Cerebral Small Vessel Disease

Jakub Litak, Marek Mazurek, Bartłomiej Kulesza, Paweł Szmygin, Joanna Litak, Piotr Kamieniak, Cezary Grochowski, Jakub Litak, Marek Mazurek, Bartłomiej Kulesza, Paweł Szmygin, Joanna Litak, Piotr Kamieniak, Cezary Grochowski

Abstract

Cerebral small vessel disease (CSVD) represents a cluster of various vascular disorders with different pathological backgrounds. The advanced vasculature net of cerebral vessels, including small arteries, capillaries, arterioles and venules, is usually affected. Processes of oxidation underlie the pathology of CSVD, promoting the degenerative status of the epithelial layer. There are several classifications of cerebral small vessel diseases; some of them include diseases such as Binswanger's disease, leukoaraiosis, cerebral microbleeds (CMBs) and lacunar strokes. This paper presents the characteristics of CSVD and the impact of the current knowledge of this topic on the diagnosis and treatment of patients.

Keywords: CMB; CSVD; cerebral microbleeds; cerebral small vessel disease.

Conflict of interest statement

The authors declare no conflict of interest in preparing this article.

References

    1. Pantoni L. Cerebral small vessel disease: From pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol. 2010;9:689–701. doi: 10.1016/S1474-4422(10)70104-6.
    1. Kwon S.M., Choi K.S., Yi H.J., Ko Y., Kim Y.S., Bak K.H., Chun H.J., Lee Y.J., Lee J.Y. Impact of brain atrophy on 90-day functional outcome after moderate-vol- ume basal ganglia hemorrhage. Sci. Rep. 2018;8:4819. doi: 10.1038/s41598-018-22916-3.
    1. Zhang A.-J., Yu X.-J., Wang M. The clinical manifestations and pathophysiology of cerebral small vessel disease. Neurosci. Bull. 2010;26:257–264. doi: 10.1007/s12264-010-1210-y.
    1. Ryu W.-S., Woo S.-H., Schellingerhout D., Jang M.U., Park K.-J., Hong K.-S., Jeong S.-W., Na J.-Y., Cho K.-H., Kim J.-T., et al. Stroke outcomes are worse with larger leukoaraiosis volumes. Brain. 2016;140:158–170. doi: 10.1093/brain/aww259.
    1. Caprio F.Z., Maas M.B., Rosenberg N.F., Kosteva A.R., Bernstein R.A., Alberts M.J., Prabhakaran S., Naidech A.M. Leukoaraiosis on magnetic resonance imaging cor- relates with worse outcomes after spontaneous intracerebral hemorrhage. Stroke. 2013;44:642–646. doi: 10.1161/STROKEAHA.112.676890.
    1. Onteddu S.R., Goddeau R.P., Jr., Minaeian A., Henninger N. Clinical impact of leukoaraiosis burden and chronological age on neurological de cit recovery and 90-day outcome after minor ischemic stroke. J. Neurol. Sci. 2015;359:418–423. doi: 10.1016/j.jns.2015.10.005.
    1. Förster A., Griebe M., Ottomeyer C., Rossmanith C., Gass A., Kern R., Hennerici M.G., Szabo K. Cerebral Network Disruption as a Possible Mechanism for Impaired Recovery after Acute Pontine Stroke. Cerebrovasc. Dis. 2011;31:499–505. doi: 10.1159/000324390.
    1. Wallin A., Kapaki E., Boban M., Engelborghs S., Hermann D.M., Huisa B., Jonsson M., Kramberger M.G., Lossi L., Malojcic B., et al. Biochemical markers in vascular cognitive impairment associ- ated with subcortical small vessel disease—A consensus report. BMC Neurol. 2017;17:102–116. doi: 10.1186/s12883-017-0877-3.
    1. Staals J., Makin S.D., Doubal F.N., Dennis M.S., Wardlaw J.M. Stroke subtype, vascular risk factors, and total MRI brain small-vessel disease burden. Neurology. 2014;83:1228–1234. doi: 10.1212/WNL.0000000000000837.
    1. Xu X., Hilal S., Collinson S.L., Chong E.J.Y., Ikram M.K., Venketasubramanian N., Chen C.L.H. Association of magnetic resonance imaging markers of cerebro- vascular disease burden and cognition. Stroke. 2015;46:2808–2814. doi: 10.1161/STROKEAHA.115.010700.
    1. Furuta A., Ishii N., Nishihara Y., Horie A. Medullary arteries in aging and dementia. Stroke. 1991;22:442–446. doi: 10.1161/01.STR.22.4.442.
    1. Vinters H.V. Cerebral amyloid angiopathy. A critical review. Stroke. 1987;18:311–324. doi: 10.1161/01.STR.18.2.311.
    1. Coria F., Rubio I. Cerebral amyloid angiopathies. Neuropathol. Appl. Neurobiol. 1996;22:216–227. doi: 10.1111/j.1365-2990.1996.tb00897.x.
    1. Smith E.E., Eichler F. Cerebral Amyloid Angiopathy and Lobar Intracerebral Hemorrhage. Arch. Neurol. 2006;63:148–151. doi: 10.1001/archneur.63.1.148.
    1. Viswanathan A., Chabriat H. Cerebral Microhemorrhage. Stroke. 2006;37:550–555. doi: 10.1161/01.STR.0000199847.96188.12.
    1. Grewal R.P. Stroke in Fabry’s disease. J. Neurol. 1994;241:153–156. doi: 10.1007/BF00868342.
    1. Joutel A., Faraci F.M. Cerebral smallv essel disease: Insights and opportunities from mouse models of collagen IV-related small vessel disease and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Stroke. 2014;45:1215–1221. doi: 10.1161/STROKEAHA.113.002878.
    1. Lie J. Primary (granulomatous) angiitis of the central nervous system: A clinicopathologic analysis of 15 new cases and a review of the literature. Hum. Pathol. 1992;23:164–171. doi: 10.1016/0046-8177(92)90238-X.
    1. Akassoglou K., Douni E., Bauer J., Lassmann H., Kollias G., Probert L. Exclusive tumor necrosis factor (TNF) signaling by the p75TNF receptor triggers inflammatory ischemia in the CNS of transgenic mice. Proc. Natl. Acad. Sci. USA. 2003;100:709–714. doi: 10.1073/pnas.0236046100.
    1. Greenan T.J., Grossman R.I., Goldberg H.I. Cerebral vasculitis: MR imaging and angiographic correlation. Radiology. 1992;182:65–72. doi: 10.1148/radiology.182.1.1727311.
    1. Moody D.M., Brown W.R., Challa V.R., Anderson R.L. Periventricular venous collagenosis: Association with leukoaraiosis. Radiology. 1995;194:469–476. doi: 10.1148/radiology.194.2.7824728.
