Статья
Артериальная гипертензия и когнитивные нарушения: причины и механизмы возникновения
Известно, что при артериальной гипертензии (АГ) развиваются значительные изменения в структуре сосудов головного мозга. Существует тесная зависимость между функциональной активностью нейронов и интенсивностью их кровоснабжения. Сосудистая деменция — гетерогенная группа заболеваний, обусловленных патологией нейронов, глии и сосудов. Наиболее типичными проявлениями патологии мозга при сосудистой деменции являются когнитивные расстройства — нарушение памяти, способности к обучению, отсутствие собственного мнения, нарушение эмоционального контроля и социального поведения. В статье приводятся литературные данные об организации церебрального кровообращения и характере его изменений при АГ. Анализируются причины, приводящие к гипоперфузии мозга при повышенном артериальном давлении. Описываются механизмы, обусловливающие когнитивные нарушения у людей с АГ. Освещается вопрос о тактике врача по отношению к пациентам с АГ и когнитивными нарушениями: «Насколько нужно снижать артериальное давление?».
1. Longstreth WT Jr, Bernick C, Manolio TA, Bryan N, Jungreis CA, Price TR. Lacunar infarcts defined by magnetic resonance imaging of 3660 elderly people: the Cardiovascular Health Study. Arch Neurol. 1998;55(9):1217–25.
2. Iadecola С. The pathobiology of vascular dementia. Neuron. 2013;80(4):844–866.
3. Tomlinson BE, Blessed G, Roth M. Observations on the brains of demented old people. J Neurol Sci. 1970;11(3):205–242.
4. Hachinski VC, Potter P, Merskey H. Leuko-araiosis. Arch Neurol. 1987;44(1):21–23.
5. Basile AM, Pantoni L, Pracucci G, Asplund K, Chabriat H, Erkinjuntti T et al. Age, hypertension, and lacunar stroke are the major determinants of the severity of age-related white matter changes. Cerebrovasc Dis. 2006;21(5–6):315–22.
6. Varghese V, Chandra SR, Christopher, Rajeswaran J, Prasad C, Subasree R et al. Factors determining cognitive dysfunction in cerebral small vessel disease. Indian J Psychol Med. 2016;38 (1):56–61.
7. Corriveau RA, Bosetti F, Emr M, Gladman JT, Koenig JI, Moy CS et al. The Science of Vascular Contributions to Cognitive Impairment and Dementia (VCID): a Framework for advancing research priorities in the cerebrovascular biology of cognitive decline. Cell Mol Neurobiol. 2016;36(2):281–288.
8. Chui H. Dementia due to subcortical ischemic vascular disease. Clin Cornerstone. 2001;3(4):40–51.
9. Venkat P, Chopp M, Chen J. Models and mechanisms of vascular dementia. Exp Neurol. 2015;272:97–108. doi:10.1016/j. expneurol.2015.05.006
10. Meissner A. Hypertension and the brain: a risk factor for more than heart disease. Cerebrovasc Dis. 2016;42(3–4):255–262. 506 24(5) / 2018
11. Flores G, Flores-Gómez GD, de Jesús Gomez-Villalobos M. Neuronal changes after chronic high blood pressure in animal models and its implication for vascular dementia. Synapse. 2016;70(5):198–205.
12. Постнов Ю. В. Мембранная теория первичной артериальной гипертензии (разработка концепции природы гипертонии). Кардиология. 1985;25(10):63–71..
13. Baron-Menguy C, Domenga-Denier V, Ghezali L, Faraci FM, Joutel A. Increased Notch3 activity mediates pathological changes in structure of cerebral arteries. Hypertension. 2017;69 (1):60–70.
14. Житкова Ю. В., Гаспарян А. А., Хасанова Д. Р., Хасанов Н. Р., Ослопов В. Н. Генетические и функциональные факторы в развитии когнитивных нарушений при артериальной гипертензии (проспективное исследование). Неврология, нейропсихиатрия, психосоматика. 2016;8(4):14–20..
15. Meissner A, Minnerup J, Soria G, Planas AM. Structural and functional brain alterations in a murine model of angiotensin IIinduced hypertension. J Neurochem. 2017;140(3):509–521.
16. Rohn TT. Is apolipoprotein E4 an important risk factor for vascular dementia? Int J Clin Exp Pathol. 2014;7(7):3504– 3511.
17. Pires PW, Dams Ramos CM, Matin N, Dorrance AM. The effects of hypertension on the cerebral circulation. Am J Physiol Heart Circ Physiol. 2013;304(12):1598–1614.
