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
Laboratory of Neuroimaging of Aging (LANVIE), University of Geneva, Geneva, Switzerland.
Geneva Memory Centre, Department of Rehabilitation and Geriatrics, Geneva University Hospitals, Geneva, Switzerland.
Alzheimers Dement. 2025 Apr;21(4):e70185. doi: 10.1002/alz.70185.
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.
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.
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.
The observed discrepancies raise questions about the reliability of the residual approach in accurately capturing resilience.
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.
复原力是指尽管存在阿尔茨海默病（AD）病理特征但仍能维持认知或脑完整性的能力，通常使用残差法进行量化。然而，这种方法在方法论和校正方法上的可变性引发了对不同研究结果可解释性的担忧。
我们使用残差法评估了记忆门诊人群的脑复原力（BR）和认知复原力（CR）。我们使用线性回归模型比较了未校正和校正后的残差与风险因素的关联，并使用线性混合效应模型比较了它们对纵向认知的影响。
校正后的BR与未校正的BR产生了明显不同，且往往相反的关联。例如，胶质纤维酸性蛋白（GFAP）与未校正的BR呈负相关（β = -0.33；p < 0.01），但与校正后的BR呈正相关（β = 0.5，p < 0.001）。只有校正后的CR测量产生了显著关联。只有校正后的残差能够预测认知能力下降。
观察到的差异引发了对残差法在准确捕捉复原力方面可靠性的质疑。
校正后的和未校正的残差与风险因素显示出明显不同的关联。校正后的和未校正的残差对认知能力下降的预测不同。这些方法可能反映的是一般脑健康状况，而非真正的复原力机制。