    1. Lampert P., Tom M.I., Rider W.D. Disseminated demyelination of the brain following Co60 (gamma) radiation. Arch. Pathol. 1959;68:322–330.
    1. Crompton M.R., Layton D.D. Delayed radionecrosis of the brain following therapeutic x-radiation of the pituitary. Brain. 1961;84:85–101. doi: 10.1093/brain/84.1.85.
    1. Rauch P.J., Park H.S., Knisely J.P., Chiang V.L., Vortmeyer A.O. Delayed Radiation-Induced Vasculitic Leukoencephalopathy. Int. J. Radiat. Oncol. 2012;83:369–375. doi: 10.1016/j.ijrobp.2011.06.1982.
    1. Viswanathan A., Greenberg S.M. Cerebral amyloid angiopathy in the elderly. Ann. Neurol. 2011;70:871–880. doi: 10.1002/ana.22516.
    1. Attems J., Jellinger K., Thal D., Van Nostrand W. Review: Sporadic cerebral amyloid angiopathy. Neuropathol. Appl. Neurobiol. 2011;37:75–93. doi: 10.1111/j.1365-2990.2010.01137.x.
    1. Shams S., Granberg T., Martola J., Li X., Shams M., Fereshtehnejad S.-M., Cavallin L., Aspelin P., Kristoffersen-Wiberg M., Wahlund L.-O. Cerebrospinal fluid profiles with increasing number of cerebral microbleeds in a continuum of cognitive impairment. Br. J. Pharmacol. 2016;36:621–628. doi: 10.1177/0271678X15606141.
    1. Martinez-Ramirez S., Greenberg S.M., Viswanathan A. Cerebral microbleeds: Overview and implications in cognitive impairment. Alzheimer’s Res. Ther. 2014;6:33. doi: 10.1186/alzrt263.
    1. Kuhn J., Sharman T. StatPearls. StatPearls Publishing; Treasure Island, FL, USA: Jan, 2020. [(accessed on 20 March 2020)]. Cerebral Amyloid Angiopathy. Updated 1 October 2020. Available online:
    1. Charidimou A., Gang Q., Werring D.J. Sporadic cerebral amyloid angiopathy revisied: Recent insights into pathophysiology and clinical spectrum. J. Neurol. Neurosurg. Psychiatry. 2012;83:124–137. doi: 10.1136/jnnp-2011-301308.
    1. Scharf J., Forsting M., Sartor K. Significance of haemorrhagic lacunes on MRI in patients with hypertensive cerebrovascular disease and intracerebral haemorrhage. Neuroradiology. 1994;36:504–508. doi: 10.1007/BF00593508.
    1. Rensink A.A., De Waal R.M., Kremer B., Verbeek M.M. Pathogenesis of cerebral amyloid angiopathy. Brain Res. Rev. 2003;43:207–223. doi: 10.1016/j.brainresrev.2003.08.001.
    1. Hofman A., Ott A., Breteler M.M., Bots M.L., Slooter A.J., van Harskamp F., van Duijn C.N., Van Broeckhoven C., Grobbee D.E. Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer’s disease in the Rotterdam Study. Lancet. 1997;349:151–154. doi: 10.1016/S0140-6736(96)09328-2.
    1. Pantelakis S. [A particular type of senile angiopathy of the central nervous system: Congophilic angiopathy, topography and frequency] Monatsschr. Psychiatr. Neurol. 1954;128:219–256. doi: 10.1159/000139788.
    1. Keable A., Fenna K., Yuen H.M., Johnston D.A., Smyth N.R., Smith C., Salman R.A.-S., Samarasekera N., Nicoll J.A., Attems J., et al. Deposition of amyloid β in the walls of human leptomeningeal arteries in relation to perivascular drainage pathways in cerebral amyloid angiopathy. Biochim. Biophys. Acta (BBA) Mol. Basis Dis. 2016;1862:1037–1046. doi: 10.1016/j.bbadis.2015.08.024.
    1. Keage H.A.D., Carare R.O., Friedland R.P., Ince P.G., Love S., Nicoll J.A.R., Wharton S.B., Weller R.O., Brayne C. Population studies of sporadic cerebral amyloid angiopathy and dementia: A systematic review. BMC Neurol. 2009;9:3. doi: 10.1186/1471-2377-9-3.
    1. Kalaria R.N., Ballard C. Overlap between pathology of Alzheimer disease and vascular dementia. Alzheimer Dis. Assoc. Disord. 1999;13(Suppl. 3):S115–S123. doi: 10.1097/00002093-199912003-00017.
    1. Mendel T.A. Sporadyczna mózgowa angiopatia amyloidowa—patofizjologia, objawy, diagnostyka i leczenie. Pol. Przegl. Neurol. 2015;11:163–172.
    1. Charidimou A., Pantoni L., Love S. The concept of sporadic cerebral small vessel disease: A road map on key definitions and current concepts. Int. J. Stroke. 2016;11:6–18. doi: 10.1177/1747493015607485.
    1. Weimar C., Benemann J., Terborg C., Walter U., Weber R., Diener H.-C., German Stroke Study Collaboration Recurrent Stroke after Lobar and Deep Intracerebral Hemorrhage: A Hospital-Based Cohort Study. Cerebrovasc. Dis. 2011;32:283–288. doi: 10.1159/000330643.
    1. Liguori I., Russo G., Curcio F., Bulli G., Aran L., Della-Morte D., Gargiulo G., Testa G., Cacciatore F., Bonaduce D., et al. Oxidative stress, aging, and diseases. Clin. Interv. Aging. 2018;26:757–772. doi: 10.2147/CIA.S158513.
    1. Zhang L., Wang K., Lei Y., Li Q., Nice E.C., Huang C. Redox signaling: Potential arbitrator of autophagy and apoptosis in therapeutic response. Free Radic. Biol. Med. 2015;89:452–465. doi: 10.1016/j.freeradbiomed.2015.08.030.
    1. Kawamura T., Muraoka I., Kawamura T., Muraoka I. Exercise-Induced Oxidative Stress and the Effects of Antioxidant Intake from a Physiological Viewpoint. Antioxidants. 2018;7:119. doi: 10.3390/antiox7090119.
    1. Höhn A., Weber D., Jung T., Ott C., Hugo M., Kochlik B., Kehm R., König J., Grune T., Castro J.P. Happily (n)ever after: Aging in the context of oxidative stress, proteostasis loss and cellular senescence. Redox Biol. 2017;11:482–501. doi: 10.1016/j.redox.2016.12.001.
    1. Rahal A., Kumar A., Singh V., Yadav B., Tiwari R., Chakraborty S., Dhama K. Oxidative stress, prooxidants, and antioxidants: The interplay. BioMed Res. Int. 2014;2014:761264. doi: 10.1155/2014/761264.
