The neuroprotective effects of oxygen therapy in Alzheimer’s disease:a narrative review

Alzheimer’s disease(AD)is a degenerative neurological disease that primarily affects the elderly.Drug therapy is the main strategy for AD treatment,but current treatments suffer from poor efficacy and a number of side effects.Non-drug therapy is attracting more attention and may be a better strategy for treatment of AD.Hypoxia is one of the important factors that contribute to the pathogenesis of AD.Multiple cellular processes synergistically promote hypoxia,including aging,hypertension,diabetes,hypoxia/obstructive sleep apnea,obesity,and traumatic brain injury.Increasing evidence has shown that hypoxia may affect multiple pathological aspects of AD,such as amyloid-beta metabolism,tau phosphorylation,autophagy,neuroinflammation,oxidative stress,endoplasmic reticulum stress,and mitochondrial and synaptic dysfunction.Treatments targeting hypoxia may delay or mitigate the progression of AD.Numerous studies have shown that oxygen therapy could improve the risk factors and clinical symptoms of AD.Increasing evidence also suggests that oxygen therapy may improve many pathological aspects of AD including amyloid-beta metabolism,tau phosphorylation,neuroinflammation,neuronal apoptosis,oxidative stress,neurotrophic factors,mitochondrial function,cerebral blood volume,and protein synthesis.In this review,we summarized the effects of oxygen therapy on AD pathogenesis and the mechanisms underlying these alterations.We expect that this review can benefit future clinical applications and therapy strategies on oxygen therapy for AD.

The Efficacy and Safety of Yokukansankachimpihange for Treating Behavioral and Psychological Symptoms of Dementia in Patients with Alzheimer’s Disease: An Open-Label Pilot Study

Previous clinical trials have demonstrated the efficacy of yokukansan, a traditional Japanese medicine, for the treatment of behavioral and psychological symptoms of dementia (BPSD). However, less evidence is available for the treatment of BPSD with yokukansankachimpihange (YKSCH), which consists of yokukansan and two additional herbal ingredients. The present study was conducted to investigate the efficacy and safety of YKSCH for treating BPSD in patients with Alzheimer’s disease (AD). We enrolled outpatients with mild-to-moderate AD who exhibited BPSD and obtained a Neuropsychiatric Inventory (NPI) score of >3 including subscale scores for “agitation”, “anxiety”, “irritability”, and “sleep and night-time behavior change”. A daily YKSCH dose of 7.5 g was administered for 12 weeks with concomitant administration of anti-dementia medication. BPSD was evaluated using the NPI at baseline and every 4 weeks during the intervention. We also examined apathy using the Japanese translation of the Apathy Scale, the short version of the Japanese version of the Zarit Caregiver Burden Interview, and the Modified Crichton Rating Scale for Predicting Activities of Daily Living. Cognitive dysfunction was evaluated using the Mini Mental State Examination and the AD Assessment Scale-Cognitive (Japanese version). Five participants were enrolled. The NPI total score tended to decrease between the baseline and 8-week evaluations during the YKSCH intervention (Wilcoxon signed rank test, P = 0.063). In terms of the NPI subscale scores, “apathy”, “agitation”, “delusions”, and “sleep and night-time behavior change” decreased after the intervention in those who exhibited each symptom at baseline. There were no significant differences in the other scores examined. No serious adverse events were observed. YKSCH could ameliorate BPSD in patients with mild-to-moderate AD with agitation, anxiety, irritability, and sleep and night-time behavior change, and it was well-tolerated.

Diagnostic value of amygdala volume on structural magnetic resonance imaging in Alzheimer’s disease

BACKGROUND The main clinical manifestation of Alzheimer’s disease(AD)is memory loss,which can be accompanied by neuropsychiatric symptoms at different stages of the disease.Amygdala is closely related to emotion and memory.AIM To evaluate the diagnostic value of amygdala on structural magnetic resonance imaging(sMRI)for AD.METHODS In this study,22 patients with AD and 26 controls were enrolled.Their amygdala volumes were measured by sMRI and analyzed using an automatic analysis software.RESULTS The bilateral amygdala volumes of AD patients were significantly lower than those of the controls and were positively correlated with the hippocampal volumes.Receiver operating characteristic curve analyses showed that the sensitivity of the left and right amygdala volumes in diagnosing AD was 80.8%and 88.5%,respectively.Subgroup analyses showed that amygdala atrophy was more serious in AD patients with neuropsychiatric symptoms,which mainly included irritability(22.73%),sleep difficulties(22.73%),apathy(18.18%),and hallucination(13.64%).CONCLUSION Amygdala volumes measured by sMRI can be used to diagnose AD,and amygdala atrophy is more serious in patients with neuropsychiatric symptoms.

