Small vessel disease to subcortical dementia: a dynamic model, which interfaces aging, cholinergic dysregulation and the neurovascular unit

References

• Dubois B, Feldman HH, Jacova C, et al. Revising the definition of Alzheimer’s disease: a new lexicon. Lancet Neurol. 2010;9(11):1118–1127. Epub 2010 Oct 9. doi: 10.1016/S1474-4422(10)70223-420934914
   PubMed Web of Science ®Google Scholar
• Sorbi S, Hort J, Erkinjuntti T, et al. EFNS-ENS guidelines on the diagnosis and management of disorders associated with dementia. Eur J Neurol. 2012;19(9):1159–1179. doi: 10.1111/j.1468-1331.2012.03784.x.22891773
   PubMed Web of Science ®Google Scholar
• Emre M. Clinical features, pathophysiology and treatment of dementia associated with Parkinson’s disease. Handb Clin Neurol. 2007;83:401–419. doi: 10.1016/S0072-9752(07)83018-1.18808925
   PubMedGoogle Scholar
• McKeith IG1, Dickson DW, Lowe J, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB consortium. Neurology. 2005;65(12):1863–1872. Epub 2005 Oct 19.16237129
   PubMed Web of Science ®Google Scholar
• Seltman RE, Matthews BR. Frontotemporal lobar degeneration: epidemiology, pathology, diagnosis and management. CNS Drugs. 2012;26(10):841–870. doi: 10.2165/11640070-000000000-00000.22950490
   PubMed Web of Science ®Google Scholar
• Chui H. Vascular dementia, a new beginning: shifting focus from clinical phenotype to ischemic brain injury. Neurol Clin. 2000;18(4):951–978.11072269
   PubMed Web of Science ®Google Scholar
• Román GC, Goldstein M. A population-based study of dementia in 85-year-olds. N Engl J Med. 1993;329(1):63; author reply 64.
   PubMedGoogle Scholar
• Román GC, Tatemichi TK, Erkinjuntti T,et al. Vascular dementia: diagnostic criteria for research studies. Reports of the NINDS-AIREN international workshop. Neurology. 1993; 43(2):250–260.8094895
   PubMed Web of Science ®Google Scholar
• World Health Organization for vascular dementia. The ICD-10 Classification of Mental and Behavioral Disorders. Diagnostic Criteria for Research, Geneva. Switzerland World Health Organization; 1993:48–50.
   Google Scholar
• Jellinger KA. Pathology and pathogenesis of vascular cognitive impairment - a critical update. Front Aging Neurosci. 2013;5:17. doi: 10.33897fnagi.2013.00017
   Web of Science ®Google Scholar
• Jellinger KA. The enigma of vascular cognitive disorder and vascular dementia. Acta Neuropathol. 2007;113:349–388.17285295
   PubMed Web of Science ®Google Scholar
• American Psychiatric Association. Major or Mild Vascular Neurocognitive Disorders. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Washington DC: American Psychiatric Publishing; 2013: 612–615.
   Google Scholar
• Pohjasvaara T, Mantyla R, Ylikoski R, Kaste M, Erkiniunnti T. Comparison of different clinical criteria (DSM.III, ADDTC, ICD-10, NINDS-AIREN, DSM-IV) for the diagnosis of vascular dementia. Stroke. 2003;31: 2952–2957. doi:10.1161/01.STR.31.12.2952.
   Google Scholar
• Sinha P, Bharath S, Chandra SR. DSM-5 in vascular dementia. Comparison with other diagnostic criteria in a retrospective study. EC Neurol. 2015;2 (3):135–143.
   Google Scholar
• Wardlaw JM, Smith EF, Biessels GJ, et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013;12:822–832. doi:10.1016/S1474-4422(13)70124-823867200
   PubMed Web of Science ®Google Scholar
• Garcia JH, Brown GG. Vascular dementia: neuropatholgic alterations and metabolic brain changes. J Neurol Sci. 1992;109:121–131.1634894
   PubMed Web of Science ®Google Scholar
• Román GC, Sachdev P, Royall DR, et al. Vascular cognitive disorder: a new diagnostic category updating vascular cognitive impairment and vascular dementia. J Neurol Sci. 2004;226:81–87. doi:10.1016/j.jns.2004.09.01615537526
   PubMed Web of Science ®Google Scholar
• Brown MM, Markus HS, Oppenheimer S. Stroke Medicine. New York: Taylor and Francis 2006: 81–83.
