Plasma MCP-1 and changes on cognitive function in community-dwelling older adults
Authors: Sanchez-Sanchez Juan Luis , Giudici Kelly V. , Guyonnet Sophie , Delrieu Julien , Li Yan , Bateman Randall J. , Parini Angelo , Vellas Bruno , de Souto Barreto Philipe ,   for the MAPT/DSA Group, Vellas Bruno , Guyonnet Sophie , Carrié Isabelle , Brigitte Lauréane , Faisant Catherine , Lala Françoise , Delrieu Julien , Villars Hélène , Combrouze Emeline , Badufle Carole , Zueras Audrey , Andrieu Sandrine , Cantet Christelle , Morin Christophe , Van Kan Gabor Abellan , Dupuy Charlotte , Rolland Yves , Caillaud Céline , Ousset Pierre-Jean , Lala Françoise , Willis Sherry , Belleville Sylvie , Gilbert Brigitte , Fontaine Francine , Dartigues Jean-François , Marcet Isabelle , Delva Fleur , Foubert Alexandra , Cerda Sandrine , Marie-Noëlle-Cuffi  , Costes Corinne , Rouaud Olivier , Manckoundia Patrick , Quipourt Valérie , Marilier Sophie , Franon Evelyne , Bories Lawrence , Pader Marie-Laure , Basset Marie-France , Lapoujade Bruno , Faure Valérie , Tong Michael Li Yung , Malick-Loiseau Christine , Cazaban-Campistron Evelyne , Desclaux Françoise , Blatge Colette , Dantoine Thierry , Laubarie-Mouret Cécile , Saulnier Isabelle , Clément Jean-Pierre , Picat Marie-Agnès , Bernard-Bourzeix Laurence , Willebois Stéphanie , Désormais Iléana , Cardinaud Noëlle , Bonnefoy Marc , Livet Pierre , Rebaudet Pascale , Gédéon Claire , Burdet Catherine , Terracol Flavien , Pesce Alain , Roth Stéphanie , Chaillou Sylvie , Louchart Sandrine , Sudres Kristel , Lebrun Nicolas , Barro-Belaygues Nadège , Touchon Jacques , Bennys Karim , Gabelle Audrey , Romano Aurélia , Touati Lynda , Marelli Cécilia , Pays Cécile , Robert Philippe , Le Duff Franck , Gervais Claire , Gonfrier Sébastien , Gasnier Yannick , Bordes Serge , Begorre Danièle , Carpuat Christian , Khales Khaled , Lefebvre Jean-François , El Idrissi Samira Misbah , Skolil Pierre , Salles Jean-Pierre , Dufouil Carole , Lehéricy Stéphane , Chupin Marie , Mangin Jean-François , Bouhayia Ali , Allard Michèle , Ricolfi Frédéric , Dubois Dominique , Martel Marie Paule Bonceour , Cotton François , Bonafé Alain , Chanalet Stéphane , Hugon Françoise , Bonneville Fabrice , Cognard Christophe , Chollet François , Payoux Pierre , Voisin Thierry , Peiffer Sophie , Hitzel Anne , Zanca Michel , Monteil Jacques , Darcourt Jacques , Molinier Laurent , Derumeaux Hélène , Costa Nadège , Perret Bertrand , Vinel Claire , Caspar-Bauguil Sylvie , Olivier-Abbal Pascale , Coley Nicola 
Published: January 2022

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—Aβ42/40) 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 Aβ42/40(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 Aβ42/40. Outcomes were measured annually over 4 years and included the following: cognitive compositez-score (CCS), the Mini-Mental State Examination (MMSE), and Clinical Dementia Rating (CDR) sum of boxes (overall cognitive function); composite executive functionz-score, composite attentionz-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 Aβ42/40, MCP-1+was not associated with greater declines in cognitive functions. The interaction with continuous biomarker valuesAβ42/40× MCP-1 × timewas 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 Aβ42/40to 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 plasmaAβ42/40.