OBJECTIVE: To observe the effects of "olfactory three needles" on cognition, learning and memory abilities, as well as hippocampal microglia (MG) phagocytic activity in vascular dementia (VD) rats, and explore the mechanisms of acupuncture in regulating MG activation and improving remyelination, so as to ameliorate VD. METHODS: Among 38 SD rats meeting experimental requirements, 9 rats were randomly assigned to a sham-operation group, and the remaining rats underwent permanent bilateral common carotid artery ligation to establish VD model. Eighteen successfully modeled rats were randomly divided into a model group and an electroacupuncture (EA) group, with 9 rats in each one. In the EA group, EA was performed at "olfactory three needles" ("Yintang" [GV24⁺] and bilateral "Yingxiang" [LI20]), at disperse-dense wave, the frequency of 2 Hz/15 Hz and the current intensity of 1 mA, for 15 min per intervention, once daily. One course was composed of 7 days, and 2 courses were required, with the interval of 2 days. The novel object recognition test was employed to assess the cognition of rats, and the Morris water maze was adopted to observe learning and memory abilities. Luxol fast blue (LFB) staining was performed to evaluate myelin sheath loss in the hippocampus, the Western blot was used to detect the protein expression of triggering receptor expressed on myeloid cells-2 (TREM2) and proteolipid protein (PLP) in the hippocampus; and the immunofluorescence staining was used to detect the positive expression of PLP, sex determining region Y-box 10 (SOX10), ionized calcium binding adaptor molecule 1 (Iba1)⁺ TREM2⁺ and Iba1⁺ lysosome-associated membrane protein 1 (LAMP1)⁺ in the hippocampus. RESULTS: Compared with the sham-operation group, the rats in the model group exhibited the prolonged escape latency on day 3 and 4 (P<0.05, P<0.01), the increase of the total distance traveling (P<0.01) and the decrease of the recognition index (RI) and platform crossing frequency (P<0.01). Compared with the model group, the rats in the EA group showed the shortened escape latency on day 3 and 4 (P<0.05), the decrease of total distance traveling (P<0.01) and the increase of RI and platform crossing frequency (P<0.05, P<0.01). When compared with the sham-operation group, the rats of the model group presented uneven staining, sparse arrangement of myelin sheath fibers, unclear contours, and prominent vacuole-like changes in the hippocampal CA1 region. When compared with the model group, the EA group showed more dense staining, the increase of myelin sheath fibers with more orderly alignment, and fewer vacuolar changes in the hippocampal CA1 region. Compared with the sham-operation group, the model group exhibited the increase of TREM2 protein expression and the decrease of PLP protein expression in the hippocampus (P<0.01), whereas the EA group showed the up-regulation of TREM2 and PLP protein expression when compared with the model group (P<0.01, P<0.05). The positive expression of the hippocampal PLP, SOX10, and Iba1⁺LAMP1⁺ in the model group was reduced in comparison with the sham-operation group (P<0.05, P<0.01), and the positive expression of Iba1⁺ TREM2⁺ was elevated (P<0.05). In the EA group, the positive expression of PLP, SOX10, Iba1⁺TREM2⁺, and Iba1⁺ LAMP1⁺ was higher compared with that in the model group (P<0.05, P<0.01). CONCLUSION "Olfactory three needles" can improve the learning and memory, and cognitive functions of VD rats, and its mechanism may be associated with the up-regulation of TREM2 and LAMP1 to adjust MG phagocytic activity and intracellular degradation, and promote remyelination.
Animals ; Dementia, Vascular/metabolism* ; Rats ; Rats, Sprague-Dawley ; Microglia/metabolism* ; Male ; Acupuncture Therapy/instrumentation* ; Acupuncture Points ; Humans ; Remyelination ; Memory ; Hippocampus/cytology* ; Cognition ; Electroacupuncture ; Needles

