Author:
Sanchez-Sanchez Juan Luis,Giudici Kelly V.,Guyonnet Sophie,Delrieu Julien,Li Yan,Bateman Randall J.,Parini Angelo,Vellas Bruno,de Souto Barreto Philipe,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,
Abstract
AbstractBackgroundMonocyte 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.MethodsSecondary 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).ResultsPlasma 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.ConclusionsBaseline 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.
Funder
region occitanie/pyrénées-méditerranée
european regional development fund
Subject
Cognitive Neuroscience,Neurology (clinical),Neurology