Depressive Symptom Endorsement among Alzheimer’s Disease, Vascular Dementia and Mild Cognitive Impairment

Background: The Geriatric Depression Scale (GDS) is widely used to assess depressive symptoms in clinical and research settings. This study utilized a 4 factor solution for the 30-item GDS to explore differences in the presentation of depressive symptoms in various types of cognitive impairment. Method: Retrospective chart review was conducted on 254 consecutive cases of community dwelling elderly newly diagnosed with mild Alzheimer’s Dementia (AD) n = 122, mild Vascular Dementia (VaD) n = 71 or Amnestic Mild Cognitive Impairment (aMCI) n = 32 and Non-Amnestic MCI (nMCI) n = 29. Results: Analysis revealed no significant differences (p 05). No statistically significant differences were found between VaD and nMCI or between the MCI groups. Conclusions: Support is provided for the use of GDS subscales in a wide range of cognitively impaired elderly. This study suggests in mild dementia the number and type of depressive symptoms vary significantly between AD and VaD. There are indications that aMCI patients are similar in their symptom endorsement to AD and nMCI are similar to VaD which is consistent with some of the notions regarding likely trajectories of the respective MCI groups.

Evaluation of the Clinical Efficacy of Acupuncture and Moxibustion Combined with Repetitive Transcranial Magnetic Stimulation on Cognitive Function and Sleep Disorders in Patients with Mild Vascular Dementia

Objective:To explore the clinical effects of acupuncture and repeated transcranial magnetic stimulation in patients with mild vascular dementia.Method:From May 2020 to May 2021,40 patients with mild vascular dementia in Harbin Fourth Hospital(our hospital)were divided into the experimental group(20 cases,using conventional drugs+acupuncture+repeated transcranial magnetic stimulation)and the control group(20 cases,for example,the application of conventional medication).The improvement of cognitive function score,sleep quality score,quality of life score,and cerebral hemodynamics before and after treatment were compared between the two groups.Result:Before treatment,the difference in cognitive function score,sleep quality score,quality of life score,and cerebral hemodynamic index between the two groups of patients did not form,that is,p>0.05;after treatment,the experimental group5s cognitive function score was(19.45±2.47)points,Sleep quality score(12.18±2.09),quality of life score(33.29±4.08),left cerebral blood flow velocity(65.76±3.32)cm/s,right cerebral blood flow velocity(64.32±3.25)cm/s,more For the control group,P<0.05・Conclusion:In the clinical treatment of patients with mild vascular dementia,based on conventional drugs,combined with acupuncture and repetitive transcranial magnetic stimulation,the patients?cognitive function can be improved,and the quality of sleep and quality of life can be improved.Comprehensive clinical promotion.

Comparative efficacy and safety of cognitive enhancers for treating vascular cognitive impairment: systematic review and Bayesian network meta-analysis

