Share This Article:

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

Abstract Full-Text HTML Download Download as PDF (Size:4278KB) PP. 171-181
DOI: 10.4236/aad.2013.24022    3,877 Downloads   7,170 Views   Citations


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.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Maksimovich, I. (2013) Disorders of cerebrovascular angioarchitectonics and microcirculation in the etiology and pathogenesis of Alzheimer’s disease. Advances in Alzheimer's Disease, 2, 171-181. doi: 10.4236/aad.2013.24022.


[1] (2011) Cognitive impairment: A call for action, now!
[2] (2013) Alzheimer’s disease facts and figures.
[3] Torack, R.M. (1979) Adult dementia: History, biopsy, pathology. Neurosurgery, 4, 434-442.
[4] Carpenter, B. and Dave, J. (2004) Disclosing a dementia diagnosis: A review of opinion and practice, and a proposed research agenda. Geronotologist, 44, 149-158.
[5] Waldemar, G., Dubois, B., Emre, M., Georges, J., Mc-Keith, I.G., Rossor, M., Scheltens, P., Tariska, P. and Winblad, B. (2007) Recommendations for the diagnosis and management of Alzheimer’s disease and other disorders associated with dementia: EFNS guideline. European Journal of Neurology, 14, e1-e26.
[6] Jack, C.R. Bentley, M.D. Twomey C.K. and Zinsmeister, A.R. (1990) MR imaging-based volume measurements of the hippocampal formation and anterior temporal lobe: Validation studies. Radiology, 176, 205-209.
[7] Jack, C.R., Petersen, R.C., Xu, Y.C., et al. (1999) Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment. Neurology, 52, 1397-1403.
[8] Pietrini, P., Alexander, G.E., Furey, M.L., et al. (2000) Cerebral metabolic response to passive audiovisual stimulation in patients with Alzheimer’s disease and healthy volunteers assessed by PET. Journal of Nuclear Medicine, 41, 575-583.
[9] Burton, E.J., Barber, R., Mukaetova-Ladinska, E.B., Robson, J., Perry, R.H., Jaros, E., Kalaria, R.N. and O’Brien, T.J. (2009) Medial temporal lobe atrophy on MRI differentiates Alzheimer’s disease from dementia with Lewy bodies and vascular cognitive impairment: A prospective study with pathological verification of diagnosis. Brain, 132, 195-203.
[10] Trojanowski, J.Q., Vandeerstichele, H., Korecka, M., et al. (2010) Update on the biomarker core of the Alzheimer’s disease neuroimaging initiative subjects. Alzheimer’s & Dementia, 6, 230-238.
[11] Perrin, R.J., Craig-Schapiro, R., Morris, J.C., et al. (2011) Identification and validation of novelcerebrospinal fluid biomarkers for staging early Alzheimer’s disease. Public Library of Science One, 12, Article ID: e16032.
[12] Adriaase, A., Sanz-Arigita, E., Binnewijzend, M., et al. (2011) Molecular markers of Alzheimer’s disease pathology and their relationship with default mode network integrity. Alzheimer’s & Dementia, 7, S2-S3.
[13] Meyer, P.T., Hellwig, S., Amtage, F., et al. (2011) Dual- biomarker imaging of regional cerebral amyloid load and neuronal activity in dementia with PET and 11C-labeled Pittsburgh compound B. Journal of Nuclear Medicine, 52, 393-400.
[14] Morel, F. (1950) An apparently dyshoric and topical angiopathy. Monatsschrift für Psychiatrie und Neurologie, 120, 352-357.
[15] Di Carlo, A., Baldereschi, M., Amaducci, L., et al. (2002) Incidence of dementia, Alzheimer’s disease, and vascular dementia in Italy. The ILSA study. Journal of the American Geriatrics Society, 50, 41-48.
[16] De la Torre, J.C. (1997) Hemodynamic consequences of deformed microvessels in the brain in Alzheimer’s disease. Annals of New York Academy Sciences, 26, 75-91.
[17] Skoog, I., Kalaria, R.N. and Breteler, M.M. (1999) Vascular factors and Alzheimer disease. Alzheimer Disease and Associated Disorders, 13, 106-114.
[18] De la Torre, J.C. and Stefano, G.B. (2000) Evidence that Alzheimer’s disease is a microvascular disorder: The role of constitutive nitric oxide. Brain Research Reviews, 34, 119-136.;jsessionid=gQgXaQg9i1yxSODYLdkV.0
