Annals of Clinical and Experimental NeurologyAnnals of Clinical and Experimental NeurologyАнналы клинической и экспериментальной неврологии2075-54732409-2533Eco-Vector56610.25692/ACEN.2018.5.11ReviewsОбзорыUnknownNeurovascular coupling and cerebral perfusion in aging, cerebral microangiopathy and Alzheimer’s diseasesНейроваскулярное взаимодействие и церебральная перфузия при старении, церебральной микроангиопатии и болезни Альцгеймераhttps://orcid.org/0000-0001-9929-2725DobryninaLarisa A.ДобрынинаЛариса Анатольевна
Russian Federation

D. Sci. (Med.), Head, 3rd Neurology department

д.м.н., г.н.с., рук. 3-го неврологического отделения

dobrla@mail.ruResearch Center of NeurologyФГБНУ «Научный центр неврологии»26122018125S879427122018Copyright ©; 2018, Dobrynina L.A.Copyright ©; 2018, Dobrynina L.A.2018Dobrynina L.A.Dobrynina L.A.https://creativecommons.org/licenses/by/4.0https://annaly-nevrologii.com/pathID/article/view/566

Integrity of neurovascular unit (NVU) and interaction of its components is the basis for brain function. Exceptional role of NVU for providing metabolism of all cerebral processes substantiates obligate participation in pathophysiology of wide range of neurological disorders. Established similarity of structural changes in NVU at early stages of aging and hypertensive cerebral microangiopathy (CMA) suggests common pathogenic mechanisms of its damage and, in view of reversibility of early changes in neurovascular coupling (NVC), allows considering several forms of CMA as variants of early accelerated vascular wall aging. Understanding small vessel damage as a significant risk factor for Alzheimer’s disease and mixed dementias has encouraged revision of the current concept of the development of cognitive decline. A universal role of early NVC impairments in the development of various dementias has been shown. Further studies should improve our understanding of mechanisms of NVC impairment, role of classical and newly specified risk factors in their development and perspectives for preventive strategies. Apparently, success can be achieved through collaboration of neuroscience researchers, which allows translation of advantages of fundamental studies into clinical practice

Сохранность нейроваскулярной единицы (НВЕ) и взаимодействия ее элементов является основой функционирования головного мозга. Исключительность НВЕ в обеспечении метаболизма всех церебральных процессов обосновывает облигатность участия в патофизиологии широкого круга неврологических заболеваний. Установленное сходство структурных изменений в НВЕ на ранних стадиях старения и гипертензивной церебральной микроангиопатии (ЦМА) позволяет предполагать единство патогенетических механизмов ее повреждения при разных типах патологических процессов и, с учетом обратимости ранних изменений нейроваскулярного взаимодействия (НВВ), дает возможность рассматривать некоторые формы ЦМА в качестве вариантов раннего ускоренного старения сосудистой стенки. Понимание повреждения мелких сосудов в качестве значимого фактора риска болезни Альцгеймера и смешанных форм деменций положило начало пересмотру представлений о развитии когнитивных расстройств. Показана универсальная роль ранних нарушений НВВ в развитии разных видов деменций. Последующие исследования должны улучшить понимание механизмов нарушений НВВ, роль классических и вновь уточняемых факторов риска в их развитии и возможности превентивных стратегий. Очевидно, что успехи могут быть достигнуты при совместной работе исследователей в области нейронаук, позволяющей адаптировать достижения в области фундаментальных исследований в прикладные разработки, востребованные в клинической практике.