Objective: To assess and compare the clinical efficacy and safety of cognitive enhancers(donepezil, galantamine, rivastigmine, and memantine) on cognition, behavior, function, and global status in patients with vascular cognitive impairment.Data sources: The initial literature search was performed with PubMed, EMBASE, the Cochrane Methodology Register, the Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing & Allied Health(CINAHL) from inception to January 2018 for studies regarding donepezil, galantamine, rivastigmine, and memantine for treatment of vascular cognitive impairment.Data selection: Randomized controlled trials on donepezil, galantamine, rivastigmine, and memantine as monotherapy in the treatment of vascular cognitive impairment were included. A Bayesian network meta-analysis was conducted. Outcome measures: Efficacy was assessed by changes in scores of the Alzheimer's Disease Assessment Scale, cognitive subscale, Mini-Mental State Examination, Neuropsychiatric Inventory scores and Clinician's Interview-Based Impression of Change Scale Plus Caregiver's Input, Activities of Daily Living, the Clinical Dementia Rating scale. Safety was evaluated by mortality, total adverse events(TAEs), serious adverse events(SAEs), nausea, vomiting. diarrhea, or cerebrovascular accidents(CVAs). Results: After screening 1717 citations, 12 randomized controlled trials were included. Donepezil and rivastigmine(mean difference(e) = –0.77, 95% confidence interval(CI): 0.25–1.32; MD = 1.05, 95% CI: 0.18–1.79) were significantly more effective than placebo in reducing Mini-Mental State Examination scores. Donepezil, galantamine, and memantine(MD = –1.30, 95% CI: –2.27 to –0.42; MD = –1.67, 95% CI: –3.36 to –0.06; MD = –2.27, 95% CI: –3.91 to –0.53) showed superior benefits on the Alzheimer's Disease Assessment Scale–cognitive scores compared with placebo. Memantine(MD = 2.71, 95% CI: 1.05–7.29) improved global status(Clinician's Interview-Based Impression of Change Scale Plus Caregiver's Input) more than the placebo. Safety results revealed that donepezil 10 mg(odds ratio(OR) = 3.04, 95% CI: 1.86–5.41) contributed to higer risk of adverse events than placebo. Galantamine(OR = 5.64, 95% CI: 1.31–26.71) increased the risk of nausea. Rivastigmine(OR = 16.80, 95% CI: 1.78–319.26) increased the risk of vomiting. No agents displayed a significant risk of serious adverse events, mortality, cerebrovascular accidents, or diarrhea.Conclusion: We found significant efficacy of donepezil, galantamine, and memantine on cognition. Memantine can provide significant efficacy in global status. They are all safe and well tolerated.

Vascular cognitive impairment, a cardiovascular complication

Over the past two decades, the term vascular cognitive impairment(VCI) has been used to refer to a spectrum of cognitive decline characterized by executive dysfunction, associated with vascular pathology. With 30% of stroke survivors showing cognitive impairments, it is regarded as the most common cause of cognitive impairment. This is a narrative review of available literature citing sources from Pub Med, MEDLINE and Google Scholar. VCI has a high prevalence both before and after a stroke and is associated with great economic and caregiver burden. Despite this, there is no standardized diagnostic criteria for VCI. Hypertension has been identified as a risk factor for VCI and causes changes in cerebral vessel structure and function predisposing to lacuna infarcts and small vessel haemorrhages in the frontostriatal loop leading to executive dysfunction and other cognitive impairments. Current trials have shown promising results in the use of antihypertensive medications in the management of VCI and prevention of disease progression to vascular dementia. Prevention of VCI is necessary in light of the looming dementia pandemic. All patients with cardiovascular risk factors would therefore benefit from cognitive screening with screening instruments sensitive to executive dysfunction as well as prompt and adequate control of hypertension.

Resveratrol improves cognition and reduces oxidative stress in rats with vascular dementia

Resveratrol possesses beneficial biological effects, which include anti-oxidant, anti-inflammatory and anti-carcinogenic properties. Recently, resveratrol has been shown to exhibit neuroprotective effects in models of Parkinson＇s disease, cerebral ischemia and Alzheimer＇s disease. However, its effects on vascular dementia remain unclear. The present study established a rat model of vascular dementia using permanent bilateral common carotid artery occlusion. At 8-12 weeks after model induction, rats were intragastrically administered 25 mg/kg resveratrol daily. Our results found that resveratrol shortened the escape latency and escape distances in the Morris water maze, and pro- longed the time spent percentage and swimming distance percentage in the target quadrant during the probe test, indicating that resveratrol improved learning and memory ability in vascular dementia rats. Further experiments found that resveratrol decreased malonyldialdehyde levels, and increased superoxide dismutase activity and glutathione levels in the hippocampus and cerebral cortex of vascular dementia rats. These results confirmed that the neuroprotective effects of resveratrol on vascular dementia were associated with its anti-oxidant properties.

