The Mediating Role of Cortical Atrophy on the Relationship between the Resilience Index and Cognitive Function: Findings from the Healthy Brain Initiative

Article type: Research Article

Authors: O’Shea, Deirdre M.^{a; *} | Camacho, Simone^a | Ezzeddine, Reem^a | Besser, Lilah^a | Tolea, Magdalena I.^a | Wang, Lily^b | Galvin, Conor^a | Gibbs, Gregory^a | Galvin, James E.^a

Affiliations: [a] Department of Neurology, Comprehensive Center for Brain Health, University of Miami Miller School of Medicine, Boca Raton, FL, USA | [b] Department of Public Health Science, University of Miami Miller School of Medicine, Miami, FL, USA

Correspondence: [*] Correspondence to: Deirdre M. O’Shea, Comprehensive Center for Brain Health, 7700 Camino Real Suite 200, Boca Raton, FL 33433, USA. Tel.: 561 869 6836; E-mail: [email protected].

Abstract: Background:Lifestyle factors are linked to differences in brain aging and risk for Alzheimer’s disease, underscored by concepts like ‘cognitive reserve’ and ‘brain maintenance’. The Resilience Index (RI), a composite of 6 factors (cognitive reserve, physical and cognitive activities, social engagement, diet, and mindfulness) provides such a holistic measure. Objective:This study aims to examine the association of RI scores with cognitive function and assess the mediating role of cortical atrophy. Methods:Baseline data from 113 participants (aged 45+, 68% female) from the Healthy Brain Initiative were included. Life course resilience was estimated with the RI, cognitive performance with Cognivue®, and brain health using a machine learning derived Cortical Atrophy Score (CAS). Mediation analysis probed the relationship between RI, cognitive outcomes, and cortical atrophy. Results:In age and sex adjusted models, the RI was significantly associated with CAS (β= –0.25, p = 0.006) and Cognivue® scores (β= 0.32, p < 0.001). The RI-Cognivue® association was partially mediated by CAS (β= 0.07; 95% CI [0.02, 0.14]). Conclusions:Findings revealed that the collective effect of early and late-life lifestyle resilience factors on cognition are partially explained by their association with less brain atrophy. These findings underscore the value of comprehensive lifestyle assessments in understanding the risk and progression of cognitive decline and Alzheimer’s disease in an aging population.

Keywords: Alzheimer’s disease, cognitive reserve, cognitive resilience, cortical atrophy, mild cognitive impairment

DOI: 10.3233/JAD-231346

Journal: Journal of Alzheimer's Disease, vol. 98, no. 3, pp. 1017-1027, 2024