neurovascular unitneurovascular couplingagingcerebral microangiopathyarterial hypertensionAlzheimer’s diseasecerebral perfusionнейроваскулярная единицанейроваскулярное взаимодействиестарениецеребральная микроангиопатияартериальная гипертензияболезнь Альцгеймерацеребральная перфузияZlokovic B. V. Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nat Rev Neurosci 2011; 12 (12): 723. DOI:org/10.1038/nrn3114. PMID: 22048062.World Health Organization. Dementia: a public health priority. 2012. www.who.int/mental_health/publications/dementia_report_2012/en/Zhao Z.; Nelson A.R.; Betsholtz C.; Zlokovic B.V. Establishment and dysfunction of the blood-brain barrier. Cell 2015; 163 (5): 1064–1078. DOI: 10.1016/j.cell.2015.10.067. PMID: 26590417.Zhao Z., Nelson A.R., Betsholtz C., Zlokovic B.V. Establishment and dysfunction of the blood-brain barrier. Cell 2015; 163 (5): 1064–1078. DOI: 10.1016/j.cell.2015.10.067. PMID: 26590417.Kisler K.; Nelson A.R.; Montagne A.; Zlokovic B.V. Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease. Nat Rev Neurosci 2017; 18 (7): 419. DOI: 10.1038/nrn.2017.48. PMID: 28515434.Kisler K., Nelson A.R., Montagne A., Zlokovic B.V. Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease. Nat Rev Neurosci 2017; 18 (7): 419. DOI: 10.1038/nrn.2017.48. PMID: 28515434.Fernández-Klett F.; Offenhauser N.; Dirnagl U. et al. Pericytes in capillaries are contractile in vivo; but arterioles mediate functional hyperemia in the mouse brain. Proc Natl Acad Sci USA 2010; 107 (51): 22290–22295. DOI: org/10.1073/pnas.1011321108. PMID: 21135230.Fernández-Klett F., Offenhauser N., Dirnagl U. et al. Pericytes in capillaries are contractile in vivo, but arterioles mediate functional hyperemia in the mouse brain. Proc Natl Acad Sci USA 2010; 107 (51): 22290–22295. DOI: org/10.1073/pnas.1011321108. PMID: 21135230.Dunn K.M.; Nelson M.T. Neurovascular signaling in the brain and the pathological consequences of hypertension. Am J Physiol Heart Circ Physiol 2013; 306 (1): H1–H14. DOI: 10.1152/ajpheart.00364.2013. PMID: 24163077.Dunn K.M., Nelson M.T. Neurovascular signaling in the brain and the pathological consequences of hypertension. Am J Physiol Heart Circ Physiol 2013; 306 (1): H1–H14. DOI: 10.1152/ajpheart.00364.2013. PMID: 24163077.Sakadžić S.; Mandeville E.T.; Gagnon L. et al. Large arteriolar component of oxygen delivery implies a safe margin of oxygen supply to cerebral tissue. Nat Commun 2014; 5: 5734. DOI: 10.1038/ncomms6734. PMID: 25483924.Sakadžić S., Mandeville E.T., Gagnon L. et al. Large arteriolar component of oxygen delivery implies a safe margin of oxygen supply to cerebral tissue. Nat Commun 2014; 5: 5734. DOI: 10.1038/ncomms6734. PMID: 25483924.Amin-Hanjani S.; Du X.; Pandey D.K. et al. Effect of age and vascular anatomy on blood flow in major cerebral vessels. J Cerebral Blood Flow Metab 2015;35 (2): 312–318. DOI: dx.DOI.org/10.1038/jcbfm.2014.203. PMID: 25388677.Amin-Hanjani S., Du X., Pandey D.K. et al. Effect of age and vascular anatomy on blood flow in major cerebral vessels. J Cerebral Blood Flow Metab 2015;35 (2): 312–318. DOI: dx.DOI.org/10.1038/jcbfm.2014.203. PMID: 25388677.Zonta M.; Angulo M.C.; Gobbo S. et al. Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation. Nat Neurosci 2003; 6 (1):43. DOI: dx.DOI.org/10.1038/nn980. PMID: 12469126.Zonta M., Angulo M.C., Gobbo S. et al. Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation. Nat Neurosci 2003; 6 (1):43. DOI: dx.DOI.org/10.1038/nn980. PMID: 12469126.Hyder F.; Patel A.B.; Gjedde A. et al. Neuronal–glial glucose oxidation and glutamatergic–GABAergic function. J Cerebral Blood Flow Metab 2006; 26 (7):865–877. DOI: org/10.1038%2Fsj.jcbfm.9600263. PMID: 16407855.Hyder F., Patel A.B., Gjedde A. et al. Neuronal–glial glucose oxidation and glutamatergic–GABAergic function. J Cerebral Blood Flow Metab 2006; 26 (7):865–877. DOI: org/10.1038%2Fsj.jcbfm.9600263. PMID: 16407855.Straub S.V.; Nelson M.T. Astrocytic calcium signaling: the information currency coupling neuronal activity to the cerebral microcirculation. Trends Cardiovasc Med 2007; 17 (6): 183–190. DOI: org/10.1016/j.tcm.2007.05.001. PMID: 17662912.Straub S.V., Nelson M.T. Astrocytic calcium signaling: the information currency coupling neuronal activity to the cerebral microcirculation. Trends Cardiovasc Med 2007; 17 (6): 183–190. DOI: org/10.1016/j.tcm.2007.05.001. PMID: 17662912.Gordon G.R.; Mulligan S.J.; MacVicar B.A. Astrocyte control of the cerebrovasculature. Glia 2007; 55 (12): 1214–1221. DOI: org/10.1002/glia.20543. PMID: 17659528.Gordon G.R., Mulligan S.J., MacVicar B.A. Astrocyte control of the cerebrovasculature. Glia 2007; 55 (12): 1214–1221. DOI: org/10.1002/glia.20543. PMID: 17659528.Rosenegger D.G.; Tran C.H.T.; Cusulin J.I.W.; Gordon G.R. Tonic local brain blood flow control by astrocytes independent of phasic neurovascular coupling. J Neurosci 2015; 35 (39): 13463–13474. DOI: dx.DOI.org/10.1523/JNEUROSCI.1780-15.2015. PMID: 26424891Rosenegger D.G., Tran C.H.T., Cusulin J.I.W., Gordon G.R. Tonic local brain blood flow control by astrocytes independent of phasic neurovascular coupling. J Neurosci 2015; 35 (39): 13463–13474. DOI: dx.DOI.org/10.1523/JNEUROSCI.1780-15.2015. PMID: 26424891Filosa J.A.; Bonev A.D.; Straub S.V. et al. Local potassium signaling couples neuronal activity to vasodilation in the brain. Nat Neurosci 2006; 9 (11): 1397. DOI: org/10.1038/nn1779. PMID: 17013381.Filosa J.A., Bonev A.D., Straub S.V. et al. Local potassium signaling couples neuronal activity to vasodilation in the brain. Nat Neurosci 2006; 9 (11): 1397. DOI: org/10.1038/nn1779. PMID: 17013381.Toth P.; Tarantini S.; Davila A. et al. Purinergic glio-endothelial coupling during neuronal activity: role of P2Y1 receptors and eNOS in functional hyperemia in the mouse somatosensory cortex. Am J Physiol Heart Circ Physiol 2015;309 (11): H1837–H1845. DOI: dx.DOI.org/10.1152/ajpheart.00463.2015.PMID: 26453330.Toth P., Tarantini S., Davila A. et al. Purinergic glio-endothelial coupling during neuronal activity: role of P2Y1 receptors and eNOS in functional hyperemia in the mouse somatosensory cortex. Am J Physiol Heart Circ Physiol 2015;309 (11): H1837–H1845. DOI: dx.DOI.org/10.1152/ajpheart.00463.2015.PMID: 26453330.Neuwelt E. A.; Bauer B.; Fahlke C. et al. Engaging neuroscience to advance translational research in brain barrier biology. Nat Rev Neurosci 2011; 12 (3): 169. DOI: org/10.1038/nrn2995. PMID: 21331083.Neuwelt E. A., Bauer B., Fahlke C. et al. Engaging neuroscience to advance translational research in brain barrier biology. Nat Rev Neurosci 2011; 12 (3): 169. DOI: org/10.1038/nrn2995. PMID: 21331083.Kliche K.; Jeggle P.; Pavenstädt H.; Oberleithner H. Role of cellular mechanics in the function and life span of vascular endothelium. Pflügers Arch 2011; 462 (2): 209–217. DOI: 10.1007/s00424-011-0929-2. PMID: 21318292.Kliche K., Jeggle P., Pavenstädt H., Oberleithner H. Role of cellular mechanics in the function and life span of vascular endothelium. Pflügers Arch 2011; 462 (2): 209–217. DOI: 10.1007/s00424-011-0929-2. PMID: 21318292.Wang M.; Jiang L.; Monticone R.E.; Lakatta E.G. Proinflammation: the key to arterial aging. Trends Endocrin Metab 2014; 25 (2): 72–79. DOI: 10.1016/j. tem.2013.10.002. PMID: 24365513.Wang M., Jiang L., Monticone R.E., Lakatta E.G. Proinflammation: the key to arterial aging. Trends Endocrin Metab 2014; 25 (2): 72–79. DOI: 10.1016/j. tem.2013.10.002. PMID: 24365513.Csiszar A.; Labinskyy N.; Zhao