A novel approach to resilience and its links with education and Alzheimer's disease genetics

IF 13 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2025-07-04 DOI:10.1002/alz.70379

Maria Carrigan, Diana I. Bocancea, Jacob Vogel, Anna C. van Loenhoud, Niccoló Tesi, Frederik Barkhof, Paul J. Lucassen, Wiesje M. van der Flier, Harm J. Krugers, Sven J. Van der Lee, Rik Ossenkoppele

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引用次数: 0

Abstract

INTRODUCTION

Cognitive resilience refers to maintaining cognitive function despite Alzheimer's disease (AD) pathophysiology.

METHODS

We analyzed amyloid-positive individuals across clinical stages of AD in two cohorts: the Amsterdam Dementia Cohort (ADC, N = 1036) and Alzheimer's Disease Neuroimaging Initiative (ADNI, N = 685). Cognitive resilience was conceptualized from a canonical correlation analysis of magnetic resonance imaging and neuropsychological data in each cohort separately. Model validation involved education as a resilience proxy and key genetic factors (apolipoprotein E [APOE] ε4 and APOE ε2) of AD. We explored associations between 83 AD risk loci and cognitive resilience.

RESULTS

Resilience was correlated with education (ADC: β = 0.144, p < 0.001; ADNI: β = 0.149, p < 0.001) and APOE ε4 (β_{meta-analysis}= –0.052, p = 0.014). Exploratory single nucleotide polymorphism meta-analysis identified potential involvement of genetic variants around genes UNC5CL, USP6NL, and TPCN1 in lower, and genes COX7C and MINDY2 in higher resilience.

DISCUSSION

Our novel resilience approach showed conceptual validity and potential for future discovery of resilience-related genetic variants.

Highlights

· We define a novel approach to resilience using canonical correlation analysis (CCA).
· Apolipoprotein E ε4 is linked to lower resilience, suggesting increased vulnerability.
· Genetic loci around COX7C and MINDY2 are potentially involved in higher resilience.
· This novel approach may be used for multi-cohort studies such as genome-wide association studies in the future.

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一种研究复原力及其与教育和阿尔茨海默病遗传学关系的新方法

认知弹性是指在阿尔茨海默病（AD）病理生理条件下维持认知功能的能力。方法：我们分析了两个队列中淀粉样蛋白阳性的AD临床分期个体：阿姆斯特丹痴呆队列（ADC, N = 1036）和阿尔茨海默病神经影像学倡议（ADNI, N = 685）。认知弹性是通过对每个队列的磁共振成像和神经心理学数据分别进行典型相关分析来概念化的。模型验证包括教育作为AD的恢复代理和关键遗传因素（载脂蛋白E [APOE] ε4和APOE ε2）。我们探索了83个AD风险位点与认知恢复力之间的关系。结果心理韧性与受教育程度相关(ADC: β = 0.144, p <；0.001;ADNI: β = 0.149, p <；0.001)和APOEε4(β= -0.052元分析,p = 0.014)。探索性单核苷酸多态性荟萃分析发现，UNC5CL、USP6NL和TPCN1基因周围的遗传变异可能与较低的恢复力有关，而COX7C和MINDY2基因则与较高的恢复力有关。我们的新弹性方法显示了概念有效性和未来发现弹性相关遗传变异的潜力。·我们使用典型相关分析（CCA）定义了一种新的弹性方法。·载脂蛋白E ε4与较低的恢复力有关，表明脆弱性增加。·COX7C和MINDY2周围的基因位点可能与更高的恢复力有关。·这种新方法可能在未来用于多队列研究，如全基因组关联研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.