The role of arterial and venous blood flow and cerebrospinal fluid flow disturbances in the development of cognitive impairments in cerebral microangiopathy

Cover Page


Cite item

Full Text

Abstract

Cerebral microangiopathy (CMA) is the main cause of vascular cognitive disorders, the leading cause of mixed dementia, and the main modifiable risk factor in Alzheimer’s disease.

Study objective. To investigate the role of arterial and venous blood flow and cerebrospinal fluid flow, as well as their interrelation in the development of cognitive disorders in patients with CMA.

Materials and methods. Ninety-six patients (32 men and 64 women, mean age 60.6±6.3 years) with cognitive complaints and CMA, diagnosed according to the STRIVE international MRI criteria, were examined. The severity of cognitive disturbance was assessed based on the overall cognitive level (MoCA scale and independence in daily life), the results of memory tests (10 words memory test) and executive brain function tests (TMT B-A). Phase contrast MRI was used to measure blood flow in the internal carotid and vertebral arteries (total arterial blood flow), the internal jugular veins and the straight and superior sagittal sinuses, as well as the aqueductal cerebrospinal fluid flow. Arterial pulsation and intracranial compliance indices were calculated.

Results. Dementia and severe memory impairment were statistically significantly associated with an increase in the arterial pulsation index, intracranial compliance index and the aqueductal CSF stroke volume. Significant disturbances in brain executive function were also associated with a decrease in the total arterial blood flow, as well as the venous blood flow in the straight and superior sagittal sinuses. The characteristics of blood flow and cerebrospinal fluid are closely related, and the arterial pulsation index affects all the studied parameters.

Conclusion. The severity of cognitive disturbance in CMA is determined by an increase in the arterial pulsation index, the intracranial compliance index and the aqueductal CSF stroke volume, while the severity of dysregulation disorders is determined by a concurrent decrease in the total arterial blood flow and venous blood flow in the straight and superior sagittal sinuses. The specific changes in blood flow and CSF flow and their interrelation in patients with cognitive impairment due to CMA suggest the pathogenetic importance of cerebral hydrodynamic disturbances in the aetiology of brain damage and the development of cognitive impairment in CMA.