Early onset versus late onset in Alzheimer’s disease: What is the reliable cut-off?

Objective: As the literature on conventional criteria for discriminating early-onset (EO) from late-onset (LO) Alzheimer’s disease (AD) is sparse and controversial, the aim of this study was to establish a precise age at onset (AAO) criterion, by using a specific statistical procedure, and to describe the clinical characteristics of the two sub-groups. Methods: Admixture analysis was performed to establish the AAO cut-off in a multi-center study including 2000 AD patients consecutively recruited in eight Italian Memory Clinics. None of the patients were taking acetylcholinesterase inhibitors, antipsychoticor anti-depressant drugs. At the first diagnosticvisit, they were administered the Mini Mental StateExamination, the Basic and Instrumental Activities of Daily Living and the Neuropsychiatric Inventorytoassess clinical phenomenology. Results: Using a specific statistical procedure, we established that AAO that discriminated EO-from LO-AD was 66. Compared with the LO-AD group, the EO-AD group showed longer duration of illness and a higher educational level as well as less severe functional impairment and delusions. Conclusions: Differences in sociodemographic and clinical characteristics, such as duration of illness, education and delusion severity, suggested the involvement of different pathogenic processes. Additional studies are needed to further investigate the mechanisms underlying the disorder in the two sub-groups of AD patients.

A Meta-analysis of Mood Stabilizers for Alzheimer's Disease

The objective of this study was to assess the clinical evidence for or against mood stabilizers as a treatment for Alzheimer’s disease (AD).We searched 5 databases from their inception to January 2010.Five randomized clinical trials of mood stabilizers to treat human patients suffering from AD were included.These trials assessed the effectiveness of mood stabilizers as an adjunct treatment to conventional anti-dementia drugs on behavioral and psychological symptoms, especially on agitation.Methodological quality was assessed using the Jadad score.The results suggested a significant effect in favor of placebo on the Mini-Mental Status Examination [n=270, weight mean difference (WMD), -0.89; 95% confidence intervals (CIs) -1.69 to -0.09, P=0.03] and on the Neuropsychiatric Inventory total (NPI total) (n=51, WMD, 3.71; 95% CIs 0.15 to 7.26, P=0.04).There were no significant differences in change scores on total Brief Psychiatric Rating Scale (BPRS total), NPI/BPRS agitation, Cohen-Mansfield Agitation Inventory total and Physical Self Maintenance Scale between mood stabilizers and placebo.Only one of these studies was free of methodological limittions (Jadad score=5).In conclusion, based on the existing evidence, mood stabilizers are ineffective or even harmful as a treatment for AD.

Risperidone Versus Yokukansan in the Treatment of Severe Alzheimer’s Disease

PURPOSE: Patients with AD commonly exhibit behavioral and psychological symptoms of dementia (BPSD). This study is aimed to compare the efficacy of yokukansan (YKS) and risperidone (RIS) on BPSD in patients with severe Alzheimer’s disease (AD). METHODS: Thirty eight inpatients with AD were investigated. Patients were randomly as-signed to the YKS group (N = 18) or the RIS group (N = 20) and treated for 4 weeks. The primary outcomes were changes in the scores on the Neuropsychiatric Inventory (NPI), the Mini-Mental State Examination (MMSE), the Bar-thel Index, and the Cohen-Mansfield Agitation Inventory (CMAI). The frequency of extrapyramidal symptoms (EPS) and other adverse events were recorded at every visit. RESULTS: All participants in both groups completed the trial. The Barthel Index did not significantly change either in the RIS group or the YKS group. The MMSE scores did not change either in the RIS group or the YKS group. Significant improvements in mean total NPI and CMAI scores showed in both groups. Between the YKS and the RIS groups, there were no significant differences in the NPI or the CMAI scores. EPS and other serious adverse effects were not observed in either group. CONCLUSIONS: In this 4-week trial, YKS treatment significantly improved BPSD in the patients with severe AD. The present study suggests that YKS is as effective as RIS on BPSD with severe AD.

