Bright Light Therapy: Improved Sensitivity to Its Effects on Rest-Activity Rhythms in Alzheimer Patients by Application of Nonparametric Methods

Sleep-wake rhythm disturbances in patients with Alzheimer's disease (AD) make a strong demand on caregivers and are among the most important reasons for institutionalization. Several previous studies reported that the disturbances improve with increased environmental light, which, through the retinohypothalamic tract, activates the suprachiasmatic nucleus (SCN), the biological clock of the brain. The data of recently published positive and negative reports on the effect of bright light on actigraphically assessed rest-activity rhythms in demented elderly were reanalyzed using several statistical procedures. It was demonstrated that the light-induced improvement in coupling of the rest-activity rhythm to the environmental zeitgeber of bright light is better detected using nonparametric procedures. Cosinor, complex demodulation, and Lomb-Scargle periodogram-derived variables are much less sensitive to this effect because of the highly nonsinusoidal waveform of the rest-activity rhythm. Guidelines for analyses of actigraphic data are given to improve the sensitivity to treatment effects in future studies.     

Bright Light Therapy: Improved Sensitivity to Its Effects on Rest-Activity Rhythms in Alzheimer Patients by Application of Nonparametric Methods

Sleep-wake rhythm disturbances in patients with Alzheimer's disease (AD) make a strong demand on caregivers and are among the most important reasons for institutionalization. Several previous studies reported that the disturbances improve with increased environmental light, which, through the retinohypothalamic tract, activates the suprachiasmatic nucleus (SCN), the biological clock of the brain. The data of recently published positive and negative reports on the effect of bright light on actigraphically assessed rest-activity rhythms in demented elderly were reanalyzed using several statistical procedures. It was demonstrated that the light-induced improvement in coupling of the rest-activity rhythm to the environmental zeitgeber of bright light is better detected using nonparametric procedures. Cosinor, complex demodulation, and Lomb-Scargle periodogram-derived variables are much less sensitive to this effect because of the highly nonsinusoidal waveform of the rest-activity rhythm. Guidelines for analyses of actigraphic data are given to improve the sensitivity to treatment effects in future studies.     

阿尔茨海默病和血管性痴呆与血糖代谢水平的关系及危险因素分析

目的:研究阿尔茨海默病和血管性痴呆与血糖代谢水平的关系及危险因素。方法:选取2013年12月到2014年12月我院收治的阿尔茨海默病80例(A组)和血管性痴呆70例(B组),另选取同时期无痴呆者70例(对照组),测量三组入选者血糖各指标水平,并分析阿尔茨海默病和血管性痴呆的危险因素。结果:A组和B组空腹血糖(FPG)均显著高于对照组,胰岛素降解酶(IDE)显著低于对照组,比较差异具有统计学意义(P0.05);B组糖尿病、冠心病和高血压疾病的发病率显著高于A组和对照组,比较差异具有统计学意义(P0.05),A组和B组高血脂发病率均显著高于对照组,比较差异具有统计学意义(P0.05)。结论:阿尔茨海默病和血管性痴呆均与FPD、IDE以及高血脂有较大关系,高血压、冠心病和糖尿病与血管性痴呆有较大关系。     

Neuroprotector effect of p,p'-methoxyl-diphenyl diselenide in a model of sporadic dementia of Alzheimer's type in mice: contribution of antioxidant mechanism

The present study investigated whether the antioxidant activity of p,p'‐methoxyl‐diphenyl diselenide [(MeOPhSe)₂] is involved in its protective effect against cognitive impairment induced by streptozotocin (STZ) in a model of sporadic dementia of Alzheimer's type (SDAT). Swiss mice were treated with STZ or vehicle [2 µl of 2·5 mg ml^?1 solution; intracerebroventricularly (i.c.v.)] twice, 48 h apart. (MeOPhSe)₂ (25 mg kg^?1) or vehicle was orally administered 30 min prior to each STZ treatment. Neuroprotector effect of (MeOPhSe)₂ on the behavioral performance of mice on spatial recognition memory consolidation was investigated in the Y‐maze test. After that, mouse brains were removed for measuring antioxidant parameters. (MeOPhSe)₂ protected against the impairment in learning and memory caused by i.c.v. administration of STZ in mice. (MeOPhSe)₂ protected against the increase in reactive species and the reduction of glutathione levels, as well as, the increase in superoxide dismutase and glutathione S‐transferase activities caused by STZ in whole brain. These results suggest that antioxidant property is involved, at least in part, in the neuroprotective effect of (MeOPhSe)₂ on SDAT induced by STZ in mice. Copyright © 2011 John Wiley & Sons, Ltd.     