About the authors

Larisa A. Dobrynina

Research Center of Neurology

Author for correspondence.
Email: dobrla@mail.ru
ORCID iD: 0000-0001-9929-2725

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

Russian Federation, Moscow

Bulat M. Akhmetzyanov

Medical and Rehabilitation Center

Email: dobrla@mail.ru
Russian Federation, Moscow

Zukhra Sh. Gadzhieva

Research Center of Neurology

Email: dobrla@mail.ru
Russian Federation, Moscow

Еlena I. Kremneva

Research Center of Neurology

Email: dobrla@mail.ru
Russian Federation, Moscow

Lyudmila A. Kalashnikova

Research Center of Neurology

Email: dobrla@mail.ru
Russian Federation, Moscow

Marina V. Krotenkova

Research Center of Neurology

Email: dobrla@mail.ru
ORCID iD: 0000-0003-3820-4554

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

Russian Federation, 125367 Moscow, Volokolamskoye shosse, 80

References

  1. 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: 2672–2713. doi: 10.1161/STR.0b013e3182299496. PMID: 21778438.
  2. Deramacourt V., Slade J.Y., Oakley A.E. et al. Staging and natural history of cerebrovascular pathology in dementia. Neurology 2012; 78: 1043–1050. doi: 10.1212/WNL.0b013e31824e8e7f. PMID: 22377814.
  3. Wardlaw J.M., Smith E.E., Biessels G.J. et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol 2013; 12: 822–838. doi: 10.1016/S1474-4422(13)70124-8. PMID: 23867200.
  4. Livingston G., Sommerlad A., Orgeta V. et al. Dementia prevention, intervention, and care. Lancet 2017; 390: 2673–2734. doi: 10.1016/S0140-6736(17)31363-6. PMID: 28735855.
  5. Smith E.E., Beaudin A.E. New insights into cerebral small vessel disease and vascular cognitive impairment from MRI. Curr Opin Neurol 2018; 31: 36–43. doi: 10.1097/WCO.0000000000000513. PMID: 29084064.
  6. Kalashnikova L.A., Kadykov A.S., Gulevskaya T.S. [Cognitive impairment and dementia in subcortical arteriosclerotic encephalopathy in elderly and senile adults.] Klinicheskaya gerontologiya 1996; 1: 22–26. (In Russ.)
  7. Yakhno N.N., Levin O.S., Damulin I.V. [Comparison of clinical and MRI data with discirculatory encephalopathy. Message 2: cognitive impairment]. Nevrologicheskiy zhurnal 2001; 6(3): 10–19. (In Russ.)
  8. O’Sullivan M., Jones D.K., Summers P.E. et al. Evidence for cortical “disconnection” as a mechanism of age-related cognitive decline. Neurology 2001. 57: 632–638. doi: 10.1212/WNL.57.4.632. PMID: 11524471.
  9. Gulevskaya T.S. [Pathology of the white matter of the cerebral hemispheres in arterial hypertension with cerebral circulation disorders: med. sci. diss.]. Moscow, 1994. (In Russ.)
  10. Fisher C.M. The arterial lesions underlying lacunes. Acta Neuropathol 1969; 12: 1–15. PMID: 5708546.
  11. Gulevskaya T.S., Lyudkovskaya I.G. [Arterial hypertension and white matter pathology]. Arkhiv patologii 1992; (2): 53–59. (In Russ.)
  12. Gulevskaya T.S., Morgunov V.A. [Patology of stroke in atherosclerosis and arterial hypertension]. Moscow, 2009. 296 p. (In Russ.)
  13. Ibayashi S., Nagao T., Kuwabara Y. et al. Mechanism for decreased cortical oxygen metabolism in patients with leukoaraiosis: Is disconnection the answer? Stroke Cerebrovasc Dis 2000; 9: 22–26. doi: 10.1016/S1052-3057(00)19327-9.
  14. Mashin V.V. [Hypertensive encephalopathy: clinical manifestations and cerebral hemodynamics in patients with chronic heart failure: med. sci. diss.]. Moscow, 2004. (In Russ.)
  15. Geraskina L.A., Sharypova T.N., Mashin V.V. et al. [Blood supply of the brain in hypertensive encephalopathy and chronic heart failure]. Kardiovaskulyarnaya terapiya i profilaktika 2009. 8 (5): 28–32. (in Russ)
  16. ten Dam V.H., van den Heuvel D.M., de Craen A.J. et al. Decline in total cerebral blood flow is linked with increase in periventricular but not deep white matter hyperintensities. Radiology; 2007; 243: 198–203. doi: 10.1148/radiol.2431052111. PMID: 17329688.
  17. van der Veen P.H., Muller M., Vincken K.L. et al. Longitudinal relationship between cerebral small-vessel disease and cerebral blood flow: the second manifestations of arterial disease — magnetic resonance study. Stroke 2015; 46: 1233–1238. doi: 10.1161/STROKEAHA.114.008030. PMID: 25804924.
  18. Shi Y., Wardlaw J. Update on cerebral small vessel disease: a dynamic whole-brain disease. Stroke Vasc Neurol 2016. 2: 83–92. doi: 10.1136/svn-2016-000035. PMID: 28959468.
  19. Gannushkina I.V., Lebedeva N.V. [Hypertensive encephalopathy]. Moscow, 1987. (In Russ.)
  20. Moody D.M., Brown W.R., Challa V.R., Anderson R.L. Periventricular venous collagenosis: association with leukoaraiosis. Radiology 1995. 194: 469–76. doi: 10.1148/radiology.194.2.7824728. PMID: 7824728.
  21. Brown W.R., Moody D.M., Challa V.R. et al. Venous collagenosis and arteriolar tortuosity in leukoaraiosis. J Neurol Sci 2002; 203–204: 159–163. PMID: 12417376.
