Acetylcholinesterase inhibitors may improve myelin integrity.

Recent clinical trials have revealed that cholinergic treatments are efficacious in a wide spectrum of neuropsychiatric disorders that span the entire human lifespan and include disorders without cholinergic deficits. Furthermore, some clinical and epidemiological data suggest that cholinergic treatments have disease modifying/preventive effects. It is proposed that these observations can be usefully understood in a myelin-centered model of the human brain. The model proposes that the human brain's extensive myelination is the central evolutionary change that defines our uniqueness as a species and our unique vulnerability to highly prevalent neuropsychiatric disorders. Within the framework of this model the clinical, biochemical, and epidemiologic data can be reinterpreted to suggest that nonsynaptic effects of cholinergic treatments on the process of myelination and myelin repair contributes to their mechanism of action and especially to their disease modifying/preventive effects. The ability to test the model in human populations with safe and noninvasive imaging technologies makes it possible to undertake novel clinical trial efforts directed at primary prevention of some of the most prevalent and devastating of human disorders.     

Influence of Imidazole-Dipeptides on Cognitive Status and Preservation in Elders: A Narrative Review

The worldwide increase in the number of patients with dementia is becoming a growing problem, while Alzheimer’s disease (AD), a primary neurodegenerative disorder, accounts for more than 70% of all dementia cases. Research on the prevention or reduction of AD occurrence through food ingredients has been widely conducted. In particular, histidine-containing dipeptides, also known as imidazole dipeptides derived from meat, have received much attention. Imidazole dipeptides are abundant in meats such as poultry, fish, and pork. As evidenced by data from recent human intervention trials conducted worldwide, daily supplementation of carnosine and anserine, which are both imidazole dipeptides, can improve memory loss in the elderly and reduce the risk of developing AD. This article also summarizes the latest researches on the biochemical properties of imidazole dipeptides and their effects on animal models associated with age-related cognitive decline. In this review, we focus on the results of human intervention studies using supplements of poultry-derived imidazole dipeptides, including anserine and carnosine, affecting the preservation of cognitive function in the elderly, and discuss how imidazole dipeptides act in the brain to prevent age-related cognitive decline and the onset of dementia.     

Diabetes and Prediabetes Inhibit Reversion from Mild Cognitive Impairment to Normal Cognition

ObjectivesDiabetes and prediabetes contribute to an increased risk of cognitive decline and dementia. Currently, it remains unclear whether elevated blood HbA1c levels, including prediabetes levels, affect reversion from mild cognitive impairment (MCI) to normal cognition. This study, therefore, aimed to examine the prospective associations of diabetes and prediabetes with reversion from MCI to normal cognition among community-dwelling older adults.DesignLongitudinal cohort study with a 4-year follow-up.Setting and ParticipantsCommunity-dwelling older adults with MCI, aged ≥65 years at baseline (n = 787).MethodsParticipants’ medical history of diabetes and blood HbA1c levels at baseline were assessed, and they were classified as control, prediabetes, and diabetes. Objective cognitive screening was performed using a multicomponent neurocognitive test at baseline and follow-up. Reversion from MCI to normal cognition over 4 years was determined. In the longitudinal analysis, we performed multiple imputations to adjust for a selection bias and loss of information.ResultsThe reversion rates of MCI in the control, prediabetes, and diabetes groups were 63.4%, 55.6%, and 42.9%, respectively, in the completed follow-up dataset, and 54.6%, 47.2%, and 34.1%, respectively, in the imputed dataset. Multivariate logistic regression showed that diabetes decreases the probability of MCI reversion both before and after multiple imputations [odds ratio (OR) 0.37; 95% confidence interval (CI) 0.18–0.74 for before imputation, OR 0.37; 95% CI 0.19–0.72 for after imputation]. Furthermore, prediabetes also showed significantly decreased probabilities of MCI reversion both before and after multiple imputations (OR 0.57; 95% CI 0.34–0.94 for before imputation, OR 0.60; 95% CI 0.37–0.97 for after imputation).Conclusions and ImplicationsDiabetes and prediabetes could inhibit MCI reversion. Adequate glycemic control may be effective in enhancing the reversion from MCI to normal cognition in a community setting.     

