Cerebral ischemic and neurodegenerative diseases are increasingly observed among the population of different countries [1]. The most common of them are atherosclero sclerosis of the brain, Alzheimer’s disease (AD), Binswanger’s disease (BD), and Parkinsonism. All these diseases lead to the progression of dementia and cognitive disorders and are also accompanied by the development of cerebral small vessel disease (CSVD) [2] [3] [4]. This condition is caused by the peculiarity of the microcirculation in the brain, since there are about 3 - 4 thousand capillaries in one cubic centimeter of the cerebral tissue. With such a high demand for blood supply, disorders in hemoperfusion and hemodynamics cause or contribute to the development of neurodegenerative processes [5].

In the early stages, clinical pictures of these diseases have much in common.

AD is one the leading neurodegenerative diseases nowadays. Currently, there are over 36 million people suffering from AD [1] [4]. In the USA, this disease affects more than 5 million people, while 5% of them acquire AD at a fairly young age [1].

AD begins to develop in secret, years or even decades before the primary manifestations of the disease [6]. The preclinical stage of AD, in which the patient does not make any classical complaints, is difficult to detect [1]. Since this disease is often hereditary, it is necessary to examine AD patients’ relatives and descendants for the detection of its preclinical stage [1]. It shows that the true number of patients suffering from AD can be much greater [1] [6].

AD is accompanied by the development of involutive changes in the hippocampus and temporal cerebral lobes, but the etiology and pathogenesis of this disease have not been fully studied [7]. In recent years, the use of CT, MRI, PET, the introduction of biomarkers, and research on biological models have made it possible to achieve serious results in the study of structural and morphological changes taking place in the brain tissue during this disease, as well as to achieve success in understanding the distribution of amyloid beta and tau [6] [8] - [14]. However, the dependence of cerebral involutive changes and the disorders in cerebral angioarchitectonics and microcirculation is not completely clear [15] [16] [17] [18] [19].

Cerebral small vessel disease (CSVD) and cerebral hypoperfusion are important in the development of AD [3] [17] [19] - [24]. These processes are specific and connected with disorders in capillary blood supply [17] [19] [20] [21]. Patients undergo a change in the distal arterial and capillary bed, which leads to damaging the neurovascular unit (NVU) in the form of reduction in the number of microvessels and damaging tissue elements [17] [18] [22].

These changes lead to neuronal degeneration, a decrease in the clearance and an increase in the accumulation of amyloid causing further neurovascular dysfunction and neurodegeneration [18] [21] [25] [26] [27]. Beta amyloid deposits in the cerebral tissue and especially in the vascular wall reduce the elasticity of microvessels and cause the narrowing of their lumen reducing in a higher degree the cerebral blood flow, which in its turn causes more active amyloid deposition and accelerates AD development [28].

There is no complete clinical picture of all CSVD components involved in the development of AD. Besides, it is not fully clear how exactly cerebrovascular dysfunction affects neurodegenerative processes and the development of atrophic changes in the brain. Moreover, there is a question of when these changes appear before the primary clinical manifestations of AD [20] [29].

The present research is devoted to clinical identification of changes in cerebral angioarchitectonics and microcirculation in AD, to determining the relationship of these changes with cerebral involutive changes, and to comparing these changes with vascular and involutive changes that occur in other neurodegenerative and ischemic cerebral diseases.

Consequently, the research includes patients suffering from various cerebral neurodegenerative and ischemic lesions: Alzheimer’s disease (AD), various types of cerebral atherosclerosis, Binswanger’s disease (BD) and vascular Parkinsonism (VP), who have been under examination in our clinic for the recent 15 years.

Research aimed at studying vascular and microcirculatory disorders in AD has been basically conducted using post-mortem autopsies [20] [21] or genetically modified mice having an experimental AD-model [4] [18] [25]. The research described here was carried out in clinical settings.

The patients of the test and control groups are comparable by the severity of dementia according to CDR, the level of cognitive impairment according to MMSE and the severity of the general condition. However, vascular and microcirculatory disorders, as well as atrophic cerebral changes in these groups are of a completely different character.

The data obtained in this research show that intracerebral vascular and microcirculatory changes in AD have a pronounced specificity in Test Group patients and, therefore, these changes are called the dyscirculatory angiopathy of Alzheimer’s type (DAAT). The combination of these changes is an important factor in the development and diagnosis of the disease.

Test Group patients, regardless of their age, practically do not have atherosclerotic changes in intracerebral vessels, and they do not feature stenotic and occlusive lesions of arteries, arterioles and capillaries.

All 93 (100%) Test Group patients showed a decrease in the number of microvessels and depletion of the capillary bed, which leads to the development of hypovascular zones in the temporal and fronto-parietal areas.

The blood flowing through larger arterial branches cannot get through reduced arterioles and capillaries, which leads to arteriovenous shunts in the corresponding cerebral regions making hypoxia worse.

Arteriovenous shunts are a natural defensive reaction of the organism against the failure of distal blood to flow smoothly through the capillary bed [5] [17] [19]. Due to these shunts, arterial blood is dumped into the venous bed.

A large flow of blood from these arteriovenous shunts leads to the development of large venous trunks that dump blood into the venous sinus, which in turn causes blood stagnation at the level of the fronto-parietal area.

As AD develops, cerebral angiogenesis declines; acquired cerebral vascular changes lead to increased curving of distal arteries and capillaries [17] [19] [34].