Progress on early diagnosing Alzheimer’s disease

Alzheimer’s disease(AD)is a progressive neurodegenerative disorder that affects both cognition and non-cognition functions.The disease follows a continuum,starting with preclinical stages,progressing to mild cognitive and behavioral impairment,ultimately leading to dementia.Early detection of AD is crucial for better diagnosis and more effective treatment.However,the current AD diagnostic tests of biomarkers using cerebrospinal fluid and/or brain imaging are invasive or expensive,and mostly are still not able to detect early disease state.Consequently,there is an urgent need to develop new diagnostic techniques with higher sensitivity and specificity during the preclinical stages of AD.Various non-cognitive manifestations,including behavioral abnormalities,sleep disturbances,sensory dysfunctions,and physical changes,have been observed in the preclinical AD stage before occurrence of notable cognitive decline.Recent research advances have identified several biofluid biomarkers as early indicators of AD.This review focuses on these non-cognitive changes and newly discovered biomarkers in AD,specifically addressing the preclinical stages of the disease.Furthermore,it is of importance to explore the potential for developing a predictive system or network to forecast disease onset and progression at the early stage of AD.

Evidence for accuracy of pain assessment and painkillers utilization in neuropsychiatric symptoms of dementia in Calabria region,Italy

During the clinical course of dementia,beside cognitive impairment and memory loss,a very complex challenge is posed by the neuropsychiatric symptoms（NPSs）.Accurate evaluation and treatment of pain impacts positively the agitation of demented patients aged ≥ 65 years.To gather information on the utilization of pain killers in demented patients a preliminary survey has been conducted in collaboration with the Calabrian Pharmacovigilance Territorial Service of the health district of Catanzaro（Italy）.The study has taken into consideration the prescriptions of acetylcholinesterase inhibitors and memantine during the period ranging from July 2015 to June 2016 and the percentage of patients treated against pain with non steroidal antinflammatory drugs,opioids,and anticonvulsants have been monitored.The latter have been evaluated statistically for difference between the treatment before（pre） and after（post） the settlement of acetylcholinesterase inhibitors（ACh EI） or memantine therapy.The results do support accuracy in painkillers utilization in the course of dementia in the regional population of Calabria（Italy）.

Effectiveness of music intervention on cognitive function and neuropsychiatric symptoms in the elderly with dementia:a meta-analysis

Dementia is increasing dramatically with an increasing elderly population.Pharmacological interventions are proven to have limited efficacy to treat many of the features of dementia.In such a situation,non-pharmacological means become important to help people with dementia,especially music therapy.The efficacy of music intervention on cognition has been barely explored in the literature,and the few studies that are available present inconsistent results.The aim of this systematic review is to have a meta-analysis on the effect of music therapy for improvements in cognitive functions as well as neuropsychiatric symptoms in the elderly with dementia.

Comprehensive Management of Daily Living Activities,behavioral and Psychological Symptoms,and Cognitive Function in Patients with Alzheimer's Disease:A Chinese Consensus on Alzheimer's Disease

Alzheimer's disease(AD)is the most common cognitive disorder in the elderly.Its main clinical manifestations are cognitive decline(C),behavioral and psychological symptoms(B),and a decline in the activities of daily living(A),also known as ABC symptoms.Early identification and evaluation of ABC symptoms are helpful for establishing the accurate diagnosis,comprehensive treatment,and prognosis of AD.To guide Chinese clinical practice for optimization of the comprehensive management of AD,in 2018,The Academy of Cognitive Disorder of China gathered 22 neurologists and gerontologists in China to build a consensus on the comprehensive management of AD.Based on a review of the evidence,the consensus summarizes the pathogenesis,pathological changes,clinical manifestations,evaluation,diagnosis,drug and non-drug treatment,and patient care for AD.Focus group discussion was used to establish a flowchart of comprehensive ABC management for AD patients.The new consensus provides a feasible AD management process for clinicians.