Cognitive disorder and dementia in type 2 diabetes mellitus

Insulin,a key pleiotropic hormone,regulates metabolism through several signaling pathways in target tissues including skeletal muscle,liver,and brain.In the brain,insulin modulates learning and memory,and impaired insulin signaling is associated with metabolic dysregulation and neurodegenerative diseases.At the receptor level,in aging and Alzheimer’s disease(AD)models,the amount of insulin receptors and their functions are decreased.Clinical and animal model studies suggest that memory improvements are due to changes in insulin levels.Furthermore,diabetes mellitus(DM)and insulin resistance are associated with age-related cognitive decline,increased levels ofβ-amyloid peptide,phosphorylation of tau protein;oxidative stress,pro-inflammatory cytokine production and dyslipidemia. Recent evidence shows that deleting brain insulin receptors leads to mildobesity and insulin resistance without influencing brain size and apoptosis development.Conversely, deleting insulin-like growth factor 1 receptor (IGF-1R) affects brain size anddevelopment, and contributes to behavior changes. Insulin is synthesized locally in the brain andis released from the neurons. Here, we reviewed proposed pathophysiological hypotheses toexplain increased risk of dementia in the presence of DM. Regardless of the exact sequence ofevents leading to neurodegeneration, there is strong evidence that mitochondrial dysfunctionplays a key role in AD and DM. A triple transgenic mouse model of AD showed mitochondrialdysfunction, oxidative stress, and loss of synaptic integrity. These alterations are comparable tothose induced in wild-type mice treated with sucrose, which is consistent with the proposal thatmitochondrial alterations are associated with DM and contribute to AD development. Alterationsin insulin/IGF-1 signaling in DM could lead to mitochondrial dysfunction and low antioxidantcapacity of the cell. Thus, insulin/IGF-1 signaling is important for increased neural processing andsystemic metabolism, and could be a specific target for therapeutic strategies to decreasealterations associated with age-related cognitive decline.

The neuroimaging of neurodegenerative and vascular disease in the secondary prevention of cognitive decline

Structural brain changes indicative of dementia occur up to 20 years before the onset of clinical symptoms. Efforts to modify the disease process after the onset of cognitive symptoms have been unsuccessful in recent years. Thus, future trials must begin during the preclinical phases of the disease before symptom onset. Age related cognitive decline is often the result of two coexisting brain pathologies: Alzheimer's disease(amyloid, tau, and neurodegeneration) and vascular disease. This review article highlights some of the common neuroimaging techniques used to visualize the accumulation of neurodegenerative and vascular pathologies during the preclinical stages of dementia such as structural magnetic resonance imaging, positron emission tomography, and white matter hyperintensities. We also describe some emerging neuroimaging techniques such as arterial spin labeling, diffusion tensor imaging, and quantitative susceptibility mapping. Recent literature suggests that structural imaging may be the most sensitive and cost-effective marker to detect cognitive decline, while molecular positron emission tomography is primarily useful for detecting disease specific pathology later in the disease process. Currently, the presence of vascular disease on magnetic resonance imaging provides a potential target for optimizing vascular risk reduction strategies, and the presence of vascular disease may be useful when combined with molecular and metabolic markers of neurodegeneration for identifying the risk of cognitive impairment.

Neuroprotection against vascular dementia after acupuncture combined with donepezil hydrochloride：P300 event related potential

Acupuncture can be used to treat various nervous system diseases.Here,168 vascular dementia patients were orally administered donepezil hydrochloride alone（5 mg/day,once a day for 56 days）,or combined with acupuncture at Shenting（DU24）,Tianzhu（BL10）,Sishencong（Extra）,Yintang（Extra）,Renzhong（DU26）,Neiguan（PC6）,Shenmen（HT7）,Fengchi（GB20）,Wangu（GB12） and Baihui（DU20）（once a day for 56 days）.Compared with donepezil hydrochloride alone,P300 event related potential latency was shorter with an increased amplitude in patients treated with donepezil hydrochloride and acupuncture.Mini-Mental State Examination score was also higher.Moreover,these differences in P300 latency were identified within different infarcted regions in patients treated with donepezil hydrochloride and acupuncture.These findings indicate that acupuncture combined with donepezil hydrochloride noticeably improves cognitive function in patients with vascular dementia,and exerts neuroprotective effects against vascular dementia.

