Subclinical cerebral manifestations and changes of brain associated with newly diagnosed asymptomatic arterial hypertension

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Background. Progressive aggravation of cerebral affection in patients with asymptomatic arterial hypertension (AH) suggests importance of the affection in the development of subclinical cerebral manifestations.
Objective. To evaluate the dependence of subclinical depression, anxiety, and memory impairments on the severity of white matter hyperintensity (WMH) and microstructural changes in a visually intact brain matter in patients with asymptomatic AH.
Materials and methods. The study involved 82 patients with newly diagnosed asymptomatic AH, aged 40−59 years. All patients were assessed for delayed memory (Luria’s test) as well as depression and anxiety (Hospital Anxiety and Depression Scale (HADS)) and underwent brain MRI (T1 and T2 weighted imaging, FLAIR, diffusion weighted imaging with calculation of apparent diffusion coefficient (ADC) maps).
Results. The earliest structural-functional relationships between subdepressive symptoms and ACD-assessed microstructural changes were found in the hippocampus, thalamus, and visually intact deep white matter of the cerebral hemispheres. AH worsening was accompanied by a growing number of areas associated with subclinical depression, anxiety, and memory impairments and characterized by WMH lesions and an increased ACD in a visually intact brain matter.
Conclusion. Microstructural changes in the hippocampus, thalamus, and deep structures of the hemispheres are the structural/functional basis of subclinical depression at the early AH stages. The AH worsening-associated involvement of new structures associated with subclinical depression, anxiety, and memory impairments, which are characterized by an increased ACD and WMH lesions, demonstrates the importance of progressive diffuse brain damage in the development of both subclinical and subsequent clinical manifestations of depression, anxiety, and memory impairments.The nature of relationships between hypertension and depression needs to be clarified. In this connection, it seems appropriate to study the role of their common stress-induced processes: inflammation and neurovascular association due to hyperactivation of the suprasegmental autonomic centers.

