Abstract

The research is devoted to the clinical study of disorders in cerebral blood flow and microcirculatior in the development of Alzhelmer's disease in comparison with other neurodegenerative and ischemic diseases.

Materials and methods: 1117 patients with various types and stages of neurodegenerative ancischemic diseases were examined. 93 (8.33%) of them had various stages of Alzhelmer's disease - Test Group. Other 1024 (91.67%) had different types and stages of other cerebral neurodegenerative and ischemic lesions - Control Group. Control Group patients were divided: 23 (2.25%) suffered from Binswanger disease; 55 (5.37%) suffered from vascular Parkinsonism; 27 (2.64%) had initial signs of chronic cerebrovascular insufficiency of atherosclerotic origin; 577 (56.35%) had marked signs of chronic cerebrovascular insufficiency of atherosclerotic origin; 342 (33.40%) had a severe form of chronic cerebrovascular insufficiency accompanied by small-focal single or multiple strokes. Examination included: laboratory diagnostics, assessment of scales «The Clinical Dementia Rating scale» (CDR), «Mini-Mental State Examination» (MMSE), IB, cerebral scintiography (SG), rheoencephalography (REG), cerebral CT, MRI, MR angiography, digital angiography (DA).

Results: all patients with Alzheimer's disease, regardless of the stage of the disease, had a specific cerebral small vessel disease (CSVD) in temporal and frontoparietal regions, which manifests itself with dyscirculatory angiopathy of Alzheimer's type (DAAT), which is not found in control group patients.

Conclusions: DAAT is a specific to Alzheimer's disease lesion of cerebral angioarchitectonics and microvessels, which changes hemodynamics, causes cerebral hypoxia and contributes to disorders in beta-amyloid metabolism. The combination of deposition of amyloid beta in the cerebral tissue and the vascular wall, as well as specific microcirculation disorders, cause together neurodegeneration and the development of Alzheimer's disease. In patients with other neurodegenerative and ischemic diseases, CSVDs are of a different nature, with no DAAT phenomena observed.

References

1.     2019 Alzheimer's disease facts and figures. J Alzheimer’s & Dementia 2019; 13(4): 325-373.

2.     Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol. 2010; 9 (7): 689-701.

3.     Cai Z., Wang C., He W. et al. Cerebral small vessel disease and Alzheimer's disease. Clin Interv Aging. 2015; 23 (10):1695-1704.

4.     Grammas P,  Martinez  J., Sanchez, A. et al. A new paradigm for the treatment of Alzheimer's disease: targeting vascular activation. J Alzheimers Dis. 2014; 40(3):619-630.

5.     Gjulev, N.M., Pustozertsev, V.G., Gjulev, S.N. Cerebrovascular Diseases. The Neva Dialect 2002.[In Russ.] 

6.     Mormino E.C., Papp K.V., Rentz D.M., et al. Early and late change on the preclinical Alzheimer's cognitive composite in clinically normal older individuals with elevated amyloid-p. J Alzheimer's & Dementia. 2017;13 (9): 10041012.

7.     Jack C.R., Petersen R.C, Xu YC., et al. Prediction of AD with MRI-based Hippocampal Volume in Mild Cognitive Impairment. Neurology. 1999; 52 (7): 1397-1403.

8.     Waldemar G., Dubois B., Emre M., et al. Recommendations for the diagnosis and management of Alzheimer’s disease and other disorders associated with dementia: EFNS guideline. European Journal of Neurology. 2007; 14, (1): e1-26.

9.     Burton E.J., Barber R., Mukaetova-Ladinska E.B., et al. 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. 2009; 132 (Pt1): 195-203.

10.   Trojanowski J.Q., Vandeerstichele H., Korecka M., et al. Update on the biomarker core of the Alzheimer’s Disease Neuroimaging Initiative subjects. J Alzheimer’s & Dementia. 2010; 6 (3): 230-238.

11.   Adriaase A., Sanz-Arigita E., Binnewijzend M., et al. Molecular markers of Alzheimer's Disease pathology and their relationship with default mode network integrity. J Alzheimer's & Dementia. 2011; 7 (4) S2-S3.

12.   Meyer PT., Hellwig S., Amtage F., et al. Dualbiomarker imaging of regional cerebral amyloid load and neuronal activity in dementia with PET and 11C-labeled Pittsburgh compound B J Nucl Med. 2011; 52 (3): 393-400.

13.   Weiner W.W., Veitch D.P, Aisen PS., et al. 2014 Update of the Alzheimer's Disease Neuroimaging Initiative: A review of papers published since its inception. Journal of Alzheimer’s & Dementi. 2015; 11(6) e1-e120.

14.   Chiang G.C., Insel Ph.S., Tosun D., et al. Identifying cognitively healthy elderly individuals with subsequent memory decline by using automated MR temporoparietal volumes. Radiology. 2011; 259 (3): 844-851.

15.   De la Torre J.C. Hemodynamic consequences of deformed microvessels in the brain in Alzheimer’s disease. Annals of New York Acadmy Sciences. 1997; 26: 75-91. 