   Google Scholar
• Tomimoto H. Subcortical vascular dementia. Neurosci Res. 2011;71:193–199 doi:10.1016/j.neures.2011.07.182021821070
   PubMed Web of Science ®Google Scholar
• Thal DR, Grinberg LT, Attems J. Vascular dementia: different forms of vessel disorders contribute to the development of dementia in the elderly brain. Exp Gerontol. 2012;47:816–824. doi:10.1016/j.exger.2012.05.02322705146
   PubMed Web of Science ®Google Scholar
• 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)70104-620610345
   PubMed Web of Science ®Google Scholar
• Bowler JV. Vascular cognitive impairment. J Neurol Neurosurg Psychiatr. 2005;76(5):35–44. doi:10.1136/jnnp.2005.082313
   Google Scholar
• Erkinjunnti T, Gauthier S. Diagnosing vascular cognitive impairment and dementia. In: Wahlund LO, Erkinjunnti T, Gauthier S, editors. Concepts and Controversies in Vascular Cognitive Impairment in Clinical Practice Cambridge: Cambridge University Press; 2009:3–9.
   Google Scholar
• Ying H, Jianping C, Jianqing Y, Shanquan Z. Cognitive variations among vascular dementia subtypes caused by small-, large-, or mixed-vessel disease. Arch Med Sci. 2016;12(4):747–753. doi:10.5114/aoms.2016.6096227478455
   PubMed Web of Science ®Google Scholar
• Patel B, Markus HS. Magnetic resonance imaging in cerebral small vessel disease and its use as a surrogate disease marker. Int J Stroke. 2011;6(1):47–59. doi:10.1111/j.1747-4949.2010.00552.x21205241
   PubMed Web of Science ®Google Scholar
• Erkinjunnti T, Inzitari D, Pantoni L, et al. Resaerch criteria for subcortical vascular dementia in clinical trials. J Neur Transm Suppl. 2000;59:23–30
   PubMedGoogle Scholar
• Roman GC, Erkinjunnti T, Wallin A, Pantoni L, Chui HC. Subcortical ischemic vascular dementia. Lancet Neurol. 2002;1:426–436.12849365
   PubMed Web of Science ®Google Scholar
• Neumann-Haefelin T, Hoelig S, Berkefeld J, et al. Leukoaraiosi is a risk factor for symptomatic intracererbal hemorrhage after trombolysis for acute stroke. Stroke. 2006;37:2463–2466. doi:10.1161/01.STR.0000239321.53203.ea16931786
   PubMed Web of Science ®Google Scholar
• Palumbo V, Boulanger JM, Hill MD, Inzitari D, Buchan AM; for the CASES Invstigators. Leukoaraiosis and intracerebral hemorrhage after trombolysis in acute stroke. Neurology. 2007;68:1020–1024. doi:10.1212/01.wnl.0000257817.29883.4817389306
   PubMed Web of Science ®Google Scholar
• Launer LJ, Masaki K, Petrovitch H, Foley D, Havlik RJ. The association between midlife blood pressure levels and late-life cognitive function. The Honolulu-Asia Aging Study. JAMA. 1995;274:846–1851.
   Web of Science ®Google Scholar
• Smith EE, Rosand J, Knudsen KA, Hylek EM, Greenberg SM. Leukaraiosis is assocaited with arfarin-related hemorrhage following ischemic stroke. Neurology. 2002;59:193–197.12136056
   PubMed Web of Science ®Google Scholar
• Streifler JY, Elasziw M, Benavente OR, et al. For the North American Symtpomatic Carotid Endarterectomy Trial Group. Prognostic importance of leukoaraiosis in patients with sympotmatic internal carotid stenosis. Stroke. 2002;33:1651–1655.12053006
   PubMed Web of Science ®Google Scholar
• Lin R, Stevensson L, Gupta R, Lytle B, Krieger D. Chronic ischemic white amtter disease is a risk factor for nonfocal neurologic injury after total aortic arch replacement. J Thor Cardiovasc Surg. 2007;133:1059–1065.