About the authors

Larisa A. Dobrynina

Research Center of Neurology

Author for correspondence.
ORCID iD: 0000-0001-9929-2725

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

Russian Federation, Moscow

Elena V. Gnedovskaya

Research Center of Neurology

Russian Federation, Moscow

Anastasiya N. Sergeeva

Research Center of Neurology

Russian Federation, Moscow

Marina V. Krotenkova

Research Center of Neurology

ORCID iD: 0000-0003-3820-4554

D. Sci. (Med.), Head, Neuroradiology department

Russian Federation, 125367 Moscow, Volokolamskoye shosse, 80

Mikhail A. Piradov

Research Center of Neurology

ORCID iD: 0000-0002-6338-0392

D. Sci. (Med.), Professor, Full Member of the Russian Academy of Sciences, Director

Russian Federation, Moscow


  1. Андрющенко А.В., Дробижев М.Ю., Добровольский А.В. Сравнительная оценка шкал CES-D, BDI и HADS(d) в диагностике депрессии в общемедицинской практике. Журн. неврол. и психиатр. им. С.С. Корсакова. 2003; 103 (5): 11–18. PMID: 12789819
  2. Ганнушкина И.В. Лебедева Н.В. Гипертоническая энцефалопатия. М.: Медицина, 1987.
  3. Клиническое руководство по ранней диагностике, лечению и профилактике сосудистых заболеваний головного мозга. Под ред. Суслина З.А., Варакин Ю.Я. М.: МЕДпресс-информ, 2015.
  4. Чазов Е.И., Оганов Р.Г., Погосова Г.В. и др. Клинико-эпидемиологическая программа изучения депрессии в кардиологической практике: у больных артериальной гипертонией и ишемической болезнью сердца (КООРДИНАТА): результаты многоцентрового исследования. Кардиология 2007; 3: 28–37.
  5. Сосудистые заболевания нервной системы. Под ред. Шмидт Е.В. М.: Медицина; 1975.
  6. Axon R.N., Zhao Y., Egede L.E. Association of depressive symptoms with all-cause and ischemic heart disease mortality in adults with self-reported hypertension. Am J Hypertens. 2010; 23: 30–37. PMID: 19893497 doi: 10.1038/ajh.2009.199
  7. Campbell St., Marriott M., Nahmias Cl., MacQueen G.M. Lower hippocampal volume in patients suffering from depression: a meta-analysis. Am J Psychiatry. 2004; 161: 598–607. PMID: 15056502 doi: 10.1176/appi.ajp.161.4.598
  8. Carvalho A.F., Köhler C.A., McIntyre R.S. et al. Peripheral vascular endothelial growth factor as a novel depression biomarker: A meta-analysis. Psychoneuroendocrinology. 2015; 62: 18–26. PMID: 26210676 doi: 10.1016/j.psyneuen.2015.07.002
  9. De Ciuceis C., Rossini C., La Boria E. et al. Immune mechanisms in hypertension. High Blood Press Cardiovasc Prev. 2014; 21 (4): 227–234. PMID: 24446309 doi: 10.1007/s40292-014-0040-9
  10. Fazekas F., Ropele S., Enzinger C. et al. MTI of white matter hyperintensities. Brain 2005; 128: 2926–2932. PMID: 15958507 doi: 10.1093/brain/awh567
  11. Filomena J., Riba-Liena I., Vinyoles E. et al. Short-Term Blood Pressure Variability Relates to the Presence of Subclinical Brain Small Vessel Disease in Primary Hypertension. Hypertension. 2015; 66 (3): 634–640; discussion 445. PMID: 26101344 doi: 10.1161/HYPERTENSIONAHA.115.05440
  12. Firbank M.J., O’Brien J.T., Pakrasi S. et al. White matter hyperintensities and depression – preliminary results from the LADIS study. Int J Geriatr Psychiatry 2005; 20: 674–679. PMID: 16021663 doi: 10.1002/gps.1342
  13. Ginty A.T., Carroll D., Roseboom T.J. et al. Depression and anxiety are associated with a diagnosis of hypertension 5 years later in a cohort of late middle-aged men and women. J Hum Hypertens. 2013; 27: 187–190. PMID: 22592133 doi: 10.1038/jhh.2012.18
  14. Gorelick P.B., Scuteri A., Black S.E. et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the american heart association/american stroke association. Stroke. 2011; 42 (9): 2672–2713. PMID: 21778438 doi: 10.1161/STR.0b013e3182299496
  15. Hamer M., Batty G.D., Stamatakis E., Kivimaki M. The combined influence of hypertension and common mental disorder on all-cause and cardiovascular disease mortality. J Hypertens. 2010; 28: 2401–2406.PMID: 20724937 doi: 10.1097/HJH.0b013e32833e9d7c
  16. Ho A.K., Thorpe C.T., Pandhi N. et al. Association of anxiety and depression with hypertension control: a US multidisciplinary group practice observational study. J Hypertens. 2015 Nov; 33 (11): 2215–2222.PMID: 26259121 doi: 10.1097/HJH.0000000000000693
  17. Kim Y.K., Na K.S., Myint A.M., Leonard B.E. The role of pro-inflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2016; 64: 277–284. PMID: 26111720 doi: 10.1016/j.pnpbp.2015.06.008
  18. Koolschijn P.C., van Haren N.E., Lensvelt-Mulders G.J. et al. (2009) Brain volume abnormalities in major depressive disorder: A meta-analysis of magnetic resonance imaging studies. Hum Brain Mapp 30: 3719–3735. PMID: 19441021 doi: 10.1002/hbm.20801
  19. Kunugi H., Hori H, Numakawa T, Ota M. The hypothalamic-pituitary-adrenal axis and depressive disorder: recent progress. Nihon Shinkei Seishin Yakurigaku Zasshi. 2012; 32 (4): 203–209. PMID: 23012888
  20. Krishnan M.S., O’Brien J.T., Firbank M.J. et al. LADIS Group: Relationship between periventricular and deep white matter lesions and depressive symptoms in older people. The LADIS Study. Int J Geriatr Psychiatry 2006; 21: 983–989. PMID: 16955428 doi: 10.1002/gps.1596
  21. Lawrence A.J., Patel B., Morris R.G. et al. Mechanisms of cognitive impairment in cerebral small vessel disease: multimodal MRI results from the St George’s cognition and neuroimaging in stroke (SCANS) study. PLoS One. 2013; 8 (4): e61014. PMID: 23613774 doi: 10.1371/journal.pone.0061014
  22. Lin W.C., Hu L.Y., Tsai S.J. et al. Depression and the risk of vascular dementia: a population-based retrospective cohort study. Int J Geriatr Psychiatry. 2016. PMID: 27161941 doi: 10.1002/gps.4493
