Diabetes Mellitus and Cognition
Éric Frison, Cécile Proust‐Lima, Jean‐François Mangin, Marie‐Odile Habert, Stéphanie Bombois, Pierre‐Jean Ousset, Florence Pasquier, Olivier Hanon, Claire Paquet, Audrey Gabelle, Mathieu Ceccaldi, Cédric Annweiler, Pierre Krolak‐Salmon, Yannick Béjot, Cathérine Belin, David Wallon, Mathilde Sauvée, É. Beaufils, Isabelle Bourdel‐Marchasson, Isabelle Jalenques, Marie Chupin, Geneviève Chêne, Carole Dufouil, on behalf of the MEMENTO Cohort Study Group, Michèle Allard, Sandrine Andrieu, Pierre Anthony, Christine Astier, A. Augier, Nicolas Auguste, Sophie Auriacombe, John Avet, Olivier Bailon, Fabrice-Guy Barral, Jean Barré, A. Barthelaix, Catherine Bayle, Olivier Beauchet, Samia Belkacem, D. Ben Salem, Karim Bennys, G. Béra, Éric Berger, Marc Berger, Emilie Bergouin, François Bertin‐Hugault, Guillaume Bertrand, F Bertrand, Catherine Beze, Valérie Boilet, Alain Bonafé, Yasmina Boudali, Hatem Bouhladour, Clémence Boully, Vincent Bouteloup, Claire Boutet, Serge Bracard, Antoine Brangier, Pierre‐Yves Brillet, Laure Caillard, Fabienne Calvas, Agnès Camus, Vincent Camus, Sandrine Canaple, Alain Carpentier, Pascaline Cassagnaud, F. Cattin, Ludivine Chamard, Stéphane Chanalet, Mathieu Chastan, Sophie Chauvelier, Valérie Chauviré, Samia Cheriet, Anthony Clotagatide, Emmanuel Cognat, Lora Cohen, Jean‐Marc Constans, Marie-Hélène Coste, Jean‐Philippe Cottier, François Cotton, I. Couret, Olivier Couturier, Pascale Cowppli-Bony, V. Cressot, Benjamin Crétin, Keren Danaila, Jacques Darcourt, Jean-François Dartigues, Ana-Maria Dăscaliţa, Renaud David, Xavier De Petigny, Delphine De Verbizier-Lonjon, M. Décousus, Isabelle Defouilloy, Christine Delmaire, Julien Delrieu, Catherine Demuyinck, Vincent Deramecourt, Hervé Deramond, Thomas Desmidt
Abstract
ObjectiveTo assess the role of biomarkers of Alzheimer disease (AD), neurodegeneration, and small vessel disease (SVD) as mediators in the association between diabetes mellitus and cognition. MethodsThe study sample was derived from MEMENTO, a cohort of French adults recruited in memory clinics and screened for either isolated subjective cognitive complaints or mild cognitive impairment. Diabetes was defined based on blood glucose assessment, use of antidiabetic agent, or self-report. We used structural equation modeling to assess whether latent variables of AD pathology (PET mean amyloid uptake, Aβ42/Aβ40 ratio, and CSF phosphorylated tau), SVD (white matter hyperintensities volume and visual grading), and neurodegeneration (mean cortical thickness, brain parenchymal fraction, hippocampal volume, and mean fluorodeoxyglucose uptake) mediate the association between diabetes and a latent variable of cognition (5 neuropsychological tests), adjusting for potential confounders. ResultsThere were 254 (11.1%) participants with diabetes among 2,288 participants (median age 71.6 years; 61.8% women). The association between diabetes and lower cognition was significantly mediated by higher neurodegeneration (standardized indirect effect: −0.061, 95% confidence interval: −0.089, −0.032), but not mediated by SVD and AD markers. Results were similar when considering latent variables of memory or executive functioning. ConclusionIn a large clinical cohort in the elderly, diabetes is associated with lower cognition through neurodegeneration, independently of SVD and AD biomarkers.