Effects of Moxa Cone Moxibustion Therapy on Cognitive Function and Brain Metabolic Changes in MCI Patients: A Pilot 1H-MRS Study.

Objective: To explore the effect of moxa cone moxibustion on N-acetyl aspartate/total creatinine (NAA/tCr) and choline/total creatinine (Cho/tCr) in the bilateral hippocampus (HIP) and bilateral posterior cingulate gyrus (PCG) in patients with mild cognitive impairment (MCI) using hydrogen proton magnetic resonance spectroscopy (1H-MRS) and to provide imaging basis for moxa cone moxibustion treatment for MCI. Methods: One hundred eight patients with MCI were served as the MCI group, and 67 age-matched subjects were enrolled as the normal control group. The MCI group was randomized and allocated into acupoint group, drug group, and sham acupoint group, with 36 cases in each group. Some patients in each group withdrew. Finally, 25 cases were included in the acupoint group, 24 cases in the drug group, and 20 cases in the sham acupoint group. The drug group was treated with oral donepezil hydrochloride. The acupoint group and sham acupoint group received moxa cone moxibustion treatment. Mini-mental state exam (MMSE) and Montreal cognitive assessment (MoCA) scores were recorded before intervention, at the end of the first and the second months of intervention, and in the 5th month of follow-up. The NAA/tCr and Cho/tCr ratios in the HIP and PCG were bilaterally measured by 1H-MRS before and after intervention. Results: Before intervention, compared with the normal control group, the MMSE and MoCA scores, the Cho/tCr ratio in the right HIP, the NAA/tCr ratio in the bilateral HIP, and the NAA/tCr ratio in the left PCG in the three treatment groups decreased significantly (both p < 0.01), and the NAA/tCr ratio in the right PCG significantly reduced in the acupoint and drug groups (p < 0.05). After two months of treatment, compared with the normal control group, there were no differences in the MoCA scores, the NAA/tCr, and Cho/tCr ratios in the bilateral PCG and bilateral HIP in the three treatment groups (p > 0.05). However, the MMSE scores in the drug group decreased when compared with the acupoint group and normal control group (p < 0.05, p < 0.01). The scores of MMSE and MoCA in the acupoint group and sham acupoint group at all time points were better than those in the drug group, which were similar to those in the normal control group. Conclusion: Our findings suggest that moxibustion could improve the cognitive function of patients with MCI. The mechanism may be related to the improvement of abnormal brain metabolism in HIP and PCG.

Fusion analysis of gray matter and white matter in subjective cognitive decline and mild cognitive impairment by multimodal CCA-joint ICA.

BACKGROUND: Previous multimodal neuroimaging studies analyzed each dataset independently in subjective cognitive decline (SCD) and mild cognitive impairment (MCI), missing the cross-information. Multi-modal fusion analysis can provide more integral and comprehensive information regarding the brain. There has been a paucity of research on fusion analysis of sMRI and DTI in SCD and MCI. MATERIALS AND METHODS: In the present study, we conducted fusion analysis of structural MRI and DTI by applying multimodal canonical correlation analysis with joint independent component analysis (mCCA-jICA) to capture the cross-information of gray matter (GM) and white matter (WM) in 62 SCD patients, 99 MCI patients, and 70 healthy controls (HCs). We further analyzed correlations between the mixing coefficients of mCCA-jICA and neuropsychological scores among the three groups. RESULTS: A set of joint-discriminative independent components of GM and fractional anisotropy (FA) exhibited significant links between SCD and HCs, as well as between MCI and HCs. The covariant abnormalities primarily involved the frontal lobe/middle temporal gyrus/calcarine sulcus-anterior thalamic radiation/superior longitudinal fasciculus in SCD, and middle temporal gyrus/ fusiform gyrus/caudate necleus-forceps minor/anterior thalamic radiation in MCI. There was no significant difference between SCD and MCI groups. CONCLUSIONS: The covariant GM-WM abnormalities in SCD and MCI were found in specific brain regions involved in cognitive processing, which confirms the simultaneous GM and WM changes underlying cognitive decline. These findings suggest that multimodal fusion analysis allows for a more comprehensive understanding of the association among different types of brain tissues and its crucial role in the neuropathological mechanism of SCD and MCI.

Corrigendum: A Pilot Study on the Cutoff Value of Related Brain Metabolite in Chinese Elderly Patients With Mild Cognitive Impairment Using MRS.

[This corrects the article DOI: 10.3389/fnagi.2021.617611.].

Auto-weighted centralised multi-task learning via integrating functional and structural connectivity for subjective cognitive decline diagnosis.

