Humans ; Dexmedetomidine/therapeutic use* ; Hypnotics and Sedatives ; Cognitive Dysfunction/drug therapy*

To evaluate the efficacy and safety of huperzine in treating patients with mild cognitive impairment. The randomized controlled trials(RCT) were retrieved from EMbase, Cochrane Library, PubMed, CNKI, Wanfang and VIP. The methodology quality of the included studies was evaluated, and a Meta-analysis was performed using RevMan 5.3 software. A total of nine RCTs were included. The Meta-analysis results showed that compared with placebo, Huperzine significantly increased the scores of memory quotient(MQ) and mini-mental state examination(MMSE). However, there was no statistical difference between oral tablet and capsule. Compared with placebo, huperzine A was superior in the scores of MQ and MMSE. Huperzine is safe with mild side effects. Due to the low quality of original studies, more high-quality studies are needed to verify its efficacy.
Alkaloids ; therapeutic use ; Cognitive Dysfunction ; drug therapy ; Humans ; Memory ; Randomized Controlled Trials as Topic ; Sesquiterpenes ; therapeutic use

Through the non-targeted metabonomics study on endogenous substances in APP/PS1 transgenic mice, this paper aimed to discover biomarkers related to APP/PS1 mice with cognitive dysfunction, and find targets of Huanglian Jiedu Decoction(HLJDD) in the treatment of Alzheimer's disease(AD) and its mechanism. The brain tissue and serum metabolic mass spectrometry of mice were analyzed by ultra-high performance liquid chromatography-Orbitrap mass spectrometry(UPLC-Orbitrap MS). Through partial least squares-discriminant analysis(PLS-DA) and orthogonal partial least squares-discriminant analysis(OPLS-DA), the metabolic data of the normal group, the model group, the high-dose and low-dose HLJDD groups, and the berberine group were compared and analyzed to screen out potential biomarkers, and the relevant metabolic pathways were constructed with the help of the Kyoto Encyclopedia of Genes and Genomes(KEGG) database. Forty-five potential endogenous metabolites were identified, including 13 in brain and 35 in serum, among which leukotriene B4, tyrosine, and adenosine were expected to be differential metabolites related to cognitive function. HLJDD recalled 22 differential metabolites, and the pathways mainly involved in aminoacyl-tRNA biosynthesis, valine, leucine and isoleucine biosynthesis, pantothenic acid and coenzyme A biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis, and arachidonic acid metabolism. These pathways suggested that the main mechanism of HLJDD in the intervention of AD was to inhibit central and peripheral inflammation, and regulate energy metabolism, fatty acid metabolism, and amino acid metabolism. HLJDD has a certain effect on the improvement of cognitive dysfunction, and regulates relative pathways by recalling endogenous differential metabolites, which helps to further discover the biomarkers of AD and clarify the intervention mechanism of HLJDD in the treatment of AD.
Animals ; Mice ; Metabolomics/methods* ; Drugs, Chinese Herbal/pharmacology* ; Biomarkers ; Cognitive Dysfunction/drug therapy* ; Mice, Transgenic ; Tyrosine

Tu-Xian decoction (TXD), a traditional Chinese medicine (TCM) formula, has been frequently administered to manage diabetic cognitive impairment (DCI). Despite its widespread use, the mechanisms underlying TXD's protective effects on DCI have yet to be fully elucidated. As a significant regulator in neurodegenerative conditions, death-associated protein kinase-1 (DAPK-1) serves as a focus for understanding the action of TXD. This study was designed to whether TXD mediates its beneficial outcomes by inhibiting DAPK-1. To this end, a diabetic model was established using Sprague-Dawley (SD) rats through a high-fat, high-sugar (HFHS) diet regimen, followed by streptozotocin (STZ) injection. The experimental cohort was stratified into six groups: Control, Diabetic, TC-DAPK6, high-dose TXD, medium-dose TXD, and low-dose TXD groups. Following a 12-week treatment period, various assessments-including blood glucose levels, body weight measurements, Morris water maze (MWM) testing for cognitive function, brain magnetic resonance imaging (MRI), and histological analyses using hematoxylin-eosin (H&E), and Nissl staining-were conducted. Protein expression in the hippocampus was quantified through Western blotting analysis. The results revealed that TXD significantly improved spatial learning and memory abilities, and preserved hippocampal structure in diabetic rats. Importantly, TXD administration led to a down-regulation of proteins indicative of neurological damage and suppressed DAPK-1 activity within the hippocampal region. These results underscore TXD's potential in mitigating DCIvia DAPK-1 inhibition, positioning it as a viable therapeutic candidate for addressing this condition. Further investigation into TXD's molecular mechanisms may elucidate new pathways for the treatment of DCI.
Animals ; Rats ; Brain/metabolism* ; Cognitive Dysfunction/drug therapy* ; Diabetes Mellitus, Experimental/metabolism* ; Hippocampus ; Rats, Sprague-Dawley

