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

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 beta-amyloid deposition-A beta(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 A beta(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 A beta(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: beta = -0.14, 95%CI = -0.26, -0.02) and the CDR sum of boxes (2-year: beta = 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 A beta(42/40), MCP-1(+) was not associated with greater declines in cognitive functions. The interaction with continuous biomarker values A beta(42/40)x MCP-1 x 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 A beta(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 A beta(42/40.)

Automated summary

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. Interaction between plasma MCP-1 and A beta(42/40) may determine cognitive decline, especially in individuals with amyloid plaques. Further research should clarify the precise mechanism of this association.