Early diagnosis and intervention of mild cognitive impairment (MCI) and its early stage (i.e., subjective cognitive decline (SCD)) is able to delay or reverse the disease progression. However, discrimination between SCD, MCI and healthy subjects accurately remains challenging. This paper proposes an auto-weighted centralised multi-task (AWCMT) learning framework for differential diagnosis of SCD and MCI. AWCMT is based on structural and functional connectivity information inferred from magnetic resonance imaging (MRI). To be specific, we devise a novel multi-task learning algorithm to combine neuroimaging functional and structural connective information. We construct a functional brain network through a sparse and low-rank machine learning method, and also a structural brain network via fibre bundle tracking. Those two networks are constructed separately and independently. Multi-task learning is then used to identify features integration of functional and structural connectivity. Hence, we can learn each task's significance automatically in a balanced way. By combining the functional and structural information, the most informative features of SCD and MCI are obtained for diagnosis. The extensive experiments on the public and self-collected datasets demonstrate that the proposed algorithm obtains better performance in classifying SCD, MCI and healthy people than traditional algorithms. The newly proposed method has good interpretability as it is able to discover the most disease-related brain regions and their connectivity. The results agree well with current clinical findings and provide new insights into early AD detection based on the multi-modal neuroimaging technique.

A Pilot Study on the Cutoff Value of Related Brain Metabolite in Chinese Elderly Patients With Mild Cognitive Impairment Using MRS.

Objective: This cross-sectional study aimed to distinguish patients with mild cognitive impairment (MCI) from patients with normal controls (NCs) by measuring the levels of N-acetyl aspartate (NAA), total creatinine (tCr), and choline (Cho) in their hippocampus (HIP) and their posterior cingulate gyrus (PCG) by using proton magnetic resonance spectroscopy (MRS) and to predict the cutoff value on the ratios of metabolites. We further aimed to provide a reference for the diagnosis of MCI in elderly patients in China. Methods: About 69 patients who underwent a clinical diagnosis of the MCI group and 67 patients with NCs, the Mini-Mental Status Examination (MMSE) score, the Montreal Cognitive Assessment (MoCA) score, and MRS of the bilateral HIP and bilateral PCG were considered. The ratio of NAA/tCr and Cho/tCr in the bilateral HIP and bilateral PCG was calculated. The relationship between the ratios of metabolites and the scores of MMSE and MoCA was analyzed, and the possible brain metabolite cutoff point for the diagnosis of MCI was evaluated. Results: Compared with the NC group, the scores of MMSE and MoCA in the MCI group decreased significantly (p < 0.05); the ratio of NAA/tCr in the bilateral HIP and bilateral PCG and the ratio of Cho/tCr at the right HIP in the MCI group decreased significantly (p < 0.05); however, there was no significant difference in the ratio of Cho/tCr in the left HIP and bilateral PCG between the two groups (p > 0.05). The correlation coefficient between MMSE/MoCA and the ratio of NAA/tCr was 0.49-0.56 in the bilateral HIP (p < 0.01). The best cutoff value of NAA/creatine (Cr) in the left HIP and the right HIP was 1.195 and 1.19. Sensitivity, specificity, and the Youden index (YDI) in the left HIP and the right HIP were (0.725, 0.803, 0.528) and (0.754, 0.803, 0.557), respectively. Conclusion: The level of metabolites in the HIP and the PCG of patients with MCI and of those with normal subjects has a certain correlation with the score of their MMSE and MoCA. When the value of NAA/tCr in the left HIP and right HIP is <1.19, it suggests that MCI may have occurred. According to this cutoff point, elderly patients with MCI in China could be screened.

Characteristics of TCM Constitution and Related Biomarkers for Mild Cognitive Impairment.

INTRODUCTION: The incidence of Alzheimer's disease is on the rise, early detection of cognitive impairment of the elderly is very important. In traditional Chinese medicine, constitution is related to the susceptibility of the human body to diseases. Based on the theory of constitution of traditional Chinese medicine (TCM), the human population can be classified into 9 constitutions. However, little is known about the characteristics of medical constitution and related biomarkers in subjects with mild cognitive impairment (MCI). METHODS: We measured the TCM Constitution of 214 subjects by using the Constitution in Chinese Medicine Questionnaire (CCMQ). MMSE and MoCA were used to assess cognitive function. The subjects were divided into mild cognitive impairment group (MCI, n = 152) and normal control group (NC, n = 62). The levels of serum Hcy and serum/urine 8-iso-PGF 2α were determined. RESULTS: 1) It was found that there was a significant difference in constitution types between MCI and NC. There were significant differences in MMSE and MoCA score, serum Hcy and serum/urine 8-iso-PGF 2a levels between the two groups. 2) In logistic regression analysis, the variables with statistical significance were TCM Constitution of Yang-Deficient, Phlegm-Dampness, Blood-Stasis and abnormal increase of Hcy (OR>1). 3) The MoCA scores had a positive correlation with the MMSE. A statistically significant inverse association was found between serum Hcy, blood and urine 8-iso-PGF 2a and scores of cognitive assessment in MCI. CONCLUSION: Constitution types (Yang-Deficient, Phlegm-Dampness and Blood-Stasis) and abnormal serum Hcy elevation can be used as risk factors for MCI. MoCA scores can serve to detect MCI at early stage. Serum/urine 8-iso-PGF 2α has a certain relationship with MCI. Higher levels of serum/urine 8-iso-PGF 2α are more likely to be associated with MCI risk.

