Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
Resilience in Alzheimer's disease: Impact of operationalization and methodological choices.
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Mutel Sophie, Quatrocchi Lara, Altomare Daniele, Chicherio Christian, Scheffler Max, Lövblad Karl-Olof, Blennow Kaj, Ashton Nicholas J, Zetterberg Henrik, Abramowicz Marc, Blouin Jean-Louis, Wang Chen, Wyss-Dominguez Carine, Mendes Augusto J, Garibotto Valentina, Frisoni Giovanni, Ribaldi Federica
Аннотация
INTRODUCTION: Resilience, the ability to maintain cognition or brain integrity despite Alzheimer's disease (AD) pathology, is often quantified using the residual approach. However, the variability in methodology and correction methods for this approach raises concerns about the interpretability of findings across studies.
METHODS: We assessed brain resilience (BR) and cognitive resilience (CR) in a memory clinic population using the residual approach. We compared non-corrected and corrected residuals' associations with risk factors using linear regression models, and their impact on longitudinal cognition using linear mixed-effects models.
RESULTS: Corrected versus non-corrected BR yielded distinct, often opposing, associations. For example, glial fibrillary acidic protein (GFAP) was negatively associated with non-corrected BR (β = -0.33; p < 0.01) but positively with corrected BR (β = 0.5, p < 0.001). Only corrected CR measures yielded significant associations. Only corrected residuals predicted cognitive decline.
DISCUSSION: The observed discrepancies raise questions about the reliability of the residual approach in accurately capturing resilience.
HIGHLIGHTS: Corrected and non-corrected residuals show distinct associations with risk factors. Corrected and non-corrected residuals show different predictions of cognitive decline. These approaches may reflect general brain health rather than true resilience mechanisms.
METHODS: We assessed brain resilience (BR) and cognitive resilience (CR) in a memory clinic population using the residual approach. We compared non-corrected and corrected residuals' associations with risk factors using linear regression models, and their impact on longitudinal cognition using linear mixed-effects models.
RESULTS: Corrected versus non-corrected BR yielded distinct, often opposing, associations. For example, glial fibrillary acidic protein (GFAP) was negatively associated with non-corrected BR (β = -0.33; p < 0.01) but positively with corrected BR (β = 0.5, p < 0.001). Only corrected CR measures yielded significant associations. Only corrected residuals predicted cognitive decline.
DISCUSSION: The observed discrepancies raise questions about the reliability of the residual approach in accurately capturing resilience.
HIGHLIGHTS: Corrected and non-corrected residuals show distinct associations with risk factors. Corrected and non-corrected residuals show different predictions of cognitive decline. These approaches may reflect general brain health rather than true resilience mechanisms.