X. et al. Vascular superoxide and hydrogen peroxide production and oxidative stress resistance in two closely related rodent species with disparate longevity. Aging Cell 2007; 6 (6): 783–797. DOI:org/10.1111/j.1474-9726.2007.00339.x. PMID: 17925005.Csiszar A., Labinskyy N., Zhao X. et al. Vascular superoxide and hydrogen peroxide production and oxidative stress resistance in two closely related rodent species with disparate longevity. Aging Cell 2007; 6 (6): 783–797. DOI:org/10.1111/j.1474-9726.2007.00339.x. PMID: 17925005.Kao C.L.; Chen L.K.; Chang Y.L. et al. Resveratrol protects human endothelium from H2O2-induced oxidative stress and senescence via SirT1 activation. J Atheroscler Thromb 2010; 17 (9): 970–979. PMID: 20644332.Kao C.L., Chen L.K., Chang Y.L. et al. Resveratrol protects human endothelium from H2O2-induced oxidative stress and senescence via SirT1 activation. J Atheroscler Thromb 2010; 17 (9): 970–979. PMID: 20644332.Asai K.; Kudej R. K.; Shen Y.T. et al. Peripheral vascular endothelial dysfunction and apoptosis in old monkeys. Arterioscler Thromb Vasc Biol 2000; 20 (6):1493–1499. DOI: 10.1161/01.ATV.20.6.1493. PMID: 10845863.Asai K., Kudej R. K., Shen Y.T. et al. Peripheral vascular endothelial dysfunction and apoptosis in old monkeys. Arterioscler Thromb Vasc Biol 2000; 20 (6):1493–1499. DOI: 10.1161/01.ATV.20.6.1493. PMID: 10845863.Tanaka Y.; Moritoh Y.; Miwa N. Age – dependent telomere – shortening is repressed by phosphorylated α-tocopherol together with cellular longevity and intracellular oxidative – stress reduction in human brain microvascular endotheliocytes. J Cell Biochem 2007; 102 (3): 689–703. DOI: org/10.1002/jcb.21322.PMID: 17407150.Tanaka Y., Moritoh Y., Miwa N. Age – dependent telomere – shortening is repressed by phosphorylated α-tocopherol together with cellular longevity and intracellular oxidative – stress reduction in human brain microvascular endotheliocytes. J Cell Biochem 2007; 102 (3): 689–703. DOI: org/10.1002/jcb.21322.PMID: 17407150.Wang M.; Zhang J.; Walker S. J. et al. Involvement of NADPH oxidase in age-associated cardiac remodeling. J Mol Cell Cardiol 2010; 48 (4): 765–772. DOI: 10.1016/j.yjmcc.2010.01.006. PMID: 20079746.Wang M., Zhang J., Walker S. J. et al. Involvement of NADPH oxidase in age-associated cardiac remodeling. J Mol Cell Cardiol 2010; 48 (4): 765–772. DOI: 10.1016/j.yjmcc.2010.01.006. PMID: 20079746.Chen J.; Huang X.; Halicka D. et al. Contribution of p16 INK4a and p21 CIP1 pathways to induction of premature senescence of human endothelial cells: permissive role of p53. Am J Physiol Heart Circ Physiol 2006; 290 (4): H1575–H1586. DOI:org/10.1152/ajpheart.00364.2005. PMID: 16243918.Chen J., Huang X., Halicka D. et al. Contribution of p16 INK4a and p21 CIP1 pathways to induction of premature senescence of human endothelial cells: permissive role of p53. Am J Physiol Heart Circ Physiol 2006; 290 (4): H1575–H1586. DOI:org/10.1152/ajpheart.00364.2005. PMID: 16243918.Wang M.; Zhang J.; Jiang L. Q. et al. Proinflammatory profile within the grossly normal aged human aortic wall. Hypertension 2007; 50 (1): 219–227. DOI: 10.1161/HYPERTENSIONAHA.107.089409. PMID: 17452499Wang M., Zhang J., Jiang L. Q. et al. Proinflammatory profile within the grossly normal aged human aortic wall. Hypertension 2007; 50 (1): 219–227. DOI: 10.1161/HYPERTENSIONAHA.107.089409. PMID: 17452499Mistry Y.; Poolman T.; Williams B.; Herbert K. E. A role for mitochondrial oxidants in stress-induced premature senescence of human vascular smooth muscle cells. Redox Biol 2013; 1 (1): 411–417. DOI: org/10.1016/j.redox.2013.08.004.PMID: 24191234.Mistry Y., Poolman T., Williams B., Herbert K. E. A role for mitochondrial oxidants in stress-induced premature senescence