An association between the location of white matter changes and the behavioral and psychological symptoms of dementia in Alzheimer's disease patients

Objective:The frontal lobe may be involved in circuits associated with depression,apathy,aggression,and other psychiatric symptoms.Although white matter changes(WMC)are related to the severity of behavioral and psychological symptoms of dementia(BPSD)in patients with Alzheimer’s disease(AD),it is unclear which part of the WMC may play the most important role in BPSD.This study was designed to investigate the relationship between the location of WMC and the severity of BPSD in AD patients.Methods:Among patients diagnosed with Alzheimer’s disease between 2009 and2014,387 patients were retrospectively reviewed after those with pre‐existing organic brain syndrome,psychiatric diseases,or toxic‐metabolic encephalopathy were excluded.Patients’demographic and laboratory data,WMC measured with brain computed tomography and scored using the age‐related white matter changes(ARWMC)scale,and neuropsychological tests,including the cognitive abilities screening instrument(CASI),the Mini‐Mental State Examination(MMSE),the clinical dementia rating scale with sum‐box(CDR‐SB),and the neuropsychiatric inventory(NPI)were analyzed.Results:There was no significant difference in the NPI between patients with and without a history of stroke,hypertension,and diabetes.No significant difference in the NPI was identified between different sexes or different Apolipoprotein E(APOE)alleles.The NPI score was significantly correlated with the duration of education(r=–0.4515,P=0.0172),CASI(r=–0.2915,P<0.0001),MMSE(r=–0.8476,P<0.0001),and CDR‐SB(r=2.2839,P<0.0001).WMC in the right frontal lobe showed a significant difference in NPI in comparison to those without WMC(P=0.0255).After adjusting for age,duration of education,and CASI,WMC in the right frontal lobe remained significantly associated with the NPI score(β=3.8934,P=0.042).Conclusions:WMC involving the right frontal lobe may play an important role in the BPSD in AD patients during their dementia diagnosis.Further studies are necessary to confirm whether controlling the risk factors of WMC can slow the progression of BPSD.

Neuropsychiatric symptoms are early indicators of an upcoming metabolic decline in Alzheimer's disease

Background:Neuropsychiatric symptoms(NPS)are increasingly recognized as early non-cognitive manifestations in the Alzheimer's disease(AD)continuum.However,the role of NPS as an early marker of pathophysiological progression in AD remains unclear.Dominantly inherited AD(DIAD)mutation carriers are young individuals who are destined to develop AD in future due to the full penetrance of the genetic mutation.Hence,the study of DIAD mutation carriers enables the evaluation of the associations between pure AD pathophysiology and metabolic correlates of NPS without the confounding effects of co-existing pathologies.In this longitudinal study,we aimed to identify regional brain metabolic dysfunctions associated with NPS in cognitively intact DIAD mutation carriers.Methods:We stratified 221 cognitively intact participants from the Dominantly Inherited Alzheimer's Network according to their mutation carrier status.The interactions of NPS measured by the Neuropsychiatric Inventory-Questionnaire(NPI-Q),age,and estimated years to symptom onset(EYO)as a function of metabolism measured by[^(18)F]flurodeoxyglucose([^(18)F]FDG)positron emission tomography,were evaluated by the mixed-effects regression model with family-level random effects in DIAD mutation carriers and non-carriers.Exploratory factor analysis was performed to identify the neuropsychiatric subsyndromes in DIAD mutation carriers using the NPI-Q subcomponents.Then the effects of interactions between specific neuropsychiatric subsyndromes and EYO on metabolism were evaluated with the mixed-effects regression model.Results:A total of 119 mutation carriers and 102 non-carriers were studied.The interaction of higher NPI-Q and shorter EYO was associated with more rapid declines of global and regional[18F]FDG uptake in the posterior cingulate and ventromedial prefrontal cortices,the bilateral parietal lobes and the right insula in DIAD mutation carriers.The neuropsychiatric subsyndromes of agitation,disinhibition,irritability and depression interacted with the EYO to drive the[^(18)F]FDG uptake decline in the DIAD mutation carriers.The interaction of NPI and EYO was not associated with[^(18)F]FDG uptake in DIAD mutation non-carriers.Conclusions:The NPS in cognitively intact DIAD mutation carriers may be a clinical indicator of subsequent metabolic decline in brain networks vulnerable to AD,which supports the emerging conceptual framework that NPS represent early manifestations of neuronal injury in AD.Further studies using different methodological approaches to identify NPS in predinical AD are needed to validate our findings.