Antipsychotic medication is the primary treatment for schizophrenia, which is effective on ameliorating positive symptoms and can reduce the risk of recurrence, but it has limited efficacy for negative symptoms and cognitive dysfunction. The negative symptoms and cognitive dysfunction seriously affects the life quality and social function for the patients with schizophrenia. Currently, there is plenty evidence that antipsychotic drugs combined with adjuvant therapy drugs can effectively improve the negative symptoms and cognitive dysfunction. These drugs include anti-oxidants, nicotinic acetylcholine receptors and neuro-inflammatory drugs (anti-inflammatory drugs, minocycline), which show potential clinical effects.
Anti-Inflammatory Agents/therapeutic use* ; Antipsychotic Agents/therapeutic use* ; Cognitive Dysfunction/etiology* ; Humans ; Minocycline/therapeutic use* ; Schizophrenia/drug therapy*

The glymphatic system plays a pivotal role in maintaining cerebral homeostasis. Chronic cerebral hypoperfusion, arising from small vessel disease or carotid stenosis, results in cerebrometabolic disturbances ultimately manifesting in white matter injury and cognitive dysfunction. However, whether the glymphatic system serves as a potential therapeutic target for white matter injury and cognitive decline during hypoperfusion remains unknown. Here, we established a mouse model of chronic cerebral hypoperfusion via bilateral common carotid artery stenosis. We found that the hypoperfusion model was associated with significant white matter injury and initial cognitive impairment in conjunction with impaired glymphatic system function. The glymphatic dysfunction was associated with altered cerebral perfusion and loss of aquaporin 4 polarization. Treatment of digoxin rescued changes in glymphatic transport, white matter structure, and cognitive function. Suppression of glymphatic functions by treatment with the AQP4 inhibitor TGN-020 abolished this protective effect of digoxin from hypoperfusion injury. Our research yields new insight into the relationship between hemodynamics, glymphatic transport, white matter injury, and cognitive changes after chronic cerebral hypoperfusion.
Animals ; Brain Ischemia ; Carotid Stenosis/drug therapy* ; Cognitive Dysfunction/etiology* ; Digoxin ; Disease Models, Animal ; Mice ; Mice, Inbred C57BL ; White Matter

Mild cognitive impairment (MCI) is the transition state between normal aging and AD. There are better detection and treatment methods to screen a population of patients with MCI. Through intervention, the probability of MCI conversion to AD can be significantly reduced. This paper first introduces the concept of cost-effectiveness analysis, reconsiders the concept of cost for the particularity of MCI, and uses QALY to evaluate the health effects of the quality of life. Then measure the health quality of life of elderly MCI population, and use Markov model to study the cost of intervention with traditional Chinese medicine-effectiveness analysis. Finally, according to the QALY measure and CEA results, we draw the conclusion that it's helpful to get early intervention in MCI.
Alzheimer Disease ; drug therapy ; economics ; Cognitive Dysfunction ; drug therapy ; economics ; Cost-Benefit Analysis ; Drugs, Chinese Herbal ; economics ; therapeutic use ; Humans ; Markov Chains ; Medicine, Chinese Traditional ; economics

OBJECTIVETo systematically analyze the therapeutic efficacy and safety of Chinese medicine on aged patients with mild cognitive impairment (MCI).

METHODSThe PubMed, EMbase, Cochrane Library, CNKI, VIP, Wanfang Database, and CBM database were retrieved by computer. On the basis of strictly assessing the quality of literatures, the evidence quality was assessed using GRADE Software.

RESULTSTotally 680 papers were primarily retrieved and analyses were conducted in the finally selected 22 RCT articles. Descriptive analyses were conduced due to different interventions in each study. The therapeutic efficacy was assessed as follows. (1) As to the conversion of MCI to Alzheimer's disease (AD), no case conversed to MCI in Jiawei Wuzi Yanzong Granule Group and Shenyin Oral Liquid Group. But there was no statistical difference when compared with that in the placebo group and the vitamin E group. Significant difference was shown between Tiantai No. 1 and the placebo. (2) As for the improvement of cognitive functions, relative therapeutic efficacies of Chinese herbs were different. (3) The improvement of the activities of daily life, serum SOD and MDA contents, and P amyloid concentration in MCI patients was different due to the application of different therapeutic drugs.