of human vascular smooth muscle cells. Redox Biol 2013; 1 (1): 411–417. DOI: org/10.1016/j.redox.2013.08.004.PMID: 24191234.Ragnauth C.D.; Warren D.T.; Liu Y. et al. Prelamin A acts to accelerate smooth muscle cell senescence and is a novel biomarker of human vascular aging. Circulation 2010; 121 (20): 2200–2210. DOI: 10.1161/CIRCULATIONAHA.109.902056. PMID: 20458013.Ragnauth C.D., Warren D.T., Liu Y. et al. Prelamin A acts to accelerate smooth muscle cell senescence and is a novel biomarker of human vascular aging. Circulation 2010; 121 (20): 2200–2210. DOI: 10.1161/CIRCULATIONAHA.109.902056. PMID: 20458013.Csiszar A.; Sosnowska D.; Wang M. et al. Age-associated proinflammatory secretory phenotype in vascular smooth muscle cells from the non-human primate Macaca mulatta: reversal by resveratrol treatment. J Gerontol A Biomed Sci Med Sci 2012; 67 (8): 811–820. DOI: org/10.1093/gerona/glr228. PMID: 22219513.Csiszar A., Sosnowska D., Wang M. et al. Age-associated proinflammatory secretory phenotype in vascular smooth muscle cells from the non-human primate Macaca mulatta: reversal by resveratrol treatment. J Gerontol A Biomed Sci Med Sci 2012; 67 (8): 811–820. DOI: org/10.1093/gerona/glr228. PMID: 22219513.Wang M.; Lakatta E. G. The salted artery and angiotensin II signaling: a deadly duo in arterial disease. J Hypertension 2009; 27 (1): 19. DOI: org/10.1097%2FHJH.0b013e32831d1fed. PMID: 19050444.Wang M., Lakatta E. G. The salted artery and angiotensin II signaling: a deadly duo in arterial disease. J Hypertension 2009; 27 (1): 19. DOI: org/10.1097%2FHJH.0b013e32831d1fed. PMID: 19050444.Wang M.; Zhang; J.; Telljohann R. et al. Chronic matrix metalloproteinase inhibition retards age-associated arterial proinflammation and increase in blood pressure. Hypertension 2012; 60 (2): 459–466. DOI: org/10.1161%2FHYPERTENSIONAHA.112.191270. PMID: 22689745.Wang M., Zhang, J., Telljohann R. et al. Chronic matrix metalloproteinase inhibition retards age-associated arterial proinflammation and increase in blood pressure. Hypertension 2012; 60 (2): 459–466. DOI: org/10.1161%2FHYPERTENSIONAHA.112.191270. PMID: 22689745.Wang Y. L; Liu L. Z.; He Z. et al. Phenotypic transformation and migration of adventitial cells following angioplasty. Exp Ther Med. 2012; 4 (1): 26–32. DOI:10.3892/etm.2012.551. PMID: 23060918.Wang Y. L, Liu L. Z., He Z. et al. Phenotypic transformation and migration of adventitial cells following angioplasty. Exp Ther Med. 2012; 4 (1): 26–32. DOI:10.3892/etm.2012.551. PMID: 23060918.Toth P.; Tarantini S.; Csiszar A. et al. Functional vascular contributions to cognitive impairment and dementia: mechanisms and consequences of cerebral autoregulatory dysfunction; endothelial impairment; and neurovascular uncoupling in aging. Am J Physiol Heart Circ Physiol 2016; 312 (1): H1–H20. DOI:10.1152/ajpheart.00581.2016. PMID: 27793855.Toth P., Tarantini S., Csiszar A. et al. Functional vascular contributions to cognitive impairment and dementia: mechanisms and consequences of cerebral autoregulatory dysfunction, endothelial impairment, and neurovascular uncoupling in aging. Am J Physiol Heart Circ Physiol 2016; 312 (1): H1–H20. DOI:10.1152/ajpheart.00581.2016. PMID: 27793855.Zhang N.; Gordon M. L.; Ma Y. et al. The age-related perfusion pattern measured with arterial spin labeling MRI in healthy subjects. Front Aging Neurosci 2018; 10: 214. DOI: 10.3389/fnagi.2018.00214. PMID: 30065646.Zhang N., Gordon M. L., Ma Y. et al. The age-related perfusion pattern measured with arterial spin labeling MRI in healthy subjects. Front Aging Neurosci 2018; 10: 214. DOI: 10.3389/fnagi.2018.00214. PMID: 30065646.Rolita L.; Verghese; J. Neurovascular coupling: Key to gait slowing in aging Ann Neurol 2011; 70 (2): 189–191. DOI: org/10.1002/ana.22503. PMID:21823151.Rolita L., Verghese, J. Neurovascular coupling: Key to gait slowing in aging Ann Neurol 2011; 70 (2): 189–191. DOI: org/10.1002/ana.22503. PMID:21823151.Tarantini S.; Tran C.H.; Gordon G.R. et al. Impaired neurovascular coupling in aging and Alzheimer’s disease: Contribution of astrocyte dysfunction and endothelial impairment to cognitive decline. Exp Gerontol. 