Interactive Associations of Age, Apolipoprotein E ε4 Gene, Physical Activity, and Physical Functioning on Processing Speed

IF 3.8 2区医学 Q2 GERIATRICS & GERONTOLOGY Journal of the American Medical Directors Association Pub Date : 2025-11-01 Epub Date: 2025-09-09 DOI:10.1016/j.jamda.2025.105489

Ricardo Aurélio Carvalho Sampaio PhD , Yukiko Nishita PhD , Chikako Tange PhD , Shu Zhang PhD , Mitsuru Shinohara PhD , Mana Tateishi MSc , Kanae Furuya PhD , Sayaka Kubota PhD , Priscila Yukari Sewo Sampaio PhD , Naoyuki Sato MD, PhD , Hiroshi Shimokata MD, PhD , Hidenori Arai MD, PhD , Rei Otsuka PhD

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Abstract

Objectives

This study investigated the interactive associations of age, apolipoprotein E ε4 (APOE4) genetic status, physical activity energy expenditure (PAEE), and physical functioning on processing speed over a 10-year period.

Design

In this longitudinal study, participants underwent biennial assessments from 2002 to 2012 as part of the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA).

Setting and Participants

We used data from 2518 middle-aged and older community-dwelling adults in Japan.

Methods

Processing speed was assessed using the Digit Symbol Substitution Test, and additional data included APOE4 genotyping, objective PAEE measurement via accelerometry (in kcal/d), and physical functioning assessments (handgrip strength and walking speed, dichotomized according to specific cutoffs: <18 kg for women and <28 kg for men [weakness], and <1 m/s [slowness], respectively). Mixed-effects models were used to analyze the data, accounting for time-varying covariates, including living arrangement, hypertension, hyperlipidemia, diabetes, depressive symptoms, smoking, sleep duration, energy intake, and body mass index.

Results

Results revealed significant 3-way interactive associations among PAEE × age × APOE4 carrier (β = 0.000025, P = .021) and among slowness × age × APOE4 carrier (β = −0.014187, P = .013) on cognitive processing speed. Higher PAEE was associated with better processing speed, whereas slowness was associated with poorer processing speed, particularly in older APOE4 carriers. Although weakness showed significant interactions with age and APOE4 carrier, no 3-way interaction was observed.

Conclusions and Implications

Our findings underscore the complex interplay among physical activity, physical functioning, age, and genetic risk on processing speed. The protective associations of higher PAEE levels and better physical functioning, especially in older APOE4 carriers, suggest that maintaining an active lifestyle and mobility may be crucial for individuals with a genetic predisposition to cognitive decline.

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年龄、载脂蛋白E ε4基因、体力活动和身体机能对加工速度的交互作用

目的：研究年龄、载脂蛋白E ε4 （APOE4）基因状态、身体活动能量消耗（PAEE）和身体机能对加工速度的交互作用。设计：在这项纵向研究中，参与者从2002年到2012年接受了两年一次的评估，作为国家长寿科学研究所-老龄化纵向研究（NILS-LSA）的一部分。环境和参与者：我们使用了日本2518名中老年社区居民的数据。方法：使用数字符号替代测试评估处理速度，其他数据包括APOE4基因分型，通过加速度计客观PAEE测量（以kcal/d为单位），以及身体功能评估（握力和步行速度，根据特定截止值进行二分类）。结果显示，PAEE ×年龄× APOE4携带者（β = 0.000025, P = 0.021）和慢速×年龄× APOE4携带者（β = -0.014187, P = 0.013）在认知加工速度上存在显著的3向交互作用。较高的PAEE与较好的处理速度相关，而较慢的处理速度与较差的处理速度相关，特别是在老年APOE4携带者中。虽然虚弱与年龄和APOE4携带者有显著的相互作用，但没有观察到3-way相互作用。结论和意义：我们的研究结果强调了身体活动、身体功能、年龄和遗传风险对加工速度的复杂相互作用。较高的PAEE水平和更好的身体功能之间的保护性联系，特别是在老年APOE4携带者中，表明保持积极的生活方式和流动性可能对具有认知能力下降遗传易感性的个体至关重要。

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

Journal of the American Medical Directors Association 医学-老年医学

CiteScore

11.10

自引率

6.60%

发文量

472

审稿时长

44 days

期刊介绍： JAMDA, the official journal of AMDA - The Society for Post-Acute and Long-Term Care Medicine, is a leading peer-reviewed publication that offers practical information and research geared towards healthcare professionals in the post-acute and long-term care fields. It is also a valuable resource for policy-makers, organizational leaders, educators, and advocates. The journal provides essential information for various healthcare professionals such as medical directors, attending physicians, nurses, consultant pharmacists, geriatric psychiatrists, nurse practitioners, physician assistants, physical and occupational therapists, social workers, and others involved in providing, overseeing, and promoting quality