Plasma MCP-1 and changes on cognitive function in community-dwelling older adults

Abstract

Background: Monocyte Chemoattractant Protein-1 (MCP-1), a glial-derived chemokine, mediates neuroinflammation and may regulate memory outcomes among older adults. We aimed to explore the associations of plasma MCP-1 levels (alone and in combination with β-amyloid deposition-Aβ_42/40) with overall and domain-specific cognitive evolution among older adults.

Methods: Secondary analyses including 1097 subjects (mean age = 75.3 years ± 4.4; 63.8% women) from the Multidomain Alzheimer Preventive Trial (MAPT). MCP-1 (higher is worse) and Aβ_42/40 (lower is worse) were measured in plasma collected at year 1. MCP-1 in continuous and as a dichotomy (values in the highest quartile (MCP-1⁺)) were used, as well as a dichotomy of Aβ_42/40. Outcomes were measured annually over 4 years and included the following: cognitive composite z-score (CCS), the Mini-Mental State Examination (MMSE), and Clinical Dementia Rating (CDR) sum of boxes (overall cognitive function); composite executive function z-score, composite attention z-score, Free and Cued Selective Reminding Test (FCSRT - memory).

Results: Plasma MCP-1 as a continuous variable was associated with the worsening of episodic memory over 4 years of follow-up, specifically in measures of free and cued delayed recall. MCP-1⁺ was associated with worse evolution in the CCS (4-year between-group difference: β = -0.14, 95%CI = -0.26, -0.02) and the CDR sum of boxes (2-year: β = 0.19, 95%CI = 0.06, 0.32). In domain-specific analyses, MCP-1⁺ was associated with declines in the FCSRT delayed recall sub-domains. In the presence of low Aβ_42/40, MCP-1⁺ was not associated with greater declines in cognitive functions. The interaction with continuous biomarker values Aβ_42/40× MCP-1 × time was significant in models with CDR sum of boxes and FCSRT DTR as dependent variables.

Conclusions: Baseline plasma MCP-1 levels were associated with longitudinal declines in overall cognitive and episodic memory performance in older adults over a 4-year follow-up. How plasma MCP-1 interacts with Aβ_42/40 to determine cognitive decline at different stages of cognitive decline/dementia should be clarified by further research. The MCP-1 association on cognitive decline was strongest in those with amyloid plaques, as measured by blood plasma Aβ_42/40.

Keywords: Alzheimer’s disease; Cognitive function; Episodic memory; MCP-1; Older adults.