2型糖尿病患者并发轻度认知功能障碍危险因素的Meta分析

目的 系统评价2型糖尿病患者并发轻度认知功能障碍的危险因素。方法 检索CNKI、WanFang、VIP、CBM、Medline(PubMed)、EMbase、Web of Science和The Cochrane Library 数据库从建库至2020年12月2日有关2型糖尿病患者并发轻度认知功能障碍危险因素的所有文献后进行Meta分析。结果 共纳入文献18篇,研究对象3083例。各危险因素的合并OR(95%CI)为:年龄1.20(1.09,1.33)、文化程度0.67(0.55,0.82)、吸烟史1.41(0.69,2.89)、糖尿病病程1.17(1.06,1.29)、糖化血红蛋白(HbA1c)1.33(1.09,1.62)、空腹血葡萄糖(fasting blood glucose,FBG)0.88(0.75,1.03)、空腹血清C肽(Fasting c-peptide,FCP)0.41(0.16,1.04)、餐后2h血糖(2h plasma glucose,2hPG)1.90(0.52,6.87)、低密度脂蛋白胆同醇(LDL-C)1.42(1.26,1.59)、超敏C反应蛋白(high sensitive C reactive protein,hs-CRP)1.52(1.06,2.20)、胰岛素抵抗指数(HOMA-IR)1.00(0.48,2.08)、冠心病2.57(1.93,3.43)、高血压2.58(1.62,4.13)、周围神经病变1.10(0.10,12.57)。结论 高龄、文化程度低、糖尿病病程长、高HbA1c、高LDL-C、高hs-CRP、冠心病、高血压是2型糖尿病患者并发轻度认知功能障碍的主要危险因素。     

Targeting whole body metabolism and mitochondrial bioenergetics in the drug development for Alzheimer's disease

Aging is by far the most prominent risk factor for Alzheimer's disease (AD), and both aging and AD are associated with apparent metabolic alterations. As developing effective therapeutic interventions to treat AD is clearly in urgent need, the impact of modulating whole-body and intracellular metabolism in preclinical models and in human patients, on disease pathogenesis, have been explored. There is also an increasing awareness of differential risk and potential targeting strategies related to biological sex, microbiome, and circadian regulation. As a major part of intracellular metabolism, mitochondrial bioenergetics, mitochondrial quality-control mechanisms, and mitochondria-linked inflammatory responses have been considered for AD therapeutic interventions. This review summarizes and highlights these efforts.     

The past,present, and future of sleep measurement in mild cognitive impairment and early dementia—towards a core outcome set: a scoping review

Study ObjectivesSleep abnormalities emerge early in dementia and may accelerate cognitive decline. Their accurate characterization may facilitate earlier clinical identification of dementia and allow for assessment of sleep intervention efficacy. This scoping review determines how sleep is currently measured and reported in Mild Cognitive Impairment (MCI) and early dementia, as a basis for future core outcome alignment.MethodsThis review follows the PRISMA Guidelines for Scoping Reviews. CINAHL, Embase, Medline, Psychinfo, and British Nursing Index databases were searched from inception—March 12, 2021. Included studies had participants diagnosed with MCI and early dementia and reported on sleep as a key objective/ outcome measure.ResultsNineteen thousand five hundred and ninety-six titles were returned following duplicate removal with 188 studies [N] included in final analysis. Sleep data was reported on 17 139 unique, diagnostically diverse participants (n). “Unspecified MCI” was the most common diagnosis amongst patients with MCI (n = 5003, 60.6%). Despite technological advances, sleep was measured most commonly by validated questionnaires (n = 12 586, N = 131). Fewer participants underwent polysomnography (PSG) (n = 3492, N = 88) and actigraphy (n = 3359, N = 38) with little adoption of non-PSG electroencephalograms (EEG) (n = 74, N = 3). Sleep outcome parameters were reported heterogeneously. 62/165 (37.6%) were described only once in the literature (33/60 (60%) in interventional studies). There was underrepresentation of circadian (n = 725, N = 25) and micro-architectural (n = 360, N = 12) sleep parameters.ConclusionsAlongside under-researched areas, there is a need for more detailed diagnostic characterization. Due to outcome heterogeneity, we advocate for international consensus on core sleep outcome parameters to support causal inference and comparison of therapeutic sleep interventions.     