[19] Kalaria, R.N. (2000) Vascular factors in Alzheimer’s disease. New York Academy of Sciences, New York.
[20] Maksimovich, I.V. and Gotman, L.N. (2006) Method of complex radiation diagnostics at preclinical and clinical stages of Alzheimer’s disease. Russian Patent No. 2315559.
[21] Maksimovich, I.V. (2008) Radiodiagnostics of Alzheimer’s disease. Diagnostics and Intervention Radiology, 2, 27-38.
[22] Di Iorio, A., Zito, M., Lupinetti, M. and Abate, G. (1999) Are vascular factors involved in Alzheimer’s disease? Facts and theories. Aging, 11, 345-352.
[23] Kalaria, R.N. (2002) Small vessel disease and Alzheimer’s dementia: Pathological considerations. Cerebrovascular Diseases, 13, 48-52.
[24] Maksimovich, I.V., Gotman, L.N. and Masyuk, S.M. (2004) Transluminal laser angioplastics for treatment of microcirculatory abnormalities in Alzheimer’s disease. Angiology and Vascular Surgery, 10, 89-90.
[25] Mielke, M.M., Rosenberg, P.B., Tschanz, J.L. Cook, L., et al. (2007) Vascular factors predict rate of progression in Alzheimer disease. Neurology, 6, 1850-1858.
[26] Dorr, A., Sahota, B., Chinta, L.V., Brown, M.E., Lai, A.Y., Ma, K., Hawkes, C.A., Mc Laurin, J. and Stefanovic, B. (2012) Amyloid-β-dependent compromise of microvascular structure and function in a model of Alzheimer’s disease. Brain. 135, 3039-3050.
[27] Chen, W., Song, X., Beyea, S., D’Arcy, R., Zhan, Y. and Rockwood, K. (2011) Advances in perfusion magnetic resonance imaging in Alzheimer’s disease. Alzheimer’s & Dementia, 7, 185-186.
[28] Grammas, P., Sanchez, A., Tripathy, D., Luo, E. and Martinez, J. (2011) Vascular signaling abnormalities in Alzheimer disease. Cleveland Clinic Journal of Medicine, 78, 50-53.
[29] Kalaria, R.N. (2003) Vascular factors in Alzheimer’s disease. International Psychogeriatrics, 15, 47-52.
[30] Maksimovich, I.V. (2009) Changes in angioarchetectonics of brain at Alzheimer’s disease. The Neurologic Bullet, XLI, 9-14.
[31] Altman, R. and Rutledge, J.C. (2010) The vascular contribution to Alzheimer’s disease. Clinical Science, 119, 407-421.
[32] Maksimovich, I.V. (2012) Vascular factors in Alzheimer’s disease. Health, 4, 735-742.
[33] Kalaria, R.N., Akinyemi, R. and Ihara, M. (2012) Does vascular pathology contribute to Alzheimer changes? Journal of the Neurological Sciences, 322, 141-147.
[34] Cameron, D.J., Galvin, C., Alkam, T., Sidhu, H., Ellison, J., Luna, S. and Ethell, D.W. (2012) Alzheimer’s related peptide amyloid-β plays a conserved role in angiogenesis. PLoS One, 7, Article ID: e39598.’s-Rlated%20Peptide%20Amyloid%CE%B2%20Plays%20a%20Conserved%20Role%20in%20Angiogenesis
[35] De la Torre, J.C. (2012) A turning point for Alzheimer’s disease? Biofactors, 38, 78-83.’s%20disease%3F
[36] Otergaard, L., Aamand, R., Gutiérrez-Jiménez, E., Ho, Y.C., Blicher, J.U., Madsen, S.M., Nagenthiraja, K., Dalby, R.B., Drasbek, K.R., Moller, A., Breandgaard, H., Mouridsen, K., Jespersen, S.N., Jensen, M.S. and West, M.J. (2013) The capillary dysfunction hypothesis of Alzheimer’s disease. Neurobiology of Aging, 34, 1018-1031.
[37] Albert, M.S., DeKosky, S.T., Dickson, D., et al. (2011) The diagnosis of mild cognitive impairment due to Alzheimer’s disease: Recommendations from the National Institute on Aging—Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & Dementia, 7, 270-279.
[38] Jack, C.R., Albert, M.S., Knopman, D.S., McKhann, G.M., Sperling, R.A., Carrillo, M.C., Thies, B. and Phelps, C.H. (2011) Introduction to the recommendations from the National Institute on Aging—Alzheimer’s Association work-groups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & Dementia, 7, 257-262.
[39] Higuchi, Y., Miyakawa, T., Shimoji, A. and Katsugari, S. (1987) Ultrastructural changes of blood vessels in the cerebral cortex in Alzheimer’s disease. The Japanese Journal of Psychiatry Neurology, 41, 283-290.
[40] Baloyannis, S.J. (2009) Dendritic pathology in Alzheimer’s disease. Journal of the Neurological Sciences, 283, 153-157.