Our findings also explain the results of research of many authors who study microcirculatory changes in AD on the materials of post mortem autopsy and experimental animals and show that the number of capillaries in the tissue of the hippocampus and the limbic system decreases [3] [4] [18] [20]. Besides, our data confirm the studies which point to the thinning of the capillaries, the reduction of their further branching [21] [27] [34] [35] [36], the reduction of the distal arterial influx and the development of cerebral hypoperfusion and hypoxia [35] [37] - [43].

DAAT begins to develop decades before possible AD development and is probably of a congenital nature [17] [36]. The signs of these changes are detected in the childhood and at the pre-clinical stage of the disease (TDR-0) of Test Group patients. It is obvious that DAAT features at a young age are not a guarantee of AD development, but it is a predictor of the possible development of this disease. The organism may compensate these disorders for a long time, which prevents AD development. At a certain stage compensatory abilities of the organism lessen, progressive disorders in amyloid metabolism occur in cerebral tissues and the vessel wall, and as a result, the process transfers into an active development stage of the disease. The process develops along with age [41] [44] [45].

As it has been noted in many works, these microvascular disorders cause neurovascular dysfunction [22] [38] [43], metabolic disorders [34] [35], and the development of hypoxia and hypometabolism in the cerebral tissue [39] [41]. Simultaneously, there occurs degeneration and neuronal death, synaptic loss, loss of mitochondria in the cells of the smooth endoplasmic reticulum and Golgi apparatus and general neurodegeneration [21] [22] [34] [41] [42]. In turn, the reduction of capillary blood inflow and venous outflow disorders lead to a decrease in the process of amyloid beta elimination and to an increase in its accumulation in cerebral tissues and vessel walls [4] [18] [25]. The combination of these processes further violates cerebral microcirculation and leads to aggravation of the patient’s condition [3] [28] [43]. This process, in turn, is accompanied by a dysfunction of the blood-brain barrier (BBB) [25] [45] [46].

The more pronounced these disorders are, the more likely the development and progression of AD are [19] [27] [32] [34] [35] [42] [47].

Initial cerebral involutive and hypotrophic changes manifested in a 4% - 8% decrease in temporal lobes tissue mass, were found in Test Group patients with preclinical AD stage (TDR-0). The data obtained indicate long stability of this condition that does not lead to the development of dementia and cognitive disorders. Further progression of atrophic changes in the temporal lobes promotes dementia and cognitive impairment and leads to the worsening of the patients’ condition and AD development. Thus, the early AD stage (TDR-1) features a 9% - 18% decrease of the temporal lobes tissue mass, middle AD stage (TDR-2)―19% - 32%, and late AD stage (TDR-3)―33% - 62%. At the same time, general atrophic changes in the brain develop in the late stages of the disease.

Control Group patients with such nosologies as atherosclerotic lesions, Binswanger’s disease, and vascular Parkinsonism show no AD-specific changes in the cerebral vascular system and CSVD, as well as no specific cerebral atrophic changes similar to those of Test Group patients.

Control Group patients showed disseminated atherosclerotic changes accompanied by stenotic and occlusive lesions of intracerebral arteries and capillaries. This process is accompanied by the formation of disseminated arteriovenous shunts in the corresponding cerebral regions, as well as by the development of local zones of ischemia and gliosis in the cerebral tissue. In these patients, arteriovenous discharge of blood is less pronounced than in AD.

Thus, with cerebral atherosclerosis, stenotic and occlusive lesions develop in the arteries and capillaries at the level of both gray and white matter of the brain, which is accompanied by the opening of small arteriovenous shunts in the same areas. However, the opening of these arteriovenous shunts does not usually lead to the development of large venous trunks or to a marked discharge of blood into the venous bed. At the same time, the hypotrophic and atrophic changes in the cerebral tissue are correspondingly widespread, which is confirmed by the results of studies by many authors [5] [48] [49].

Patients with BD feature the disseminated lesions of the distal subcortical arterioles and capillaries at the white matter level of the brain. The opening arteriovenous shunts are usually small in size, and also have a disseminated character. Obviously, the volume of blood discharged through them is not large, which does not lead to the development of large venous trunks and overflow of venous sinuses. Involutive and atrophic changes in the cerebral tissue also have a disseminated subcartical character. The data obtained by us are confirmed by studies carried out earlier [50] [51] [52] [53].

Patients with VP have a similar pattern, the difference being that arterioles and capillaries are affected in the thalamus, basal ganglia and bridge. Small arteriovenous shunts have a corresponding localization. Involutive changes are usually less pronounced and of limited character [34].

Involutive and hypotrophic changes in the brain in Control Group patients develop according to the ischemic, often disseminated type; they differ from the involutive changes occurring in Test Group patients with AD and are usually associated with the zones of cerebral ischemia.

Cerebral vascular and microcirculatory disorders in AD represent dyscirculatory angiopathy of Alzheimer’s type (DAAT). These specific changes lead to the development of hypoxia, cause intercellular disorders, contribute to disorders in the metabolism of amyloid beta and to involutive changes in the temporal regions. The combination of these changes is a distinctive feature of AD in comparison with other ischemic and neurodegenerative diseases.

Vascular and microcirculatory changes in Control Group patients are of different genesis and do not lead to the development of DAAT. These changes are different, and often atherosclerotic, and lead to the development of other cerebral ischemic and neurodegenerative lesions.

The authors received no financial support for the research, authorship, and/or publication of this article.

The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Maksimovich, I.V. (2018) Differences in Cerebral Angioarchitectonics in Alzheimer’s Disease in Comparison with other Neurodegenerative and Ischemic Lesions. World Journal of Neuroscience, 8, 454-469. https://doi.org/10.4236/wjns.2018.84036