Zamrini Edward, Cheng Yan, Kokkinos Peter, Morgan Charity J, Faselis Charles, Sheriff Helen M, Shao Yijun, Sui Xuemei, Ahmed Ali, Zeng Qing
Washington DC VA Medical Center, Washington, DC, USA; George Washington University, Washington, DC, USA; Irvine Clinical Research, Irvine, CA, USA.
Washington DC VA Medical Center, Washington, DC, USA; George Washington University, Washington, DC, USA.
J Prev Alzheimers Dis. 2025 Sep;12(8):100222. doi: 10.1016/j.tjpad.2025.100222. Epub 2025 Jun 9.
Higher fitness levels have been reported to protect against Alzheimer's Disease and Related Dementias (ADRD). However, the association between changes in fitness over time and ADRD risk remains unknown. This study aims to identify clusters of metabolic equivalents (METs) trajectories and examine their correlation with incident ADRD.
A retrospective cohort study was conducted among Veterans with ≥3 standardized exercise treadmill tests (ETT) between 2000 and 2017. The exposure was change in fitness expressed in metabolic equivalents (METs). METs are based on treadmill speed, grade, and time. One MET is equivalent to 3.5 ml per kg of body weight per minute. The outcome was incident ADRD after the final ETT test, identified by diagnosis codes. Standardized METs scores were generated using mean and standard deviation for each age and sex stratum. Latent class growth analysis (LCGA) identified trajectory clusters. We assessed the association between clusters and ADRD using unadjusted Kaplan-Meier curves (overall and by age groups) and a multivariate Cox regression model adjusted for baseline characteristics at the first ETT.
A total of 75,851 veterans were included. The average number of ETTs was 4.0 ± 1.8, with the average time gap of 6.5 ± 3.8 years between first and last test. We identified five trajectory clusters: Group 1 (n = 22,485), Group 2 (n = 22,694), Group 3 (n = 6691), Group 4 (n = 19,386), and Group 5 (n = 4595). All groups, except for Group 3, showed a stable and slight improvement or decline over time, differing only in their initial standardized METs scores: Group 5 had the highest initial score, Group 1 had the lowest initial score, while Group 3 started out with a score almost as high as Group 4 and dropped to as low as Group 1. Compared to Group 1, Group 3 had a 12 % reduced risk of developing ADRD (HR = 0.88; 95 % CI: 0.77 - 1.01; p = 0.0660), with a greater reduction than Group 2 (10 %) but less than Group 4 (17 %) or Group 5 (24 %).
Our findings underscore the potential benefits of maintaining fitness to reduce the risk of ADRD with age. Although declining fitness levels are associated with an increased risk, the initial higher baseline fitness provides a degree of ongoing protection against ADRD.
据报道，较高的健康水平可预防阿尔茨海默病及相关痴呆症（ADRD）。然而，随时间变化的健康状况与ADRD风险之间的关联仍不清楚。本研究旨在识别代谢当量（METs）轨迹集群，并检验它们与ADRD发病的相关性。
对2000年至2017年间进行过≥3次标准化运动平板试验（ETT）的退伍军人进行了一项回顾性队列研究。暴露因素为用代谢当量（METs）表示的健康状况变化。METs基于平板速度、坡度和时间。1个MET相当于每公斤体重每分钟3.5毫升。结局为最后一次ETT测试后发生的ADRD，通过诊断编码确定。使用每个年龄和性别分层的均值和标准差生成标准化METs分数。潜在类别增长分析（LCGA）识别轨迹集群。我们使用未调整的Kaplan-Meier曲线（总体和按年龄组）以及针对第一次ETT时的基线特征进行调整的多变量Cox回归模型评估集群与ADRD之间的关联。
共纳入75851名退伍军人。ETT的平均次数为4.0±1.8次，第一次和最后一次测试之间的平均时间间隔为6.5±3.8年。我们识别出五个轨迹集群：第1组（n = 22485）、第2组（n = 22694）、第3组（n = 6691）、第4组（n = 19386）和第5组（n = 4595）。除第3组外，所有组随时间均显示出稳定且轻微的改善或下降，仅初始标准化METs分数不同：第5组初始分数最高，第1组初始分数最低，而第3组开始时的分数几乎与第4组一样高，随后降至与第1组一样低。与第1组相比，第3组发生ADRD的风险降低了12%（HR = 0.88；95%CI：0.77 - 1.01；p = 0.0660），降低幅度大于第2组（10%），但小于第4组（17%）或第5组（24%）。
我们的研究结果强调了保持健康以降低随年龄增长发生ADRD风险的潜在益处。尽管健康水平下降与风险增加相关，但初始较高的基线健康水平可为预防ADRD提供一定程度的持续保护。