Heart Rate Variation, Age, and Behavior in Subjects with Senile Dementia of Alzheimer Type

Minute-by-minute heart rate (HR) recordings over a period of 24 h were obtained once for 30 elderly subjects diagnosed as having senile dementia of Alzheimer type (SDAT). Twenty-one of the subjects were studied in a hospital ward setting, and nine were studied in their own homes. Twelve were men and 18 were women. Eleven took some form of sedative medication; 10 took no medication. Thirty-minute mean values were unmasked to take account of the effects of activity and sleep on HR. Results indicate that the masked HR circadian rhythm of SDAT may be more often unimodal than that of normal subjects of similar age, and that phase shift of the endogenous, clock-mediated component of the rhythm (with higher HR at night) is to be expected in a proportion of individuals with SDAT.     

丁苯酞联合美金刚对阿尔茨海默病患者氧化应激、内皮功能及认知功能的影响

目的:探讨丁苯酞联合美金刚对阿尔茨海默病(AD)患者氧化应激、内皮功能及认知功能的影响。方法:根据随机数表法将80例AD患者分为对照组(n=40,采用美金刚治疗)和研究组(n=40,采用丁苯酞联合美金刚治疗),比较两组患者临床疗效,并比较分析治疗前后氧化应激、内皮功能以及认知功能相关指标变化,观察两组不良反应发生情况。结果:研究组总有效率为87.50%,显著高于对照组的67.50%(P0.05)。治疗6个月后,两组患者丙二醛(MDA)、β淀粉样蛋白(Aβ)水平均降低,且研究组低于对照组(P0.05),两组患者超氧化物歧化酶(SOD)水平升高,且研究组高于对照组(P0.05)。治疗6个月后,两组患者一氧化氮(NO)、血管内皮生长因子(VEGF)水平均升高,且研究组高于对照组(P0.05)。治疗后第3个月、治疗后第6个月、治疗后第12个月,两组患者MMSE评分逐渐升高,且各时间点研究组MMSE评分均高于对照组(P0.05)。两组不良反应发生率比较无统计学差异(P0.05)。结论:丁苯酞联合美金刚治疗AD患者疗效确切,可有效减轻患者氧化应激反应,提高患者内皮功能和认知功能,安全可靠。     

通督调神针刺法联合胞磷胆碱对脑梗死后血管性痴呆患者认知功能、血液流变学和脑血流动力学的影响

摘要 目的：观察通督调神针刺法联合胞磷胆碱对脑梗死后血管性痴呆（VD）患者认知功能、血液流变学和脑血流动力学的影响。方法：选择2018年3月～2021年3月期间安徽中医药大学第二附属医院收治的98例脑梗死后VD患者,采用随机数字表法分为对照组（49例,胞磷胆碱联合传统针刺治疗）和观察组（49例,通督调神针刺法联合胞磷胆碱治疗）。对比两组疗效、认知功能、痴呆症状、日常生活能力、血液流变学和脑血流动力学。结果：观察组的临床总有效率高于对照组（P<0.05）。治疗后,观察组日常活动能力量表（ADL）、长谷川痴呆修正量表（HDS-R）、简易智力状态检查量表（MMSE）评分高于对照组（P<0.05）;观察组血细胞比容、血浆黏度、全血高切黏度、全血低切黏度低于对照组（P<0.05）;观察组收缩期峰值速度（Vmax）、搏动指数（PI）高于对照组;舒张期峰值速度（Vmin）、阻力指数（RI）低于对照组（P<0.05）。结论：胞磷胆碱联合通督调神针刺法治疗脑梗死后VD,可促进其痴呆症状、认知功能和日常生活能力改善,可能与调节血液流变学和脑血流动力学有关。     