OBJECTIVE: To observe the clinical efficacy of acupuncture on mild cognitive impairment (MCI) and its effect on gut microbiota. METHODS: A total of 62 MCI patients were randomly divided into an experimental group (31 cases, 2 cases dropped out) and a control group (31 cases). Both groups received exercise and cognitive training. In addition, the experimental group underwent acupuncture treatment at acupoints including Baihui (GV20), Sishencong (EX-HN1), and bilateral Fengchi (GB20), Xuanzhong (GB39), Zusanli (ST36), Yanglao (SI6), Xinshu (BL15), and etc., once every other day, three times per week, for a total of 12 weeks. Before and after treatment, the Montreal cognitive assessment (MoCA) and mini-mental state examination (MMSE) scores were evaluated in the two groups, changes in gut microbiota were detected using 16S rDNA sequencing technology. The clinical efficacy was assessed after treatment. RESULTS: Compared before treatment, MoCA and MMSE scores were increased in both groups after treatment (P<0.001), with higher scores in the experimental group than those in the control group (P<0.001, P<0.05). After treatment, the relative abundance of Faecalibacterium, Clostridia, and Ruminococcaceae was increased in the experimental group compared with that before treatment (P<0.05). Moreover, the relative abundance of Faecalibacterium in the experimental group was higher than that in the control group (P<0.05). The total effective rate was 82.8% (24/29) in the experimental group, which was higher than 61.3% (19/31) in the control group (P<0.05). CONCLUSION Acupuncture could improve cognitive dysfunction in patients with MCI, and its mechanism may be related to increasing the relative abundance of butyrate-producing bacteria such as Faecalibacterium, Clostridia, and Ruminococcaceae, maintaining the intestinal barrier, and inhibiting related inflammatory responses.
Humans ; Acupuncture Therapy ; Gastrointestinal Microbiome ; Cognitive Dysfunction/psychology* ; Male ; Female ; Aged ; Middle Aged ; Acupuncture Points ; Treatment Outcome ; Aged, 80 and over ; Cognition

OBJECTIVE: To observe the effects of moxibustion at different temperatures on cognitive function and blood glucose levels in patients with cognitive impairment associated with type 2 diabetes mellitus (T2DM). METHODS: A total of 66 T2DM patients with cognitive impairment were randomly assigned to a high-temperature group (22 cases, 1 case dropped out, 1 case was eliminated), a medium-temperature group (22 cases, 2 cases were eliminated), and a low-temperature group (22 cases, 2 cases were eliminated). All groups received moxibustion at Baihui (GV20), Dazhui (GV14), and Shenting (GV24) based on their existing glycemic control treatment. Moxibustion temperatures were maintained at 44-46 ℃ (high-temperature group), 41-43 ℃ (medium-temperature group), and 38-40 ℃ (low-temperature group), respectively, for 20 min per session, every other day, 3 times a week for 3 months. The Montreal cognitive assessment (MoCA) score, mini-mental state examination (MMSE) score, short-term memory (STM) accuracy and average reaction time, Rey-Osterrieth complex figure (ROCF) score, fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c) were assessed before and after treatment. Clinical efficacy was evaluated after treatment. RESULTS: After treatment, MMSE scores in all three groups were higher than those before treatment (P<0.05). In the high-temperature group, the total MoCA score and the scores of visuospatial and executive function, memory and delayed recall, attention, naming, language, and abstraction were higher than those before treatment (P<0.05); the scores of ROCF copy, immediate recall, and delayed recall were higher than those before treatment (P<0.05); the HbA1c level was lower than that before treatment (P<0.05). In the medium-temperature group, the total MoCA score and the scores of memory and delayed recall, attention, and language were higher than those before treatment (P<0.05). STM accuracy was higher than before treatment (P<0.05), and STM average reaction time was shorter than before treatment (P<0.05) in both the high-temperature and medium-temperature groups. After treatment, the total MoCA score and the scores of visuospatial and executive function, memory and delayed recall, attention, and language in the high-temperature group were higher than those in the medium- and low-temperature groups (P<0.05); MMSE score, STM accuracy, and ROCF immediate recall and delayed recall scores were higher than those in the medium- and low-temperature groups (P<0.05); STM average reaction time was shorter than that in the medium- and low-temperature groups (P<0.05); HbA1c level was lower than that in the low-temperature group (P<0.05). The total MoCA score, attention score, and MMSE score in the medium-temperature group were higher than those in the low-temperature group (P<0.05), and STM average reaction time was shorter than that in the low-temperature group (P<0.05). There were no statistically significant differences in FPG within or between the three groups before and after treatment (P>0.05). The total effective rates were 75.0% (15/20) in the high-temperature group, 50.0% (10/20) in the medium-temperature group, and 15.0% (3/20) in the low-temperature group; the total effective rate in the high-temperature group was significantly higher than that in the low-temperature group (P<0.05). CONCLUSION Moxibustion at different temperatures has a dose-effect relationship in treating cognitive impairment in T2DM patients. A temperature range of 44-46 ℃ is more effective in improving cognitive function and stabilizing average blood glucose levels over 2-3 months.
Humans ; Diabetes Mellitus, Type 2/therapy* ; Male ; Female ; Moxibustion ; Middle Aged ; Aged ; Cognitive Dysfunction/psychology* ; Cognition ; Temperature ; Blood Glucose/metabolism* ; Adult ; Acupuncture Points