16.   Kalaria R. Small vessel disease and Alzheimer’s dementia: Pathological considerations. Cerebrovascular Diseases. 2002:13: 48-52.

17.   Maksimovich I.V. Dyscirculatory Angiopathy of Alzheimer’s Type. Journal of Behavioral and Brain Science. 2011 1 (2): 57-68.

18.   Zlokovic B.V. Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nature Reviews. Neuroscience. 2011; 3: 723-738.

19.   Maksimovich I.V. Vascular factors in Alzheimer’s disease. Health. 2012; 4 (9A): 735-742.

20.   Baloiannis S.J., Baloiannis I.S. The vascular factor in Alzheimer’s disease: A study in Golgi technique and electron microscopy. Journal of the Neurological Sciences. 2012; 322: 117-121.

21.   Baloyannis S.J. (2015) Brain capillaries in Alzheimer's disease. Hell J Nucl Med.2015; 1 (Suppl 1): 152.

22.   Iadecola C. Neurovascular regulation in the normal brain and in Alzheimer's disease. Nat Rev Neurosci. 2004; 5, (5): 347-360.

23.   Maksimovich I.V., Gotman L.N. Method of complex radiation diagnostics at preclinical and clinical stages of Alzheimer’s disease. Patent RF №. 2315559. 2006. [In Russ.]

24.   Maksimovich I.V., Gotmanm L.N., Masyuk S.M. Method of Determining Dimensions of Temporal Brain Lobes in Patients Suffering from Alzheimer’s Disease. Patent RF № 2306102. 2006. [In Russ.]

25.   Bell R.D., Zlokovic B.V. Neurovascular mechanisms and blood-brain barrier disorder in Alzheimer’s disease. Acta Neuropathologica. 2009; 118: 103-113.

26.   Koike M.A., Green K.N., Blurton-Jones M. Oligemic hypoperfusion differentially affects tau and amyloid-{beta}. Am J Pathol. 2010; 177: 300-310.

27.   Nelson A.R., Sweeney M.D., Sagare A.P, Zlokovic A. V. Neurovascular dysfunction and neurodegeneration in dementia and Alzheimer's disease. Biochim Biophys Acta. 2016; 1862, (5): 887-900.

28.   Kimbrough I.F., Robel S., Roberson E.D., Son- theimer H. (2015) Vascular amyloidosis impairs the glio- vascular unit in a mouse model of Alzheimer's disease. Brain, 2015; 138, (Pt 12): 3716-3733.

29.   Maksimovich I.V. Radiodiagnostics of Alzheimer’s disease. Diagnostics and Intervention Radiology. 2008; 4: 27-38. [In Russ.]

30.   Morris J.C. The Clinical Dementia Rating (CDR): Current Version and Scoring Rules. Neurology. 1993; 11 (43): 2412-2414.

31.   Folstein M.F., Folstein S.E., McHugh PR. Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975; 12 (3): 189-198.

32.   Maksimovich I.V. The tomography dementia rating scale (TDR) - The rating scale of Alzheimer’s disease stages. Health. 2012; 4 (9A): 712-719.

33.   De Lin M., Jackson E.F. Applications of Imaging Technology in Radiation Research. Radiat Res. 2012; 177 (4): 387-397. 

34.   Brown W.R., Thore C.R. Review: cerebral microvas- cular pathology in ageing and neurodegeneration. Neu- ropatholApplNeurobiol. 2011; 37 (1): 56-74.

35.   Henry-Feugeas M.C. Alzheimer’s disease in late- life dementia: a minor toxic consequence of devastating cerebrovascular dysfunction. Med Hypotheses. 2008; 70 (3): 866-875.

36.   Maksimovich I.V. Certain new aspects of etiology and pathogenesis of Alzheimer’s disease. Advances in Alzheimer’s Disease. 2012; 1 (3): 68-76.

37.   Maksimovich I.V. Disorders of cerebrovascular angioarchitectonics and microcirculation in the etiology and pathogenesis of Alzheimer’s disease Advances in Alzheimer’s Disease. 2013; 2, (4): 171-181.

38.   Zlokovic B.V. Neurodegeneration and the neurovascular unit. Nat Med. 2010; 16 (12): 1370-1371.

39.   Iadecola C. The overlap between neurodegenera- tive and vascular factors in the pathogenesis of dementia. Acta Neuropathol.2010 120 (3): 287-396.

40.   De la Torre J.C. A turning point for Alzheimer's disease? Bio Factors. 2012; 38 (2): 78-83.

41.   De la Torre J.C. Cerebral Perfusion Enhancing Interventions: A New Strategy for the Prevention of Alzheimer Dementia. Brain Pathology. 2016; 26 (5): 618-631.

42.   Love S., Miners J.S. Cerebral Hypoperfusion and the Energy Deficit in Alzheimer's Disease Brain Pathology. 2016; 26 (5): 607-617.

43.   Nielsen R.B., Egefjord L., Angleys H., et al. Capillary dysfunction is associated with symptom severity and neurodegeneration in Alzheimer's disease. J Alzheimer's & Dementia. 2017; 13 (10): 1143-1153. 4 4 . Bosco P., Redolfi A., Bocchetta M., et al. The impact of automated hippocampal volumetry on diagnostic confidence in patients with suspected Alzheimer's disease: An EADC study. J Alzheimer's & Dementia. 2017; 13 (9): 10131023.