Transcatheter treatment of atherosclerotic lesions of the brain complicated by vascular dementia development

The research focuses on the effectiveness of transluminal laser revascularization of the brain in the treatment of atherosclerotic lesions accompanied by vascular dementia development. 1125 patients aged from 29 to 81 (average age 75) suffering from various kinds of atherosclerotic lesions of cerebral vessels were examined during the research. The examination plan included: computed tomography of the brain (CT), magnetic resonance imaging (MRI), scintigraphy of the brain (SG), rheoencephalography (REG), cerebral multi-gated angiography (MUGA). 665 (59.11%) patients suffered from diseases accompanied by the development of vascular dementia. To perform transcatheter treatment, 639 patients were selected: Group 1 (CDR-1)—352 patients, Group 2 (CDR-2)—184 patients, Group 3 (CDR-3)—103 patients. To conduct revascularization of main intracranial arteries high-energy laser systems were used;for revascularization of the distal intracranial branches low-energy laser systems were used. The clinical outcome depended on the severity of dementia and the timing of the intervention. A good clinical outcome in Group 1 was obtained in 281 (79.82%) cases, in Group 2 in 81 (44.02%) cases, in Group 3 in 9 (8.73%) cases. A satisfactory clinical outcome in Group 1 was obtained in 53 (15.34%) cases, in Group 2 in 62 (33.70%) cases, in Group 3 in 31 (30.09%) cases. A relatively satisfactory clinical outcome in Group 1 was obtained in 17 (4.83%) cases, in Group 2 in 41 (22.28%) cases, in Group 3 in 63 (61.16%) cases. No negative effect was observed after the intervention. Evaluating the data obtained it can be concluded that the method of transluminal laser revascularization of cerebral blood vessels is an effective one for the treatment of atherosclerotic lesions of the brain accompanied by dementia.

Assessment of Sleep Pattern in Egyptian Elderly with Vascular Dementia

Study Objectives: Growing evidence suggests that sleep disturbances is common in vascular dementia (VaD). The goal of the current study is to assess the disturbance in sleep pattern in patients with VaD, and compare it to healthy normally cognitive elderly individuals. We next studied whether there are meaningful differences in the Subjective sleep assessment: Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI) and sleep measurements by polysomnography (PSG) in VaD patients. Study design: Case control study. Subject and methods: Overnight PSG recordings and self-reported sleep measures were obtained from 20 healthy elderly subjects and 20 VaD patients at the sleep laboratory. Results: This study showed abnormal subjective sleep quality in all patients and revealed that the most common sleep complaints among VaD patients were: excessive daytime sleepiness (EDS), sleep disordered breathing (SDB), insomnia, restless leg syndrome (RLS), periodic limb movements (PLMS) and REM behavioral disordered (RBD) respectively. Moreover, patients spent more time in stage I sleep, but less time in slow wave sleep (SWS) and REM sleep compared to control populations, with delayed REML and less 1st REML. Also, increased sleep fragmentation;wakefulness after sleep onset (WASO) & sleep fragmentation index (SFI), increased arousal index (AI) & PLMS index were detected in VaD patients. Finally, VaD patients had significant high Apnea, Hypopnea and Respiratory Distress Index (RDI) score with high average SpO2 Desaturation. Conclusions: Sleep is significantly impaired in patients with VaD at both the objective and subjective level, which may be used as a diagnostic marker of VaD. SDB is a common feature of VaD and leads to fragmented sleep, increased nocturnal confusion, and excessive daytime sleepiness. Subjective sleep assessment questionnaire (ESS and PSQI) can be used in VaD patients when objective sleep assessment by PSG recordings is difficult to be done. The PSG study of sleep continuity, sleep architecture, and REM sleep may help in the prevention of progression of VaD.

