Network topology and machine learning analyses reveal microstructural white matter changes underlying Chinese medicine Dengzhan Shengmai treatment on patients with vascular cognitive impairment.

With the increasing incidence of cerebrovascular diseases and dementia, considerable efforts have been made to develop effective treatments on vascular cognitive impairment (VCI), among which accumulating practice-based evidence has shown great potential of the traditional Chinese medicine (TCM). Current randomized double-blind controlled trial has been designed to evaluate the 6-month treatment effects of Dengzhan Shengmai (DZSM) capsules, one TCM herbal preparations on VCI, and to explore the underlying neural mechanisms with graph theory-based analysis and machine learning method based on diffusion tensor imaging (DTI) data. A total of 82 VCI patients were recruited and randomly assigned to drug (45 with DZSM) and placebo (37 with placebo) groups, and neuropsychological and neuroimaging data were acquired at baseline and after 6-month treatment. After treatment, compared to the placebo group, the drug groups showed significantly improved performance in Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-cog) score (p < 0.001) and the other cognitive domains. And with the reconstruction of white matter structural network, there were more streamlines connecting the left thalamus and right hippocampus in the drug groups (p < 0.001 uncorrected), with decreasing nodal efficiency of the right olfactory associated with slower decline in the general cognition (r = -0.364, p = 0.048). Moreover, support vector machine classification analyses revealed significant white matter network alterations after treatment in the drug groups (accuracy of baseline vs. 6-month later, 68.18 %). Taking together, the present study showed significant efficacy of DZSM treatment on VCI, which might result from white matter microstructure alterations and the topological changes in brain structural network.

Long-term efficacy of Chinese medicine Bushen Capsule on cognition and brain activity in patients with amnestic mild cognitive impairment.

Mild cognitive impairment (MCI), regarded as the prodromal stage before the clinical phase of Alzheimer's disease (AD), has been considered for early intervention. Unfortunately, many trials in this stage with drugs with single-target turned out to be little or no effect. Multi-targeting in nature based on the theory of Traditional Chinese Medicine (TCM) offers another prospect for intervention. Together with advanced functional magnetic resonance imaging (fMRI) technique for more sensitive and objective evaluation, we investigated the long-term therapeutic effects of a TCM compound on cognition and task-related neuronal activity. Sixty amnestic MCI (aMCI) participants from randomly divided into drug (30 with Bushen capsules (BSC)) and placebo (30 with placebo capsules) groups for this 2-years trial. Neuropsychological and N-back task-fMRI data were acquired at baseline and two follow-ups to assess, via linear mixed effect models, the changes of cognitive ability and brain activation over treatments. The drug group, compared with placebo group, exhibited improvement or stabilization in memory measures over time. Analyses of fMRI revealed that the placebo group exhibited higher activation magnitude and spatial extents at left superior parietal lobule; importantly, the greater activation identified in placebo group was related to more decline in the digit span. BSC showed long-term ameliorative effects on cognitive performances in aMCI patients, which might result from the regulation of abnormal brain activities. Our study provided evidence for the potential of TCM in early prevention of AD, as well as the feasibility of neuroimaging biomarkers in clinical trials.

A Two-Year Treatment of Amnestic Mild Cognitive Impairment using a Compound Chinese Medicine: A Placebo Controlled Randomized Trial.

We aimed to investigate the long-term therapeutic effects of a compound Chinese medicine, the Bushen capsule, on cognition and brain connectivity in patients with amnestic mild cognitive impairment (aMCI). Thus, sixty aMCI participants were recruited to this 24-month study and were randomly divided into treatment (30 with a Bushen capsule) and placebo (30 with a placebo capsule) groups. Neuropsychological tests with MMSE and episodic memory as the primary outcomes and resting-state functional magnetic resonance imaging (fMRI) were analyzed before and after the treatment over 24 month period. In contrast to the placebo group, the drug group presented improved or stable general cognitive function, memory, language and executive function especially the primary outcomes MMSE and episodic memory with Bushen capsule treatment. FMRI results showed increased connectivity in the right precuneus and the global connectivity indexed with goodness of fit (GOF) of the default mode network (DMN) in the drug group and decreased GOF in the placebo group. More importantly, we found the GOF change was positively correlated with changes in MMSE and memory scores after 24 months in the drug group. Over 24 months, treatment with the compound Chinese medicine Bushen capsule can improve multiple domains of cognition and increase the functional local (right precuneus) and global connectivity within the DMN, which are associated with better performance.