45.   Iadecola C. Dangerous leaks: blood-brain barrier woes in the aging hippocampus. Neuron. 2015; 85 (2): 231-233.

46.   Montagne A., Barnes S.R., Sweeney M.D. et al. Blood-brain barrier breakdown in the aging human hippocampus. Neuron. 2015; 85 (2): 296-302.

47.   Maksimovich I.V. Morphometric Definition of Alzheimer's Disease Stages by Means of The Tomography Dementia Rating Scale (TDR). Brain Disord Ther. 2017; 6, (2): 1-4.

48.   Schmidtke K., Hull M. Cerebral small vessel disease: how does it progress? J Neurol Sci. 2005; 229-230: 13-20.

49.   Qureshi A.I., Caplan L.R. Intracranial atherosclerosis. Lancet. 2014; 15, 383 (9921), 984-998.

50.   Caplan L.R. The Effect of Small Artery Disease on the Occurrence and Management of Large Artery Disease. JAMA Neurol. 2016; 73 (1): 19-20.

51.   Ramos-Estebanez C., Moral-ArceI., Gonzalez- Mandly A. et al. Vascular cognitive impairment in small vessel disease: Clinical and neuropsychological features of lacunar state and Binswanger's disease. Age Ageing. 2011; 40 (2): 175-180. 

52.   AkiguchiI., Budka H., Shirakashi Y, et al. MRI features of Binswanger's disease predict prognosis and associated pathology. Ann Clin Transl Neurol. 2014; 1 (10): 813-821. 

53.   Maksimovich I.V. Possibilities of Application of Transcatheter Treatment of Vascular Dementia with Bin- swanger’s Disease. Global Journal of Health Science. 2017; 9 (6): 13-21.

Abstract:

A group of patients, including 88 diabetics and 93 non-diabetics (patients were diagnosed according to A. Bollinger system) was studied in terms of occlusive-stentic lesions. The occlusive-stentic affection of low-extremities combined with diabetes is characterized by a number of distinctive features. The majority of diabetics are suffering the distal type of arterial lesion, while atherosclerotics suffer the proximal type. Diabetes functions as a complicating factor, forcing the development of occlusive-stentic process largely in distal segments of low extremities, meaning popliteal and crural arteries. This process eventually leads to the ischemia of low extremities.

References

1.     Gensler S.W, Haimovici H, Hoffert P., Steinman С, Beneventano Т.С. Study of vascular lesions in diabetic, nondiabetic patients. Clinical, arteriographic, and surgical considerations. Arch. Surg. 1965; 91:617 - 622.

2.     Haimovici H. Patterns of arteriosclerotic lesions of the lower extremity. Arch. Surg. 1967; 95:918 - 933.

3.     Conrad M.C. Large and small artery occlusion in diabetics and nondiabetics with severe vascular disease. Circulation. 1967; 36:83 - 91.

4.     Bollinger A., Breddin K., Hess H., Heystraten F.M.J., Kollath J., Kontilla A., Pouliadis G., Marshall M., Mey Т., Mietaschk A., Roth F.-J. Semiquantitative assessment of lower limb atherosclerosis from routine angiographic images. Atherosclerosis. 1981; 38: 339-346.

5.     Van der Feen C, Neijens F.S., Kanters S.D.J.M., Mali WP.Th.M., Stolk R.P., Banga J.D. Angiographic distribution of lower extremity atherosclerosis in patients with and without diabetes. Diabetic Medicine. 2002;19:366-370.

6.     Покровский А.В., Дан В.Н., Чупин А.В.. Ишемическая диабетическая стопа. Синдром диабетической стопы. Клиника, диагностика, лечение и профилактика. Москва. 1998; 18 - 35.

7.     Балаболкин М.И.. Эндокринология. М.: Универсум паблишинг. 1998; 421, 423.

8.     Атанов Ю.П., Шамычкова А.А.. Диабетическая ангиопатия нижних конечностей. Российский медицинский журнал. 2001;5: 14- 15.

9.     Donnelly R. Vascular complications of diabetes. B.M.J. 2000; 320:1062- 1066.

10.   Faglia E. et al. Extensive use of peripheral angioplasty, particularly infrapopliteal, in the treatment of ischaemic diabetic foot ulcers: clinical results of a multicentric study of 221 consecutive diabetic subjects. Journal of Internal Medicine. 2002; 252: 225 - 232

11.   Awad S., Karkos CD., Serrachino-Inglott E, Cooper N.J., Butterfield J.S., Ashleigh R., Nasim A. The impact of diabetes on current revascularisation practice and clinical outcome in patients with critical lower limb ischaemia. European journal of vascular and endovascular surgery. 2006; 32 (1): 51-59.

12.   Bosiers M, Hart J.P, Deloose K., Verbist J., Peeters P. Endovascular therapy as the primary approach for limb salvage in patients with critical limb ischemia: experience with 443 infrapopliteal procedures. Vascular. 2006; 14 (2):63 - 69.