    1. Navarro-Yepes J., Burns M., Anandhan A., Khalimonchuk O., Del Razo L.M., Quintanilla-Vega B., Pappa A., Panayiotidis M.I., Franco R. Oxidative stress, redox signaling, and autophagy: Cell death versus survival. Antioxid. Redox Signal. 2014;21:66–85. doi: 10.1089/ars.2014.5837.
    1. Kapuy O., Papp D., Vellai T., Bánhegyi G., Korcsmáros T. Systems-Level Feedbacks of NRF2 Controlling Autophagy upon Oxidative Stress Response. Antioxidants. 2018;7:39. doi: 10.3390/antiox7030039.
    1. Van’t Erve T.J. Strategies to decrease oxidative stress biomarker levels in human medical conditions: A meta-analysis on 8-iso-prostaglandin F2α. Redox Biol. 2018;17:284–296. doi: 10.1016/j.redox.2018.05.003.
    1. Debevec T., Millet G.P., Pialoux V. Hypoxia-Induced Oxidative Stress Modulation with Physical Activity. Front. Physiol. 2017;8:84. doi: 10.3389/fphys.2017.00084.
    1. Aikens J., A Dix T. Perhydroxyl radical (HOO.) initiated lipid peroxidation. The role of fatty acid hydroperoxides. J. Biol. Chem. 1991;266:15091–15098.
    1. Halliwell B., Gutteridge J.M. Free Radicals in Biology and Medicin. 3rd ed. Oxford University Press; Oxford, UK: 1999.
    1. Dröge W. Free Radicals in the Physiological Control of Cell Function. Physiol. Rev. 2002;82:47–95. doi: 10.1152/physrev.00018.2001.
    1. Kupsco A., Schlenk D. Oxidative Stress, Unfolded Protein Response, and Apoptosis in Developmental Toxicity. Int. Rev. Cell Mol. Biol. 2015;317:1–66. doi: 10.1016/bs.ircmb.2015.02.002.
    1. González J. Essential hypertension and oxidative stress: New insights. World J. Cardiol. 2014;6:353–566. doi: 10.4330/wjc.v6.i6.353.
    1. Yao Y., Wang Y., Zhang Y., Liu C. Klotho ameliorates oxidized low density lipoprotein (ox-LDL)-induced oxidative stress via regulating LOX-1 and PI3K/Akt/eNOS pathways. Lipids Health Dis. 2017;16:1–10. doi: 10.1186/s12944-017-0447-0.
    1. Liu Y., Chen X., Li J. Resveratrol protects against oxidized low‑density lipoprotein‑induced human umbilical vein endothelial cell apoptosis via inhibition of mitochondrial‑derived oxidative stress. Mol. Med. Rep. 2017;15:2457–2464. doi: 10.3892/mmr.2017.6304.
    1. Corpas F.J., Sandalio L.M., Palma J.M. Impact of Nitric Oxide (NO) on the ROS Metabolism of Peroxisomes. Plants. 2019;8:37. doi: 10.3390/plants8020037.
    1. Hsieh H.-J., Liu C.-A., Huang B., Tseng A.H., Wang D.L. Shear-induced endothelial mechanotransduction: The interplay between reactive oxygen species (ROS) and nitric oxide (NO) and the pathophysiological implications. J. Biomed. Sci. 2014;21:3. doi: 10.1186/1423-0127-21-3.
    1. Grochowski C., Litak J., Kamieniak P., Maciejewski R. Oxidative stress in cerebral small vessel disease. Role of reactive species. Free. Radic. Res. 2017;52:1–13. doi: 10.1080/10715762.2017.1402304.
    1. Beck C., Kruetzelmann A., Forkert N.D., Juettler E., Singer O.C., Köhrmann M., Kersten J.F., Sobesky J., Gerloff C., Fiehler J., et al. A simple brain atrophy measure improves the prediction of malignant middle cerebral artery infarction by acute DWI lesion volume. J. Neurol. 2014;261:1097–1103. doi: 10.1007/s00415-014-7324-9.
    1. Whitwell J.L., Jack C.R., Parisi J.E., Knopman D.S., Boeve B.F., Petersen R.C., Ferman T.J., Dickson D.W., Josephs K.A. Rates of cerebral atrophy differ in different degenerative pathologies. Brain. 2007;130:1148–1158. doi: 10.1093/brain/awm021.
    1. Muller M.M., Appelman A.P., Van Der Graaf Y., Vincken K.L., Mali W.P., I Geerlings M. Brain atrophy and cognition: Interaction with cerebrovascular pathology? Neurobiol. Aging. 2011;32:885–893. doi: 10.1016/j.neurobiolaging.2009.05.005.
    1. Thong J.Y.J., Hilal S., Wang Y., Soon H.W., Dong Y., Collinson S.L., Anh T.T., Ikram M.K., Wong T.Y., Venketasubramanian N., et al. Association of silent lacunar infarct with brain atrophy and cognitive impairment. J. Neurol. Neurosurg. Psychiatry. 2013;84:1219–1225. doi: 10.1136/jnnp-2013-305310.
    1. Caplan L.R. Binswanger’s disease—Revisited. Neurology. 1995;45:626–633. doi: 10.1212/WNL.45.4.626.
    1. Sala S., Agosta F., Pagani E., Copetti M., Comi G., Filippi M. Microstructural changes and atrophy in brain white matter tracts with aging. Neurobiol. Aging. 2012;33:488–498.e2. doi: 10.1016/j.neurobiolaging.2010.04.027.
    1. Nitkunan A., Lanfranconi S., Charlton R.A., Barrick T.R., Markus H.S. Brain atrophy and cerebral small vessel disease: A prospective follow-up study. Stroke. 2011;42:133–138. doi: 10.1161/STROKEAHA.110.594267.
    1. Jokinen H., Lipsanen J., Schmidt R., Fazekas F., Gouw A., Van Der Flier W.M., Barkhof F., Madureira S., Verdelho A., Ferro J.M., et al. Brain atrophy accelerates cognitive decline in cerebral small vessel disease: The LADIS study. Neurology. 2012;78:1785–1792. doi: 10.1212/WNL.0b013e3182583070.
    1. Wikgren M., Karlsson T., Söderlund H., Nordin A., Roos G., Nilsson L.-G., Adolfsson R., Norrback K.-F. Shorter telomere length is linked to brain atrophy and white matter hyperintensities. Age Ageing. 2013;43:212–217. doi: 10.1093/ageing/aft172.
    1. Guo H., Song X., Vandorpe R., Zhang Y., Chen W., Zhang N., Schmidt M., Rockwood K. Evaluation of common structural brain changes in aging and alzheimer disease with the use of an MRI-based brain atrophy and lesion index: A comparison between T1WI and T2WI at 1.5T and 3T. Am. J. Neuroradiol. 2013;35:504–512. doi: 10.3174/ajnr.A3709.