  23. Li Z., Li Y., Chen L. et al. Prevalence of depression in patients with hypertension: a systematic review and meta-analysis. Medicine (Baltimore) 2015 Aug; 94 (31): e1317. PMID: 26252317 doi: 10.1097/MD.0000000000001317
  24. Maletic V., Robinson M., Oakes T. et al. Neurobiology of depression: an integrated view of key findings. Int J Clin Pract. 2007 Dec; 61 (12): 2030–2040. PMID: 17944926 doi: 10.1111/j.1742-1241.2007.01602.x
  25. Mancia G., Fagard R., Narkiewicz K. et al. ESH/ESC Guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Journal of Hypertension 2013, 31 (7): 1281–357. PMID: 26252317 doi: 10.1097/MD.0000000000001317
  26. McMaster W.G., Kirabo A., Madhur M.S., Harrison D.G. Inflammation, immunity, and hypertensive end-organ damage. Circ Res. 2015 Mar 13; 116 (6): 1022–1033. PMID: 25767287 doi: 10.1161/CIRCRESAHA.116.303697
  27. Meissner A. Hypertension and the Brain: A Risk Factor for More Than Heart Disease. Cerebrovasc Dis. 2016; 42 (3–4): 255–262. PMID: 27173592 doi: 10.1159/000446082
  28. Meng L., Chen D., Yang Y. et al. Depression increases the risk of hypertension incidence: a meta-analysis of prospective cohort studies.J Hypertens. 2012; 30: 842–851. PMID: 22343537 DOI: 10.1097/ HJH.0b013e32835080b7
  29. Miller B.R., Hen R. The current state of the neurogenic theory of depression and anxiety. Curr Opin Neurobiol. 2015; 30: 51–58. PMID: 5240202 doi: 10.1016/j.conb.2014.08.012
  30. O’Brien J.T., Firbank M.J., Krishnan M.S. et al. LADIS Group: White matter hyperintensities rather than lacunar infarcts are associated with depressive symptoms in older people: the LADIS study. Am J Geriatr Psychiatry 2006; 14: 834–841. PMID: 17001023 doi: 10.1097/01.JGP.0000214558.63358.94
  31. Philip N.S., Tyrka A.R., Albright S.E. et al. Early life stress predicts thalamic hyperconnectivity: A transdiagnostic study of global connectivity. J Psychiatr Res. 2016; 79: 93–100. PMID: 27214526 doi: 10.1016/j.jpsychires.2016.05.003
  32. Raison C.L., Capuron L., Miller A.H. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol 2006; 27: 24–31. PMID: 16316783 doi: 10.1016/
  33. Riba-Llena I., Jarca C., Mundet X. et al. Investigating silent strokes in hypertensives: a magnetic resonance imaging study (ISSYS): rationale and protocol design. BMC Neurol. 2013; 13: 130. PMID: 24083440 doi: 10.1186/1471-2377-13-130
  34. Saboya P.M., Zimmermann P.R., Bodanese L.C. Association between anxiety or depressive symptoms and arterial hypertension, and their impact on the quality of life. Int J Psychiatry Med. 2010; 40 (3): 307–320. PMID: 21166340
  35. Schmidt R., Ropele S., Ferro J. et al. LADIS study Group: Diffusion weighted imaging and cognition in the leukoariosis and disability in the elderly study. Stroke 2010; 41: e402–e408. PMID: 20203319 doi: 10.1161/STROKEAHA.109.576629
  36. Sheline Y.I., Wang P., Gado M.H. et al. Hippocampal atrophy in recurrent major depression. Proc Natl Acad Sci USA. 1996; 93: 3908–3913. PMID: 8632988
  37. Stumpf C., Jukic J., Yilmaz A. et al. Elevated VEGF-plasma levels in young patients with mild essential hypertension. Eur J Clin Invest.2009; 39 (1): 31–36. PMID: 19067736 doi: 10.1111/j.1365-2362.2008.02056.x
  38. Sudlow C.L., Warlow C.P. Comparable studies of the incidence of stroke and its pathological types: results from an international collaboration.International Stroke Incidence Collaboration. Stroke. 1997; 28 (3): 491–499. PMID: 9056601
  39. Teodorczuk A., Firbank M.J., Pantoni L., et al. LADIS Group: Relationship between baseline white-matter changes and development of late-life depressive symptoms: 3-year results from the LADIS study. Psychol Med 2010; 40: 603–610. PMID: 19671212 doi: 10.1017/S0033291709990857
  40. Teodorczuk A., O’Brien J.T., Firbank M.J., et al. LADIS Group: White matter changes and late-life depressive symptoms: longitudinal study. Br J Psychiatry 2007; 191: 212–217. PMID: 17766760 doi: 10.1192/bjp.bp.107.036756
  41. The LADIS Study Group. 2001–2011: A Decade of the LADIS (Leukoaraiosis And DISability) Study: What Have We Learned about White Matter Changes and Small-Vessel Disease? Cerebrovasc Dis.2011; 32: 577–588. PMID: 22277351 doi: 10.1159/000334498
  42. Tuladhar A.M., van Norden A.G., de Laat K.F. et al. White matter integrity in small vessel disease is related to cognition. Neuroimage Clin. 2015; 7: 518–524. PMID: 25737960 doi: 10.1016/j.nicl.2015.02.003
  43. Van der Flier W.M., van Straaten E.C., Barkhof F. et al. Small vessel disease and general cognitive function in nondisabled elderly: the LADIS study. Stroke 2005; 36: 2116–2120. PMID: 16141425 doi: 10.1161/01.STR.0000179092.59909.42
  44. Wen M.C., Steffens D.C., Chen M.K., Zainal N.H. Diffusion tensor imaging studies in late-life depression: systematic review and meta-analysis. Int J Geriatr Psychiatry. 2014; 29 (12): 1173–1184. PMID: 24798480 doi: 10.1002/gps.4129
  45. Zeng L.L., Shen H., Liu L. et al. Identifying major depression using whole-brain functional connectivity: a multivariate pattern analysis. Brain. 2012; 135 (Pt 5): 1498–1507. PMID: 22418737 doi: 10.1093/brain/aws059
  46. Zigmond AS, Snaith RP. The Hospital Anxiety and Depression Scale. Acta Psychiatr Scand. 1983 Jun; 67 (6): 361–370. PMID: 6880820

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Copyright (c) 2016 Dobrynina L.A., Gnedovskaya E.V., Sergeeva A.N., Krotenkova M.V., Piradov M.A.

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