  22. Shim Y.S., Yang D.W., Roe C.M. et al. Pathological correlates of white matter hyperintensities on magnetic resonance imaging. Dement Geriatr Cogn Disord 2015; 39: 92–104. doi: 10.1159/000366411. PMID: 25401390.
  23. Mashin V.V., Belova L.A., Kadykov A.S. [Venous discirculation of the brain in hypertensive encephalopathy]. Nevrologicheskiy vestnik 2005. (3–4): 17–21. (In Russ.)
  24. Belova L.A. [The role of arteriovenous relationships in the formation of clinical and pathogenetic variants of hypertensive encephalopathy]. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova 2012; (6): 8–12. (In Russ.)
  25. Sachdev P., Kalaria R., O’Brien J. et al. Diagnostic criteria for vascular cognitive disorders: a VASCOG statement. Alzheimer Dis Assoc Disord 2014; 28: 206–218. doi: 10.1097/WAD.0000000000000034. PMID: 24632990.
  26. Pantoni L., Fierini F., Poggesi A.; LADIS Study Group. Impact of cerebral white matter changes on functionality in older adults: An overview of the LADIS Study results and future directions. Geriatr Gerontol Int 2015; 15 Suppl 1: 10–6. doi: 10.1111/ggi.12665. PMID: 26671152.
  27. Bateman G.A. Pulse-wave encephalopathy: a comparative study of the hydrodynamics of leukoaraiosis and normal pressure hydrocephalus. Neuroradiology 2002; 44: 740–748. doi: 10.1007/s00234-002-0812-0. PMID: 12221445.
  28. Bateman G.A. Pulse wave encephalopathy: a spectrum hypothesis incorporating Alzheimer’s disease, vascular dementia and normal pressure hydrocephalus. Med Hypotheses 2004; 62: 182–187. doi: 10.1016/S0306-9877(03)00330-X. PMID: 14962623.
  29. Bateman G.A., Levi C.R., Schofield P. et al. The venous manifestations of pulse wave encephalopathy: windkessel dysfunction in normal aging and senile dementia. Neuroradiology 2008; 50: 491–497. doi: 10.1007/s00234-008-0374-x. PMID: 18379767.
  30. Henry-Feugeas M.C., Roy C., Baron G., Schouman-Claeys E. Leukoaraiosis and pulse-wave encephalopathy: observations with phase contrast MRI in mild cognitive impairment. J Neuroradiol 2009; 36: 212–218. doi: 10.1016/j.neurad.2009.01.003. PMID: 19250677.
  31. Henry-Feugeas M.C., Koskas P. Cerebral vascular aging: extending the concept of pulse wave encephalopathy through capillaries to the cerebral veins. Curr Aging Sci 2012; 5: 157–167. PMID: 22894741.
  32. Iliff J.J., Wang M., Liao Y. et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid beta. Sci Transl Med 2012; 4: 1–11. doi: 10.1126/scitranslmed.3003748. PMID: 22896675.
  33. Iliff J.J., Wang M., Zeppenfeld D.M. et al. Cerebral arterial pulsation drives paravascular CSF-interstitial fluid exchange in the murine brain. J Neurosci 2013; 33: 18190–18199. doi: 10.1523/JNEUROSCI.1592-13.2013. PMID: 24227727.
  34. Zlokovic B.V. Neurovascular pathways to neurodegeneration in Alzheimer's disease and other disorders. Nat Rev Neurosci 2011; 12: 723–738. doi: 10.1038/nrn3114. PMID: 22048062.
  35. Mestre H., Kostrikov S., Mehta R.I., Nedergaard M. Perivascular spaces, glymphatic dysfunction, and small vessel disease. Clin Sci (Lond.) 2017; 131: 2257–2274. doi: 10.1042/CS20160381. PMID: 28798076.
  36. Dobrynina L.A., Gadzhieva Z.Sh., Kalashnikova L.A. et al. [Neuropsychological profile and vascular risk factors in patients with cerebral microangiopathy]. Annals of clinical and experimental neurology 2018; (4): 5–15. doi: 10.25692/ACEN.2018.4.1 (In Russ.)
  37. Nasreddine Z.S., Phillips N.A., Bedirian V. et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 2005; 4: 695–699. doi: 10.1111/j.1532-5415.2005.53221.x. PMID: 15817019.
  38. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington, 2013. 970 p. doi: 10.1176/appi.books.9780890425596.
  39. Lezak M.D., Howieson D.B., Loring D.W. et al. Neuropsychological assessment (4th ed.). New York, 2004.
  40. Luriya A.R. [Higher cortical functions of man.] Moscow, 1969. (In Russ.)
  41. El Sankari S., Gondry-Jouet C., Fichten A. et al. Cerebrospinal fluid and blood flow in mild cognitive impairment and Alzheimer's diseas: a differential diagnosis from idiopathic normal pressure hydrocephalus. Fluids Barriers CNS 2011. 8: 12. doi: 10.1186/2045-8118-8-12. PMID: 21349149.
  42. Balédent O., Henry-Feugeas M.C., Idy-Peretti I. Cerebrospinal fluid dynamics and relation with blood flow: a magnetic resonance study with semi-automated cerebrospinal fluid segmentation. Invest Radiol 2001; 36: 368–377. PMID: 11496092.
  43. Mokri B. The Monro–Kellie hypothesis: applications in CSF volume depletion. Neurology 2001; 56: 1746–1748. PMID: 11425944.
  44. Ambarki K., Baledent O., Kongolo G. et al. A new lumped-parameter model of cerebrospinal hydrodynamics during the cardiac cycle in healthy volunteers. IEEE Trans Biomed Eng 2007; 54: 483–491. doi: 10.1109/TBME.2006.890492. PMID: 17355060.
