Dementia and Cognitive Impairment Reduction after Laser Transcatheter Treatment of Alzheimer’s Disease

Reduced cerebral perfusion and microcirculation are found among AD causes, which should be considered in the development of new treatments for the disease. 165 patients with AD were examined. The examination plan included clinical assessment of dementia severity (CDR), cognitive function assessment (MMSE), laboratory examination, cerebral scintigraphy (SG), rheoencephalography (REG), cerebral CT and MRI, morphometric AD stages assessment (TDR) and cerebral multi-gated angiography (MUGA). 89 patients aged 34 - 79 (average age 67) were selected for the treatment: 31 (34.83%) male, 58 (65.17%) female patients. According to their AD stage, the patients were divided into: TDR-0 (preclinical stage)—10 (11.24%) patients, TDR-1 (early stage with mild dementia, mild cognitive impairment)—28 (31.46%) patients, TDR-2 (medium stage with moderate dementia, cognitive impairment sufficiently persistent)—34 (38.20%) patients, TDR-3 (late stage with sufficiently severe dementia and cognitive impairment)—17 (19.10%) patients. Test Group—46 (51.68%) patients—had transcatheter treatment with low-energy lasers. Control Group—43 (48.31%)—had conservative treatment with Memantin and Rivastigmine. The Test Group had cerebral microcirculation improvement leading to permanent dementia reduction and cognitive recovery which allowed transferring the patients to a lighter TDR group or withdrawing them from the scale. Control Group patients with earlier AD stages (TDR-0, TDR-1, TDR-2) obtained stabilization for a period of 6 months-3 years, with subsequent growth of dementia and cognitive impairment;patients with late AD stage (TDR-3) showed further increase of cognitive impairment and dementia. Transcatheter treatment allows reducing the effects of dyscirculatory angiopathy of Alzheimer’s type (DAAT) improving cerebral microcirculation and metabolism, which leads to permanent dementia regression and cognitive impairment reduction. These data show that AD treatment should be comprehensive and aimed at both the recovery of cerebral microcirculation and blood supply and the normalization of amyloid beta metabolism in the cerebral tissue.

Endovascular Application of Low-Energy Laser in the Treatment of Dyscirculatory Angiopathy of Alzheimer’s Type

Purpose: We propose an analysis of dyscirculatory angiopathy of Alzheimer’s type (DAAT) endovascular treatment method based on transcatheter revascularization and recovery of collateral and microvascular bed of the brain by means of low-energy transluminal laser irradiation as well as its comparison with traditional Alzheimer’s disease (AD) treatment methods. Methods: The research involved 81 patients aged 34 - 79 (average age 67). 46 (46.8%) patients were treated using endovascular method—Test Group. 35 (43.2%) patients were given conventional treatment—Control Group. Patients were subdivided: Group (CDR-0): 9 (11.1%), pre-clinical stage or increased AD risk;Group (CDR-1): 24 (29.6%), mild dementia and cognitive impairment;Group (CDR-2): 31 (38.3%), moderate dementia and persistent cognitive impairment;Group (CDR-3): 17 (21.0%), severe dementia and cognitive impairment. Research plan included CT or MRI with subsequent temporal lobes volume calculation, brain scintigraphy (SG), rheoencephalography (REG), and cerebral MUGA. There were indications and contraindications for treatment in Test Group. In Group CDR-0, endovascular intervention was prophylactic, against the background of increasing memory impairment;in Groups CDR-1, CDR-2, CDR-3, it was conducted in 1 to 12 years period from AD symptoms appear-ance. Conservative treatment with Memantin and Rivastigmine was carried out in Control Group. Results: In Test Group, positive outcome accompanied by prolonged dementia decline, cognitive impairment decrease, and patients’ transition to CDR group of an earlier stage, was obtained in all cases. In Control Group, patients’ temporary stabilization in their own CDR group was achieved. Conclusions: Endovascular treatment of patients with AD different stages can not only reduce DAAT phenomena but can also cause AD regression possibly accompanied by regenerative processes in the cerebral tissue. Conservative treatment only allows stabilizing the patient’s condition for a while.

