Can cognitive reserve offset APOE-related Alzheimer’s risk? A systematic review

IF 12.4 1区医学 Q1 CELL BIOLOGY

Ageing Research Reviews Pub Date : 2025-06-17 DOI:10.1016/j.arr.2025.102809

Sayonara Pereira da Silva , Charikleia Lampraki , Tainá dos Santos Rêgo , Paolo Ghisletta , Matthias Kliegel , Jürgen Maurer , Matthias Studer , Élvio Rúbio Gouveia , Marcelo de Maio Nascimento , Andreas Ihle

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Abstract

Alzheimer's disease (AD) is a neurocognitive disorder that affects a significant part of the population. Its symptoms include progressive loss of memory and executive dysfunction. Genetic susceptibility to AD can be influenced by allele variants of the APOE gene. On the other hand, lifelong experiences such as educational attainment, occupational complexity, and leisure activities, known proxies for cognitive reserve (CR), may modulate gene expression, ultimately impacting AD susceptibility. In this study, we systematically investigated research that explored the interaction between APOE-related AD outcomes and CR. The literature search was conducted using PubMed and all Web of Science databases. We screened 33,861 references, of which 15 met the inclusion criteria. The studies varied in research design, population characteristics, proxies for CR, and measured outcomes. The publications presented mixed results, with some indicating protective effects (n = 7), others showing detrimental effects (n = 4), and still others suggesting no significant interaction effects (n = 4). Some of these findings may be attributed to the reliance on individual proxies, which may capture only limited aspects or different dimensions of the broader CR framework. Overall, our analysis suggests that individual risk factors may interact in complex ways and that even genetic predispositions can potentially be influenced by CR. Implications for CR and aging research as well as public health policies are discussed.

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认知储备能否抵消apoe相关的阿尔茨海默病风险？系统回顾

阿尔茨海默病（AD）是一种影响很大一部分人群的神经认知障碍。其症状包括进行性记忆丧失和执行功能障碍。对AD的遗传易感性可能受到APOE基因等位基因变异的影响。另一方面，教育程度、职业复杂性和休闲活动等已知的认知储备（CR）代用物可能会调节基因表达，最终影响阿尔茨海默病的易感性。在本研究中，我们系统地调查了apoe相关AD结果与CR之间相互作用的研究，并使用PubMed和所有Web of Science数据库进行了文献检索。我们筛选了33,861篇文献，其中15篇符合纳入标准。这些研究在研究设计、人群特征、CR替代指标和测量结果方面各不相同。这些出版物给出了不同的结果，有些表明了保护作用（n = 7），有些表明了有害作用（n = 4），还有一些表明没有显著的相互作用作用（n = 4）。其中一些发现可能归因于对单个代理的依赖，这些代理可能只捕获了更广泛的CR框架的有限方面或不同维度。总体而言，我们的分析表明，个体风险因素可能以复杂的方式相互作用，甚至遗传易感性也可能受到CR的影响。本文讨论了CR和老龄化研究以及公共卫生政策的意义。

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

Ageing Research Reviews 医学-老年医学

CiteScore

19.80

自引率

2.30%

发文量

216

审稿时长

55 days

期刊介绍： With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends. ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research. The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.