2017; 94: 52–58. DOI:10.1016/j.exger.2016.11.004. PMID: 27845201.Tarantini S., Tran C.H., Gordon G.R. et al. Impaired neurovascular coupling in aging and Alzheimer’s disease: Contribution of astrocyte dysfunction and endothelial impairment to cognitive decline. Exp Gerontol. 2017; 94: 52–58. DOI:10.1016/j.exger.2016.11.004. PMID: 27845201.Østergaard L.; Engedal T.S.; Moreton F. et al. Cerebral small vessel disease: capillary pathways to stroke and cognitive decline. J Cerebral Blood Flow Metab 2016; 36 (2): 302–325. DOI: 10.1177/0271678X15606723. PMID: 26661176.Østergaard L., Engedal T.S., Moreton F. et al. Cerebral small vessel disease: capillary pathways to stroke and cognitive decline. J Cerebral Blood Flow Metab 2016; 36 (2): 302–325. DOI: 10.1177/0271678X15606723. PMID: 26661176.Stanimirovic; D.B.; Friedman A. Pathophysiology of the neurovascular unit: disease cause or consequence? J Cerebral Blood Flow Metab 2012; 32 (7): 1207–1221. DOI: 10.1038/jcbfm.2012.25. PMID: 22395208.Stanimirovic, D.B., Friedman A. Pathophysiology of the neurovascular unit: disease cause or consequence? J Cerebral Blood Flow Metab 2012; 32 (7): 1207–1221. DOI: 10.1038/jcbfm.2012.25. PMID: 22395208.Kotsis V.; Antza C.; Doundoulakis I.; Stabouli S. Markers of early vascular ageing. Curr Pharm Des 2017; 23 (22): 3200–3204. DOI:org/1381612823666170328142433. PMID: 28356037.Kotsis V., Antza C., Doundoulakis I., Stabouli S. Markers of early vascular ageing. Curr Pharm Des 2017; 23 (22): 3200–3204. DOI:org/1381612823666170328142433. PMID: 28356037.Schreiber S.; Bueche C. Z.; Garz C. et al. The pathologic cascade of cerebrovascular lesions in SHRSP: is erythrocyte accumulation an early phase? J Cerebral Blood Flow Metab 2012; 32 (2): 278–290. DOI: 10.1038/jcbfm.2011.122.PMID: 21878945.Schreiber S., Bueche C. Z., Garz C. et al. The pathologic cascade of cerebrovascular lesions in SHRSP: is erythrocyte accumulation an early phase? J Cerebral Blood Flow Metab 2012; 32 (2): 278–290. DOI: 10.1038/jcbfm.2011.122.PMID: 21878945.Sokolova I.A.; Manukhina E.B.; Blinkov et al. Rarefication of the arterioles and capillary network in the brain of rats with different forms of hypertension.Microvasc Res. 1985; 30 (1): 1–9. DOI: org/10.1016/0026-2862(85)90032-9.PMID: 4021832.Sokolova I.A., Manukhina E.B., Blinkov et al. Rarefication of the arterioles and capillary network in the brain of rats with different forms of hypertension.Microvasc Res. 1985; 30 (1): 1–9. DOI: org/10.1016/0026-2862(85)90032-9.PMID: 4021832.Gannushkina I.V.; Lebedeva N.V. Gipertonicheskaya ehncefalopatiya [Hypertensive encephalopathy]. Moscow: Medicine; 1987. (in Russ.).Ганнушкина И.В., Лебедева Н.В. Гипертоническая энцефалопатия. М.: Медицина, 1987.Gulevskaya T.S.; Morgunov V.A. Patologicheskaya anatomiya narushenij mozgovogo krovoobrashcheniya pri ateroskleroze i arterial’noj gipertonii [Pathologic anatomy of cerebrovascular diseases in atherosclerosis and arterial hypertension].Moscow: Medicine; 2009. (in Russ.).Гулевская Т.С., Моргунов В.