18. Iadecola С. The pathobiology of vascular dementia. Neuron. 2013;80(4):844–866.
19. Москаленко Ю. Е. Кровообращение головного мозга. Физиология кровообращения. Физиология сосудистой системы. Л.: Наука, 1984; Гл. 11: 352–381..
20. Iadecola C. Neurovascular regulation in the normal brain and in Alzheimer’s disease. Nat Rev Neurosci. 2004;5(5):347–360.
21. Armulik A, Genové G, Mäe M, Nisancioglu MH, Wallgard E, Niaudet C et al. Pericytes regulate the blood-brain barrier. Nature. 2010;468(7323):557–561.
22. Chen BR, Kozberg MG, Bouchard MB, Shaik MA, Hillman EM. A critical role for the vascular endothelium in functional neurovascular coupling in the brain. J Am Heart Assoc. 2014;3(3):e000787.
23. Sokolova IA, Manukhina EB, Blinkov SM, Koshelev VB, Pinelis VG, Rodionov IM. Rarefication of the arterioles and capillary network in the brain of rats with different forms of hypertension. Microvasc Res. 1985;30(1):1–9.
24. Suzuki K, Masawa N, Sakata N, Takatama M. Pathologic evidence of microvascular rarefaction in the brain of renal hypertensive rats. J Stroke Cerebrovasc Dis. 2003;12(1):8–16.
25. Paiardi S, Rodella LF, De Ciuceis C, Porteri E, Boari GE, Rezzani R et al. Immunohistochemical evaluation of microvas- cular rarefaction in hypertensive humans and in spontaneously hypertensive rats. Clin Hemorheol Microcirc. 2009;42(4):259–268.
26. Sokolova IB, Sergeev IV, Dvoretskii DP. Influence of high blood pressure on microcirculation in cerebral cortex of young rats. Bull Exp Biol Med. 2016;160(3):298–299.
27. Фолков Б., Нил Э. Кровообращение. М.: Медицина, 1976. 463 с..
28. Iadecola C, Davisson RL. Hypertension and cerebrovascular dysfunction. Cell Metab. 2008;7(6):476–484.
29. Arribas SM, Costa R, Salomone S, Morel N, Godfraind T, McGrath JC. Functional reduction and associated cellular rearrangement in SHRSP rat basilar arteries are affected by salt load and calcium antagonist treatment. J Cereb Blood Flow Metab. 1999;19(5):517–527.
30. Korner PI. Cardiovascular hypertrophy and hypertension: causes and consequences. Blood Press Suppl. 1995;2:6–16.
31. Гераскина Л. А., Фонякина А. В., Магомедова А. Р. Артериальная ригидность и цереброваскулярные нарушения. Неврология, нейропсихиатрия, психосоматика. 2011;3(2):4–8..
32. Breithaupt-Grogler K, Belz GG. Epidemiology of arterial stiffness. Pathol Biol (Paris). 1999;47(6):604–613.
33. Lindesay G, Ragonnet C, Chimenti S, Villeneuve N, Vayssettes-Courchay C. Age and hypertension strongly induce aortic stiffening in rats at basal and matched blood pressure levels. Physiol Rep. 2016;4(10): e12805.
34. Harper SL, Bohlen HG. Microvascular adaptation in the cerebral cortex of adult spontaneously hypertensive rats. Hypertension. 1984;6(3):408–419.
35. Li Y, Shen Q, Huang S, Li W, Muir ER, Long JA et al. Cerebral angiography, blood flow and vascular reactivity in progressive hypertension. Neuroimage. 2015;111:329–337. doi:10. 1016/j.neuroimage.2015.02.053
36. Faraco G, Sugiyama Y, Lane D, Garcia-Bonilla L, Chang H, Santisteban MM et al. Perivascular macrophages mediate the neurovascular and cognitive dysfunction associated with hypertension. J Clin Invest. 2016;126(12):4674–4689.
37. Iddings JA, Kim KJ, Zhou Y, Higashimori H, Filosa JA. Enhanced parenchymal arteriole tone and astrocyte signaling protect neurovascular coupling mediated parenchymal arteriole vasodilation in the spontaneously hypertensive rat. J Cereb Blood Flow Metab. 2015;35(7):1127–1136.
38. Rosenberg GA. Extracellular matrix inflammation in vascular cognitive impairment and dementia. Clin Sci. (Lond). 2017;131(6):425–437.