Evaluation of retinal and choroidal changes in patients with Alzheimer’s type dementia using optical coherence tomography angiography

AIM:To evaluate the changes in fundus parameters in patients with Alzheimer’s type dementia(ATD)using optical coherence tomography angiography(OCTA),to record flash electroretinograms(ERG)using the RETeval system and to explore changes in retinal function.METHODS:Twenty-nine patients with ATD and 26 age-matched normal subjects were enrolled.All subjects underwent OCTA scans to analyse the superficial retinal vessel parameters in the macular area,including the vessel length density,the vessel perfusion density and the area of foveal avascular zone(FAZ),as well as the choroidal thickness.The differences between the patients with ATD and the normal control group were compared and explored the relevant factors affecting vessel parameters.We also recorded the flash ERGs using the RETeval system and intended to explore changes in retinal function by analysing the ERG image amplitude in patients with ATD.RESULTS:The vessel parameters[Pvessel length density=0.005 and Pvessel perfusion density=0.006]and average choroid thickness(P<0.001)in the macular area of the ATD group was less than the control group.The FAZ area was statistically significantly enlarged in the ATD group(P<0.001).These parameters were correlated with the Mini-Mental State Examination(MMSE)score and the Montreal Cognitive Assessment(MoCA).CONCLUSION:Patients with ATD exhibit decreases in the parameters associated with fundus.In addition,these indicators significantly correlate with the MMSE score and the MoCA score.OCTA may be an adjunct tool with strong potential to track changes in the diagnosis and monitoring the progression of the disease.

A pancreatic player in dementia:pathological role for islet amyloid polypeptide accumulation in the brain

Type 2 diabetes mellitus patients have a markedly higher risk of developing dementia.While multiple factors contribute to this predisposition,one of these involves the increased secretion of amylin,or islet amyloid polypeptide,that accompanies the pathophysiology of type 2 diabetes mellitus.Islet amyloid polypeptide accumulation has undoubtedly been implicated in various forms of dementia,including Alzheimer’s disease and vascular dementia,but the exact mechanisms underlying islet amyloid polypeptide’s causative role in dementia are unclear.In this review,we have summarized the literature supporting the various mechanisms by which islet amyloid polypeptide accumulation may cause neuronal damage,ultimately leading to the clinical symptoms of dementia.We discuss the evidence for islet amyloid polypeptide deposition in the brain,islet amyloid polypeptide interaction with other amyloids implicated in neurodegeneration,neuroinflammation caused by islet amyloid polypeptide deposition,vascular damage induced by islet amyloid polypeptide accumulation,and islet amyloid polypeptide-induced cytotoxicity.There are very few therapies approved for the treatment of dementia,and of these,clinical responses have been controversial at best.Therefore,investigating new,targetable pathways is vital for identifying novel therapeutic strategies for treating dementia.As such,we conclude this review by discussing islet amyloid polypeptide accumulation as a potential therapeutic target not only in treating type 2 diabetes mellitus but as a future target in treating or even preventing dementia associated with type 2 diabetes mellitus.

Disorders of cerebrovascular angioarchitectonics and microcirculation in the etiology and pathogenesis of Alzheimer’s disease

There have recently appeared many reports dedicated to cerebral hemodynamics disorders in AD. However, certain specific aspects of cerebral blood flow and microcirculation during this disease are not fully understood. This research focuses on the identification of particular features of cerebral angioarchitectonics and microcirculation at preclinical and clinical AD stages and on the determination of their importance in AD etiology and pathogenesis. 164 patients participated in the research: Test Group—81 patients with different AD stages;Control Group— 83 patients with etiologically different neurodegenerative brain lesions with manifestations of dementia and cognitive impairment but without AD. All patients underwent: assessment of cognitive function (MMSE), severity of dementia (CDR) and AD stages (TDR), laboratory examination, computed tomography (CT), magnetic resonance imaging (MRI), brain scintigraphy (SG), rheoencephalography (REG) and cerebral multigated angiography (MUGA). All Test Group patients, irrespective of their AD stage, had abnormalities of the cerebral microcirculation manifested in dyscirculatory angiopathy of Alzheimer’s type (DAAT), namely: reduction of the capillary bed in the hippocampus and frontal-parietal regions;development of multiple arteriovenous shunts in the same regions;early venous dumping of arterial blood through these shunts with simultaneous filling of arteries and veins;development of abnormally enlarged lateral venous trunks that receive blood from the arterio-venous shunts;anomalous venous congestion at the border of frontal and parietal region;increased loop formation of distal intracranial arterial branches. Control group patients did not have combinations of such changes. These abnormalities are specific for AD and can affect amyloid beta metabolism contributing to its accumulation in the brain tissue and thereby stimulating AD progression.

