Plasma neurofilament light chain is associated with cognitive decline in non-dementia older adults
Authors: He Lingxiao , Morley John E. , Aggarwal Geetika , Nguyen Andrew D. , Vellas Bruno , de Souto Barreto Philipe ,   the MAPT/DSA Group,   MAPT Study Group,   Principal investigator, Vellas Bruno ,   Coordination, Guyonnet Sophie ,   Project leader, Carrié Isabelle ,   CRA, Brigitte Lauréane ,   Investigators, Faisant Catherine , Lala Françoise , Delrieu Julien , Villars Hélène ,   Psychologists, Combrouze Emeline , Badufle Carole , Zueras Audrey ,   Methodology, statistical analysis and data management, Andrieu Sandrine , Cantet Christelle , Morin Christophe ,   Multidomain group, Van Kan Gabor Abellan , Dupuy Charlotte , Rolland Yves , Caillaud Céline , Ousset Pierre-Jean , Lala Françoise , Willis Sherry , Belleville Sylvie , Gilbert Brigitte , Fontaine Francine ,   Co-Investigators in associated centres, 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 , Idrissi Samira Misbah El , Skolil Pierre , Salles Jean-Pierre ,   MRI group, 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 ,   PET scans group, Payoux Pierre , Voisin Thierry , Delrieu Julien , Peiffer Sophie , Hitzel Anne , Allard Michèle , Zanca Michel , Monteil Jacques , Darcourt Jacques ,   Medico-economics group, Molinier Laurent , Derumeaux Hélène , Costa Nadège ,   Biological sample collection, Perret Bertrand , Vinel Claire , Caspar-Bauguil Sylvie ,   Safety management, Olivier-Abbal Pascale ,   DSA Group, Andrieu Sandrine , Cantet Christelle , Coley Nicola 
Published: June 2021

Neurofilament light chain (NfL) has been associated with cognitive status in multiple neurodegenerative conditions. Studies about plasma NfL and cognitive decline in older adults are still limited. 504 older adults (median age 75 years) who expressed memory complaints were selected from the Multidomain Alzheimer’s Preventive Trial (MAPT) and were classified as normal cognition (NC) or mild cognitive impairment (MCI). Cognitive functions were measured as mini mental state examination (MMSE) and composite cognitive score (CCS) over a 4-year period. Plasma NfL was measured at the first or the second year of the MAPT. Mixed-effects linear models were performed to evaluate cross-sectional and longitudinal associations. In the whole population, higher plasma NfL was cross-sectionally associated with lower cognitive functions (MMSE: β =  − 0.007, 95% CI [− 0.013, − 0.001]; CCS: β =  − 0.003, 95% CI [− 0.006, − 0.001]). In adults with MCI, but not NC, higher plasma NfL was associated with lower CCS at the cross-sectional level (β =  − 0.003, 95% CI [− 0.005, − 0.0002]). The upper quartile NfL group further demonstrated more over time decline in CCS (β =  − 0.07, 95% CI [− 0.12, − 0.01]) under the MCI status. Plasma NfL can be a promising biomarker of progressive cognition decline in older adults with MCI.