Plasma Aβ and neurofilament light chain are associated with cognitive and physical function decline in non-dementia older adults
Authors: He Lingxiao , de Souto Barreto Philipe , Aggarwal Geetika , Nguyen Andrew D. , Morley John E. , Li Yan , Bateman Randall J. , Vellas Bruno ,   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 , Dartigues Jean-François , Marcet Isabelle , Delva Fleur , Foubert Alexandra , Cerda Sandrine , 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 Kristelle , 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 , Delrieu Julien , Peiffer Sophie , Hitzel Anne , Allard Michèle , Zanca Michel , Monteil Jacques , Darcourt Jacques , Molinier Laurent , Derumeaux Hélène , Costa Nadège , Perret Bertrand , Vinel Claire , Caspar-Bauguil Sylvie , Olivier-Abbal Pascale , Andrieu Sandrine , Cantet Christelle , Coley Nicola 
Published: October 2020

AbstractBackgroundCognition is closely associated with physical function. Although high brain amyloid-β (Aβ) deposition and neurofilament light chain (NfL) are associated with cognitive and gait speed decline, relationships of combined plasma Aβ and NfL profiles with cognitive and physical functions in older adults remain unknown. The research aim of this study was to investigate the prospective associations of combined plasma Aβ and NfL profiles with cognitive and physical functions in older adults.MethodsParticipants (n = 452, aged 76 ± 5 years) who had both plasma Aβ and NfL data collected from the Multidomain Alzheimer’s Preventive Trial (MAPT, May 2008 to April 2016) were included in the current study. These participants were from four MAPT groups (multidomain interventions [physical activity and nutritional counselling, and cognitive training], omega-3 supplementation, multidomain plus omega-3 supplementation and control group) and had received a 3-year intervention, followed by a 2-year observational follow-up. Cognitive function was evaluated as Mini-Mental State Examination and composite cognitive score (CCS, a meanZ-score combining four cognitive tests). Physical function was evaluated as gait speed (4-m usual-pace walk test) and chair-stand time (5-time maximal chair-stand test). Cognitive and physical function data measured at the time of and after blood Aβ and NfL tests were used for analysis. Participants with plasma Aβ42/Aβ40ratios lower than 0.107 and NfL levels greater than 93.04 pg/ml were classified as Aβ+ and NfL+. Multivariable regressions and mixed-effects linear models were used for the analysis.ResultsAt the cross-sectional level, no significant association was found between Aβ+NfL+ and cognitive or physical function after controlling for age, sex, body mass index, education level and MAPT group. Evaluating longitudinal changes, participants with Aβ+NfL+ had greater annual declines in the CCS (β = − 0.11, 95%CI [− 0.17, − 0.05]) and gait speed (β = − 0.03, 95%CI [− 0.05, − 0.005]). After adjusting for APOE ɛ4 genotype, Aβ+NfL+ was associated with a greater decline only in the CCS (β = − 0.09, 95%CI [− 0.15, − 0.02]).ConclusionsCombined low plasma Aβ42/Aβ40ratio and high plasma NfL level was associated with greater declines in cognition and gait speed over time, providing further evidence of the links between cognitive and physical function.Trial registrationwww.clinicaltrials.gov[NCT00672685].