А. Патологическая анатомия нарушений мозгового кровообращения при атеросклерозе и артериальной гипертонии. М.: Медицина, 2009.de La Torre J. C. Cardiovascular risk factors promote brain hypoperfusion leading to cognitive decline and dementia. Cardiovasc Psychiatry Neurol 2012; 2012: 1–15. DOI: 10.1155/2012/367516.Pires P.W.; Dams Ramos C.M.; Matin N.; Dorrance A.M. The effects of hypertension on the cerebral circulation. Am J Physiol Heart Circ Physiol 2013; 304 (12): H1598–H1614. DOI: 10.1152/ajpheart.00490.2012. PMID: 23585139.Pires P.W., Dams Ramos C.M., Matin N., Dorrance A.M. The effects of hypertension on the cerebral circulation. Am J Physiol Heart Circ Physiol 2013; 304 (12): H1598–H1614. DOI: 10.1152/ajpheart.00490.2012. PMID: 23585139.Cipolla M.J. The cerebral circulation. Integrated systems physiology: From molecule to function. 2009; 1 (1): 1–59. PMID: 21452434.Coyle P. Dorsal cerebral collaterals of stroke – prone spontaneously hypertensive rats (SHRSP) and Wistar Kyoto rats (WKY). Anat Rec 1987; 218 (1):40–44. DOI: 10.1002/ar.1092180108. PMID: 3605659.Oyama N.; Yagita Y.; Kawamura M. et al. Cilostazol; not aspirin; reduces ischemic brain injury via endothelial protection in spontaneously hypertensive rats. Stroke 2011; 2571–2577. DOI: 10.1161/STROKEAHA.110.60983. PMID:21799161.Oyama N., Yagita Y., Kawamura M. et al. Cilostazol, not aspirin, reduces ischemic brain injury via endothelial protection in spontaneously hypertensive rats. Stroke 2011; 2571–2577. DOI: 10.1161/STROKEAHA.110.60983. PMID:21799161.Touyz R.M.; Briones A.M. Reactive oxygen species and vascular biology: implications in human hypertension. Hypertens Res 2011; 34 (1): 5. DOI: 10.1038/hr.2010.201. PMID: 20981034.Touyz R.M., Briones A.M. Reactive oxygen species and vascular biology: implications in human hypertension. Hypertens Res 2011; 34 (1): 5. DOI: 10.1038/hr.2010.201. PMID: 20981034.Yenari M.A.; Xu L.; Tang X.N. et al. Microglia potentiate damage to blood– brain barrier constituents: improvement by minocycline in vivo and in vitro. Stroke. 2006; 37(4): 1087–1093. DOI: 10.1161/01.str.0000206281.77178.ac. PMID: 16497985.Yenari M.A., Xu L., Tang X.N. et al. Microglia potentiate damage to blood– brain barrier constituents: improvement by minocycline in vivo and in vitro. Stroke. 2006; 37(4): 1087–1093. DOI: 10.1161/01.str.0000206281.77178.ac. PMID: 16497985.Oberleithner H.; Wilhelmi M. Vascular glycocalyx sodium store-determinant of salt sensitivity? Blood Purif 2015; 39 (1–3): 7–10. DOI: 10.1159/000368922.PMID: 25659848.Oberleithner H., Wilhelmi M. Vascular glycocalyx sodium store-determinant of salt sensitivity? Blood Purif 2015; 39 (1–3): 7–10. DOI: 10.1159/000368922.PMID: 25659848.Iadecola C. The overlap between neurodegenerative and vascular factors in the pathogenesis of dementia. Acta Neuropathol 2010; 120 (3): 287–296. DOI:10.1007/s00401-010-0718-6. PMID: 20623294.Deramacourt V.; Slade J.Y.; Oakley A. E. et al. Staging and natural history of cerebrovascular pathology in dementia. Neurology 2012; 78 (14): 1043–1050. DOI: org/10.1212/wnl.0b013e31824e8e7f. PMID: 22377814.Deramacourt V., Slade J.Y., Oakley A. E. et al. Staging and natural history of cerebrovascular pathology in dementia. Neurology 2012; 78 (14): 1043–1050. DOI: org/10.1212/wnl.0b013e31824e8e7f. PMID: 22377814.Grinberg L.T.; Nitrini R.; Suemoto C.K. et al. Prevalence of dementia subtypes in a developing country: a clinicopathological study. Clinics 2013; 68 (8):1140–1145. DOI: 10.6061/clinics/2013(08)13. PMID: 24037011.Grinberg L.T., Nitrini R., Suemoto C.K. et al. Prevalence of dementia subtypes in a developing country: a clinicopathological study. Clinics 2013; 68 (8):1140–1145. DOI: 10.6061/clinics/2013(08)13. PMID: 24037011.Livingston G.; Sommerlad A.; Orgeta V. et al. Dementia prevention; intervention; and care. Lancet 2017; 390 (10113): 2673–2734. DOI: 10.1016/S0140-6736(17)31363-6. PMID: 28735855.Livingston G., Sommerlad A., Orgeta V. et al. Dementia prevention, intervention, and care. Lancet 2017; 390 (10113): 2673–2734. DOI: 