[41] Deane, R., Bell, R.D., Sagare, A. and Zlokovic, B.V. (2009) Clearance of amyloid-beta peptide across the blood-brain barrier: Implication for therapies in Alzheimer’s disease. CNS & Neurological Disorders Drug Targets, 8, 16-30.
[42] Maksimovich, I.V. (2010) Dyscirculatory angiopathy of the brain of Alzheimer’s type. Alzheimer’s & Dementia, 6, e34.
[43] Nishimura, T., Hashikawa, K., Fukuyama, H., Kubota, T., Kitamura, S., Matsuda, H., Hanyu, H., Nabatame, H., Oku, N., Tanabe, H., Kuwabara, Y., Jinnouchi, S. and Kubol, A. (2007) Decreased cerebral blood flow and prognosis of Alzheimer’s disease: A multicenter HMPAO-SPECT study. Annals of Nuclear Medicine, 21, 15-23.
[44] Folstein, M.F., Folstein, S.E. and McHugh, P.R. (1975) “Mini-Mental state”. A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189-198.
[45] Morris, J.C. (1993) The Clinical Dementia Rating (CDR): Current version and scoring rules. Neurology, 43, 2412- 2414.
[46] Maksimovich, I.V. (2012) The tomography dementia rating scale: Morphologically determined scale of Alzheimer’s disease stages. Alzheimer’s & Dementia: The Jour- nal of the Alzheimer’s Association, 8, P335-P336.
[47] Maksimovich, I.V. (2012) The tomography dementia rating scale (TDR)—The rating scale of Alzheimer’s disease stages. Health, 4, 712-719.
[48] Maksimovich, I.V. (2012) Morphologically determined scale of Alzheimer’s disease stages—The tomography dementia rating scale (TDR). Diagnostics and Intervention Radiology, 6, 23-32.
[49] Maksimovich, I.V. (2013) A morphologically based scale of Alzheimer’s disease stages “the tomography dementia rating scale” (TDR). European Psychiatry, 28, 1.
[50] Maksimovich, I.V. (2011) Dyscirculatory angiopathy of Alzheimer’s type. Journal of Behavioral and Brain Science, 1, 57-68.
[51] Baloiannis, S.J. and Baloiannis, I.S. (2012) The vascular factor in Alzheimer’s disease: A study in Golgi technique and electron microscopy. Journal of the Neurological Sciences, 322, 117-121.
[52] Kuleshov, E.V. and Maksimovich, I.V. (1994) Endovascular surgery in patients over 65 with disseminated atherosclerosis of the vessels of the pelvis and lower extremities. Vestnik Khirurgii Imeni I. I. Grekova, 152, 27-30.
[53] Bell, R.D. and Zlokovic, B.V. (2009) Neurovascular mechanisms and blood-brain barrier disorder in Alzheimer’s disease. Acta Neuropathologica, 118, 103-113.
[54] Zlokovic, B.V. (2011) Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nature Reviews. Neuroscience, 12, 723-738.
[55] Maksimovich, I.V. and Polyaev, Y.A. (2010) The importance of early diagnosis of dyscircular angiopathy of Alzheimer’s type in the study of heredity of Alzheimer’s disease. Alzheimer’s & Dementia, 6, e43.
[56] Maksimovich, I.V. (2012) Certain new aspects of etiology and pathogenesis of Alzheimer’s disease. Advances in Alzheimer’s Disease, 1, 68-76.
[57] Chételat, G., Villemagne, V.L., Pike K.E., Ellis, K.A., Ames, D., Masters, C.L. and Rowe, C.C. (2012) Relationship between memory performance and β-amyloid deposition at different stages of Alzheimer’s disease. Neurodegenerative Diseases, 10, 141-144.
[58] Provenzano, F.A., Muraskin, J., Tosto, G., Narkhede, A., Wasserman, B.T., Griffith, E.Y., Guzman, V.A., Meier, I.B., Zimmerman, M.E. and Brick-man, A.M. (2013) White matter hyperintensities and cerebral amyloidosis: Necessary and sufficient for clinical expression of Alzheimer disease? JAMA Neurology, 70, 455-461.
[59] Nishimura, T., Hashikawa, K., Fukuyama, H., Kubota, T., Kitamura, S., Matsuda, H., Hanyu, H., Nabatame, H., Oku, N., Tanabe, H., Kuwabara, Y., Jinnouchi, S. and Kubol, A. (2007) Decreased cerebral blood flow and prognosis of Alzheimer’s disease: A multicenter HMPAO-SPECT study. Annals of Nuclear Medicine, 21, 15-23.
[60] Knickmeyer RC, Wang J, Zhu H, Geng X, Woolson S, Hamer RM, Konneker T, Lin W, Styner M, Gilmore JH. (2013) Common variants in psychiatric risk genes predict brain structure at birth. Cerebral Cortex, 1, 2.

comments powered by Disqus

Copyright © 2019 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.