黄连解毒汤有效部位对动物脑缺血缺氧的保护作用

目的研究黄连解毒汤有效部位(HLJDTAF)对小鼠的抗缺氧作用及对多发脑梗死大鼠能量代谢的影响.方法通过小鼠常压耐缺氧、小鼠亚硝酸钠中毒和断头试验,观察黄连解毒汤有效部位连续灌胃给药4d对缺氧的保护作用,同时观察该药对血细胞的影响;采用大鼠多发性脑梗死模型观察HLJDTAF对模型大鼠脑组织乳酸(LA)、乳酸脱氢酶(LDH)、Na -K ATP酶和Ca2 -Mg2 ATP酶的影响.结果HLJDTAF865,433,216mg·kg-1可明显延长小鼠常压密闭状态下的存活时间(与对照组比较P＜0.05);216mg·kg-1可明显延长小鼠亚硝酸钠中毒缺氧存活时间(与对照组比较P＜0.05);HLJDTAF865,433,216mg·kg-1可明显延长正常小鼠断头张口喘气时间(与对照组比较P＜0.05;P＜0.01),433mg·kg-1可提高小鼠血液中血红蛋白含量,同时升高白细胞和淋巴细胞数量(与对照组比较P＜0.05);HLJDTAF610,305mg·kg-1组可显著降低多发性脑梗塞大鼠脑组织中LA含量,提高LDH活性,提高Na -K ATP酶活性,153mg·kg-1也可提高LDH与Na -K ATP酶活性(与模型组比较P＜0.05;P＜0.01).结论HLJDTAF可提高小鼠耐缺氧能力,同时改善多发脑梗死大鼠脑组织能量代谢障碍,这可能是其脑保护作用的机制.     

上海浦东新区MCI人群的痴呆相关知识知晓的调查 及慢性病的关注度对知晓率的影响

目的 调查上海市浦东新区入册MCI老人痴呆相关知识知晓情况及慢性病的关注度对知晓率的影响。方法 采用自行设计的老年痴呆防治相关知识知晓率的调查表，包括性别、年龄、学历等一般情况及相关知识问卷等测量工具对2016年入档的942名MCI干预项目老人痴呆知识知晓率开展调查，根据客观及主观认为有无慢性病将MCI分为四组，分别为无慢性病（A组），仅客观有慢性病（B组），仅主观有慢性病（C组），客观及主观均有慢性病（D组），比较各组对痴呆相关知识知晓率的情况。结果 通过独立样本T检验提示，有慢性病组的痴呆严重性、影响因素、总分准确率显著高于无慢性病组,其差异具有统计学意义(P﹤0.01)，通过多重比较的LSD法进一步两两比较，在痴呆严重性准确率维度上，D组准确率最低,具有显著性差异（P﹤0.01）; 在就医信息、概念、总分准确率上， B组最低，其差异具有统计学意义（P ﹤0.05）；在影响因素准确率上，C组显著高于B组及D组,其结果具有显著性差异（P ﹤0.01）；在总分准确率上， C组高于D组，其差异具有统计学意义（P ﹤0.01）。结论：有慢性病组对痴呆相关知识知晓率高于无慢性病组。无慢性病MCI对慢性病的适度关注及注意力有益于对痴呆相关知识的了解，同时有慢性病MCI对患慢性病关注不足或回避态度将不利于MCI的早期识别，进一步延误病情。加强社区慢性病健康相关知识的宣教，积极的关注自身的健康，对慢性病引起足够的重视，有助于减少痴呆的发病。     

Wellbeing,resilience, and coping: Are there differences between healthy older adults,adults with mild cognitive impairment,and adults with Alzheimer-type dementia?

The changes that occur with cognitive impairment and Alzheimer’s disease could affect psychological aspects unrelated to memory. The purpose of this study is to compare 32 healthy older adults, 31 amnestic mild cognitively impaired (aMCI) adults, and 32 patients diagnosed with Alzheimer's disease (AD), in order to determine whether there are differences in their psychological wellbeing, resilience, and coping strategies. Unifactorial MANOVAS and ANOVAS were performed to analyze the between-group differences. The results reveal that the AD group showed lower levels of resilience and orientation toward problem-solving and greater use of religious strategies. In addition, they had significantly lower wellbeing scores than the other groups. The worsening of the pathology impedes the capacity for adaptation and resilience and the application of strategies oriented toward the problem, and it increases the application of strategies based on magical thinking. Moreover, it also produces a reduction in wellbeing.