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

Advances in Alzheimer's Disease 2012年第3期1卷 68-76页

作者： ivan v. Maksimovich Clinic of Cardiovascular Diseases Named after Most Holy John Tobolsky Moscow Russia

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.

关键词： Alzheimer's Disease CDR TDR Dementia vascular Factors in Alzheimer’s Disease Dyscirculatory Angiopathy of Alzheimer’s Type DAAT Hippocampus Temporal Lobes Atrophy

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vascular factors in Alzheimer’s disease

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Health 2012年第9期4卷 735-742页

作者： ivan v. Maksimovich Clinic of Cardiovascular Diseases Named after Most Holy John Tobolsky Moscow Russia

The vascular factor in Alzheimer’s disease (AD), affecting its development and progression, is one of the most urgent problems of modern neuroangiology. The research investigates the characteristics of cerebral angioarchitectonics identified at different stages of AD. The research included 106 patients: 1) The Test Group—47 patients suffering from various stages of AD;2) The Control Group—59 patients suffering from the most common lesions of the brain accompanied by neurodegenerative changes, the development of dementia and cognitive impairment, but not having AD. All the patients underwent: the testing of cognitive functions (MMSE), the determination of severity of dementia (CDR) and AD stages (TDR), computed tomography (CT), magnetic resonance imaging (MRI), scintigraphy of the brain (SG), rheoencephalography (REG), and cerebral multigated angiography (MUGA). Patients with AD different stages showed the following changes in angioarchitectonics and microcirculation: Absence of pronounced atherosclerotic lesions of intracranial vessels, reduction of the capillary bed in the temporal and temporo-parietal regions, development of multiple arteriovenous shunts in the same areas, early venous discharge, abnormal expansion of venous trunks that receive blood from arteriovenous shunts, venous congestion at the border of the frontal and parietal region, increased looping of intracranial arteries. Control Group patients had no combination of the abovementioned changes. These vascular changes are specific for AD and are in fact the vascular factor of this disease;they may also be called dyscirculatory angiopathy of Alzheimer’s type (DAAT). Patients suffering from other diseases that are accompanied by neurodegenerative changes in the brain, dementia and cognitive impairment do not have them.

关键词： Alzheimer’s Disease CDR TDR Dementia vascular Factors in Alzheimer’s Disease Dyscirculatory Angiopathy of Alzheimer’s Type DAAT

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

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Journal of Behavioral and Brain Science 2012年第1期2卷 67-81页

作者： ivan v. Maksimovich Clinic of Cardiovascular Diseases Named after Most Holy John Tobolsky Moscow Russia

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 whi

关键词： Alzheimer’s Disease Dementia Dyscirculatory Angiopathy of Alzheimer’s Type DAAT Hippocampus Temporal Lobes Atrophy Hypovascular Zone Laser Revascularization Brain Tissue Regeneration

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Dyscirculatory Angiopathy of Alzheimer's Type

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Journal of Behavioral and Brain Science 2011年第2期1卷 57-68页

作者： ivan v. Maksimovich 不详

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, time

关键词： Alzheimer’s Disease Dementia Hippocampus Temporal Lobes Atrophy Dyscirculatory Angiopathy of Alzheimer’s Type

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The tomography dementia rating scale (TDR)—The rating scale of Alzheimer’s disease stages

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Health 2012年第9期4卷 712-719页

作者： ivan v. Maksimovich Clinic of Cardiovascular Diseases Named after Most Holy John Tobolsky Moscow Russia