Dyscirculatory Angiopathy of Alzheimer's Type

Purpose: We assess the significance of dyscirculatory angiopathy of Alzheimer’s type (DAAT) in identify- ing the predisposition to the development and diagnosis of Alzheimer’s disease (AD) different stages. Meth- ods: 108 patients took part in the research:1) 49 aged 34-79 suffering from AD or running an increased risk of its development (those not diagnosed with AD but having growing memory disorders without any mani- festations of dementia or specific cognitive impairments, and having 2 or more immediate relatives with AD) - Test Group;2) 59 aged 28-78 suffering from different types of brain lesions accompanied by dementia but not suffering from AD or corresponding to their age norm - Control Group. All the patients underwent MRI, CT with subsequent calculation of the temporal lobes atrophy degree, brain scintigraphy (SG), rheoencepha- lography (REG), and MUGA. Results: Characteristic features of patients with an increased risk of AD as well as at its various stages are: 1) Temporal lobes and hippocampus atrophy ranging from 4% among those with an increased risk of AD to 62% among those at its advanced stages;2) DAAT manifestations: reduction of the capillary bed in the temporal and frontoparietal regions with the development of multiple arterioven- ous shunts of the same localization and correspondent early venous discharge accompanied by venous stasis on the border of the frontal and parietal region;3) DAAT phenomena equally develop both among those with an increased risk of developing AD and those at various AD stages. Similar changes are not observed among Control Group patients with other brain lesions, regardless of the severity of dementia, as well as among practically healthy people of the corresponding age group. Conclusion: Timely identification of the above- mentioned changes can reveal a predisposition to AD development long before its initial manifestations, and it allows differentiating AD from other diseases attended by dementia. In both cases, timely diagnosis allows beginning timely treatment and thus achieving more stable results.

Hearing Impairment in Senile Dementia of Alzhaimer's Type

Objectives To evaluate peripheral auditory dysfunction in senile dementia of Alzheimer’s disease (AD) and its relationship with cognitive dysfunction. Methods Pure tone thresholds,word recognition scores (WRS), acoustic immittance and auditory brain-stem responses (ABR) were tested to evaluate the auditory function in 43 AD patients and 50 normal subjects. The test reliability in these subjects was examined before the test results were evaluated for their correlation with the Mini Mental State Examination(MMSE) score. Results There were no statistically significant differences in peripheral auditory functions between the two ears in the tested subjects or between the two groups when the auditometric results of the right ear were compared(P > 0.05). Also, there were no statistically significant differences between the two groups when audiometric test reliability, acoustic impedance and ABR results were compared(P > 0.05). Conclutions The pure tone audiometric threshold and WRS in AD patients are similar to those in comparable non-AD senile subjects. Peripheral auditory dysfunction is not related to cognitive dysfunction.

Type 2 diabetes mellitus and Alzheimer's disease

Epidemiological and biological evidences support a link between type 2 diabetes mellitus(DM2) and Alzheimer's disease(AD). Persons with diabetes have a higher incidence of cognitive decline and an increased risk of developing all types of dementia. Cognitive deficits in persons with diabetes mainly affect the areas of psychomotor efficiency, attention, learning and memory, mental flexibility and speed, and executive function. The strong epidemiological association has suggested the existence of a physiopathological link. The determinants of the accelerated cognitive decline in DM2, however, are less clear. Increased cortical and subcortical atrophy have been evidenced after controlling for diabetic vascular disease and inadequate cerebral circulation. Most recent studies have focused on the role of insulin and insulin resistance as possible links between diabetes and AD. Disturbances in brain insulin signaling mechanisms may contribute to the molecular, biochemical, and histopathological lesions in AD. Hyperglycemia itself is a risk factor for cognitive dysfunction and dementia. Hypoglycemia may also have deleterious effects on cognitive function. Recurrent symptomatic and asymptomatic hypoglycemic episodes have been suggested to cause sub-clinical brain damage, and permanent cognitive impairment. Futuretrials are required to clarify the mechanistic link, to address the question whether cognitive decline may be prevented by an adequate metabolic control, and to elucidate the role of drugs that may cause hypoglycemic episodes.

