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。     

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.     

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.     

复方利福平片对结核分枝杆菌的抗菌作用

目的:研究复方利福平片剂对结核分枝杆菌的体内、体外抗菌活性,并与抗结核药利福平进行比较.方法:采用琼脂稀释法体外检测最小抑菌浓度(MIC);建立结核分枝杆菌的动物感染模型,观察药物在体内的保护作用.结果:体外实验复方利福平对26株结核分枝杆菌有抑制作用,复方利福平片剂中所含利福平的MIC低于单纯利福平的;体内保护实验结果表明,阴性对照组感染小鼠半数存活时间(50% survival time,ST50)为17 d,复方利福平片剂(337.5 mg*kg-1)组其ST50则达29 d.复方利福平片剂的病变指数分别为0.4、0.34、0.24;复方利福平片剂组与空白对照组相比肺重量指数差异有显著性(P<0.01).结论:复方利福平具有较好的抗菌活性.     

老年轻度认知障碍综合干预效果初步研究

目的通过对老年轻度认知障碍患者综合干预的效果分析,评价综合干预方案的有效性。方法采用随机对照试验方法,将目标社区MCI患者（130例）随机分为干预组（65例）和对照组（65例）,对干预组采取认知干预和体力活动相结合的方法进行综合干预。结果干预组和对照组分别在干预前后3个月比较,差别都有统计学意义（各自P〈0.05）;两组分别在干预后3个月与6个月比较,差别都有统计学意义（各自P〈0.05）。结论认知干预和体育锻炼有益于维持或改善老年人的认知状况,并能给老年人的生活态度和精神状态产生积极的影响。     

帕金森病伴发轻度认知障碍患者血浆磷脂分子含量变化及意义

目的：分析探讨帕金森病伴发轻度认知障碍患者血浆磷脂分子含量变化和意义。方法选择2012年3月-2014年3月该院治疗的帕金森病伴发轻度认知障碍患者50例,并选择同期在该院健康体检的50例和帕金森病无认知障碍的50例分别作为对照组A和对照组月,测定三组研究对象的血浆磷脂含量,并评定研究对象的智能状态,分析研究对象智能状态与血浆磷脂含量之间的关系。结果观察组MMSE得分、CDT得分以及MoCA得分均明显低于对照组A和对照组月(P<0.01);观察组的磷脂分子含量明显高于对照组A和对照组B(P<0.01);两组之间各项指标差异无统计学意义(P>0.05)。结论帕金森病伴发轻度认知障碍患者细胞膜受到了严重的损伤,血浆磷脂分子可作为新生物标记物,通过其含量变化可判断认知功能受损情况。     

Neuropsychological and genetic differences between age-associated memory impairment and mild cognitive impairment entities

OBJECTIVE: To neuropsychologically and genetically compare age-associated memory impairment (AAMI) and mild cognitive impairment (MCI) entities and to determine what proportion of AAMI diagnosed individuals could also receive a MCI diagnosis. To compare the distribution of a previously known genetic risk factor for Alzheimer's disease (apolipoprotein E common polymorphism) associated with these two conditions with a sample of the normal aging. DESIGN: Neuropsychological and genetic assessments in AAMI and MCI individuals. Genetic assessment in AAMI, MCI, and control subjects. SETTING: General health centers and geriatric homes from northeastern Spain (Catalunya). PARTICIPANTS: One hundred and four subjects presenting subjective memory complaints were selected and the AAMI and MCI criteria were applied. One hundred and twenty-four healthy Spanish subjects age 50 and older were defined as controls. MEASUREMENTS: Memory, language, and frontal lobe functions were assessed using standard neuropsychological tests. The apolipoprotein E (apo E) polymorphism was obtained by using polymerase chain reaction (PCR) and HhaI restriction endonuclease. RESULTS: Sixty-seven percent of previously diagnosed AAMI individuals could also be identified as MCI subjects. These MCI cases differed from those only-AAMI individuals both in neuropsychological and genetic analyses, performing worse not only on memory but also on language and frontal lobe tests and presenting high and low prevalences of the apo E epsilon 3/epsilon 4 and epsilon 3/epsilon 3 genotypes, respectively. The general AAMI sample of 93 individuals also differed from controls in the apo E genotype and allele distributions but these differences were no longer present after subtracting the MCI cases (63 subjects). These findings reflect that the differences between the memory impaired sample and the control sample regarding the apo E polymorphism were mainly attributable to MCI individuals and not to those who received only a diagnosis of AAMI alone. CONCLUSIONS: Our findings suggest that among AAMI subjects, those who also fulfill the MCI criteria present a neuropsychological and genetic profile closer to that previously related to Alzheimer's disease than those individuals only eligible for a diagnosis of AAMI. However, our findings also suggest that using only the AAMI criteria still appears to select a population that differs genetically from the normal older population.