10.1016/S0140-6736(17)31363-6. PMID: 28735855.Den Abeelen A.S.; Lagro J.; van Beek A.H.; Claassen J.A. Impaired cerebral autoregulation and vasomotor reactivity in sporadic Alzheimer’s disease. Curr Alzheimer Res 2014; 11: 11–17. DOI: org/10.2174/1567205010666131119234845.Den Abeelen A.S., Lagro J., van Beek A.H., Claassen J.A. Impaired cerebral autoregulation and vasomotor reactivity in sporadic Alzheimer’s disease. Curr Alzheimer Res 2014; 11: 11–17. DOI: org/10.2174/1567205010666131119234845.Suri S.; Mackay C. E.; Kelly M. E. et al. Reduced cerebrovascular reactivity in young adults carrying the APOE ε4 allele. Alzheimers Dement 2015; 11 (6):648–657. DOI: 10.1016/j.jalz.2014.05.1755. PMID: 25160043.Suri S., Mackay C. E., Kelly M. E. et al. Reduced cerebrovascular reactivity in young adults carrying the APOE ε4 allele. Alzheimers Dement 2015; 11 (6):648–657. DOI: 10.1016/j.jalz.2014.05.1755. PMID: 25160043.Yezhuvath U.S.; Uh J.; Cheng Y. et al. Forebrain-dominant deficit in cerebrovascular reactivity in Alzheimer’s disease. Neurobiol Aging 2012; 33 (1): 75–82. DOI: org/10.1016/j.neurobiolaging.2010.02.005. PMID: 20359779.Yezhuvath U.S., Uh J., Cheng Y. et al. Forebrain-dominant deficit in cerebrovascular reactivity in Alzheimer’s disease. Neurobiol Aging 2012; 33 (1): 75–82. DOI: org/10.1016/j.neurobiolaging.2010.02.005. PMID: 20359779.Ruitenberg A.; den Heijer T.; Bakker S. L. et al. Cerebral hypoperfusion and clinical onset of dementia: the Rotterdam Study. Ann Neurol 2005; 57 (6): 789–794. DOI: 10.1002/ana.20493. PMID: 15929050.Ruitenberg A., den Heijer T., Bakker S. L. et al. Cerebral hypoperfusion and clinical onset of dementia: the Rotterdam Study. Ann Neurol 2005; 57 (6): 789–794. DOI: 10.1002/ana.20493. PMID: 15929050.Hirao K.; Ohnishi T.; Matsuda H. et al. Functional interactions between entorhinal cortex and posterior cingulate cortex at the very early stage of Alzheimer’s disease using brain perfusion single-photon emission computed tomography. Nucl Med Commun 2006; 27 (2): 151–156. DOI: 10.1097/01.mnm.0000189783.39411.ef. PMID: 16404228.Hirao K., Ohnishi T., Matsuda H. et al. Functional interactions between entorhinal cortex and posterior cingulate cortex at the very early stage of Alzheimer’s disease using brain perfusion single-photon emission computed tomography. Nucl Med Commun 2006; 27 (2): 151–156. DOI: 10.1097/01.mnm.0000189783.39411.ef. PMID: 16404228.Daulatzai M.A. Cerebral hypoperfusion and glucose hypometabolism: key pathophysiological modulators promote neurodegeneration; cognitive impairment; and Alzheimer’s disease. J Neurosci Res 2016; 95: 943–972. DOI: 10.1002/jnr.23777. PMID: 27350397.Daulatzai M.A. Cerebral hypoperfusion and glucose hypometabolism: key pathophysiological modulators promote neurodegeneration, cognitive impairment, and Alzheimer’s disease. J Neurosci Res 2016; 95: 943–972. DOI: 10.1002/jnr.23777. PMID: 27350397.Thambisetty M.; Beason-Held L.; An Y. et al. APOE ε4 genotype and longitudinal changes in cerebral blood flow in normal aging. Arch Neurol 2010; 67:93–98. DOI: 10.1001/archneurol.2009.913. PMID: 20065135.Thambisetty M., Beason-Held L., An Y. et al. APOE ε4 genotype and longitudinal changes in cerebral blood flow in normal aging. Arch Neurol 2010; 67:93–98. DOI: 10.1001/archneurol.2009.913. PMID: 20065135.Reiman E. M.; Chen K.; Alexander G. E.; Caselli R. J et al. Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer’s dementia. Proc Natl Acad Sci USA 2004; 101 (1): 284-289. DOI:10.1073/pnas.2635903100.PMID: 14688411Reiman E. M., Chen K., Alexander G. E., Caselli R. J et al. Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer’s dementia. Proc Natl Acad Sci USA 2004; 101 (1): 284-289. DOI:10.1073/pnas.2635903100.PMID: 14688411.