rTMS对阿尔茨海默病认知障碍和精神行为症状的治疗进展

阿尔茨海默病(Alzheimer′s disease,AD)是老年期最为常见的一种痴呆类型,是一种病因不明的慢性、进行性、原发性大脑神经系统退行性病变,以记忆力减退、行为能力下降、认知能力损失、日常自理能力下降等为主要特征。AD发病率高,疾病负担重,患者在认知功能减退的同时,常会出现一系列精神行为症状(Behavioral and psychological symptoms of dementia,BPSD)。传统的药物治疗存在疗效不理想、副作用明显等局限,重复经颅磁刺激(Repetitive transcranial magnetic stimulation,rTMS)作为一种重要的非侵入性脑刺激治疗技术,可经脉冲磁场对中枢神经产生作用,影响脑神经电活动及脑内代谢,与AD常用药物联合应用,可获得理想效果。本文就rTMS治疗AD患者的认知障碍和精神行为症状进行综述。

盐酸美金刚片联合喹硫平治疗阿尔茨海默病伴发痴呆精神行为症状患者的效果分析

目的探讨盐酸美金刚片与喹硫平联合用药在伴痴呆精神行为症状的阿尔茨海默病患者中的临床价值。方法选取2022年7月—2023年6月白银市第一人民医院神经内科收治的84例伴发痴呆精神行为症状的阿尔茨海默病患者为研究对象。采用随机数表法分为两组,各42例。对照组采用盐酸美金刚片进行治疗,观察组在对照组基础上加用喹硫平治疗,比较两组症状行为与认知评分、睡眠质量、不良反应发生情况、治疗总有效率。结果观察组阿尔兹海默症行为量表评分为(13.52±3.36)分,低于对照组的(15.34±4.25)分,差异有统计学意义(t=2.177,P=0.032)。观察组总睡眠时间长于对照组,睡眠潜伏时间短于对照组,差异有统计学意义(P均<0.05)。研究组治疗总有效率高于对照组,差异有统计学意义(P<0.05)。两组认知评分以及不良反应发生率对比,差异无统计学意义(P均>0.05)。结论在金刚片治疗的基础上加用喹硫平并严格控制剂量,能够改善患者的精神行为症状与睡眠质量,提升疗效,且用药过程较安全。

营养状况和认知功能在APOE ε4与阿尔茨海默病精神行为症状相关性的中介效应

目的探讨营养状况和认知功能在载脂蛋白E等位基因4(APOEε4)与阿尔茨海默病(AD)精神行为症状(NPS)及其亚型相关性的中介效应。方法连续性收集2021年6月至2023年1月首都医科大学附属北京天坛医院阿尔茨海默病生物标志物与生活方式研究(CIBL)队列中293例AD疾病谱[包括遗忘型轻度认知障碍(aMCI)和AD痴呆期]患者,根据是否携带APOEε4将患者分为携带组(107例)和非携带组(186例)。对各NPS亚型患者分别进一步分析入组年龄、性别、体质量指数(BMI)、简易精神状态评价量表(MMSE)、蒙特利尔认知评估量表(MoCA)和微型营养评估量表(MNA)评分等差异。采用SPSS 26.0统计软件进行数据处理。根据数据类型,分别采用t检验、Mann-Whitney U检验或χ^(2)检验进行组间比较。将假设检验中有统计学意义的因素定为后面中介效应分析的混杂因素,采用简单中介效应模型分析营养状况和认知功能在APOEε4与NPS及其亚型中的潜在中介作用。结果与对照组相比,携带组患者出现幻觉、淡漠和异常运动行为的比例更高,差异有统计学意义(P<0.05)。对NPS亚型患者分别进行分析,与非幻觉组相比,幻觉组年龄更大,受教育年限更少,携带APOEε4比例更高,MMSE、MoCA和MNA评分均更低;与非淡漠组相比,淡漠组男性比例更高,携带APOEε4比例更高,MMSE、MoCA和MNA评分均更低;与非异常运动行为组相比,异常运动行为组年龄更大,高脂血症比例更低,携带APOEε4比例更低,MMSE、MoCA及MNA评分更低,差异有统计学意义(P<0.05)。校正混杂因素后,MNA评分介导了29.80%(95%CI 0.062~0.522)APOEε4与淡漠的相关性,19.95%(95%CI 0.011~0.419)APOEε4与异常运动行为的相关性。MMSE评分介导APOEε4与幻觉、淡漠和异常运动行为的相关性分别是24.21%(95%CI 0.078~0.573),39.01%(95%IC 0.155~0.914)和23.37%(95%CI 0.068~0.576)。结论对于aMCI和AD患者而言,营养状况和认知功能部分介导了APOEε4和淡漠或异常运动行为的相关性,而认知功能还部分介导了APOEε4和幻觉的相关性。