血清尿酸、白介素6、P-tau181与阿尔茨海默病患者认知功能、日常生活能力和预后的关系分析

摘要 目的：探讨血清尿酸（UA）、白细胞介素-6（IL-6）、磷酸化Tau181（P-tau181）与阿尔茨海默病（AD）患者认知功能、日常生活能力和预后的关系。方法：选择2018年5月至2021年1月上海交通大学医学院附属第九人民医院与上海交通大学医学院附属第九人民医院黄浦分院收治的98例AD患者（AD组）和71例门诊体检的健康志愿者（对照组）,检测血清UA、IL-6、P-tau181水平,使用简易智力状态检查量表（MMSE）、蒙特利尔认知评估量表（MoCA）评估患者认知功能,Barthel指数（BI）评估患者日常生活能力。所有患者出院后随访1年,统计随访期间不良预后发生情况。Pearson相关性分析UA、IL-6、P-tau181与MMSE、MoCA、BI的相关性,多因素Logistic回归分析AD患者预后不良的危险因素。结果：AD组血清UA水平和MMSE、MoCA评分、BI低于对照组（P＜0.05）,IL-6、P-tau181水平高于对照组（P＜0.05）。AD患者血清UA水平与MMSE、MoCA评分、BI呈正相关（P＜0.05）,IL-6、P-tau181水平与MMSE、MoCA评分、BI呈负相关（P＜0.05）。多因素Logistic回归分析结果显示：长期卧床、AD痴呆阶段、高水平IL-6、高水平P-tau181是AD患者预后不良的危险因素（P＜0.05）,高水平UA是保护因素（P＜0.05）。结论：AD患者血清UA水平降低,IL-6、P-tau181水平升高,且与认知功能障碍、日常生活能力降低以及预后不良有关,检测血清UA、IL-6、P-tau181可辅助评估AD病情和预后。     

阿尔茨海默病患者血清IL-10、IL-17、IL-33与肠道菌群相对丰度和认知功能的相关性分析

摘要 目的：分析阿尔茨海默病（AD）患者血清白介素（IL）-10、IL-17、IL-33与肠道菌群相对丰度和认知功能的相关性。方法：选择上海交通大学医学院附属第九人民医院老年科以及黄浦分院神经内科于2020年4月~2023年4月期间收治的AD患者 98例作为研究对象。根据临床痴呆评定量表（CDR）将AD患者分为轻度组（n=36）、中度组（n=39）、重度组（n=23）。对比三组患者的IL-10、IL-17、IL-33、肠道菌群相对丰度、认知功能评分。采用Pearson相关性分析AD患者血清IL-10、IL-17、IL-33与肠道菌群相对丰度和认知功能的相关性。结果：重度组、中度组的IL-17水平高于轻度组,且重度组高于中度组（P<0.05）。重度组、中度组IL-10、IL-33水平低于轻度组,且重度组低于中度组（P<0.05）。重度组、中度组的梭菌纲、厚壁菌门、梭菌科、梭菌目低于轻度组,且重度组低于中度组（P<0.05）。重度组、中度组的拟杆菌门、拟杆菌纲、拟杆菌目、产碱杆菌科高于轻度组,且重度组高于中度组（P<0.05）。重度组、中度组简易精神状态量表（MMSE）评分低于轻度组,且重度组低于中度组（P<0.05）。Pearson相关性分析结果显示,IL-10、IL-33与MMSE评分、厚壁菌门、梭菌纲、梭菌目、梭菌科呈正相关,与拟杆菌门、拟杆菌纲、拟杆菌目、产碱杆菌科呈负相关（P<0.05）。IL-17与MMSE评分、厚壁菌门、梭菌纲、梭菌目、梭菌科呈负相关,与拟杆菌门、拟杆菌纲、拟杆菌目、产碱杆菌科呈正相关（P<0.05）。结论：AD患者认知功能下降,血清IL-10、IL-17、IL-33水平异常变化,患者体内肠道菌群相对丰度异常,且IL-10、IL-17、IL-33水平与肠道菌群相对丰度、认知功能存在一定的相关性。     

Tyrosine Hydroxylase, Tryptophan Hydroxylase, Biopterin, and Neopterin in the Brains of Normal Controls and Patients with Senile Dementia of Alzheimer Type

The activities of tyrosine hydroxylase and tryptophan hydroxylase, and the concentrations of the biopterin cofactor and the precursor neopterin were measured in 14 regions of postmortem brains from four histologically verified patients of senile dementia of the Alzheimer type (SDAT) and eight histologically normal controls. Neopterin concentrations were measured in the human brain for the first time. The activities of tyrosine hydroxylase and tryptophan hydroxylase in the brains of patients with SDAT were significantly reduced in the substantia nigra and in the lateral segment of the globus pallidus, locus ceruleus, and substantia nigra, respectively. The concentrations of total biopterin in the brains of patients with SDAT were significantly reduced in the putamen and substantia nigra, but the total neopterin concentrations did not change significantly. These results suggest that the reduction in biogenic amines in SDAT might be related to reductions in biosynthetic enzymes associated with biogenic amines, due to destruction of monoaminergic neurons.     