滋肾活血方对血管性痴呆大鼠认知功能障碍的治疗作用

目的 探究滋肾活血方改善血管性痴呆(vascular dementia, VD)大鼠认知功能障碍的分子机制。方法 采用双侧颈总动脉闭塞法(bilateral common carotid artery occlusion, BCCAO)构建VD大鼠模型,随机分为假手术组(sham组)、模型组(VD组)、滋肾活血方高剂量组(15.2 g/kg)、滋肾活血方中剂量组(7.6 g/kg)、滋肾活血方低剂量组(3.8 g/kg)、奥拉西坦组(阳性对照)。通过Morris水迷宫实验记录大鼠的逃避潜伏时间以及穿越平台的次数评估大鼠认知功能;HE染色观察海马组织病理学改变和炎性浸润;尼氏染色评估海马神经元损伤;免疫荧光检测海马组织小胶质细胞M1/M2极化情况;ELISA试剂盒检测海马组织促炎因子(TNF-α、IL-1β)和抗炎因子(TGF-β、IL-4)的水平;Western blot法检测TLR4、p65核蛋白水平。结果 与sham组相比,VD组大鼠逃避潜伏期延长(P<0.001),穿越平台次数减少(P<0.001),海马神经元排列不规则,炎性细胞浸润增多,Iba-1、CD16/32以及CD206的水平,促炎因子(TNF-α、IL-1β),抗炎因子(TGF-β、IL-4)水平以及TLR4和p65核蛋白水平均显著升高(P<0.001)。与VD组相比,滋肾活血方高、中、低剂量组和奥拉西坦组大鼠的逃避潜伏期缩短(P<0.05),穿越平台次数增加(P<0.01),大鼠神经元病理变化得到改善,Iba-1、CD16/32以及CD206的水平,促炎因子(TNF-α、IL-1β)以及TLR4和p65核蛋白水平的表达均明显降低(P<0.01),抗炎因子(TGF-β、IL-4)水平上调(P<0.01)。结论 滋肾活血方通过抑制TLR4/NF-κB信号通路促进小胶质细胞M2型极化缓解VD大鼠认知功能障碍。

醒脑开窍针法联合VR技术干预卒中后非痴呆型血管性认知障碍的临床观察

目的:观察醒脑开窍针法联合VR技术干预卒中后非痴呆型血管性认知障碍(VCIND)的临床疗效。方法:采用随机数字表法将2021年10月至2022年9月江西省南昌市洪都中医院住院治疗的首发脑卒中后VCIND患者78例分为三组,各26例。对照组实施常规认知训练,醒脑开窍针法组实施醒脑开窍针法针刺治疗,醒脑开窍针法+VR技术组是在醒脑开窍针法组基础上联合VR技术康复训练,三组均进行为期4周的康复训练。比较三组康复训练前后认知功能、日常生活能力状况。结果:康复训练4周后,三组认知功能MoCA评分、MMSE评分均提高,且醒脑开窍针法+VR技术组高于醒脑开窍针法组、对照组(P<0.05);三组日常生活能力MBI评分均提高,且醒脑开窍针法+VR技术组高于醒脑开窍针法组、对照组(P<0.05)。结论:醒脑开窍针法联合VR技术干预可改善卒中后VCIND患者认知障碍,提高患者认知能力及日常生活能力。