Certain new aspects of etiology and pathogenesis of Alzheimer’s disease

The research focuses on the possibility of early detection of AD-specific vascular and atrophic brain changes in families which have a tendency to inherit the disease. The research includedthree families with AD inheritance. All patientsunderwent: cognitive function assessment(MMSE),determination of dementia severity(CDR) and AD stages (TDR), computed tomography (CT), magnetic resonance imaging (MRI), scintigraphy of the brain (SG), rheoencephalography (REG), and cerebral multigated angiography (MUGA). All patients with different AD stages, as well as their descendants, have specific atrophic changes in the temporal lobes of the brain. The degree of these changes increases as AD becomes more severe and ranges from 4% - 8% (TDR-0) to 33% - 62% (TDR-3) of the total mass of a healthy person’s temporal lobes. Simultaneously, thepatients examined have changes of microcirculation manifested by reduction of the capillarybed in the temporal and frontalparietal regions,the development of multiple arteriovenousshunts in the same areas, early venous dumping, anomalous expansion of venoustrunks that receive blood from the arterialvenous shunts, venous stasis on the frontoparietal boundary. Similar changes are found among AD patients’ descendants aged 8 - 11, the only difference being in the degree of temporal lobes atrophy which is 4.7%. This proves that microcirculatory disorders are primary and atrophic changes of the temporal lobes are secondary in AD development. The data obtained indicate that the examination of AD patients’ relatives should begin well before the possible manifestations of the disease, even in childhood. It will allow to reveal the possibility of inheritance and the signs of the disease at the earliest possible stage and to begin its treatment in time.

Differences in Cerebral Angioarchitectonics in Alzheimer’s Disease in Comparison with Other Neurodegenerative and Ischemic Lesions

Introduction: The research focuses on the clinical study of cerebral angioarchitectonics and microcirculation disorders in the development of Alzheimer’s disease (AD) in comparison with other neurodegenerative and ischemic lesions. Materials and methods: 1117 patients with different types and stages of neurodegenerative and ischemic lesions were examined, 93 of whom (8.33%) had different stages of AD—Test Group;1024 (91.67%) had cerebral atherosclerosis, Binswanger disease (BD), vascular Parkinsonism (VP)—Control Group. The examination included definition of CDR, MMSE, cerebral CT, MRI, cerebral sciagraphy (SG), rheoencephalography (REG), morphometric detection of AD stages with TDR, and cerebral multi-gated angiography (MUGA). Results: In all patients with AD, regardless of the disease stage, specific сerebral small vessel disease (CSVD), manifested by dyscirculatory angiopathy of Alzheimer’s type (DAAT), was detected in the temporal and fronto-parietal areas. Conclusions: DAAT is an AD-specific lesion of cerebral microvessels that changes hemodynamics, causes cerebral hypoxia, and contributes to impaired amyloid beta metabolism. The combination of deposition of amyloid beta in the cerebral tissue and vascular wall, as well as specific disorders of microcirculation, cause neurodegeneration and AD development. Patients with other neurodegenerative and ischemic lesions had no DAAT manifestations.

STUDY OF THE EXTERNAL COUNTERPULSATION (ECP) THERAPY FOR SENILE DEMENTIA OF THE ALZHEIMER'S TYPE (SDAT)

Ten patients with SDAT received the ECP therapy.The examination of Hasegawa’s Dementia Scale(HDS),single photor emission computed tomography (SPECT) brain imaging,and some biochemical parameters in blood and CSF were selected to evaluate the effect of ECP for SDAT.

