Department of Psychiatry and Behavioral Sciences, School of Medicine, Stanford University, Stanford, CA, USA.
Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
Transl Psychiatry. 2024 Oct 23;14(1):447. doi: 10.1038/s41398-024-03153-x.
Amnestic mild cognitive impairment (aMCI) is a risk factor for Alzheimer's disease (AD). Multi-domain cognitive training (CT) may slow cognitive decline and delay AD onset. However, most work involves short interventions, targeting single cognitive domains or lacking active controls. We conducted a single-blind randomized controlled trial to investigate the effect of a 6-month, multi-domain CT on Fluid Cognition, functional connectivity in memory and executive functioning networks (primary outcomes), and white matter microstructural properties (secondary outcome) in aMCI. Sixty participants were randomly assigned to either a multi-domain CT or crossword training (CW) group, and thirty-four participants completed the intervention. We found a significant group-by-time interaction in Fluid Cognition (p = 0.007, F (1,28) = 8.26, Cohen's d = 0.38, 95% confidence interval [CI]: 2.45-14.4), with 90% of CT patients showing post-intervention improvements (p < 0.01, Cohen's d = 0.7). The CT group also showed better post-intervention Fluid Cognition than healthy controls (HCs, N = 45, p = 0.045). Functional connectivity analyses showed a significant group-by-time interaction (Cohen's d ≥ 0.8) in the dorsolateral prefrontal cortex (DLPFC) and inferior parietal cortex (IPC) networks. Specifically, CT displayed post-intervention increases whereas CW displayed decreases in functional connectivity. Moreover, increased connectivity strength between the left DLPFC and medial PFC was associated with improved Fluid Cognition. At a microstructural level, we observed a decline in fiber density (FD) for both groups, but the CT group declined less steeply (1.3 vs. 2%). The slower decline in FD for the CT group in several tracts, including the cingulum-hippocampus tract, was associated with better working memory. Finally, we identified regions in cognitive control and memory networks for which baseline functional connectivity and microstructural properties were associated with changes in Fluid Cognition. Long-term, multi-domain CT improves cognitive functioning and functional connectivity and delays structural brain decline in aMCI (ClinicalTrials.gov number: NCT03883308).
遗忘型轻度认知障碍 (aMCI) 是阿尔茨海默病 (AD) 的危险因素。多领域认知训练 (CT) 可能会减缓认知能力下降并延迟 AD 发病。然而，大多数工作涉及短期干预，针对单一认知领域或缺乏主动对照。我们进行了一项单盲随机对照试验，以调查 6 个月的多领域 CT 对 aMCI 中流体认知、记忆和执行功能网络的功能连接（主要结果）以及白质微观结构特性（次要结果）的影响。60 名参与者被随机分配到多领域 CT 或纵横字谜训练 (CW) 组，34 名参与者完成了干预。我们发现流体认知方面存在显著的组间时间交互作用 (p=0.007, F(1,28)=8.26, Cohen's d=0.38, 95%置信区间 [CI]:2.45-14.4)，90%的 CT 患者在干预后表现出改善 (p<0.01, Cohen's d=0.7)。CT 组在干预后流体认知也优于健康对照组 (HCs, N=45, p=0.045)。功能连接分析显示，在背外侧前额叶皮层 (DLPFC) 和下顶叶皮层 (IPC) 网络中存在显著的组间时间交互作用 (Cohen's d≥0.8)。具体来说，CT 显示干预后功能连接增强，而 CW 显示功能连接减弱。此外，左 DLPFC 与内侧前额叶皮层之间连接强度的增加与流体认知的改善相关。在微观结构水平上，我们观察到两组的纤维密度 (FD) 都有所下降，但 CT 组的下降幅度较小 (1.3 对 2%)。在几个束，包括扣带-海马束中，CT 组的 FD 下降速度较慢，与更好的工作记忆相关。最后，我们确定了认知控制和记忆网络中的区域，其基线功能连接和微观结构特性与流体认知的变化相关。长期多领域 CT 可改善 aMCI 的认知功能和功能连接，并延缓结构性脑衰退 (ClinicalTrials.gov 编号：NCT03883308)。