    1. Tate D.F., Khedraki R., Neeley E.S., Ryser D.K., Bigler E.D. Cerebral Volume Loss, Cognitive Deficit, and Neuropsychological Performance: Comparative Measures of Brain Atrophy: II. Traumatic Brain Injury. J. Int. Neuropsychol. Soc. 2011;17:308–316. doi: 10.1017/S1355617710001670.
    1. Kassubek J., Landwehrmeyer G.B., Ecker D., Juengling F.D., Muche R., Schuller S., Weindl A., Peinemann A. Global cerebral atrophy in early stages of Huntington’s disease: Quantitative MRI study. Neuroreport. 2004;15:363–365. doi: 10.1097/00001756-200402090-00030.
    1. Aribisala B.S., Hernández M.C.V., Royle N.A., Morris Z., Maniega S.M., Bastin M.E., Deary I.J., Wardlaw J.M. Brain atrophy associations with white matter lesions in the ageing brain: The Lothian Birth Cohort 1936. Eur. Radiol. 2013;23:1084–1092. doi: 10.1007/s00330-012-2677-x.
    1. García-Valdecasas-Campelo E., González-Reimers E., Santolaria-Fernández F., De La Vega-Prieto M.J., Milena-Abril A., Sánchez-Pérez M.J., Martínez-Riera A., Rodríguez-Rodríguez E. Brain atrophy in alcoholics: Relationship with alcohol intake; liver disease; nutritional status, and inflammation. Alcohol. Alcohol. 2007;42:533–538. doi: 10.1093/alcalc/agm065.
    1. Henny C., A Despland P., Regli F. Initial epileptic crisis after the age of 60: Etiology, clinical aspects and EEG. Schweiz. Med. Wochenschr. 1990;120:787–792.
    1. Anandh K.R., Sujatha C.M., Ramakrishnan S. Atrophy analysis of corpus callosum in Alzheimer brain MR images using anisotropic diffusion filtering and level sets; Proceedings of the 2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society; Chicago, IL, USA. 26–30 August 2014; pp. 1945–1948.
    1. Sluimer J.D., Vrenken H., Blankenstein M.A., Fox N.C., Scheltens P., Barkhof F., Van Der Flier W.M. Whole-brain atrophy rate in Alzheimer disease: Identifying fast progressors. Neurology. 2008;70:1836–1841. doi: 10.1212/01.wnl.0000311446.61861.e3.
    1. Bokde A.L.W., Pietrini P., Ibáñez V., Furey M.L., Alexander G.E., Graff-Radford N.R., Rapoport S.I., Schapiro M.B., Horwitz B. The Effect of Brain Atrophy on Cerebral Hypometabolism in the Visual Variant of Alzheimer Disease. Arch. Neurol. 2001;58:480–486. doi: 10.1001/archneur.58.3.480.
    1. Henneman W., Sluimer J.D., Barnes J., Van Der Flier W.M., Sluimer I.C., Fox N.C., Scheltens P., Vrenken H., Barkhof F. Hippocampal atrophy rates in Alzheimer disease: Added value over whole brain volume measures. Neurology. 2009;72:999–1007. doi: 10.1212/01.wnl.0000344568.09360.31.
    1. Prins N.D., Scheltens P. White matter hyperintensities, cognitive impairment and dementia: An update. Nat. Rev. Neurol. 2015;11:157–165. doi: 10.1038/nrneurol.2015.10.
    1. Pantoni L. Pathophysiology of age-related cerebral white matter changes. Cerebrovasc. Dis. 2002;13:7–10. doi: 10.1159/000049143.
    1. Thal D.R., Ghebremedhin E., Orantes M., Wiestler O.D. Vas-cular pathology in Alzheimer disease: Correlation of cerebral amyloid angiopathy and arteriosclerosis/ lipohyalinosis with cognitive decline. J. Neuropathol. Exp. Neurol. 2003;62:1287–1301. doi: 10.1093/jnen/62.12.1287.
    1. Moody D.M., Brown W.R., Challa V.R., Reboussin D.M., Ghazi-Birry H.S. Cerebral Microvascular Alterations in Aging, Leukoaraiosis, and Alzheimer’s Disease. Ann. N. Y. Acad. Sci. 1997;826:103–116. doi: 10.1111/j.1749-6632.1997.tb48464.x.
    1. Makedonov I., E Black S., MacIntosh B.J. Cerebral small vessel disease in aging and Alzheimer’s disease: A comparative study using MRI and SPECT. Eur. J. Neurol. 2012;20:243–250. doi: 10.1111/j.1468-1331.2012.03785.x.
    1. Brown W.R., Moody D.M., Thore C.R., Challa V.R. Cere- brovascular pathology in Alzheimer’s disease and leukoaraiosis. Ann. N. Y. Acad. Sci. 2000;903:39–45. doi: 10.1111/j.1749-6632.2000.tb06348.x.
    1. Smith E.E. Cerebral amyloid angiopathy as a cause of neurodegeneration. J. Neurochem. 2018;144:651–658. doi: 10.1111/jnc.14157.
    1. Ylikoski A., Erkinjuntti T., Raininko R., Sarna S., Sulkava R., Tilvis R. White Matter Hyperintensities on MRI in the Neurologically Nondiseased Elderly. Stroke. 1995;26:1171–1177. doi: 10.1161/01.STR.26.7.1171.
    1. Garde E., Mortensen E.L., Krabbe K., Rostrup E., Larsson H.B. Relation between age-related decline in intelligence and cerebral white-matter hyperintensities in healthy octogenarians: A longitudinal study. Lancet. 2000;356:628–634. doi: 10.1016/S0140-6736(00)02604-0.
    1. Diaz J.F., Merskey H., Hachinski V., Lee D.H., Boniferro M., Wong C.J., Mirsen T.R., Fox H. Improved Recognition of Leukoaraiosis and Cognitive Impairment in Alzheimer’s Disease. Arch. Neurol. 1991;48:1022–1025. doi: 10.1001/archneur.1991.00530220038016.
    1. Hermosilla C., De Lorena P., Sarabia-Cobo C., Pérez V., Núñez M.J. Apathy and Leukoaraiosis in Mild Cognitive Impairment and Alzheimer’s Disease: Multicenter Diagnostic Criteria according to the Latest Studies. Dement. Geriatr. Cogn. Disord. Extra. 2014;4:228–235. doi: 10.1159/000363227.
    1. Launer L.J. Epidemiology of White Matter Lesions. Top. Magn. Reson. Imaging. 2004;15:365–367. doi: 10.1097/01.rmr.0000168216.98338.8d.