CONCLUSIONChinese herbs showed certain therapeutic efficacy in improving MCI. But clinical application could not be recommended due to poor qualities of literatures and evidence.

Alzheimer Disease ; drug therapy ; Cognitive Dysfunction ; drug therapy ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Humans ; Phytotherapy ; Randomized Controlled Trials as Topic ; Treatment Outcome

OBJECTIVE: To investigate the effects of berberine on learning and memory ability in vascular cognitive impairment rats. METHODS: Sixty-eight Wistar rats were randomly divided into control group (n=10), sham operated group (n=10) and the modeling group of vascular cognitive impairment rat (n=48), then the rats in modeling group were randomly divided into four groups (n=10): vehicle group, berberine low dose group (20 mg/kg), medium dose group (40 mg/kg) and high dose group (60 mg/kg). Bilateral common carotid arteries were occluded in rats to establish vascular cognitive impairment (VCI) model. Different doses of berberine were intraperitoneally injected into the treatment group and normal saline was intraperitoneally injected into the other groups once a day for a total of 34 days. After 28 days of administration, Morris water maze was used to test the learning and memory ability of rats. After the water maze experiment, the levels of superoxide dismutase (SOD) activity, glutathione (GSH), malondialdehyde (MDA), tumor necrosis factor alpha(TNF-α), interleukin-1 beta (IL-1β), 5-hydroxytryptamine (5-HT) and monoamine oxidase (MAO) in the forebrain cortex were detected. RESULTS: Compared to sham group, the escape latency in VCI group was significantly extended (P＜0.01) and the times of passing through the platform were decreased remarkably (P＜0.01). The levels of SOD, GSH and 5-HT in the hippocampus or anterior cortex were decreased significantly (P＜0.01), while the contents of MDA, TNF-α, IL-1β and MAO were increased remarkably (P＜0.01). Compared with VCI group, the escape latency in berberine-treated groups was shortened significantly (P＜0.01, P＜0.05) and the times of passing through the platform were increased remarkably (P＜0.01, P＜0.05), the levels of SOD, GSH and 5-HT were increased significantly (P＜0.01), while the contents of TNF-α, IL-1β and MAO were decreased remarkably (P＜0.01). CONCLUSION Berberine could significantly improve the spatial learning and memory abilities of rats with vascular cognitive impairment. The mechanism may be related to the effects of berberine on the hippocampal antioxidant stress, anti-inflammatory response and the monoamine neurotransmitter system in the forebrain cortex. Berberine 60 mg/kg dose group had better effect.
Animals ; Berberine ; pharmacology ; Cognitive Dysfunction ; drug therapy ; Hippocampus ; Inflammation ; Maze Learning ; drug effects ; Memory ; drug effects ; Oxidative Stress ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar

OBJECTIVETo observe the clinical efficacy of modified Huanglian Wendan Decoction (HWD) in treating senile mild cognitive impairment (MCI) of turbid-phlegm blocking orifice syndrome.

METHODSWith a block randomized, double-blinded and controlled design adopted, the 64 patients of MCI selected from December 2007 to February 2009 were randomly and equally assigned to two groups. The treatment group was treated with HWD in dose of 200 mL, twice a day; the control group was given Aniracetam 0.2 g (for patients over 70-years-old, 0.1 g) three times a day. And the illusive medicine in dosage-form of capsule/decoction simulated to that used in the opposite group was applied. The medication and observation lasted for three months. Chinese medicine syndrome, cognition capacity (by MMSE), laboratory indexes [acetylcholine (Ach), superoxide dismutase (SOD), malondialdehyde (MDA)] and safety related indexes in patients were observed.

RESULTSAfter treatment, MMSE score increased in both groups, but the increment in the treatment group was significantly higher than that in the control group (P<0.01); Chinese medicine syndrome estimated by scoring showed that after treatment, all scores of syndromes, excepting the expectoration, were improved in the treatment group with the post-treatment scores significantly lower than those in the control group respectively (P<0.05 or P<0.01); while in the control group, lowering of scores only showed in some symptoms such as poor memory, heavy head or dizziness, and heavy sensation in limbs and body. Serum levels of Ach and SOD decreased and MDA increased in both groups after treatment, but the change of Ach was more significant in the treatment group (P<0.01). No obvious adverse reactions were found during the treatment.

CONCLUSIONFor treatment of MCI, HWD shows effects in improving patients' symptoms, cognition capacity and elevating serum Ach content better than that of Aniracetam; and with effects for raising SOD activity and reducing MDA level similar to those of Aniracetam.

Aged ; Aged, 80 and over ; Cognitive Dysfunction ; diagnosis ; drug therapy ; Double-Blind Method ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Pyrrolidinones ; therapeutic use