Serum‐based inflammatory biomarker profiles and structural brain measures in older adults without dementia

Abstract

AbstractBackgroundInflammatory markers may play a crucial role in early stages of Alzheimer’s disease (AD). We previously found C‐reactive protein (CRP) was associated with reduced brain volumes. Whether systemic inflammation profiles using multiple inflammatory biomarkers are associated with brain measures remains unclear.MethodThe study included 662 older (mean age=75.6 years) participants without dementia from the community‐based, multiethnic Washington Heights‐Inwood Columbia Aging Project. Thirty‐six cytokines in serum collected at baseline were quantified with multiplex technology. High‐resolution structural MRI was collected approximately 4 years later. Global brain volumetric measurements, including total brain volume (TBV), total gray matter volume (TGMV), and total white matter volume (TWMV), were quantified from T1‐weighted images via Freesurfer and adjusted for intracranial volume in the analyses. Mean cortical thickness was estimated by the average cortical thickness of 68 regions of interest. Principal component analyses were run to derive cytokine patterns (CPs). Multivariable linear regression models were used to assess the association between cytokines and brain MRI measures, adjusted for demographic and clinical factors.ResultEight different cytokine patterns were derived. The CP8, characterized by high (>0.3) positive loadings of α2‐Macroglobulin (A2MG) (loading=0.55), CRP (0.76), and IP‐10 (0.32), was positively correlated with increasing age (r=0.11, p=0.005). In adjusted model, the CP8 was associated with reduced TBV [β (95% confidence interval), p‐value: ‐6.88 (‐13.17, ‐0.58), 0.032], TGMVR [‐5.34 (‐8.61, ‐2.07), 0.001], and TWMV [‐4.69 (‐8.62, ‐0.76), 0.019]. Other CPs were not associated with any of the brain measures. In secondary analyses on individual cytokines, we found CRP was associated with reduced brain volumetric measures and reduced cortical thickness, but no association with brain was found for A2MG or IP‐10. Additionally, compared to the lowest tertile, moderate level (middle tertile) of platelet‐derived growth factor (PDGF‐AB/BB) was associated with larger TGMV; moderate level of macrophage inflammatory protein 1‐alpha was associated with smaller TBV and TWMV; and moderate level of PDGF‐AA was associated with smaller TWMV.ConclusionIn this cross‐sectional study of non‐demented older adults, we found a cytokine pattern characterized by high CRP, A2MG, and IP‐10 was associated with reduced brain volume, which seemed to be mainly driven by CRP.