帕金森病患者睡眠障碍与脑电图活动、神经心理学指标和健康相关生活质量的关系研究

摘要 目的：研究帕金森病（PD）患者睡眠障碍与脑电图活动、神经心理学指标和健康相关生活质量的关系。方法：选择我院2018年5月～2021年5月收治100例PD患者。将其根据匹兹堡睡眠质量指数（PSQI）评分的差异分作睡眠障碍组（PSQI评分＞7分）68例及无睡眠障碍组（PSQI评分≤7分）32例。比较两组脑电图活动、神经心理学指标以及39项帕金森病生活质量调查表（PDQ39）评分,并分析PSQI评分与脑电图活动、神经心理学指标及PDQ39评分的相关性。结果：睡眠障碍组的δ波和θ波相对功率值高于无睡眠障碍组,而β1、β2两个频段的相对功率值低于无睡眠障碍组（P＜0.05）;睡眠障碍组脑电图轻度异常、中度异常以及重度异常的患者比例高于无睡眠障碍组,而脑电图正常的患者比例低于无睡眠障碍组（P＜0.05）。睡眠障碍组蒙特利尔认知评估中文量表（MoCA）评分低于无睡眠障碍组,而汉密尔顿焦虑量表（HAMA）、汉密尔顿抑郁量表（HAMD）评分均高于无睡眠障碍组（P＜0.05）。睡眠障碍组PDQ39各项目评分及总分均高于无睡眠障碍组（P＜0.05）。经Pearson及Spearman相关性分析可得：PD患者的PSQI评分与脑电图异常程度、HAMA评分、HAMD评分及PDQ39评分均呈正相关,而与MoCA评分呈负相关（P＜0.05）。结论：睡眠障碍可能对PD患者认知功能造成损害,加剧焦虑、抑郁等负性情绪,并降低其健康相关生活质量,监测脑电图活动可在一定程度上判断PD患者睡眠障碍严重程度。     

何氏益气养血补肾方治疗气血亏虚型类风湿关节炎并血液系统受累患者的效果分析

摘要 目的：探讨何氏益气养血补肾方治疗气血亏虚型类风湿关节炎并血液系统受累患者的治疗效果。方法：选取我院2020年10月到2022年10月收治的60例气血亏虚型类风湿关节炎并血液系统受累患者作为研究对象,分为观察组与对照组,每组30例。对照组采取常规本病治疗与对症治疗,观察组采取何氏益气养血补肾方与本病治疗,对比两组患者临床疗效,治疗前后中医证候积分变化,血红蛋白（Hb）、白细胞计数（WBC）、超敏C反应蛋白（hsCRP）及血沉（ESR）相关血液指标水平变化,CD4⁺、CD3⁺、CD4⁺/ CD8⁺相关T淋巴细胞亚群水平变化,并应用谷丙转氨酶（ALT）表达水平、谷草转氨酶（AST）评价患者治疗前后肝功能,应用血肌酐（Scr）、尿素氮(BUN)来评价患者肾功能变化。结果：观察组总有效率为93.33%明显高于对照组总有效率86.66%（P<0.05）;治疗后,两组患者神疲乏力、心悸气短、自汗、头晕眼花、怕冷、睡眠障碍相关中医证候积分均降低,且观察组低于对照组（P＜0.05）;治疗后两组患者Hb、WBC升高,观察组较对照组高,ESR、hsCRP降低,且观察组低于对照组（P＜0.05）;治疗后两组患者CD4⁺、CD3⁺和CD4⁺/ CD8⁺数值均升高,且观察组高于对照组（P＜0.05）;治疗后两组患者ALT、AST水平无明显变化,但两组患者SCr、BUN水平降低,观察组低于对照组（P＜0.05）。结论：何氏益气养血补肾方治疗气血亏虚型类风湿关节炎并血液系统受累疗效显著,可改善患者相关中医症状,提升血红蛋白和白细胞计数,提高患者免疫功能,且不对肝肾功能造成损伤,能够轻度提升患者肾功能水平,值得临床应用推广。