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Explaining the association between social and lifestyle factors and cognitive functions: a pathway analysis in the Memento cohort

Leslie Grasset 1 Cecile Proust-Lima 1 Jean-Francois Mangin 2, 3 Marie-Odile Habert 2, 4 Bruno Dubois 5 Claire Paquet 6 Olivier Hanon 7 Audrey Gabelle 8 Mathieu Ceccaldi 9 Cedric Annweiler 10, 11 Renaud David 12, 13 Therese Jonveaux 14 Catherine Belin 15 Adrien Julian 16 Isabelle Rouch-Leroyer 17 Jeremie Pariente 18 Maxime Locatelli 2, 19, 4 Marie Chupin 5, 2 Genevieve Chene 1 Carole Dufouil 1 
Abstract : BACKGROUND: This work aimed to investigate the potential pathways involved in the association between social and lifestyle factors, biomarkers of Alzheimer's disease and related dementia (ADRD), and cognition. METHODS: The authors studied 2323 participants from the Memento study, a French nationwide clinical cohort. Social and lifestyle factors were education level, current household incomes, physical activity, leisure activities, and social network from which two continuous latent variables were computed: an early to midlife (EML) and a latelife (LL) indicator. Brain magnetic resonance imaging (MRI), lumbar puncture, and amyloid-positron emission tomography (PET) were used to define three latent variables: neurodegeneration, small vessel disease (SVD), and AD pathology. Cognitive function was defined as the underlying factor of a latent variable with four cognitive tests. Structural equation models were used to evaluate cross-sectional pathways between social and lifestyle factors and cognition. RESULTS: Participants' mean age was 70.9 years old, 62% were women, 28% were apolipoprotein-ε4 carriers, and 59% had a Clinical Dementia Rating (CDR) score of 0.5. Higher early to midlife social indicator was only directly associated with better cognitive function (direct β = 0.364 (0.322; 0.405), with no indirect pathway through ADRD biomarkers (total β = 0.392 (0.351; 0.429)). In addition to a direct effect on cognition (direct β = 0.076 (0.033; 0.118)), the association between latelife lifestyle indicator and cognition was also mostly mediated by an indirect effect through lower neurodegeneration (indirect β = 0.066 (0.042; 0.090) and direct β =  - 0.116 (- 0.153; - 0.079)), but not through AD pathology nor SVD. CONCLUSIONS: Early to midlife social factors are directly associated with higher cognitive functions. Latelife lifestyle factors may help preserve cognitive functions through lower neurodegeneration.
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Leslie Grasset, Cecile Proust-Lima, Jean-Francois Mangin, Marie-Odile Habert, Bruno Dubois, et al.. Explaining the association between social and lifestyle factors and cognitive functions: a pathway analysis in the Memento cohort. Alzheimer's Research and Therapy, BioMed Central, 2022, 14 (1), pp.68. ⟨10.1186/s13195-022-01013-8⟩. ⟨hal-03700869⟩

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