甘露特钠联合高频重复经颅磁刺激对阿尔茨海默病患者日常生活能力与智力水平的影响

目的探讨甘露特钠联合高频重复经颅磁刺激对阿尔茨海默病患者日常生活能力与智力水平的影响。方法选择2021年9月至2023年9月河南省职工医院收治的100例阿尔茨海默病患者为研究对象,按随机数字表法将患者分为观察组和对照组,每组50例。对照组患者给予高频重复经颅磁刺激治疗,观察组患者给予甘露特钠联合高频重复经颅磁刺激治疗。应用酶联免疫吸附试验法检测2组患者治疗前后β淀粉样蛋白(Aβ)1-42、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平,化学发光法检测2组患者治疗前后的神经递质水平;采用阿尔茨海默病理行为评分表评估2组患者治疗前后的精神症状,简易智力状态检查量表(MMSE)和蒙特利尔认知评估量表(MOCA)评估2组患者治疗前后的智力水平,阿尔茨海默病协作研究日常能力量表(ADCS-ADL)评估2组患者治疗前后的生活能力,老年性痴呆生活质量量表评估2组患者治疗前后的生活质量。结果治疗前,2组患者Aβ1-42、TNF-α和IL-6水平比较差异无统计学意义(P>0.05);治疗后,2组患者Aβ1-42、TNF-α和IL-6水平均低于治疗前,且观察组患者Aβ1-42、TNF-α、IL-6水平低于对照组(P<0.05)。治疗前,2组患者5-羟色胺(5-HT)、乙酰胆碱(ACh)、γ-氨基丁酸(GABA)和阿尔茨海默病相关神经丝蛋白(AD7c-NTP)水平比较差异无统计学意义(P>0.05);治疗后,2组患者5-HT、ACh、GABA水平高于治疗前,AD7c-NTP水平低于治疗前(P<0.05);治疗后,观察组患者5-HT、ACh、GABA水平高于对照组,AD7c-NTP水平低于对照组(P<0.05)。治疗前,2组患者偏执与妄想观念、幻觉、行为紊乱、攻击行为、日常节律紊乱、情感障碍、焦虑和恐惧及总评分比较差异无统计学意义(P>0.05);治疗后,2组患者偏执与妄想观念、幻觉、行为紊乱、攻击行为、日常节律紊乱、情感障碍、焦虑和恐惧及总评分低于治疗前,且观察组患者偏执与妄想观念、幻觉、行为紊乱、攻击行为、日常节律紊乱、情感障碍、焦虑和恐惧及总评分低于对照组(P<0.05)。治疗前,2组患者MMSE、MoCA和ADCS-ADL评分比较差异无统计学意义(P>0.05);治疗后,2组患者MMSE、MoCA和ADCS-ADL评分高于治疗前,且观察组患者MMSE、MoCA和ADCS-ADL评分高于对照组(P<0.05)。治疗前,2组患者生理功能、心理功能、行为能力、人际关系评分和总评分比较差异无统计学意义(P>0.05);治疗后,2组患者生理功能、心理功能、行为能力、人际关系评分和总评分高于治疗前,且观察组者生理功能、心理功能、行为能力、人际关系评分和总评分高于对照组(P<0.05)。结论甘露特钠联合高频重复经颅磁刺激可显著改善阿尔茨海默病患者炎症状态,调节神经递质水平,缓解精神症状,提高智力水平和日常生活能力,改善生活质量。