Alzheimer型痴呆临床量表检查与MRI边缘系统体积测量的相关研究

目的 :探讨Alzheimer型痴呆海马结构、杏仁核、侧脑室颞角等MRI体积与临床量表检查的相关性。方法 :使用Siemens 1.5T超导MRI扫描机 ,对 2 7例临床诊断Alzheimer型痴呆病人的左右侧海马结构、杏仁核、侧脑室颞角等体积进行定量测量 ,同时对病人进行临床常用量表的检查。结果 :MMSE和WMS与杏仁核、海马旁回总体积和侧脑室颞角体积有高度相关性。结论 :脑结构测量与脑功能测量有一定的相关。

多梗塞性痴呆和Alzheimer型痴呆的SPECT和MRI比较研究

对２２例多梗塞性痴呆（ＭＩＤ）、１５例Ａｌｚｈｅｉｍｅｒ型痴呆（ＤＡＴ）病人和２４例同龄、同利手健康对照组作了单光子发射计算机断层显象（ＳＰＥＣＴ）和磁共振成象（ＭＲＩ）检查（对照组仅１２例作ＭＲＩ）。结果发现ＳＰＥＣＴ在ＭＩＤ病人主要表现为多发性、局灶性脑放射性减低，两侧不对称，以额皮质、皮质下明显；ＤＡＴ病人主要表现为大脑皮质放射性对称性降低，以颞顶枕明显。ＭＲＩ在ＭＩＤ病人主要表现为顶皮质萎缩、大脑不同部位梗塞灶；ＤＡＴ病人主要表现为大脑皮质萎缩，颞顶枕为甚，半数以上病例海马萎缩。结果提示两种检查对诊断和鉴别ＭＩＤ、ＤＡＴ有一定价值。

补肾生髓益智汤联合甘露特钠胶囊治疗老年髓海不足型阿尔茨海默病痴呆临床研究

目的:观察补肾生髓益智汤联合甘露特钠胶囊治疗老年髓海不足型阿尔茨海默病痴呆的临床疗效。方法:选取124例老年髓海不足型阿尔茨海默病痴呆进行研究,按照随机数字表法分为治疗组与对照组各62例。治疗组给予补肾生髓益智汤联合甘露特钠胶囊治疗,对照组给予甘露特钠胶囊治疗。比较2组临床疗效,以及治疗前后简易精神状态量表(MMSE)、阿尔茨海默病评定量表-认知部分(ADAS-cog)、长谷川痴呆量表(HDS)、痴呆行为量表(BEHAVE-AD)评分。结果:治疗后,治疗组总有效率为90.32%,对照组为75.81%。2组比较,差异有统计学意义(P<0.05)。治疗后,2组MMSE评分均较治疗前上升(P<0.05),且治疗组MMSE评分高于对照组(P<0.05);2组ADAS-cog评分均较治疗前下降(P<0.05),且治疗组ADAS-cog评分低于对照组(P<0.05)。治疗后,2组HDS评分均较治疗前上升(P<0.05),且治疗组HDS评分高于对照组(P<0.05);2组BEHAVE-AD评分均较治疗前下降(P<0.05),且治疗组BEHAVE-AD评分低于对照组(P<0.05)。结论:补肾生髓益智汤联合甘露特钠胶囊治疗老年髓海不足型阿尔茨海默病痴呆临床疗效良好,可改善患者认知功能及痴呆症状。

Alzheimer型痴呆的失写特点

观察Ａｌｚｈｅｉｍｅｒ型痴呆（ＤＡＴ）的失写情况及其语言行为学特点，探讨其机制。方法选择轻中度ＤＡＴ患者６例，通过汉语失写检查法（ＣＡＢ）计算失写指数（ＡｇＱ），分析失写性质。结果６例患者ＡｇＱ明显高于常模；损害程度由重到轻为主动书写、看图书写、听写、自动书写、抄写；失写性质全部表现为失语性失写，均有明显有构字障碍，字词错写中以字音替代为主，仅２例能写出语句，均见语法错误。结论ＤＡＴ的构字障碍是由于按一定顺序和数量提取笔划的程序记忆损所致，而字词错写和语法错误则很可能语义记忆的缺陷有关，主要是长程记忆的问题。