OBJECTIVE: To investigate the effects of Huayu Tongluo (transforming stasis and unblocking collaterals) moxibustion on cognitive function and insulin resistance in patients with type 2 diabetes mellitus (T2DM) and cognitive decline. METHODS: Ninety patients with T2DM and cognitive decline were randomly divided into a moxibustion group (n=45, 3 cases dropped out, 2 cases were eliminated) and a waiting moxibustion group (n=45, 2 cases dropped out). Both groups received routine hypoglycemic treatment for 12 weeks. The moxibustion group additionally received Huayu Tongluo moxibustion at Baihui (GV20), Shenting (GV24), and Dazhui (GV14). Pressing moxibustion was applied to Baihui (GV20) for 20 min, while suspended moxibustion was applied to Shenting (GV24) and Dazhui (GV14) for 20 min each. Treatments of moxibustion were administered every other day (three times per week) for 12 weeks. All patients were followed up for 12 weeks, during which their original hypoglycemic medication regimen was maintained. Before treatment, after 12 weeks of treatment, and at the 12-week follow-up, the scores of Montreal cognitive assessment (MoCA), mini-mental state examination (MMSE), Addenbrooke's cognitive examination Ⅲ (ACE-Ⅲ), symbol digit modalities test (SDMT), and Athens insomnia scale (AIS) and the insulin resistance index (HOMA-IR) were observed in the two groups. RESULTS: Compared with before treatment, the MoCA scores, MMSE scores, ACE-Ⅲ subscale scores (attention, memory, language fluency, language, visuospatial ability) and total scores, and SDMT scores were increased (P<0.01), while the AIS scores were decreased (P<0.05) in the moxibustion group after treatment and at follow-up. Compared with before treatment, the MMSE score, ACE-Ⅲ subscale scores (memory, attention) and total score after treatment, as well as the ACE-Ⅲ subscale scores (language, memory, attention) and total score, and SDMT score at follow-up were increased (P<0.05, P<0.01) in the waiting moxibustion group. Compared with before treatment, HOMA-IR was decreased in both groups after treatment and at follow-up (P<0.01). At follow-up, ACE-Ⅲ subscale scores (attention, memory), and the total score in the moxibustion group were lower than those after treatment (P<0.05, P<0.01), and the ACE-Ⅲ language subscale score, total ACE-Ⅲ score, and SDMT score in the waiting moxibustion group were higher than those after treatment (P<0.01, P<0.05). After treatment and at follow-up, compared with the waiting moxibustion group, the moxibustion group had higher MoCA scores, MMSE scores, SDMT scores, ACE-Ⅲ subscale scores (attention, memory, language fluency) and total scores (P<0.05, P<0.01), and lower HOMA-IR (P<0.05). CONCLUSION Huayu Tongluo moxibustion can effectively improve cognitive function in patients with T2DM and cognitive decline. This improvement may be associated with the reduction in insulin resistance.
Humans ; Insulin Resistance ; Diabetes Mellitus, Type 2/complications* ; Male ; Female ; Moxibustion ; Middle Aged ; Aged ; Cognition ; Acupuncture Points ; Adult ; Cognitive Dysfunction/therapy*