    1. Dufouil C., Chalmers J., Coskun O., Besancon V., Bousser M.G., Guillon P., Macmahon S., Mazoyer B., Neal B., Woodward M., et al. Effects of blood pressure lowering on cerebral white matter hyperintensities in patients with stroke: The PROGRESS (Peri- ndopril Protection Against Recurrent Stroke Study) Magnetic Reso- nance Imaging Substudy. Circulation. 2005;112:1644–1650. doi: 10.1161/CIRCULATIONAHA.104.501163.
    1. Debette S., Markus H.S. The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: Systematic review and meta-analysis. BMJ. 2010;341:c3666. doi: 10.1136/bmj.c3666.
    1. Baezner H., Blahak C., Poggesi A., Pantoni L., Inzitari D., Chabriat H., Erkinjuntti T., Fazekas F., Ferro J.M., Langhorne P., et al. Association of gait and balance disorders with age-related white matter changes: The LADIS study. Neurology. 2008;70:935–942. doi: 10.1212/01.wnl.0000305959.46197.e6.
    1. Wardlaw J.M., E Smith E., Biessels G.J., Cordonnier C., Fazekas F., Frayne R., I Lindley R., O’Brien J.T., Barkhof F., Benavente O.R., 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.
    1. Del Bene A., Makin S.D., Doubal F.N., Inzitari D., Wardlaw J.M. Variation in Risk Factors for Recent Small Subcortical Infarcts With Infarct Size, Shape, and Location. Stroke. 2013;44:3000–3006. doi: 10.1161/STROKEAHA.113.002227.
    1. 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;28:491–499. doi: 10.1161/01.STR.28.3.491.
    1. E Vermeer S., Longstreth W.T., Koudstaal P.J. Silent brain infarcts: A systematic review. Lancet Neurol. 2007;6:611–619. doi: 10.1016/S1474-4422(07)70170-9.
    1. Kase C.S., A Wolf P., Chodosh E.H., Zacker H.B., Kelly-Hayes M., Kannel W.B., D’Agostino R.B., Scampini L. Prevalence of silent stroke in patients presenting with initial stroke: The Framingham Study. Stroke. 1989;20:850–852. doi: 10.1161/01.STR.20.7.850.
    1. Rabinstein A. Differing Risk Factor Profiles of Ischemic Stroke Subtypes: Evidence for a Distinct Lacunar Arteriopathy? Yearb. Neurol. Neurosurg. 2010;2010:24–25. doi: 10.1016/S0513-5117(10)79244-9.
    1. Jerrard-Dunne P., Cloud G., Hassan A., Markus H.S. Evaluating the genetic component of ischemic stroke subtypes: A family history study. Stroke. 2003;34:1364–1369. doi: 10.1161/01.STR.0000069723.17984.FD.
    1. Del Brutto O.H., Mera R.M., Gillman J., Ha J.-E., Zambrano M. Calcifications in the carotid siphon correlate with silent cerebral small vessel disease in community-dwelling older adults: A population-based study in rural Ecuador. Geriatr. Gerontol. Int. 2015;16:1063–1067. doi: 10.1111/ggi.12599.
    1. Xiao L., Lan W., Sun W., Dai Q., Xiong Y., Li L., Zhou Y., Zheng P., Fan W., Ma N., et al. Chronickidney disease in patients with lacunar stroke: Association with enlarged perivascular spaces and total magnetic resonance imaging burden of cerebral small vessel disease. Stroke. 2015;46:2081–2086. doi: 10.1161/STROKEAHA.114.008155.
    1. Yang S., Cai J., Lu R., Wu J., Zhang M., Zhou X. Association Between Serum Cystatin C Level and Total Magnetic Resonance Imaging Burden of Cerebral Small Vessel Disease in Patients With Acute Lacunar Stroke. J. Stroke Cerebrovasc. Dis. 2017;26:186–191. doi: 10.1016/j.jstrokecerebrovasdis.2016.09.007.
    1. Giwa M.O., Williams J., Elderfield K., Jiwa N.S., Bridges L.R., Kalaria R.N., Markus H.S., Esiri M.M., Hainsworth A.H. Neuropathologic evidence of endothelial changes in cerebral small vessel disease. Neurology. 2012;78:167–174. doi: 10.1212/WNL.0b013e3182407968.
    1. Lawrence E.S., Coshall C., Dundas R., Stewart J., Rudd A.G., Howard R., Wolfe C.D. Estimates of the prevalence of acute stroke impairments and disability in a multiethnic population. Stroke. 2001;32:1279–1284. doi: 10.1161/01.STR.32.6.1279.
    1. Chen Y., Chen X., Mok V.C., Lam W.W., Wong K.S., Tang W.K. Poststroke depression in patients with small subcortical infarcts. Clin. Neurol. Neurosurg. 2009;111:256–260.
    1. Ross G.W., Petrovitch H., White L.R., Masaki K.H., Li C.Y., Curb J., Yano K., Rodriguez B.L., Foley D.J., Blanchette P.L., et al. Characterization of risk factors for vascular dementia: The Honolulu-Asia Aging Study. Neurology. 1999;53:337. doi: 10.1212/WNL.53.2.337.
    1. Barba R., Martinez-Espinosa S., Rodríguez-Garcia E., Pondal M., Vivancos J., Del Ser T. Poststroke dementia: Clinical features and risk factors. Stroke. 2000;31:1494–1501. doi: 10.1161/01.STR.31.7.1494.
    1. Joshi S., Morley J.E. Cognitive impairment. Med. Clin. N. Am. 2006;90:769–787. doi: 10.1016/j.mcna.2006.05.014.
    1. Roob G., Schmidt R., Kapeller P., Lechner A., Hartung H.-P., Fazekas F. MRI evidence of past cerebral microbleeds in a healthy elderly population. Neurology. 1999;52:991. doi: 10.1212/WNL.52.5.991.
    1. Lawrence T.P., Pretorius P., Ezra M., Cadoux-Hudson T., Voets N.L. Early detection of cerebral microbleeds following traumatic brain injury using MRI in the hyper-acute phase. Neurosci. Lett. 2017;655:143–150. doi: 10.1016/j.neulet.2017.06.046.
    1. Pasi M., Boulouis G., Fotiadis P., Auriel E., Charidimou A., Haley K., Ayres A., Schwab K.M., Goldstein J.N., Rosand J., et al. Distribution of lacunes in cerebral amyloid angiopathy and hypertensive small vessel disease. Neurology. 2017;88:2162–2168. doi: 10.1212/WNL.0000000000004007.
    1. Cordonnier C., Van Der Flier W.M., Sluimer J.D., Leys D., Barkhof F., Scheltens P. Prevalence and severity of microbleeds in a memory clinic setting. Neurology. 2006;66:1356–1360. doi: 10.1212/.
