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Diabetes mellitus and cognition: A pathway analysis in the MEMENTO cohort

Eric Frison 1 Cecile Proust-Lima 1 Jean-Francois Mangin 2, 3 Marie-Odile Habert 2, 4, 5 Stephanie Bombois 6, 7 Pierre-Jean Ousset 8 Florence Pasquier 9 Olivier Hanon 10 Claire Paquet 11, 12 Audrey Gabelle 13 Mathieu Ceccaldi 14 Cédric Annweiler 15, 16 Pierre Krolak-Salmon 17 Yannick Béjot 18 Catherine Belin 19 David Wallon 20 Mathilde Sauvee 21 Emilie Beaufils 22 Isabelle Bourdel-Marchasson 23 Isabelle Jalenques 24 Marie Chupin 7, 2 Geneviève Chêne 1 Carole Dufouil 1, *
Abstract : Objective: To assess the role of biomarkers of Alzheimer's Disease (AD), neurodegeneration and small vessel disease (SVD) as mediators in the association between diabetes mellitus and cognition. Methods: The 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 modelling 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 (five neuropsychological tests), adjusting for potential confounders. Results: There 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. Conclusion: In a large clinical cohort in the elderly, diabetes is associated with lower cognition through neurodegeneration, independently of SVD and AD biomarkers.
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Submitted on : Monday, July 5, 2021 - 3:13:36 PM
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Eric Frison, Cecile Proust-Lima, Jean-Francois Mangin, Marie-Odile Habert, Stephanie Bombois, et al.. Diabetes mellitus and cognition: A pathway analysis in the MEMENTO cohort. Neurology, American Academy of Neurology, 2021, 2021, ⟨10.1212/WNL.0000000000012440⟩. ⟨hal-03278377⟩

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