INTRODUCTION: This study aimed to examine patterns of diagnosis, cognitive and adaptive functioning, and school placement outcomes in autistic children in Singapore, and to assess earlier predictive factors of cognitive outcomes. METHOD: Retrospective data were extracted from medical records of a specialist developmental paediatrics service for children born in 2008-2011 and referred to the autism clinic or were given a diagnosis of autism. Data items included demographic data, diagnostic methods, psychological assessment results, early intervention attendance and school placement outcomes. RESULTS: A total of 2124 children (82.6% male; 66.4% Chinese, 13.4% Malay, 9.8% Indian and 10.5% Others) were diagnosed with autism from the 4 birth-year cohorts. The mean (SD) age of the first clinical diagnosis of autism was 3.56 (1.14) years, with 81.0% of children receiving a concordant initial clinical diagnosis. A total of 1811 (85.2%) had a formal diagnostic assessment using the Autism Diagnostic Observation Schedule (ADOS) at a mean (SD) age of 4.16 (1.11) years. Of 1326 with cognitive and adaptive assessment results, 16.6% had mild and 19.8% had moderate-severe cognitive impairment. Of 1483 with school placement outcomes, 45.9% went to mainstream schools, 21.8% entered SPED schools offering the national curriculum and 32.3% required customised curriculum SPED schools. Logistic regression showed that factors predicting intellectual impairment included higher ADOS scores (aOR 95% CI 1.13 [1.08-1.19] for Comm+SI total and 1.53 [1.33-1.75] for SBRI total), higher social communication level of support (based on the DSM-5 criteria) (aOR [95% CI] 2.14 [1.10-4.16] for level 2 and 14.94 [5.77-38.64] for level 3), and minority race (aOR [95% CI] 2.82 [1.52-5.20] for Malay, 5.19 [2.36-11.44] for Indian, and 4.54 [1.91-10.79] for Others). CONCLUSION These findings could guide policymakers and practitioners worldwide to strategically allocate diagnostic, intervention and educational resources, maximising developmental outcomes for autistic children across diverse settings.
Humans ; Singapore/epidemiology* ; Male ; Female ; Retrospective Studies ; Child, Preschool ; Autistic Disorder/complications* ; Child ; Early Intervention, Educational ; Cognitive Dysfunction/diagnosis* ; Cognition

Hypotension is a leading cause of age-related cognitive impairment. The available literature evidences that vascular factors are associated with dementia and that hypotension alters cerebral perfusion flow and can aggravate the neurodegeneration of Alzheimer's disease (AD). Despite the discovery of biomarkers and the recent progress made in neurovascular biology, epidemiology, and brain imaging, some key issues remain largely unresolved: the potential mechanisms underlying the neural deterioration observed in AD, the effect of cerebrovascular alterations on cognitive deficits, and the positive effects of hypotension treatment on cognition. Therefore, further well-designed studies are needed to unravel the potential association between hypotension and cognitive dysfunction and reveal the potential benefits of hypotension treatment for AD patients. Here, we review the current epidemiological, pathobiological, and treatment-related literature on neurovascular changes and hypotension-related cognitive dysfunction and highlight the unsettled but imminent issues that warrant future research endeavors.
Humans ; Hypotension/complications* ; Cognitive Dysfunction/etiology* ; Alzheimer Disease/epidemiology* ; Cerebrovascular Circulation/physiology* ; Cognition Disorders/etiology*

The neurophysiological mechanisms by which exercise improves cognitive function have not been fully elucidated. A comprehensive and systematic review of current domestic and international neurophysiological evidence on exercise improving cognitive function was conducted from multiple perspectives. At the molecular level, exercise promotes nerve cell regeneration and synaptogenesis and maintains cellular development and homeostasis through the modulation of a variety of neurotrophic factors, receptor activity, neuropeptides, and monoamine neurotransmitters, and by decreasing the levels of inflammatory factors and other modulators of neuroplasticity. At the cellular level, exercise enhances neural activation and control and improves brain structure through nerve regeneration, synaptogenesis, improved glial cell function and angiogenesis. At the structural level of the brain, exercise promotes cognitive function by affecting white and gray matter volumes, neural activation and brain region connectivity, as well as increasing cerebral blood flow. This review elucidates how exercise improves the internal environment at the molecular level, promotes cell regeneration and functional differentiation, and enhances the brain structure and neural efficiency. It provides a comprehensive, multi-dimensional explanation of the neurophysiological mechanisms through which exercise promotes cognitive function.
Animals ; Humans ; Brain/physiology* ; Cognition/physiology* ; Exercise/physiology* ; Nerve Regeneration/physiology* ; Neuronal Plasticity/physiology*