Recurrent and concurrent patterns of regional BOLD dynamics and functional connectivity dynamics in cognitive decline.

BACKGROUND: The brain's dynamic spontaneous neural activity and dynamic functional connectivity (dFC) are both important in supporting cognition, but how these two types of brain dynamics evolve and co-evolve in subjective cognitive decline (SCD) and mild cognitive impairment (MCI) remain unclear. The aim of the present study was to investigate recurrent and concurrent patterns of two types of dynamic brain states correlated with cognitive decline. METHODS: The present study analyzed resting-state functional magnetic resonance imaging data from 62 SCD patients, 75 MCI patients, and 70 healthy controls (HCs). We used the sliding-window and clustering method to identify two types of recurrent brain states from both dFC and dynamic regional spontaneous activity, as measured by dynamic fractional amplitude of low-frequency fluctuations (dfALFF). Then, the occurrence frequency of a dFC or dfALFF state and the co-occurrence frequency of a pair of dFC and dfALFF states among all time points are extracted for each participant to describe their dynamics brain patterns. RESULTS: We identified a few recurrent states of dfALFF and dFC and further ascertained the co-occurrent patterns of these two types of dynamic brain states (i.e., dfALFF and dFC states). Importantly, the occurrence frequency of a default-mode network (DMN)-dominated dFC state was significantly different between HCs and SCD patients, and the co-occurrence frequencies of a DMN-dominated dFC state and a DMN-dominated dfALFF state were also significantly different between SCD and MCI patients. These two dynamic features were both significantly positively correlated with Mini-Mental State Examination scores. CONCLUSION: Our findings revealed novel fMRI-based neural signatures of cognitive decline from recurrent and concurrent patterns of dfALFF and dFC, providing strong evidence supporting SCD as the transition phase between normal aging and MCI. This finding holds potential to differentiate SCD patients from HCs via both dFC and dfALFF as objective neuroimaging biomarkers, which may aid in the early diagnosis and intervention of Alzheimer's disease.

Structural and Functional Hippocampal Changes in Subjective Cognitive Decline From the Community.

BACKGROUND: Recently, subjective cognitive decline (SCD) has been described as the earliest at-risk state of Alzheimer's disease (AD), and drawn attention of investigators. Studies suggested that SCD-community individuals may constitute a more vulnerable population than SCD-clinic patients, therefore, to investigate the early changes of the brain may provide guidance for treatment of the disease. We sought to investigate the changes of structure and functional connectivity alternation of the hippocampus in individuals with SCD recruited from the community using structural and resting-state functional MRI (fMRI). METHODS: Thirty-five SCD patients and 32 healthy controls were recruited. Resting-state fMRI data and high-resolution T1-weighted images were collected. Whole-brain voxel-based morphometry was used to examine the brain structural changes. We also used the hippocampal tail and the whole hippocampus as seeds to investigate functional connectivity alternation in SCD. RESULTS: Individuals with SCD showed significant gray matter volume decreases in the bilateral hippocampal tails and enlargement of the bilateral paracentral lobules. We also found that individuals with SCD showed decreased hippocampal tail resting-state functional connectivity (rsFC) with the right medial prefrontal cortex (mPFC) and the left temporoparietal junction (TPJ), and decreased whole hippocampus rsFC with the bilateral mPFC and TPJ. These brain region and FC showing significant differences also showed significantly correlation with Montreal Cognitive Assessment (MoCA) scores. CONCLUSION: Individuals with SCD recruited from the community is associated with structural and functional changes of the hippocampus, and these changes may serve as potential biomarkers of SCD. CLINICAL TRIAL REGISTRATION: The Declaration of Helsinki, and the study was registered in http://www.chictr.org.cn. The Clinical Trial Registration Number was ChiCTR-IPR-16009144.