正常脑老化和Alzheimer型老年性痴呆的脑改变与影像学研究进展

正常脑老化和Alzheimer型老年性痴呆的发生发展是一个复杂的过程。本文主要介绍其脑部解剖形态和组织学改变及影像学研究进展。

Alzheimer型痴呆的中医证型研究

为研究不同病情程度的Alzheimer型痴呆 (DAT)中医证型的分布规律与特征 ,将 1 3 9例DAT患者按照自拟标准 (以专项认知能力变化为主 ,结合MMSE计分及日常生活能力变化 )分为轻、中、重 3级 ,中医辨证分为心血不足、肾精虚衰等 6个主型及痰浊内蒙、瘀阻脑窍、火扰神明 3个兼型。结果表明 :DAT的病情轻重与不同中医证型直接相关 ,以一脏病变为主或多脏受累与其病情严重程度呈正相关 ,有无痰、瘀、火病邪相兼 ,既是促进病情转化的重要因素 ,亦直接影响DAT的病情严重程度。

Alzheimer型痴呆的单光子发射型计算机断层扫描脑血流量测定的研究

目的99Tcm-双半胱乙酯(99Tcm-ECD)单光子发射型计算机断层扫描(single photon emission computed tomography,SPECT)脑血流灌注显像测定Alzheimer型痴呆(dementia of Alzheimer type,DAT)患者脑血流量(CBF)的价值。方法用NINCDS-ADRDA(national institute of neurological and communicative disorders and stroke and the Alzheimer’s disease and related disorders association)推荐的DAT诊断标准对以健忘为主诉来院检查的患者进行诊断,分为可能的DAT患者组(A组)14例,很有可能的DAT患者组(B组)21例,并设置正常对照组11例,进行99Tcm-ECD SPECT脑血流灌注显像,对其平均及局部CBF进行对比分析。结果B组DAT患者平均脑血流较正常对照有明显降低,局部脑血流表现为A组病人双侧顶叶、海马回、单侧颞叶中下回、颞极血流降低区;B组患者双侧额叶、颞叶、顶叶、枕叶血流明显下降。结论99Tcm-ECD SPECT脑血流灌注显像测定CBF是一种非侵袭性、简便可靠的方法,对DAT的诊断有一定的临床价值。

Alzheimer型痴呆和多发梗塞痴呆的定量脑电地形图研究

对１２例Ａｌｚｈｅｉｍｅｒ型痴呆（ＤＡＴ）、１５例多发梗塞性痴呆（ＭＩＤ）、１５例健康对照组的脑电地形图的定量研究显示：痴呆病人慢波功率的增多不同于正常老化，θ功率是最早增高的指标；ＭＩＤ较ＤＡＴ有更多的不对称性改变；脑电功率不仅与痴呆程度有量化联系，而且和特定认知功能也有量化联系；首次发现ＤＡＴ和ＭＩＤ各有不同的脑电功率和认知功能的量化联系方式。结果表明定量脑电地形图在痴呆研究中有一定应用前景。

多梗塞痴呆和Alzheimer型痴呆认知功能与局部脑血流的关系

目的：探讨多梗塞痴呆和Ａｌｚｈｅｉｍｅｒ型痴呆患者神经心理功能与局部脑血流的关系。方法：对３３例多梗塞痴呆（ＭＩＤ）、２１例Ａｌｚｈｅｉｍｅｒ型痴呆（ＤＡＴ）病人和２４例健康对照组作了单光子发射计算机断层显像（ＳＰＥＣＴ）检查，采用相对定量法测定局部脑血流（ｒＣＢＦ）。并作神经心理学测验。结果：ＭＩＤ病人左额颞叶ｒＣＢＦ与言语智商（ＶＩＱ）相关显著；左额、右顶、丘脑ｒＣＢＦ与总智商（ＦＩＱ）明显相关；左颞、右顶叶ｒＣＢＦ与脑损伤指数（ＤＱ）相关明显。ＤＡＴ病人左颞、右额叶ｒＣＢＦ与ＶＩＱ，右顶枕叶ｒＣＢＦ与操作智商（ＰＩＱ），左额颞、右顶叶ｒＣＢＦ与ＤＱ相关明显。ＭＩＤ、ＤＡＴ病人左颞叶ｒＣＢＦ与记忆商数（ＭＱ）相关显著。结论：提示ＭＩＤ、ＤＡＴ病人智能减退与脑血流降低有关。