39. Girouard H, Iadecola C. Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease. J Appl Physiol. 2006;100(1):328–335.
40. Jennings JR, Muldoon MF, Ryan C, Price JC, Greer P, Sutton-Tyrrell K et al. Reduced cerebral blood flow response and compensation among patients with untreated hypertension. Neurology. 2005;64(8):1358–1365.
41. Seryapina AA, Shevelev OB, Moshkin MP, Markel AL, Akulov AE et al. Stress-sensitive arterial hypertension, hemodynamic changes and brain metabolites in hypertensive ISIAH rats: MRI investigation. Exp Physiol. 2017;102(5):523–532.
42. Flores G, Flores-Gómez GD, de Jesús Gomez-Villalobos M. Neuronal changes after chronic high blood pressure in animal models and its implication for vascular dementia. Synapse. 2016;70 (5):198–205.
43. Sánchez F, Gómez-Villalobos Mde J, Juarez I, Quevedo L, Flores G. Dendritic morphology of neurons in medial prefrontal cortex, hippocampus, and nucleus accumbens in adult SH rats. Synapse. 2011;65(3):198–206.
44. Messerli FH, Williams B, Ritz E. Essential hypertension. Lancet. 2007;370(9587):591–603.
45. Hart EC. Human hypertension, sympathetic activity and the selfish brain. Exp Physiol. 2016;101(12):1451–1462.
46. Harrison DG. The mosaic theory revisited: common molecular mechanisms coordinating diverse organ and cellular events in hypertension. J Am Soc Hypertens. 2013;7(1):68–74. 50724(5) / 2018
47. Warnert EA, Rodrigues JC, Burchell AE, Neumann S, Ratcliffe LE, Manghat NE et al. Is high blood pressure selfprotection for the brain? Circ Res. 2016;119(12):140–151.
48. Tadic M, Cuspidi C, Hering D. Hypertension and cognitive dysfunction in elderly: blood pressure management for this global burden. J Clin Invest. 2016;126(12):4674–4689.
49. Kitagawa K. Cerebral blood flow measurement by PET in hypertensive subjects as a marker of cognitive decline. J Alzheimers Dis. 2010;20(3):855–859.
50. Foster-Dingley JC, Moonen JE, de Craen AJ, de Ruijter W, van der Mast RC, van der Grond J. Blood pressure is not associated with cerebral blood flow in older persons. Hypertension. 2015;66 (5):954–960.
51. Tryambake D, He J, Firbank MJ, O’Brien JT, Blamire AM, Ford GA. Intensive blood pressure lowering increases cerebral blood flow in older subjects with hypertension. Hypertension. 2013;61(6):1309–1315.
52. Yasar S, Schuchman M, Peters J, Anstey KJ, Carlson MC, Peters R. Relationship between antihypertensive medications and cognitive impairment: Part I. Review of human studies and clinical trials. Curr Hypertens Rep. 2016;18(8):67.
53. Edwards JD, Ramirez J, Callahan BL, Tobe SW, Oh P, Berezuk C et al. Alzheimer’s disease neuroimaging initiative. Antihypertensive treatment is associated with MRI-Derived markers of neurodegeneration and impaired cognition: a propensityweighted cohort study. J Alzheimers Dis. 2017;59(3):1113– 1122.
54. van Middelaar T, van Vught LA, van Charante EPM, Eurelings LSM, Ligthart SA, van Dalen JW et al. Lower dementia risk with different classes of antihypertensive medication in older patients. J Hypertens. 2017;35(10):2095–2101.
55. Gelber R, Webster Ross G, Petrovitch H, Masaki KH, Launer LJ, White L. Antihypertensive medication use and risk of cognitive impairment. The Honolulu-Asia Aging Study Neurology. 2013;81(10):888–895.
56. Peters R, Schuchman M, Peters J, Carlson MC, Yasar S. Relationship between antihypertensive medications and cognitive impairment: Part II. Review of Physiology and Animal Studies. Curr Hypertens Rep. 2016;18(8):66.
57. Gupta S, Sharma B. Pharmacological modulation of I(1)-imidazoline and α2-adrenoceptors in sub acute brain ischemia induced vascular dementia. Eur J Pharmacol. 2014;723:80–90. doi:10.1016/j.ejphar.2013.12.003
58. Daulatzai MA. Cerebral hypoperfusion and glucose hypometabolism: key pathophysiological modulators promote neurodegeneration, cognitive impairment, and Alzheimer’s disease. J Neurosci Res. 2017;95(4):943–972.