    1. Jeerakathil T., Wolf P.A., Beiser A., Hald J.K., Au R., Kase C.S., Massaro J.M., De Carli C. Cerebral microbleeds: Prevalence and associations with cardiovascular risk factors in the Framingham Study. Stroke. 2004;35:1831–1835. doi: 10.1161/01.STR.0000131809.35202.1b.
    1. Ding J., Sigurdsson S., Garcia M., Phillips C.L., Eiriksdottir G., Gudnason V., van Buchem M.A., Launer L.J. Risk factors associated with incident cerebral microbleeds according to location in older people: The Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study. JAMA Neurol. 2015;72:682–688. doi: 10.1001/jamaneurol.2015.0174.
    1. Cordonnier C., Salman R.A.-S., Wardlaw J.M. Spontaneous brain microbleeds: Systematic review, subgroup analyses and standards for study design and reporting. Brain. 2007;130:1988–2003. doi: 10.1093/brain/awl387.
    1. Del Brutto O.H., Mera R.M., Ha J.E., Del Brutto V.J., Castillo P.R., Zambrano M., Gillman J. Oil fish consumption is inversely correlated with cerebral microbleeds in community-dwelling older adults: Results from the Atahualpa Project. Aging Clin. Exp. Res. 2016;28:737–743. doi: 10.1007/s40520-015-0473-6.
    1. Gregoire S.M., Brown M.M., Kallis C., Jäger H.R., Yousry T.A., Werring D.J. MRI detection of new microbleeds in patients with ischemic stroke: Fve-year cohort follow-up study. Stroke. 2010;41:184–186. doi: 10.1161/STROKEAHA.109.568469.
    1. Saito T., Kawamura Y., Tanabe Y., Asanome A., Takahashi K., Sawada J., Katayama T., Sato N., Aizawa H., Hasebe N. Cerebral microbleeds and asymptomatic cerebral infarctions in patients with atrial fbrillation. J. Stroke Cerebrovasc. Dis. 2014;23:1616–1622. doi: 10.1016/j.jstrokecerebrovasdis.2014.01.005.
    1. Lee S.-H., Lee S.-T., Kim B.J., Park H.-K., Kim C.-K., Jung K.-H., Roh J.-K. Dynamic Temporal Change of Cerebral Microbleeds: Long-Term Follow-Up MRI Study. PLoS ONE. 2011;6:e25930. doi: 10.1371/journal.pone.0025930.
    1. Woerdeman J., Van Duinkerken E., Wattjes M.P., Barkhof F., Snoek F.J., Moll A.C., Klein M., De Boer M.P., Ijzerman R.G., Serné E., et al. Proliferative Retinopathy in Type 1 Diabetes Is Associated With Cerebral Microbleeds, Which Is Part of Generalized Microangiopathy. Diabetes Care. 2013;37:1165–1168. doi: 10.2337/dc13-1586.
    1. Cianchetti F.A., Kim D.H., Dimiduk S., Nishimura N., Schaffer C. Stimulus-Evoked Calcium Transients in Somatosensory Cortex Are Temporarily Inhibited by a Nearby Microhemorrhage. PLoS ONE. 2013;8:e65663. doi: 10.1371/journal.pone.0065663.
    1. Vernooij M.W., Van Der Lugt A., Ikram M.A., Wielopolski P.A., Niessen W.J., Hofman A., Krestin G.P., Breteler M. Prevalence and risk factors of cerebral microbleeds: The Rotterdam Scan Study. Neurology. 2008;70:1208–1214. doi: 10.1212/01.wnl.0000307750.41970.d9.
    1. Brundel M., Heringa S., De Bresser J., Koek H.L., Zwanenburg J.J., Kappelle L.J., Luijten P.R., Biessels G.J. High Prevalence of Cerebral Microbleeds at 7Tesla MRI in Patients with Early Alzheimer’s Disease. J. Alzheimer’s Dis. 2012;31:259–263. doi: 10.3233/JAD-2012-120364.
    1. Akoudad S., De Groot M., Koudstaal P.J., Van Der Lugt A., Niessen W., Hofman A., Ikram M.K., Vernooij M.W. Cerebral microbleeds are related to loss of white matter structural integrity. Neurology. 2013;81:1930–1937. doi: 10.1212/01.wnl.0000436609.20587.65.
    1. Henneman W., Sluimer J.D., Cordonnier C., Baak M.M., Scheltens P., Barkhof F., Van Der Flier W. MRI Biomarkers of Vascular Damage and Atrophy Predicting Mortality in a Memory Clinic Population. Stroke. 2009;40:492–498. doi: 10.1161/STROKEAHA.108.516286.
    1. Papma J., De Groot M., De Koning I., Mattace-Raso F.U., Van Der Lugt A., Vernooij M.W., Niessen W.J., Van Swieten J.C., Koudstaal P.J., Prins N.D., et al. Cerebral small vessel disease affects white matter microstructure in mild cognitive impairment. Hum. Brain Mapp. 2014;35:2836–2851. doi: 10.1002/hbm.22370.
    1. Kim B.J., Yoon Y., Sohn H., Kang D.W., Kim J.S., Kwon S.U. Diference in the Location and Risk Factors of Cerebral Microbleeds According to Ischemic Stroke Subtypes. J. Stroke. 2016;18:297–303. doi: 10.5853/jos.2016.00360.
    1. Van Der Flier W.M., Cordonnier C. Microbleeds in vascular dementia: Clinical aspects. Exp. Gerontol. 2012;47:853–857. doi: 10.1016/j.exger.2012.07.007.
    1. Polyakova T.A., Levin O.S. Cerebral Microbleeds in Cerebrovascular and Neurodegenerative Diseases with Cognitive Impairments. Neurosci. Behav. Physiol. 2017;47:1078–1085. doi: 10.1007/s11055-017-0515-y.
    1. Sparacia G., Agnello F., La Tona G., Iaia A., Midiri F., Sparacia B. Assessment of cerebral microbleeds by susceptibility-weighted imaging in Alzheimer’s disease patients: A neuroimaging biomarker of the disease. Neuroradiol. J. 2017;30:330–335. doi: 10.1177/1971400916689483.
    1. Vijayan M., Reddy P.H. Stroke, Vascular Dementia, and Alzheimer’s Disease: Molecular Links. J. Alzheimer’s Dis. 2016;54:427–443. doi: 10.3233/JAD-160527.
    1. Chung C.-P., Chou K.-H., Chen W.-T., Liu L.-K., Lee W.-J., Chen L.-K., Lin C.-P., Wang P.-N. Strictly Lobar Cerebral Microbleeds Are Associated With Cognitive Impairment. Stroke. 2016;47:2497–2502. doi: 10.1161/STROKEAHA.116.014166.
