Yu Fang, Mathiason Michelle A, Han SeungYong, Gunter Jeffrey L, Jones David, Botha Hugo, Jack Clifford
Arizona State University Edson College of Nursing and Health Innovation, Phoenix, AZ, United States.
University of Minnesota School of Nursing, Minneapolis, MN, United States.
Front Aging Neurosci. 2021 Oct 7;13:703691. doi: 10.3389/fnagi.2021.703691. eCollection 2021.
Despite strong evidence from animal models of Alzheimer's disease (AD) supporting aerobic exercise as a disease-modifying treatment for AD, human mechanistic studies are limited with mixed findings. The objective of this pilot randomized controlled trial was to examine the effects of 6-month aerobic exercise on hippocampal volume, temporal meta-regions of interest (ROI) cortical thickness, white matter hyperintensity (WMH) volume, and network failure quotient (NFQ), measured with MRI, in community-dwelling older adults with AD dementia. Additionally, the relationships between 6- and 12-month changes in MRI biomarkers and the AD Assessment Scale-Cognition (ADAS-Cog) were examined. Sixty participants were randomized, but one was excluded because baseline MRI failed quality control: 38 randomized to cycling and 21 to stretching. The intervention was moderate-intensity cycling for 20-50 mins, three times a week for 6 months. Control was low-intensity stretching. The study outcomes include hippocampal volume, temporal meta-ROI cortical thickness, WMH volume, and NFQ. Outcomes were measured at baseline, 6 months, and 12 months. The sample averaged 77.3 ± 6.3 years old with 15.6 ± 2.9 years of education and 53% men. Both groups experienced significant declines over 6 months in hippocampal volume (2.64% in cycling vs. 2.89% in stretching) and temporal meta-ROI cortical thickness (0.94 vs. 1.54%), and over 12 months in hippocampal volume (4.47 vs. 3.84%) and temporal meta-ROI cortical thickness (2.27 vs. 1.79%). These declines did not differ between groups. WMH volume increased significantly with the cycling group increasing less (10.9%) than stretching (24.5%) over 6 months ( = 4.47, = 0.04) and over 12 months (12.1 vs. 27.6%, = 5.88, = 0.02). NFQ did not change significantly over time. Pairwise correlational analyses showed a significant negative correlation between 6-month changes in hippocampal volume and ADAS-Cog ( = -0.34, < 0.05). To conclude, aerobic exercise may reduce the decline in hippocampal volume and temporal meta-ROI cortical thickness during the intervention period, but the effect sizes are likely to be very small and dose-dependent and reverse once the intervention stops. Aerobic exercise is effective on slowing down WMH progression but has no effect on NFQ. Hippocampal atrophy was associated with cognitive decline during the intervention period. www.ClinicalTrials.gov, identifier: NCT01954550.
尽管阿尔茨海默病（AD）动物模型有强有力的证据支持有氧运动作为AD的疾病修饰治疗方法，但人体机制研究有限且结果不一。这项初步随机对照试验的目的是研究在社区居住的患有AD痴呆的老年人中，6个月有氧运动对海马体积、颞叶感兴趣元区域（ROI）皮质厚度、白质高信号（WMH）体积和网络衰竭商（NFQ）的影响，这些指标通过磁共振成像（MRI）测量。此外，还研究了MRI生物标志物6个月和12个月变化与AD认知评估量表（ADAS - Cog）之间的关系。60名参与者被随机分组，但有1名因基线MRI未通过质量控制而被排除：38名被随机分配到骑行组，21名被分配到拉伸组。干预措施是进行20 - 50分钟的中等强度骑行，每周三次，持续6个月。对照组是低强度拉伸。研究结果包括海马体积、颞叶元ROI皮质厚度、WMH体积和NFQ。在基线、6个月和12个月时测量结果。样本平均年龄为77.3±6.3岁，受教育年限为15.6±2.9年，男性占53%。两组在6个月内海马体积（骑行组下降2.64%，拉伸组下降2.89%）和颞叶元ROI皮质厚度（分别下降0.94和1.54%）以及12个月内海马体积（分别下降4.47和3.84%）和颞叶元ROI皮质厚度（分别下降2.27和1.79%）均出现显著下降。两组之间这些下降情况没有差异。在6个月（F = 4.47，P = 0.04）和12个月（分别为12.1%和27.6%，F = 5.88，P = 0.02）时，WMH体积显著增加，骑行组增加量（10.9%）低于拉伸组（24.5%）。NFQ随时间没有显著变化。两两相关分析显示，海马体积6个月变化与ADAS - Cog之间存在显著负相关（r = -0.34，P < 0.05）。总之，有氧运动可能在干预期内减少海马体积和颞叶元ROI皮质厚度的下降，但效应大小可能非常小且与剂量相关，并且一旦干预停止就会逆转。有氧运动对减缓WMH进展有效，但对NFQ没有影响。在干预期内，海马萎缩与认知下降有关。ClinicalTrials.gov网站，标识符：NCT01954550。
