Objective: Perceived stress and systemic inflammation relationships have each been associated with cognitive decline, but few studies have examined inflammation normalized to total sample protein content as a predictor of cognition in mild cognitive impairment (MCI). C-reactive protein (CRP) is a widespread biomarker that mirrors the severity of systemic inflammation and is used as a clinical indicator of immune responses (Sproston & Ashworth, 2018). The present pilot study tested whether a protein-normalized inflammatory index (CRP:total protein) is associated with baseline cognitive performance and perceived stress in individuals with MCI. Participants and Methods: Four participants meeting criteria for MCI from an ongoing NIA study provided dried blood spot (DBS) samples and completed the Montreal Cognitive Assessment (MoCA) and the 10-item Perceived Stress Scale (PSS) at baseline; PSS was repeated at 6 months. CRP was quantified by ELISA and total protein by BCA; a CRP:total protein ratio was calculated for each participant. Descriptive statistics, Pearson correlations, and Spearman's rank analyses were conducted.
Results: The mean CRP:total protein ratio was 0.0185 μg/mL (SD = 0.0115). Mean baseline MoCA score was 22.5 (SD = 6.45). Mean PSS scores were 11.25 (SD = 1.71) at baseline and 14.0 (SD = 4.76) at six months. A strong positive correlation was found between CRP:total protein ratio and MoCA scores (r = .973, p = .027, r² = .947), indicating a large effect size (ρ = .80), though interpretation is limited (df = 2). Moderate associations were observed between the CRP:total protein ratio and baseline PSS (r = .770, p = .230, r² = .593), effect size (ρ =.80), and between baseline PSS and MoCA (r = .741, p = .259, r² = .549), effect size (ρ =.60). Conclusions: In this small pilot sample, higher CRP normalized to total protein was unexpectedly associated with better baseline cognitive screening scores; however, given the sample size and variability, this finding is preliminary and requires further research. Future studies may look to examine whether protein-normalized inflammatory markers provide valid and reliable signals of cognitive risk in MCI, to clarify the role of perceived stress in those relationships, and to improve control for confounds.
Acknowledgements: National Institutes of Aging (NIA)