Biomarkers of chronic inflammation and cognitive decline: A prospective observational study

Abstract

We sought to determine whether the biomarkers of chronic inflammation predict cognitive decline in a prospective observational study. We measured baseline serum soluble urokinase plasminogen activator receptor (suPAR) and high sensitivity C-reactive protein (hs-CRP) levels in 282 participants of the University of Michigan Memory and Aging Project. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) and the Clinical Dementia Rating (CDR) scale for up to five time points. SuPAR and hs-CRP levels were not significantly higher in participants with mild cognitive impairment (n = 97) or dementia (n = 59), compared to those with normal cognitive function (n = 126). Overall, 14% of participants experienced significant cognitive decline over the study period. The change in MoCA or CDR scores over time did not differ significantly according to baseline suPAR or hs-CRP levels. Chronic systemic inflammation, as measured by serum suPAR or hs-CRP levels, is unlikely to contribute significantly to cognitive decline.

Keywords: Alzheimer's disease; cognition; dementia; hs‐CRP; suPAR.

FIGURE 1

Longitudinal MoCA and CDR‐SB scores stratified by baseline cognitive function. Plot of the average (A) MoCA score and (B) CDR‐SB score over follow‐up time stratified by baseline cognitive function: normal cognition (red), mild cognitive impairment (green), and dementia (blue). The gray area represents the 95% confidence interval. Abbreviations: CDR‐SB, Clinical Dementia Rating scale – Sum of Boxes; MoCA, Montreal Cognitive Assessment.

FIGURE 2

Longitudinal MoCA and CDR‐SB Scores Stratified by SuPAR and Hs‐CRP Tertiles. Plot of the average MoCA score and CDR‐SB score over follow‐up time stratified by baseline suPAR and hs‐CRP tertiles. (A) MoCA and suPAR tertiles, (B) CDR and suPAR tertiles, (C) MoCA and hs‐CRP tertiles, and (D) CDR and hs‐CRP tertiles. In each biomarker, first tertile (red), second tertile (green), and third tertile (blue). The gray area represents the 95% confidence interval. Abbreviations: CDR‐SB, Clinical Dementia Rating scale – Sum of Boxes; hs‐CRP, high sensitivity C‐reactive protein; MoCA, Montreal Cognitive Assessment; suPAR, soluble urokinase plasminogen activator receptor.