通督醒神电针法联合复智胶囊治疗血管性痴呆患者的临床观察

【目的】观察通督醒神电针法联合复智胶囊治疗血管性痴呆的临床疗效。【方法】将100例血管性痴呆患者随机分为观察组和对照组,每组各50例。2组患者均给予常规治疗。对照组给予尼莫地平治疗,观察组在对照组治疗的基础上,给予通督醒神电针法联合复智胶囊治疗。连续治疗4周。治疗1个月后,评价2组临床疗效,观察2组患者治疗前后执行性画钟作业(CLOX)、Stroop测验的变化情况,以及简易精神状态检查量表(MMSE)、临床痴呆量表(CDR)评分的情况。比较2组患者治疗前后精神功能评价量表(GAF)、简明精神病评定量表(BPRS)的变化情况。并观察2组患者治疗前后的超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)水平的变化情况。【结果】(1)治疗后,2组患者的CLOX、Stroop1、Stroop2明显改善(P<0.05),且观察组在改善CLOX、Stroop1、Stroop2方面明显优于对照组,差异有统计学意义(P<0.05)。(2)治疗后,2组患者的MMSE、CDR评分明显改善(P<0.05),且观察组在改善MMSE、CDR评分方面明显优于对照组,差异有统计学意义(P<0.05)。(3)治疗后,2组患者的GAF、BPRS评分明显改善(P<0.05),且观察组在改善GAF、BPRS评分方面明显优于对照组,差异有统计学意义(P<0.05)。(4)治疗后,2组患者的SOD、MDA、GSH-Px水平明显改善(P<0.05),且观察组在改善SOD、MDA、GSH-Px水平方面明显优于对照组,差异有统计学意义(P<0.05)。【结论】通督醒神电针法联合复智胶囊治疗血管性痴呆,能明显改善患者的临床症状,提高患者SOD、GSH-Px水平,降低其MDA水平,疗效显著。

丁苯酞联合盐酸多奈哌齐对血管性痴呆患者认知功能及血清黑色素瘤凋亡抑制蛋和或肾凋亡抑制蛋白与β转化生长因子的影响

目的探讨丁苯酞联合盐酸多奈哌齐治疗血管性痴呆的临床疗效。方法选取2018年1月至2020年1月山东省荣军总医院收治的93例血管性痴呆患者作为研究对象,按照随机数字表法分为参比组(n=45)与研究组(n=48)。参比组在常规基础治疗上给予盐酸多奈哌齐片治疗,研究组在参比组的基础上给予丁苯酞软胶囊治疗。比较两组血液指标、病情发展进程、认知功能、日常生活能力。结果治疗6个月后,研究组血浆转化生长因子β(TGF-β)、胰岛素样生长因子-1(IGF-1)、血清抗凋亡因子(Livin)、血管内皮生长因子(VEGF)水平及长谷川痴呆量表(HDS)、简易智力状态检查量表(MMES)、日常生活能力量表(ADL)评分均高于参比组,血浆细胞间黏附分子-1(IGAM-1)、血清干扰素-γ(IFN-γ)水平均低于参比组,差异有统计学意义(P<0.05)。结论丁苯酞联合盐酸多奈哌齐治疗血管性痴呆效果显著,可缓解患者病情发展进程,降低血管炎症反应,保护脑组织细胞功能,提高患者认知功能及生活自理能力。

血清神经丝轻链蛋白与认知障碍的相关性研究

目的 研究包括轻度认知障碍(MCI)、阿尔茨海默病(AD)、血管性痴呆(VD)诊断在内的认知障碍疾病中血清神经丝轻链蛋白(NFL)水平测定的临床意义。方法 收集门诊及住院确诊认知功能障碍的住院患者,根据纳入及排除标准分为MCI组47例、 AD组46例、 VD组43例及在门诊体检的健康人群45例作为正常对照组,其中AD组及VD组根据病情严重程度分为轻度组及中重度组,所有患者在确诊后当天进行认知功能评价,在确诊后第二天清晨行血清NFL检查。结果 4组之间的血清NFL水平的比较差异有统计学意义(P<0.05);组间两两比较中,MCI组和AD组的血清NFL水平之间的比较差异无统计学意义(P>0.05);亚组分析中AD组轻度痴呆患者与中重度痴呆患者的血清NFL水平的比较,中重度痴呆患者的血清NFL水平高于轻度痴呆患者,差异有统计学意义(P<0.05);VD组轻度痴呆患者与中重度痴呆患者的血清NFL水平的比较,中重度痴呆患者的血清NFL水平高于轻度痴呆患者,差异有统计学意义(P<0.05)。结论 血清NFL水平检测在临床中可以作为AD及VD早期诊断和病情严重程度判断的外周血生物标志物。