NGF-BMSCs移植对AD动物模型症状改善及对脑组织中凋亡相关基因Bcl-2、Bax水平的影响

目的 探讨神经生长因子-骨髓基质干细胞(NGF-BMSCs)移植对阿尔兹海默病(AD)动物模型症状改善及对脑组织中凋亡相关基因B淋巴细胞瘤-2(Bcl-2)、Bax水平的影响.方法 将50只AD大鼠随机分为5组,分别为对照组、盐水注射组、模型组、BMSCs移植组和NGF-BMSCs移植组,每组各10只.观察AD大鼠的行为学变化情况,检测大鼠海马区Bcl-2、Bax水平.结果 模型组和盐水注射组第1~6天的逃避潜伏期均短于对照组,差异有统计学意义(P<0.05);BMSCs移植组、NGF-BMSCs移植组第1~6天的逃避潜伏期均长于对照组、模型组和盐水注射组,差异有统计学意义(P<0.05);NGF-BMSCs移植组第1~6天的逃避潜伏期长于BMSCs移植组,差异有统计学意义(P<0.05).模型组、盐水注射组、BMSCs移植组、NGF-BMSCs移植组的Bcl-2、Bax水平均高于对照组,差异有统计学意义(P<0.05);盐水注射组和BMSCs移植组的Bcl-2水平均高于模型组,Bax水平均低于模型组,差异有统计学意义(P<0.05);BMSCs移植组和NGF-BMSCs移植组的Bcl-2均低于盐水注射组,差异有统计学意义(P<0.05);NGF-BMSCs移植组的Bcl-2水平低于BMSCs移植组,Bax水平高于盐水注射组、BMSCs移植组,差异有统计学意义(P<0.05).结论 NGF-BMSCs移植通过调节AD动物模型海马组织中Bcl-2、Bax表达水平抑制其神经细胞凋亡.

左前额叶高频重复经颅磁刺激改善阿尔茨海默病精神行为症状的随机双盲对照研究

目的通过随机双盲对照研究,探索左前额叶高频重复经颅磁刺激(repetitivetranscranial magnetic stimulation,rTMS)对阿尔茨海默病(Alzheimer s disease,AD)的精神行为症状(behavioral and psychological symptoms of dementia,BPSD)的疗效及安全性。方法筛选2020年4月至2022年1月在上海市精神卫生中心老年科住院的AD患者45例,年龄6085岁,符合简明精神状况量表(MMSE):224分;临床痴呆评定量表(CDR):13分;Hachinski缺血指数量表(HIS)≤4分;痴呆病理行为评定量表(BEHAVE-AD)≥8分。采用随机、双盲、伪刺激对照的临床实验设计,将患者分为rTMS干预真刺激组和伪刺激组,每天治疗1次,持续约22 min左右,每周5次,4周,共20次,最终完成实验的患者28例(真刺激组13例,伪刺激组15例)。2组均给予常规药物治疗,在基线期和4周干预结束后,分别进行疗效和安全性评估。结果干预后,真刺激组的神经精神症状量表(NPI)、AD病理行为评分表(BEHAVE-AD)及柯恩-曼斯菲尔德激越情绪行为量表(CMAI)的减分高于伪刺激组,分别为(28.85±8.23)vs(8.20±6.79)、(12.85±7.76)vs(7.07±4.57)、(16.31±6.68)vs(9.47±6.86),差异均存在统计学意义(p<0.05);真刺激组的NPI量表妄想、激越、情绪不稳和异常行为4个因子减分高于伪刺激组,差异存在统计学意义(p<0.05);真刺激组抗精神病药物日剂量增量低于伪刺激组(9 vs 50),差异存在统计学意义(p<0.05);真刺激组不良反应为短暂的头皮发紧2例和轻度头痛1例,伪刺激组为短暂的头皮发紧1例和面部肌肉收缩感1例,2组患者均能耐受,发生率无统计学差异,均无严重不良事件。结论左前额叶高频rTMS可能可以改善阿尔茨海默病患者精神行为症状,是一种安全有效的治疗方法。