    1. Benedictus M.R., Prins N.D., Goos J.D., Scheltens P., Barkhof F., van der Flier W.M. Microbleeds, Mortality, and Stroke in Alzheimer Disease The MISTRAL Study. JAMA Neurol. 2015;72:539–545. doi: 10.1001/jamaneurol.2015.14.
    1. Goos J.D., Teunissen C.E., Veerhuis R., Verwey N.A., Barkhof F., Blankenstein M.A., Scheltens P., van der Flier W.M. Microbleeds relate to altered amyloid metabolism in Alzheimer’s disease. Neurobiol. Aging. 2012;33:e1–e9. doi: 10.1016/j.neurobiolaging.2011.10.026.
    1. Ham J.H., Yi H., Sunwoo M.K., Hong J.Y., Sohn Y.H., Lee P.H. Cerebral microbleeds in patients with Parkinson’s disease. J. Neurol. 2014;261:1628–1635. doi: 10.1007/s00415-014-7403-y.
    1. Thijs V., Lemmens R., Schoofs C., Görner A., Van Damme P., Schrooten M., Demaerel P. Microbleeds and the Risk of Recurrent Stroke. Stroke. 2010;41:2005–2009. doi: 10.1161/STROKEAHA.110.588020.
    1. Kim B.J., Lee S.-H. Cerebral Microbleeds: Their Associated Factors, Radiologic Findings, and Clinical Implications. J. Stroke. 2013;15:153–163. doi: 10.5853/jos.2013.15.3.153.
    1. Gao T., Wang Y., Zhang Z. Silent cerebral microbleeds on susceptibility-weighted imaging of patients with ischemic stroke and leukoaraiosis. Neurol. Res. 2008;30:272–276. doi: 10.1179/016164107X251556.
    1. Kato H., Izumiyama M., Izumiyama K., Takahashi A., Itoyama Y. Silent cerebral microbleeds on T2*-weighted MRI: Correlation with stroke subtype, stroke recurrence, and leukoaraiosis. Stroke. 2002;33:1536–1540. doi: 10.1161/01.STR.0000018012.65108.86.
    1. Blennow K., de Leon M.J., Zetterberg H. Alzheimer’s disease. Lancet. 2006;368:387–403. doi: 10.1016/S0140-6736(06)69113-7.
    1. Alzheimer’s Association 2015 Alzheimer’s disease facts and figures. Alzheimer’s Dement. 2015;11:332–384. doi: 10.1016/j.jalz.2015.02.003.
    1. Velkoff V. The Next Four Decades: The Older Population in the United States: 2010–2050. U.S. Department of Commerce Economics and Statistics Administration U.S. CENSUS BUREAU; Washington, DC, USA: 2010. pp. 1–14. Current Population Reports. P25-1138.
    1. Poels M.M.F., Vernooij M.W., Ikram M.A., Hofman A., Krestin G.P., Van Der Lugt A., Breteler M.M.B. Prevalence and Risk Factors of Cerebral Microbleeds: An Update of the Rotterdam Scan Study. Stroke. 2010;41:S103–S106. doi: 10.1161/STROKEAHA.110.595181.
    1. Cuadrado-Godia E., Dwivedi P., Sharma S., Ois Santiago A., Roquer Gonzalez J., Balcells M., Laird J., Turk M., Suri H.S., Nicolaides A., et al. Cerebral Small Vessel Disease: A Review Focusing on Pathophysiology, Biomarkers, and Machine Learning Strategies. J. Stroke. 2018;20:302–320. doi: 10.5853/jos.2017.02922.
    1. Fazekas F., Kleinert R., Roob G., Kleinert G., Kapeller P., Schmidt R., Hartung H.-P. Histopathologic Analysis of Foci of Signal Loss on Gradient-Echo T2*-Weighted MR Images in Patients with Spontaneous Intracerebral Hemorrhage: Evidence of Microangiopathy-Related Microbleeds. Am. J. Neuroradiol. 1999;20:637–642.
    1. Fisher M.J. Cerebral microbleeds: Where are we now? Neurology. 2014;83:1304–1305. doi: 10.1212/WNL.0000000000000871.
    1. Roher A.E., Tyas S.L., Maarouf C.L., Daugs I.D., Kokjohn T.A., Emmerling M.R., Garami Z., Belohlavek M., Sabbagh M.N., Sue L.I., et al. Intracranial atherosclerosis as a contributing factor to Alzheimer’s disease dementia. Alzheimer’s Dement. 2011;7:436–444. doi: 10.1016/j.jalz.2010.08.228.
    1. Beach T.G., Wilson J.R., Sue L.I., Newell A., Poston M., Cisneros R., Pandya Y., Esh C., Connor D.J., Sabbagh M., et al. Circle of Willis atherosclerosis: Association with Alzheimer’s disease, neuritic plaques and neurofibrillary tangles. Acta Neuropathol. 2007;113:13–21. doi: 10.1007/s00401-006-0136-y.
    1. Arvanitakis Z., Capuano A.W., Leurgans S.E., Bennett D.A., Schneider J.A. Relation of Cerebral Vessel Disease to Alzheimer’s Disease Dementia and Cognitive Function in Older Persons: A Cross-sectional Study. Lancet Neurol. 2016;15:934–943. doi: 10.1016/S1474-4422(16)30029-1.
    1. Shaaban C.E., Jorgensen D.R., Gianaros P.J., Mettenburg J., Rosano C. Cerebrovascular disease: Neuroimaging of cerebral small vessel disease. Prog. Mol. Biol. Transl. Sci. 2019;165:225–255. doi: 10.1016/bs.pmbts.2019.07.008.
    1. White L., Petrovitch H., Hardman J., Nelson J., Davis D.G., Ross G.W., Masaki K., Launer L., Markesbery W.R. Cerebrovascular pathology and dementia in autopsied Honolulu-Asia Aging Study participants. Ann. N. Y. Acad. Sci. 2002;977:9–23. doi: 10.1111/j.1749-6632.2002.tb04794.x.
    1. Morris H.R., Waite A.J., Williams N.M., Neal J.W., Blake D.J. Recent Advances in the Genetics of the ALS-FTLD Complex. Curr. Neurol. Neurosci. Rep. 2012;12:243–250. doi: 10.1007/s11910-012-0268-5.
    1. Andreason P.J., Zametkin A.J., Guo A.C., Baldwin P., Cohen R.M. Gender-related differences in regional cerebral glucose metabolism in normal volunteers. Psychiatry Res. 1994;51:175–183. doi: 10.1016/0165-1781(94)90037-X.
    1. Mok V., Liu T., Lam W.W., Wong A., Hu X., Guo L., Chen X.Y., Tang W.K., Wong K.S., Wong S. Neuroimaging Predictors of Cognitive Impairment in Confluent White Matter Lesion: Volumetric Analyses of 99 Brain Regions. Dement. Geriatr. Cogn. Disord. 2008;25:67–73. doi: 10.1159/000111692.