理性情绪疗法联合中医情志干预对血管性痴呆患者焦虑抑郁症状的影响

目的观察理性情绪疗法联合中医情志干预对血管性痴呆患者焦虑抑郁症状的影响。方法将80例血管性痴呆患者按照随机数字表法分为2组,对照组40例予常规基础干预,观察组40例在对照组干预基础上采用理性情绪疗法联合中医情志干预,2组均干预4周。比较2组干预前后简易智能状态检查表(MMSE)、日常生活能力量表(ADL)、老年痴呆患者生活质量量表(QOL-AD)评分、汉密尔顿抑郁量表(HAMD)评分、汉密尔顿焦虑量表(HAMA)评分变化;比较2组干预满意度。结果2组干预后MMSE评分均较本组干预前升高(P<0.05),干预后观察组高于对照组(P<0.05)。2组干预后ADL评分均较本组干预前降低(P<0.05),QOL-AD评分均较本组干预前升高(P<0.05);干预后观察组ADL评分低于对照组(P<0.05),QOL-AD评分高于对照组(P<0.05)。2组干预后HAMD评分、HAMA评分均较本组干预前降低(P<0.05),干预后观察组HAMD评分、HAMA评分均低于对照组(P<0.05)。观察组各项满意度均高于对照组(P<0.05)。结论理性情绪疗法联合中医情志干预,能有效改善血管性痴呆患者心理状态和认知功能,提高其日常生活能力、生活质量和干预满意度。

血浆Hcy、ApoE基因多态性对血管性痴呆患者认知功能及治疗效果的影响

目的探讨血清同型半胱氨酸(homocysteine,Hcy)、载脂蛋白E(apolipoprotein E,ApoE)基因多态性对血管性痴呆患者认知功能的影响。方法回顾性分析于医院接受治疗的100例血管性痴呆患者病例资料作为研究对象,使用简易智力状态检查量表(mini-mental state examination,MMSE)评估患者认知功能,将MMSE评分为21~26分患者纳入轻度组,将10~20分患者纳入中度组,将0~9分患者纳入重度组。参照《中国痴呆与认知障碍诊治指南》给予患者常规治疗,治疗前主要检查项目包括血浆Hcy、ApoE基因多态性,治疗3个月后记录患者临床疗效;分析ApoE基因多态性、Hcy与血管性痴呆患者认知功能障碍及临床疗效的关系。结果100例血管性痴呆患者MMSE评分为16.50(9.00,20.00)分,其中轻度24例,中度49例,重度27例;重度组ApoE基因表型为ε2/4、ε4/4患者占比高于轻度组、中度组,入院时血浆Hcy水平高于轻度组、中度组,差异有统计学意义(P<0.05);行多元Logistic回归分析结果显示,血浆Hcy、ApoE基因是导致血管性痴呆患者认知功能障碍加重的危险因素(P<0.05);100例血管性痴呆患者,治疗3个月后,显效47例,好转30例,无效23例,总有效率为77.00%;行二元Logistic回归分析显示,血浆Hcy、ApoE基因均是影响血管性痴呆患者治疗效果的危险因素(P<0.05)。结论ApoE基因多态性、Hcy与血管性痴呆患者认知功能障碍病情严重程度及临床关系密切,未来临床可通过检测患者ApoE基因多态性、Hcy水平,评估患者认知障碍严重程度及治疗无效风险,针对病情严重治疗无效风险较高者,采取针对性干预,以改善患者临床疗效。

