Guzmán-Vélez Edmarie, Aguillón David, Rivera-Hernández Angelys, Baena Ana Y, Londoño-Sotomayor Natalia, Picard Glen, Kramer Arthur F, Arnold Steven E, Caraballo-Gracia Domingo I, Taylor J Andrew, Quiroz Yakeel T
Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Grupo de Neurociencias, Universidad de Antioquia, Medellín, Antioquia, Colombia.
J Alzheimers Dis. 2025 Jul;106(2):678-685. doi: 10.1177/13872877251344327. Epub 2025 Jul 1.
BackgroundHigh cardiorespiratory fitness has been associated with greater neuroplasticity, and slower neurodegeneration and cognitive decline in healthy adults. Yet, less is known about whether low-to-intermediate cardiorespiratory fitness is associated with lower markers of disease progression in the preclinical stage of Alzheimer's disease (AD).ObjectiveWe investigated whether cardiorespiratory fitness was associated with plasma biomarkers for AD-related pathology, neural injury and astrocyte reactivity, and episodic memory in Presenilin-1 E280A carriers without dementia from the world's largest kindred with autosomal-dominant AD.MethodsTwenty-seven mutation carriers (25 cognitively unimpaired, 2 with mild cognitive impairment; ages: μ=30.22 years, SD = 5.24; 74% female) participated in the study. Participants underwent a graded aerobic fitness test to assess cardiorespiratory fitness, measured in maximum metabolic equivalent of task (MET). Plasma biomarkers included amyloid 42/40, phosphorylated tau-181, neurofilament light chain, and glial fibrillary acidic protein. Participants completed the Consortium to Establish a Registry for AD word list learning and delayed recall. We conducted multiple linear regressions controlling for age, sex, and years of education.ResultsFourteen participants' MET values were indicative of low cardiorespiratory fitness (< MET), and 13 participants' MET values of intermediate cardiorespiratory fitness (9-14 MET). METs were not associated with age, biomarkers, or episodic memory.ConclusionsOur findings suggest that low-to-intermediate cardiorespiratory fitness may not be associated with biomarkers for AD-related pathology, neural injury and astrocyte reactivity, or memory in people at genetic risk for dementia. Longitudinal studies and randomized-controlled trials are needed to better understand the relationships among cardiorespiratory fitness and AD progression.
背景
高心肺适能与健康成年人更大的神经可塑性、更缓慢的神经退行性变和认知衰退相关。然而，关于低至中等心肺适能是否与阿尔茨海默病（AD）临床前期疾病进展的较低标志物相关，人们了解较少。
目的
我们调查了心肺适能是否与来自世界上最大的常染色体显性AD家族的早老素-1 E280A携带者（无痴呆）的AD相关病理、神经损伤和星形胶质细胞反应性的血浆生物标志物以及情景记忆相关。
方法
27名突变携带者（25名认知未受损，2名轻度认知障碍；年龄：μ = 30.22岁，标准差 = 5.24；74%为女性）参与了研究。参与者接受了分级有氧适能测试以评估心肺适能，以最大代谢当量（MET）衡量。血浆生物标志物包括淀粉样蛋白42/40、磷酸化tau-181、神经丝轻链和胶质纤维酸性蛋白。参与者完成了阿尔茨海默病注册协会的单词列表学习和延迟回忆测试。我们进行了多元线性回归，控制了年龄、性别和受教育年限。
结果
14名参与者的MET值表明心肺适能低（< MET），13名参与者的MET值为中等心肺适能（9 - 14 MET）。MET与年龄、生物标志物或情景记忆无关。
结论
我们的研究结果表明，低至中等心肺适能可能与痴呆遗传风险人群的AD相关病理、神经损伤和星形胶质细胞反应性的生物标志物或记忆无关。需要进行纵向研究和随机对照试验，以更好地了解心肺适能与AD进展之间的关系。