Repeated transcranial magnetic stimulation (rTMS) is one of the commonly used brain stimulation techniques. In order to investigate the effects of rTMS on the excitability of different types of neurons, this study is conducted to investigate the effects of rTMS on the cognitive function of mice and the excitability of hippocampal glutaminergic neurons and gamma-aminobutyric neurons from the perspective of electrophysiology. In this study, mice were randomly divided into glutaminergic control group, glutaminergic magnetic stimulation group, gamma-aminobutyric acid energy control group, and gamma-aminobutyric acid magnetic stimulation group. The four groups of mice were injected with adeno-associated virus to label two types of neurons and were implanted optical fiber. The stimulation groups received 14 days of stimulation and the control groups received 14 days of pseudo-stimulation. The fluorescence intensity of calcium ions in mice was recorded by optical fiber system. Behavioral experiments were conducted to explore the changes of cognitive function in mice. The patch-clamp system was used to detect the changes of neuronal action potential characteristics. The results showed that rTMS significantly improved the cognitive function of mice, increased the amplitude of calcium fluorescence of glutamergic neurons and gamma-aminobutyric neurons in the hippocampus, and enhanced the action potential related indexes of glutamergic neurons and gamma-aminobutyric neurons. The results suggest that rTMS can improve the cognitive ability of mice by enhancing the excitability of hippocampal glutaminergic neurons and gamma-aminobutyric neurons.
Animals ; Mice ; Hippocampus/cytology* ; Transcranial Magnetic Stimulation ; Neurons/physiology* ; Male ; Cognition/physiology* ; gamma-Aminobutyric Acid/metabolism* ; Action Potentials/physiology*

In recent years, it has become a new direction in the field of neuroscience to explore the mode characteristics, functional significance and interaction mechanism of resting spontaneous electroencephalography (EEG) and task-evoked EEG. This paper introduced the basic characteristics of spontaneous EEG and task-evoked EEG, and summarized the core role of spontaneous EEG in shaping the adaptability of the nervous system. It focused on how the spontaneous EEG interacted with the task-evoked EEG in the process of task processing, and emphasized that the spontaneous EEG could significantly affect the performance of tasks such as perception, cognition and movement by regulating neural activities and predicting external stimuli. These studies provide an important theoretical basis for in-depth understanding of the principle and mechanism of brain information processing in resting and task states, and point out the direction for further exploring the complex relationship between them in the future.
Humans ; Electroencephalography/methods* ; Brain/physiology* ; Rest/physiology* ; Cognition/physiology* ; Evoked Potentials/physiology* ; Task Performance and Analysis

Alzheimer's disease (AD) is the most common degenerative disease of the nervous system. Studies have found that the 40 Hz pulsed magnetic field has the effect of improving cognitive ability in AD, but the mechanism of action is not clear. In this study, APP/PS1 double transgenic AD model mice were used as the research object, the water maze was used to group dementia, and 40 Hz/10 mT pulsed magnetic field stimulation was applied to AD model mice with different degrees of dementia. The behavioral indicators, mitochondrial samples of hippocampal CA1 region and electrocardiogram signals were collected from each group, and the effects of 40 Hz pulsed magnetic field on mouse behavior, mitochondrial kinetic indexes and heart rate variability (HRV) parameters were analyzed. The results showed that compared with the AD group, the loss of mitochondrial crest structure was alleviated and the mitochondrial dynamics related indexes were significantly improved in the AD + stimulated group ( P < 0.001), sympathetic nerve excitation and parasympathetic nerve inhibition were improved, and the spatial cognitive memory ability of mice was significantly improved ( P < 0.05). The preliminary results of this study show that 40 Hz pulsed magnetic field stimulation can improve the mitochondrial structure and mitochondrial kinetic homeostasis imbalance of AD mice, and significantly improve the autonomic neuromodulation ability and spatial cognition ability of AD mice, which lays a foundation for further exploring the mechanism of ultra-low frequency magnetic field in delaying the course of AD disease and realizing personalized neurofeedback therapy for AD.
Animals ; Heart Rate/physiology* ; Mice ; Alzheimer Disease/therapy* ; Mice, Transgenic ; Mitochondrial Dynamics/radiation effects* ; Magnetic Field Therapy/methods* ; Magnetic Fields ; Disease Models, Animal ; Mitochondria ; Male ; Maze Learning ; Cognition ; Dementia/therapy*