    1. Fox N.C., Schott J.M. Imaging cerebral atrophy: Normal ageing to Alzheimer’s disease. Lancet. 2004;363:392–394. doi: 10.1016/S0140-6736(04)15441-X.
    1. Hilal S., Saini M., Tan C.S. Cerebral microbleeds and cognition: The epidemiology of dementia in Singapore study. Alzheimer Dis. Assoc. Disord. 2014;28:106–112. doi: 10.1097/WAD.0000000000000015.
    1. van Veluw S.J., Biessels G.J., Klijn C.J., Rozemuller A.J. Heterogeneous histopathology of cortical microbleeds in cerebral amyloid angiopathy. Neurology. 2016;86:867–871. doi: 10.1212/WNL.0000000000002419.
    1. Lee J., Sohn E.-H., Oh E., Lee A.Y. Characteristics of Cerebral Microbleeds. Dement. Neurocogn. Disord. 2018;17:73–82. doi: 10.12779/dnd.2018.17.3.73.
    1. Lee S.J., Kim J.-S., Song I.-U., An J.-Y., Kim W., Kim Y.I., Kim B.S., Jung S.L. The leukoaraiosis is more prevalent in the large artery atherosclerosis stroke subtype among Korean patients with ischemic stroke. BMC Neurol. 2008;8:31. doi: 10.1186/1471-2377-8-31.
    1. Kloppenborg R.P., Nederkoorn P.J., Geerlings M.I., Berg E.V.D. Presence and progression of white matter hyperintensities and cognition: A meta-analysis. Neurology. 2014;82:2127–2138. doi: 10.1212/WNL.0000000000000505.
    1. Cai Z., Wang C., He W., Tu H., Tang Z., Xiao M., Yan L.-J. Cerebral small vessel disease and Alzheimer’s disease. Clin. Interv. Aging. 2015;10:1695–1704. doi: 10.2147/CIA.S90871.
    1. Sandyk R. Subcortical arteriosclerotic encephalopathy (Binswanger’s disease) S. Afr. Med. J. 1983;63:204–205.
    1. A Bennett D., Wilson R.S., Gilley D.W., Fox J.H. Clinical diagnosis of Binswanger’s disease. J. Neurol. Neurosurg. Psychiatry. 1990;53:961–965. doi: 10.1136/jnnp.53.11.961.
    1. Tomimoto H., Akiguchi I., Akiyama H., Ikeda K., Wakita H., Lin J.-X., Budka H. Vascular changes in white matter lesions of Alzheimer’s disease. Acta Neuropathol. 1999;97:629–634. doi: 10.1007/s004010051039.
    1. Kosaka K., Ikeda K., Matsushita M., Iizuka R. A combination of Alzheimer’s and Binswanger’s diseases—A clinicopathological study of four cases. Jpn. J. Psychiatry Neurol. 1986;40:685–692. doi: 10.1111/j.1440-1819.1986.tb03185.x.
    1. Watanabe T., Shiino A., Akiguchi I. Absolute Quantification in Proton Magnetic Resonance Spectroscopy Is Superior to Relative Ratio to Discriminate Alzheimer’s Disease from Binswanger’s Disease. Dement. Geriatr. Cogn. Disord. 2008;26:89–100. doi: 10.1159/000144044.
    1. Leung K.K., Bartlett J.W., Barnes J., Manning E.N., Ourselin S., Fox N.C., Initiative A.D.N. Cerebral atrophy in mild cognitive impairment and Alzheimer disease: Rates and acceleration. Neurology. 2013;80:648–654. doi: 10.1212/WNL.0b013e318281ccd3.
    1. Chabriat H., Joutel A., Dichgans M., Tournier-Lasserve E., Bousser M.G. Cadasil. Lancet Neurol. 2009;8:643–653. doi: 10.1016/S1474-4422(09)70127-9.
    1. Guey S., Mawet J., Hervé D., Duering M., Godin O., Jouvent E., Opherk C., Alili N., Dichgans M., Hugues C. Prevalence and characteristics of migraine in CADASIL. Cephalalgia. 2016;36:1038–1047. doi: 10.1177/0333102415620909.
    1. Adib-Samii P., Brice G., Martin R.J., Markus H.S. Clinical spectrum of CADASIL and the effect of cardiovascular risk factors on phenotype: Study in 200 consecutively recruited individuals. Stroke. 2010;41:630–634. doi: 10.1161/STROKEAHA.109.568402.
    1. Joutel A., Favrole P., Labauge P., Chabriat H., Lescoat C., Andreux F., Domenga V., Cécillon M., Vahedi K., Ducros A., et al. Skin biopsy immunostaining with a Notch3 monoclonal antibody for CADASIL diagnosis. Lancet. 2001;358:2049–2051. doi: 10.1016/S0140-6736(01)07142-2.
    1. Craggs L.J., Yamamoto Y., Ihara M., Fenwick R., Burke M., Oakley A.E., Roeber S., Duering M., Kretzschmar H., Kalaria R.N. White matter pa- thology and disconnection in the frontal lobe in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencepha- lopathy (CADASIL) Neuropathol. Appl. Neu-Robiol. 2014;40:591–602. doi: 10.1111/nan.12073.
    1. Tuominen S., Miao Q., Kurki M.T., Tuisku S., Pöyhönen M., Kalimo H., Viitanen M., Sipilä H.T., Bergman M.J.R., Rinne J.O. Positron Emission Tomography Examination of Cerebral Blood Flow and Glucose Metabolism in Young CADASIL Patients. Stroke. 2004;35:1063–1067. doi: 10.1161/01.STR.0000124124.69842.2d.
    1. Pescini F., Nannucci S., Bertaccini B., Salvadori E., Bianchi S., Ragno M., Sarti C., Valenti R., Zicari E., Moretti M., et al. The cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (cadasil) scale: A screening tool to select patients for NOTCH3 gene analysis. Stroke. 2012;43:2871–2876. doi: 10.1161/STROKEAHA.112.665927.
    1. Oberstein S.A.J.L., Boom R.V.D., Van Buchem M.A., Van Houwelingen H.C., Bakker E., Vollebregt E., Ferrari M.D., Breuning M., Haan J. Cerebral microbleeds in CADASIL. Neurology. 2001;57:1066–1070. doi: 10.1212/WNL.57.6.1066.
    1. Dichgans M., Holtmannspötter M., Herzog J., Peters N., Bergmann M., Yousry T.A. Cerebral microbleeds in CADASIL: A gradient-echo magnetic resonance imaging and autopsy study. Stroke. 2002;33:67–71. doi: 10.1161/hs0102.100885.

Source: PubMed

3
Abonner