PATHOLOGY OF CEREBROVASCULAR ANGIOARCHITECTONICS AND MICROCIRCULATION IN ETIOLOGY AND PATHOGENESIS OF ALZHEIMER'S DISEASE

Abstract

There have recently appeared many reports dedicated to cerebral hemodynamics disorders during AD progression. However, certain aspects of cerebral blood flow and microcirculation during AD are not fully understood. This research focuses on the identification of cerebral angioarchitectonics features and the study of microcirculatory disorders arising during AD progression, 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 accompanied by manifestations of dementia and cognitive impairment of varying severity 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 multi-gated angiography (MUGA). All Test Group patients, with both pre-clinical and clinical AD stages, had disorders of cerebral microcirculation manifested in dyscirculatory angiopathy of Alzheimer's type (DAAT), namely: capillary bed reduction in the hippocampus and frontal-parietal regions; multiple arteriovenous shunts in the basin of arterial branches supplying the hippocampus and fronto-parietal brain regions; early venous dumping of arterial blood through these shunts with simultaneous filling of arteries and veins; abnormally enhanced lateral venous trunks receiving blood from the arterio-venous shunts; anomalous venous congestion at the border of frontal and parietal lobe caused by the increased blood inflow from the arterial-venous shunts; increased looping of distal intracranial arterial branches. Control group patients had no combinations of such changes in angioarchitectonics and microcirculation. The primary basis for these changes is cerebral microcirculation disorders manifested in capillary bed reduction and decreased blood flow to cerebral tissues. The process is accompanied by natural arteriovenous shunts leading to arterial blood dumping to the venous bed followed by temporal and fronto-parietal lateral veins enlargement and subsequent blood congestion. Finally, long-term chronic hypoperfusion of these areas follows causing specific cerebral tissue hypoxia and ischemia. These changes may then affect amyloid beta metabolism and facilitate its accumulation in brain tissue stimulating AD progression. Patient Sh., 68 years old. Angiogram of the right internal carotid artery; TDR-3; lateral projection, arterial phase; Absence of atherosclerotic changes of intracranial vessels. 1: Development of hypovascular region; 2: Multiple arteriovenous shunts in fronto-parietal and temporal regions Patient O., 72 years old. Angiogram of the left internal carotid artery; TDR-2; lateral projection, capillary phase; Absence of atherosclerotic changes of intracranial vessels. 1: Development of hypovascular area; 2: Multiple arteriovenous shunts in fronto-parietal and temporal regions; 3: The development of early venous discharge in the temporal and fronto- parietal region. Simul-taneous filling of arteries and veins. Patient P., 75 years old. Angiogram of the right internal carotid artery; TDR-3; lateral projection, venous phase; 4: The development of pathologically enlarged veins that receive blood from arteriovenous shunts in the temporal and fronto-parietal region; 5: Blood congestion on the border of the fronto-parietal region. Patient P., 75 years old. Angiogram of the right internal carotid artery; TDR-3; lateral projection, early arterial phase; Absence of atherosclerotic changes of intracranial vessels. 1: Development of hypovascular area; 6: Multiple loop formation.