The purpose of this research is to develop a morphologically determined scale—the Tomography Dementia Rating scale (TDR) to diagnose AD stages, based on the measurement of the severity of voluminal atrophic changes of the temporal lobes of the brain detected among patients during CT and MRI at various stages of the disease. The research included 140 patients aged 28 - 79. Test Group comprised 81 patients aged 34 - 79 suffering from various AD stages. Control Group consisted of 59 patients aged 28 - 78 who had various types of brain lesions with manifestations of dementia and cognitive impairment but who did not suffer from AD. CT and MRI data obtained has made it possible to create a scale that allows determining the severity of atrophic changes in the temporal lobes at each stage of AD development: 1) Pre-clinical AD stage—TDR-0: temporal lobes atrophy with a 4% - 8% decrease in tissue mass (corresponds to 26 - 28 MMSE points);2) Early AD Stage—mild dementia—TDR-1: temporal lobes atrophy with a 9% - 18% decrease in tissue mass (corresponds to CDR-1 and to 20 - 25 MMSE points);3) Middle AD stage—moderate dementia—TDR-2: temporal lobes atrophy with a 19% - 32% decrease in tissue mass (corresponds to CDR-2 and to 12 - 19 MMSE points);4) Late AD stage—heavy dementia—TDR-3: temporal lobes atrophy with a 33% - 62% decrease in tissue mass (corresponds to CDR-3 and to 7 - 11 MMSE points). Thereby, the developed Tomography Dementia Rating scale (TDR) complements the Clinical Dementia Rating scale (CDR) and allows a correct and objective determination of AD stages as well as an easy differentiation of existing lesions with neurodegenerative changes characteristic for other diseases accompanied by dementia and cognitive impairment.

关键词： Alzheimer's Disease AD Stage TDR CDR Dementia Hippocampus Atrophy of the Temporal Lobes of the Brain

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

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World Journal of Neuroscience 2015年第3期5卷 189-203页

作者： ivan v. Maksimovich Clinic of Cardiovascular Diseases Named after Most Holy John Tobolsky Moscow Russia

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 ai

关键词： Alzheimer’s Disease Dementia vascular Dysfunction Dyscirculatory Angiopathy of Alzheimer’s Type DAAT TDR Temporal Lobes Atrophy Laser Revascularization

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

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Advances in Alzheimer's Disease 2013年第4期2卷 171-181页

作者： ivan v. Maksimovich Clinic of Cardiovascular Diseases Named after Most Holy John Tobolsky Moscow Russia

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.

关键词： Alzheimer’s Disease Dementia TDR Microcirculation Microcirculatory Disorders Dyscirculatory Angiopathy of Alzheimer’s Type DAAT

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Transcatheter Technologies in Treating Brain Atherosclerosis Complicated by Chronic Cerebrovascular Insufficiency

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Neuroscience & Medicine 2014年第4期5卷 161-176页

作者： ivan v. Maksimovich Clinic of Cardiovascular Diseases Named after Most Holy John Tobolsky Moscow Russia

The research investigates the possibility of restoring the blood supply in patients with atherosclerosis of the brain, as well as the treatment of chronic cerebrovascular insufficiency. The research involves 946 patients aged 29 - 81 (average age 74) suffering from various types of cerebral atherosclerosis. 568 (60.04%) patients underwent transcatheter treatment—Test Group. 378 (39.96%) patients underwent conservative treatment—Control Group. The examination plan included laboratory diagnostics, assessment of dementia severity (CDR), assessment of cognitive impairment (MMSE), evaluation of the activities of daily living (IB), cerebral computed tomography (CT), cerebral magnetic resonance imaging (MRI), cerebral scintigraphy (SG), rheoencephalography (REG), cerebral multi-gated angiography (MUGA). To restore the blood supply, the method of transcatheter laser revascularization was applied;high-energy pulsed lasers were used for major intracranial arteries treatment, and low energy CW lasers—for distal intracranial branches treatment. Test Group: 459 (80.81%) patients had good clinical outcome, 91 (16.02%)—satisfactory clinical outcome, 18 (3.17%)—relatively satisfactory clinical outcome;relatively positive clinical outcome was not obtained in any case. Control Group: good clinical outcome was not obtained in any case;65 (17.20%) patients had satisfactory clinical outcome, 121 (23.26%)—relatively satisfactory clinical outcome, 192 (50.79%)—relatively positive clinical outcome. The method of transcatheter laser revascularization of cerebral vessels is a physiological, effective and low-invasive treatment for patients suffering from atherosclerosis of the brain. The obtained results last up to 10 years and more;it causes regression of mental and motor disorders, promotes regression of dementia and largely improves the patients’ quality of life;it has virtually no alternative—which makes the proposed method significantly different from conservative treatment methods.

关键词： Cerebrovascular Disease Cerebrovascular Insufficiency Cognitive Impairment Transcatheter Laser Revascularization Regeneration Ischemic Stroke

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Mortality of Amur tigers:The more things change,the more they stay the same

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Integrative Zoology 2015年第4期10卷 344-353页

作者： Hugh S.ROBINSON John M.GOODRICH Dale G.MIQUELLE Clayton S.MILLER ivan v.SERYODKIN Panthera New YorkNew YorkUSA Wildlife Conservation Society BronxNew YorkUSA Wildlife Biology Program College of Forestry and ConservationUniversity of MontanaMissoulaMontanaUSA Pacific Geographical Institute Far Eastern Branch of the Russian Academy of SciencesVladivostokRussia Far Eastern Federal University VladivostokRussia

Poaching as well as loss of habitat and prey are identified as causes of tiger population *** some studies have examined habitat requirements and prey availability,few studies have quantified cause-specific mortality of *** used cumulative incidence functions(CIFs)to quantify cause-specific mortality rates of tigers,expanding and refining earlier studies to assess the potential impact of a newly emerging *** quantify changes in tiger mortality over time,we re-examined data first collected by Goodrich et al.(2008;study period 1:1992–2004)as well as new telemetry data collected since January 2005(study period 2:2005–2012)using a total of 57 tigers(27 males and 30 females)monitored for an average of 747 days(range 26–4718 days).Across the entire study period(1992 to 2012)we found an estimated average annual survival rate of 0.75 for all tigers *** was the primary cause of mortality during both study periods,followed by suspected poaching,distemper and natural/unknown *** 2005,poaching mortality has remained relatively constant and,if combined with suspected poaching,may account for a loss of 17–19%of the population each *** distemper virus(CDv)may be an additive form of mortality to the population,currently accounting for an additional 5%.Despite this relatively new source of mortality,poaching remains the main threat to Amur tiger survival and,therefore,population growth.

关键词： canine distemper virus cause-specific mortality cumulative incidence function Panthera tigris altaica poaching

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The Use of Transcatheter Laser Exposure in the Treatment of Cerebral vessels Hypoplasia Accompanied by Migraine

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Journal of Behavioral and Brain Science 2014年第10期4卷 443-452页

作者： ivan v. Maksimovich Clinic of Cardiovascular Diseases Named after Most Holy John Tobolsky Moscow Russia

The research is dedicated to the possibility of restoring cerebral blood supply in patients with brain vessels hypoplasia accompanied by migraine. The research involved 67 patients aged 29 - 58 (average age 42) with severe migraine. The examination plan included laboratory diagnostics, assessment of dementia severity (CDR), assessment of cognitive impairment (MMSE), cerebral computed tomography (CT), cerebral magnetic resonance imaging (MRI), cerebral scintigraphy (SG), rheoencephalography (REG), cerebral multi-gated angiography (MUGA). Hypoplasia symptoms were detected in 56 (83.58%) patients. To improve cerebral blood supply, the method of transcateter laser revascularization by means of low-energy CW lasers was used. Good immediate angiographic outcome manifested in persistent improvement of the intracranial vascular bed and marked collateral vascularization was obtained in 53 (94.64%) patients. Good clinical outcome— almost complete regression of migraine and vestibular disorders—was obtained in 49 (87.50%) patients. Satisfactory clinical outcome—partial regression of migraine and vestibular disorders— was observed in 7 (12.50%) patients. The method of transcatheter laser revascularization of cerebral vessels is a physiological, effective and low-invasive treatment for patients suffering from cerebral vessels hypoplasia accompanied by migraine. This method has virtually no alternative;it stimulates natural angiogenesis causing collateral and capillary vascularization steadily improving the blood supply of the brain. The effect obtained after the treatment persists for a long time (9 years and longer), it causes regression of migraine, reduces mental disorders, and can improve the patients’ quality of life.

关键词： Headache Migraine Hypoplasia of Cerebral vessels Cerebrovascular Lesions Angiogenesis Transcatheter Laser Revascularization

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