  45. Frydrychowski A.F., Winklewski P.J., Guminski W. Influence of acute jugular vein compression on the cerebral blood flow velocity, pial artery pulsation and width of subarachnoid space in humans. PLoS One 2012; 7: e48245. doi: 10.1371/journal.pone.0048245. PMID: 23110218.
  46. Schaller B. Physiology of cerebral venous blood flow: from experimental data in animals to normal function in humans. Brain Res Brain Res Rev 2004; 46: 243–260. doi: 10.1016/j.brainresrev.2004.04.0057. PMID: 15571768.
  47. Vignes J.R., Dagain A., Guérin J., Liguoro D. A hypothesis of cerebral venous system regulation based on a study of the junction between the cortical bridging veins and the superior sagittal sinus. Laboratory investigation. J Neurosurg 2007; 107: 1205–1210. doi: 10.3171/JNS-07/12/1205. PMID: 18077958.
  48. Egnor M., Rosiello A., Zheng L. A model of intracranial pulsations. Pediatr Neurosurg 2001; 35: 284–298. doi: 10.1159/000050440. PMID: 11786696.
  49. Williams H. A unifying hypothesis for hydrocephalus, Chiari malformation, syringomyelia, anencephaly and spina bifida. Cerebrospinal Fluid Res 2008; 5: 7. doi: 10.1186/1743-8454-5-7. PMID: 18405364.
  50. Yakhno N.N., Zakharov V.V., Lokshina A.B. [Mild cognitive impairment in dyscirculatory encephalopathy]. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. 2005; (2): 13–7. (In Russ.)
  51. 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. doi: 10.1159/000334498. PMID: 22279631.
  52. 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 140 stroke (SCANS) study. PloS One 2013; 8: e61014. doi: 10.1371/journal.pone.0061014. PMID: 23613774.
  53. Albert M.S., DeKosky S.T., Dickson D. et al. 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. Alzheimers Dement 2011; 7: 270–279. doi: 10.1016/j.jalz.2011.03.008. PMID: 21514249.
  54. Prins N.D., van Dijk E.J., den Heijer T. et al. Cerebral small-vessel disease and decline in information processing speed, executive function and memory. Brain 2005; 128: 2034–2041. doi: 10.1093/brain/awh553. PMID: 15947059.
  55. Nordahl C.W., Ranganath C., Yonelinas A.P. et al. Different mechanisms of episodic memory failure in mild cognitive impairment. Neuropsychologia 2005; 43: 1688-1697. doi: 10.1016/j.neuropsychologia.2005.01.003. PMID: 16009250.
  56. Reed B.R., Mungas D.M., Kramer J.H. et al. Profiles of neuropsychological impairment in autopsy-defined Alzheimer's disease and cerebrovascular disease. Brain 2007. 130: 731–739. doi: 10.1093/brain/awl385. PMID: 17267522.
  57. Vasquez B.P., Zakzanis K.K. The neuropsychological profile of vascular cognitive impairment not demented: a meta-analysis. J Neuropsychol 2015; 9: 109–136. doi: 10.1111/jnp.12039. PMID: 24612847.
  58. McAleese K.E., Alafuzoff I., Charidimou A. et al. Post-mortem assessment in vascular dementia: advances and aspirations. BMC Med 2016; 14: 129. doi: 10.1186/s12916-016-0676-5. PMID: 27600683.
  59. Grinberg L.T., Nitrini R., Suemoto C.K. et al. Prevalence of dementia subtypes in a developing country: a clinicopathological study. Clinics 2013; 68: 1140–1145. doi: 10.6061/clinics/2013(08)13. PMID: 24037011.
  60. Koltover A.N., Lyudkovskaya I.G., GulevskayaT.S. et al. [Hypertensive angioencephalopathy in the pathological aspect]. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova 1984. 84: 1016–1020. (In Russ.)
  61. Fisher C.M. Lacunar strokes and infarcts: a review. Neurology 1982; 32: 871–871. doi: 10.1212/WNL.32.8.871. PMID: 7048128.
  62. Geschwind N. Disconnexion syndromes in animals and man. II. Brain 1965; 88: 585–644. PMID: 5318824.
  63. O’Sullivan M., Morris R.G., Huckstep B. et al. Diffusion tensor MRI correlates with executive dysfunction in patients with ischaemic leukoaraiosis. J Neurol Neurosurg Psychiatry 2004; 75: 441–447. doi: 10.1136/jnnp.2003.014910. PMID: 14966162.
  64. Fazekas F., Kleinert R., Offenbacher H. et al. The morphologic correlate of incidental punctate white matter hyperintensities on MR images. Am J Neuroradiol 1991. 12: 915–921. PMID: 1950921.
  65. Jolly T.A., Bateman G.A., Levi C.R. et al. Early detection of microstructural white matter changes associated with arterial pulsatility. Front Hum Neurosci 2013; 7: 782. doi: 10.3389/fnhum.2013.00782. PMID: 24302906.
  66. Ekstedt J. CSF hydrodynamic studies in man. 2. Normal hydrodynamic variables related to CSF pressure and flow. J Neurol Neurosurg Psychiatry 1978; 41: 345–353. doi: 10.1136/jnnp.41.4.345. PMID: 650242.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2019 Dobrynina L.A., Akhmetzyanov B.M., Gadzhieva Z.S., Kremneva E.I., Kalashnikova L.A., Krotenkova M.V.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77-83204 от 12.05.2022.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies