多靶点抗AD bis-MEP-乙二酰胺杂合物ZLA抑制神经元型AChE活性及促智作用研究

目的:探究ZLA对神经元型AChE的抑制活性及其对中枢胆碱能神经功能障碍导致的学习记忆功能减退的改善作用。方法:通过体外实验观察ZLA对神经元型AChE活性的影响;通过ex vivo实验观察ZLA体内AChE抑制活性;利用Morris水迷宫行为学实验探讨ZLA对东莨菪碱诱发的小鼠学习记忆功能障碍的改善作用。结果:ZLA明显抑制人SH-SY5Y神经元细胞和小鼠海马神经元来源的AChE活性。另外,ZLA腹腔注射后以剂量依赖性方式抑制小鼠脑内AChE活性。Morris水迷宫实验结果显示,ZLA显著改善东莨菪碱引起的学习和记忆功能障碍。结论:ZLA能够抑制神经元型AChE活性并具有促智作用。     

七氟烷复合麻醉对老年骨科患者术后早期认知功能的影响

摘要 目的：探讨七氟烷复合麻醉对老年骨科患者术后早期认知功能的影响。方法：选择2017年12月~2019年6月在西安医学院第二附属医院（本院）骨科诊治单侧老年全膝关节置换手术患者112例,随机数字表法分为七氟烷组与对照组,各56例。对照组给予常规静脉注射全身麻醉,在此基础上七氟烷组给予七氟烷吸入麻醉,记录与调查两组术后早期认知功能。结果：经过对比,两组手术时间、术中出血量对比差异无统计学意义(P>0.05),而七氟烷组的术后苏醒时间(7.10±0.22)min、拔管时间(8.65±0.46)min等都显著短于对照组(14.09±1.09)min、(18.76±1.44)min,两组对比有统计学意义(P<0.05)。所有患者在T1、T2、T3与T4时间点的心率和血氧饱和度均表现正常,对比均无统计学意义(P>0.05)。七氟烷组术后1 d、术后14 d的血清白介素(Interleukin,IL)-6、肿瘤坏死因子(Tumor necrosis factor,TNF)-α值显著低于对照组,对比有统计学意义(P<0.05),且两组术后14 d的血清IL-6与TNF-α值均显著低于术后1 d (P<0.05)。术后1个月七氟烷组的认知功能障碍发生率为1.8 %（1/56）,显著低于对照组的12.5 %（7/56）,两组间对比有统计学意义(x²=4.846,P=0.028)。结论：七氟烷复合麻醉在老年骨科患者中的应用能促进患者康复,安全性比较好,能抑制炎症因子的释放,从而减少术后早期认知功能障碍的发生。     

心力衰竭致认知功能紊乱机制的研究进展

心力衰竭(Heart Failure, HF)的主要特征在于异常的心脏收缩和(或)舒张功能,能够导致全身多脏器、多组织功能紊乱。其中HF常见的中枢系统并发症--认知功能紊乱(Cognitive Disorders, CDs)主要表现为学习能力和记忆力减退、定向力障碍以及执行力受损等;其主要病理生理机制包括:血流动力学改变及脑血流自身调节功能受损导致的脑灌注不足、自身免疫系统激活导致的神经炎症反应和神经-内分泌轴紊乱导致的内分泌紊乱等。流行病学调查发现,HF患者罹患CDs的风险明显高于非HF患者;CDs严重影响HF患者的生活质量,并显著增加不良预后的风险。本文对目前HF导致CDs的发病机制进行了详细地阐述和总结,以期有助于疾病的治疗和后续科学研究。     

Symmetric faces are a sign of successful cognitive aging

It has been proposed that a common cause underlies individual differences in bodily and cognitive decline in old age. No good marker for this common cause has been identified to date. Here, fluctuating asymmetry (FA), an indicator of developmental stability that relates to intelligence differences in young adults, was measured from facial photographs of 216 surviving members of the Lothian Birth Cohort 1921 at age 83 and related to their intelligence at ages 11, 79 and 83 years. FA at age 83 was unrelated to intelligence at ages 11 and 79 and to cognitive change between 11 and 79 years. It was, however, associated with intelligence and information processing efficiency at age 83 and with cognitive change between 79 and 83 years. Significant results were limited to men, a result predicted by sex differences in life history tradeoffs and life expectancy. Results were stronger when directional asymmetries were corrected in facial FA measures. Thus, FA is a candidate marker for the common cause of differential senescence.     

Influence of manganese exposure on cognitive function,plasma APP and Aβ levels in older men

BackgroundElevated manganese (Mn) exposure impairs cognition in adults and children, but the association between Mn and cognitive function in elderly people is unclear. Previous studies have linked Mn neurotoxicity in AD to Aβ-dependent mechanisms. However, the association between Mn and plasma APP and Aβ in the general elderly population remains unknown. This study aimed to investigate the association between Mn exposure and cognitive function, plasma APP and plasma Aβ in older adults.MethodsCognitive abilities in 375 men aged 60 and older in Guangxi, China were assessed using the Mini-Mental State Examination (MMSE) and cognitive impairment were identified using education-stratified cut-off points of MMSE scores. Urinary Mn levels and plasma APP, and Aβ levels were measured using ICP-MS and ELISA, respectively.ResultsA total of 109 (29.07 %) older men were identified as having cognitive impairment. The median urinary Mn level was 0.22 μg/g creatinine. Urinary Mn levels were negatively correlated with MMSE scores (β = −1.35, 95 % CI: −2.65 to −0.06; p = 0.041). In addition, higher concentrations of urinary manganese were associated with a greater risk of cognitive impairment (OR = 2.03, 95 % CI: 1.14–3.59; comparing the highest and lowest manganese; p = 0.025). Moreover, plasma APP levels were inversely associated with urinary Mn levels (r = −0.123, p = 0.020), and positively associated with MMSE scores (r = 0.158, p = 0.002). Surprisingly, no correlations were observed between plasma Aβ42, Aβ40, Aβ40/Aβ42, or Aβ42/Aβ40 and urinary Mn levels and MMSE scores.ConclusionThese results suggested that Mn exposure is negatively associated with older men’s cognition and plasma APP levels, but not plasma Aβ levels.     

Long-term persistence of vaccine-derived aluminum hydroxide is associated with chronic cognitive dysfunction

Macrophagic myofasciitis (MMF) is an emerging condition, characterized by specific muscle lesions assessing long-term persistence of aluminum hydroxide within macrophages at the site of previous immunization. Affected patients mainly complain of arthromyalgias, chronic fatigue, and cognitive difficulties. We designed a comprehensive battery of neuropsychological tests to prospectively delineate MMF-associated cognitive dysfunction (MACD). Compared to control patients with arthritis and chronic pain, MMF patients had pronounced and specific cognitive impairment. MACD mainly affected (i) both visual and verbal memory; (ii) executive functions, including attention, working memory, and planning; and (iii) left ear extinction at dichotic listening test. Cognitive deficits did not correlate with pain, fatigue, depression, or disease duration. Pathophysiological mechanisms underlying MACD remain to be determined. In conclusion, long-term persistence of vaccine-derived aluminum hydroxide within the body assessed by MMF is associated with cognitive dysfunction, not solely due to chronic pain, fatigue and depression.     

自拟益气通阳活血方治疗阿尔茨海默病的临床研究

摘要 目的：分析自拟益气通阳活血方治疗阿尔茨海默病的临床效果。方法：选取2020年10月~2022年4月于中国人民解放军空军军医大学第一附属医院接受治疗的阿尔茨海默病患者104例，依据入院先后顺序编号，按单双号分为对照组（n=52）和研究组（n=52）。对照组进行常规西药治疗，研究组在此基础上进行自拟益气通阳活血方治疗。比较两组临床疗效、治疗前后中医证候积分、日常生活活动能力、认知功能、血清去甲肾上腺素（NE）、多巴胺（DA）、乙酰胆碱转移酶（ChAT）水平、β淀粉样蛋白前体（APP）、β淀粉样蛋白1-42（Aβ1-42）、丙二醛（MDA)、超氧化物歧化酶（SOD）水平，并比较两组安全性。结果：治疗后，两组中医证候积分均降低，且研究组显著低于对照组（P<0.05）；研究组总有效率为94.23%，明显高于对照组的78.85%（P<0.05）；治疗后，两组简易智能精神状态检查量表（MMSE）评分与蒙特利尔认知评估量表（MoCA）评分研究组均高于对照组（P<0.05）；治疗后，两组barthel指数评分及日常生活能力量表（ADL）评分研究组均显著高于对照组（P<0.05）；治疗后，两组DA、NE、ChAT水平均升高，且研究组明显高于对照组（P<0.05）；治疗后，两组SOD水平升高，APP、Aβ1-42、MDA水平均降低（P<0.05），且与对照组相比研究组各指标变化更显著（P<0.05）；两组治疗期间的不良反应均较轻微，经对症处理后均缓解，不良反应发生率比较无明显差异（P>0.05）。结论：自拟益气通阳活血方治疗阿尔茨海默病疗效显著，可降低中医证候积分，提高认知功能，调节NE、DA、ChAT水平，抑制APP、Aβ1-42水平，提高其日常生活活动能力，且安全性高。     

颈内动脉支架置入术对颈动脉狭窄患者认知功能影响的研究

目的：研究颈动脉狭窄对认知功能的影响,探讨颈动脉支架置入术（CAS）患者术后不同时期认知功能的变化及其可能的机制。方法：选取2010年1月至2012年12月我院神经内科收住的急性脑梗死（前循环）患者75例,按颈内动脉狭窄程度,分成无狭窄组,轻度狭窄组（狭窄程度〈30％）,中度狭窄组（30-69％）和治疗组（70．99％）,前三组给予药物治疗,治疗组同时给予颈内动脉支架置入术,应用蒙特利尔认知评估量表（MoCA）、简易精神状态检查表（MMSE）、搭火柴测验（stickTest）,对患者进行认知功能评估,比较术前、术后不同时期认知功能的变化,同时利用SPECT／CT对治疗组20例患者术后局部脑血流改善状况进行评价。结果：治疗组和对照组在术前比较MoCA总分、MMSE评分、StickTest评分,发现治疗组评分低于对照组,且随着颈动脉狭窄程度的加重,认知功能受损越明显;治疗组在术后1周与术前比较,评分反而降低,差异有统计学意义;术后3个月、术后6个月与术前比较,评分均有所提高,差异有统计学意义;通过SPECT／CT对治疗组术前感兴趣区血流量与同侧小脑平均脑血流量比较,术后再与同侧小脑比较,结果显示术后脑灌注明显改善。结论：颈动脉狭窄与血管性认知功能障碍有关,而且认知功能障碍的程度与颈动脉狭窄程度呈正相关,颈内动脉支架置入术可最终改善认知功能,尤其表现在视空间／执行能力,延迟回忆能力,注意力等方面。     

Thermodynamic view on decision-making process: emotions as a potential power vector of realization of the choice

This research is devoted to possible mechanisms of decision-making in frames of thermodynamic principles. It is also shown that the decision-making system in reply to emotion includes vector component which seems to be often a necessary condition to transfer system from one state to another. The phases of decision-making system can be described as supposed to be nonequilibrium and irreversible to which thermodynamics laws are applied. The mathematical model of a decision choice, proceeding from principles of the nonlinear dynamics considering instability of movement and bifurcation is offered. The thermodynamic component of decision-making process on the basis of vector transfer of energy induced by emotion at the given time is surveyed. It is proposed a three-modular model of decision making based on principles of thermodynamics. Here it is suggested that at entropy impact due to effect of emotion, on the closed system—the human brain,—initially arises chaos, then after fluctuations of possible alternatives which were going on—reactions of brain zones in reply to external influence, an order is forming and there is choice of alternatives, according to primary entrance conditions and a state of the closed system. Entropy calculation of a choice expectation of negative and positive emotion shows judgment possibility of existence of “the law of emotion conservation” in accordance with several experimental data.