initiative. We evaluated those associations cross-sectionally at baseline, followed by an evaluation of whether baseline GlycA can inform about future disease progression. Our results support the following findings: 1) GlycA is elevated in participants diagnosed with AD compared to cognitively normal participants; 2) GlycA level correlates negatively with regional brain volumes in females diagnosed with late mild cognitive impairment (LMCI) or AD; 3) baseline GlycA level is associated with executive function decline at 3-9 year follow-up in both male and female participants diagnosed with LMCI at baseline; and 4) baseline GlycA is associated with decline in entorhinal cortex volume at years 2, 4 and 6-8 of follow-up in both male and female participants diagnosed with LMCI at baseline. In conclusion, peripheral inflammation was found to be positively associated with AD diagnosis and future decline in cognition and regional brain volumes. However, we note that the cross-sectional relationship between peripheral inflammation and AD-related brain atrophy is specific to sex and diagnostic status. Our findings point to peripheral inflammation as a risk factor in AD development, which enables the identification of potential markers and therapeutic intervention for participants who are at risk.