老年性痴呆患者精神行为症状的影响因素及认知行为疗法干预效果研究

目的:探讨老年性痴呆患者精神行为症状的影响因素及认知行为疗法干预的效果。方法:选取2020年6月—2022年6月上海市静安区精神卫生中心收治的86例老年性痴呆患者作为研究对象,将患者随机分为认知行为干预组(n=43)及常规干预组(n=43),分别进行认知行为疗法干预和常规干预,对比干预前后两组患者精神行为症状调查表(NPI-Q)、简易智能精神状态量表(MMSE)、Barthel指数(BI)及健康状态调查表(GQOL-74)评分。结果:发生精神行为症状的患者有80例,发病率为93.02%(80/86),不同年龄、病程、睡眠障碍、婚姻状况、生活自理情况患者NPI-Q评分比较,差异有统计学意义(P<0.05)。logistic回归分析结果显示,年龄、病程、婚姻状况、睡眠障碍、生活自理情况是精神行为症状的影响因素(P<0.05)。干预后认知行为干预组MMSE评分为(24.61±2.19)分、BI评分为(70.19±4.22)分,明显高于常规干预组的(22.18±2.46)分、(66.28±3.29)分;干预后认知行为干预组NPI-Q评分为(13.51±1.61)分,低于常规干预组的(14.70±1.22)分,差异均有统计学意义(P值均<0.05)。干预后认知行为干预组心理功能评分为(27.51±6.78)分、社会功能评分为(18.86±3.64)分、躯体功能评分为(15.74±1.83)分、物质生活评分为(20.36±2.71)分,均高于常规干预组的(23.53±5.59)分、(15.73±2.26)分、(13.39±1.59)分、(18.57±2.58)分,差异均有统计学意义(P值均<0.05)。结论:老年性痴呆患者精神行为症状的发生率较高,其发生与年龄、病程、婚姻状况、睡眠障碍、生活自理情况等因素有关。认知行为疗法干预能明显改善老年性痴呆患者的精神行为症状和认知功能,改善患者的自理能力及生活质量。

不同剂量多奈哌齐联合美金刚治疗阿尔茨海默病的疗效比较

目的比较不同剂量多奈哌齐联合美金刚对阿尔茨海默病(AD)患者认知功能、精神行为症状、血清学指标及日常生活能力的影响。方法将149例AD患者随机分为高剂量组(n=57)、低剂量组(n=49)和对照组(n=43)。3组患者均接受美金刚治疗,在此基础上,高剂量组给予高剂量多奈哌齐(5 mg/次、1次/d,4周后增至10 mg/次、1次/d)治疗,低剂量组给予常规剂量多奈哌齐(5 mg/次、1次/d)治疗,对照组给予等量安慰剂治疗。比较3组患者治疗前、治疗3个月后的认知功能[简易智能精神状态检查(MMSE)量表评分、阿尔茨海默病评价量表-认知分量表(ADAS-Cog)评分]、精神行为症状[Cohen-Mansfield激越问卷(CMAI)评分、阿尔茨海默病病理行为评价量表(BEHAVE-AD)评分和痴呆行为评定量表(BRSD)评分]、血清学指标[β淀粉样蛋白1-42(Aβ1-42)、β淀粉样蛋白前体蛋白(APP)、胰岛素样生长因子1(IGF-1)]和日常生活能力[日常生活能力(ADL)量表评分]的变化。结果治疗后,高剂量组、低剂量组、对照组的MMSE量表评分、ADL量表评分和血清IGF-1水平依次降低;ADAS-Cog评分、CMAI评分、BEHAVE-AD评分、BRSD评分和血清APP、Aβ1-42水平依次升高(均P<0.05)。结论与美金刚单独治疗相比,多奈哌齐联合美金刚可以更好地降低AD患者的血清APP水平、促进Aβ1-42清除、上调IGF-1的表达,从而改善患者的认知功能、精神行为症状及日常生活能力,且高剂量多奈哌齐与美金刚联合应用的效果更佳。