经颅重复针刺对血管性痴呆模型大鼠认知功能及海马突触超微结构的影响

目的 观察经颅重复针刺对血管性痴呆(vascular dementia, VaD)大鼠认知功能及海马CA1区突触素(synaptophysin, SYN)、微管相关蛋白-2(microtubule associated protein-2, MAP-2)表达的影响。方法 将56只SD大鼠随机分为空白组(14只)和造模组(42只)。造模组建立VaD模型,将造模成功大鼠随机分为模型组(14只)、常规针刺组(14只)和经颅重复针刺刺激(repetitive transcranial acupuncture stimulation, rTAS)组(14只)。造模成功后第2天,rTAS组采用经颅重复针刺;常规针刺组仅给予常规针刺手法;模型组与空白组给予以同等条件抓取及固定,不予针刺。采用水迷宫评价大鼠学习记忆能力,采用旷场实验评价大鼠探索行为和自主活动能力,免疫印迹法检测海马CA1区SYP、MAP-2蛋白表达水平,透射电镜观察海马组织中突触超微结构。结果与空白组比较,模型组逃避潜伏时间明显增加(P<0.05),穿越平台次数明显减少(P<0.05);与模型组比较,常规针刺组与rTAS组逃避潜伏时间明显减少(P<0.05),穿越平台次数明显增加(P<0.05);与常规针刺组比较,rTAS组逃避潜伏时间与穿越平台次数改变不明显(P>0.05)。与空白组比较,模型组穿越格子数与后肢站立数明显减少(P<0.05);与模型组比较,常规针刺组与rTAS组穿越格子数与后肢站立数明显增加(P<0.05);与常规针刺组比较,rTAS组穿越格子数与后肢站立数明显增加(P<0.05)。与空白组比较,模型组SYP、MAP-2表达水平显著降低(P<0.05);与模型组比较,常规针刺组与rTAS组SYP、MAP-2表达水平显著增高(P<0.05);与常规针刺组比较,rTAS组SYP、MAP-2表达水平显著增高(P<0.05)。电镜下,模型组突触结构欠清晰,突触间隙模糊不清,突触小泡较少,突触前致密物质减少,胞浆内细胞器稀疏,线粒体变形肿大明显;而rTAS组突触结构较完整,突触间隙、突触前后膜分界清晰,突触前膜内囊泡较多,突触后膜均匀增厚,周边线粒体丰富、结构完整。结论 经颅重复针刺较常规针刺可能通过调控SYP、MAP-2表达,更有效促进突触再生,改善突触可塑性,修复受损神经元,从而改善认知功能。

经皮穴位电刺激通过PGC-1α介导的线粒体生物生成和抗氧化应激改善血管性痴呆大鼠的认知功能

目的探讨经皮穴位电刺激(transcutaneous electrical acupoint stimulation,TEAS)对血管性痴呆(vascular dementia,VD)大鼠认知功能的影响及其机制。方法采用改良的双血管闭塞(2-VO)法建立VD大鼠模型。造模后分别采用TEAS和电针(EA)刺激大鼠百会穴和足三里穴,连续刺激14 d。治疗后,采用新物体识别实验、Morris水迷宫实验、Y迷宫实验评估大鼠空间记忆和学习能力。苏木精-伊红染色观察海马神经元形态;透射电镜观察海马线粒体超微结构;采用酶联免疫吸附测定试剂盒检测大鼠血清中SOD、CAT、GSH-Px、MDA和ROS水平。采用蛋白质免疫印迹法(Western blot)检测各组大鼠海马组织中PGC-1α、TFAM、HO-1、NQO1蛋白及细胞质中Keap1蛋白及细胞核中Nrf2、NRF1蛋白的表达。结果治疗14 d后,与模型组比较,VD组大鼠逃避潜伏期缩短,辨别指数、穿越原平台区域次数、原平台所在象限停留时间、交替百分比增加;TEAS可改善VD大鼠海马神经元及线粒体结构,病理染色结果显示神经元排列更规则、分布更均匀,核膜、核仁更清晰,线粒体肿胀减轻,线粒体基质密度增加,线粒体嵴更明显。血清中SOD、GSH-Px和CAT水平显著升高,MDA和ROS浓度降低。TEAS还上调了海马区PGC-1α、TFAM、NQO1、HO-1蛋白和核内NRF2、NRF1蛋白的表达水平,但下调了胞浆中Keap1蛋白的表达。结论TEAS可改善VD大鼠的认知功能,改善海马神经元和线粒体结构,且效果优于电针,其机制可能是激活PGC-1α介导的线粒体生物发生和抗氧化应激,这也为VD的治疗提供了潜在的治疗技术和实验依据。