   PubMed Web of Science ®Google Scholar
• O’Donnell MJ, Xavier D, Liu L, et al. Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case- control study. Lancet. 2010;376:112–123.20561675
   PubMed Web of Science ®Google Scholar
• Iadecola C, Park L, Capone C. Threats to the mind: aging, amyloid, and hypertension. Stroke. 2009;40:40–44.
   PubMed Web of Science ®Google Scholar
• Moretti R, Torre P, Antonello RM, Manganaro D, Vilotti C, Pizzolato G. Risk factors for vascular dementia: hypotension as a key point. Vasc Health Risk Manag. 2008;4(2):2432–2444.
   Google Scholar
• Skoog I, Nilsson L, Palmertz B. A population-based study of dementia in 85-year olds. NEJM. 1993;328:153–158.8417380
   PubMed Web of Science ®Google Scholar
• Brookmeyer R, Gray S, Kawas C. Projections of Alzheimer’s disease in the United States and the public health impact of delaying disease onset. Am J Public Health. 1998;88(9):1337–1342.9736873
   PubMed Web of Science ®Google Scholar
• Posner HB, Tang MX, Luchsinger J, Lantigua R, Stern Y, Mayeux R. The relationship of hypertension in the elderly to AD, vascular dementia, and cognitive function. Neurology. 2002;58:1175–1181.11971083
   PubMed Web of Science ®Google Scholar
• Prince MJ, Bird AS, Blizard RA, Mann AH. Is the cognitve function of older aptients affectd by antihypertensive tratement? Results from 54 months of the Medica Research Council’s trial of hypertension in older adults. BMJ. 1996;312:801–805.8608285
   PubMed Web of Science ®Google Scholar
• Hofman A, Ott A, Bretler MM, et al. Atherosclerosis, apolipoproteinE, and prevalence of dementia and Alzheimer’s Dementia in the Rotterdam Study. Lancet. 1997;349:151–154.9111537
   PubMed Web of Science ®Google Scholar
• Tzourio C, Anderson C, Chapman N, et al., Effects of the blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in aptients with cerebrovascualr disease. Arch Intern Med. 2003;163:1069–1075.12742805
   PubMed Web of Science ®Google Scholar
• Forette F, Seux ML, Staessen JA, et al. The prevention of dementia with antihypertensive treatment: new evidence from the systolic hypertension in Europe (syst-Eur) study. Arch Intern Med;2002;162:20146–22052.
   Google Scholar
• Knopman DS, Parisi JE, Boeve BF, et al. Vascular dementia in a population-based autopsy study. Arch Neurol. 2003;60(4):569–575.12707071
   PubMedGoogle Scholar
• Fitzpatrick AL, Kuller LH, Lopez OL, Kawas CH, Jagust W. Survival following dementia onset: alzheimer’s disease and vascular dementia. J Neurol Sci. 2005;229-230:43–49. Epub 2004 Dec 23.15760618
   PubMed Web of Science ®Google Scholar
• Sicras A, Rejas J, Arco S, et al. Prevalence, resource utilization and costs of vascular dementia compared to Alzheimer’s dementia in a population setting. Dement Geriatr Cogn Disord. 2005;19(5–6):305–315. Epub 2005 Mar 22.15785031
   PubMed Web of Science ®Google Scholar
• Ramirez-Gomez C, Zheng C, Reed B, et al. Neuropsychological profiles differentiate Alzheimer disease from subcortical ischemic vascular dementia in an autopsy-defined cohort. Dement Ag Cogn Disord. 2017;44(1–2):1–11. Doi:10.1159/000477344.
   PubMed Web of Science ®Google Scholar
• Kalaria RN, Erkinjuntti T. Small vessel disease and subcortical vascular dementia. J Clin Neurol 2006;2(1):1–11.20396480
   PubMedGoogle Scholar
• Coker LH, Shumaker SA. Type 2 diabetes mellitus and cognition: an understudied issue in women’s health. J Psychosom Res. 2003;54:129–139.12573734
   PubMed Web of Science ®Google Scholar
• Okereke O, Hankinson SE, Hu FB, Grodstein F. Plasma C peptide level and cognitive function among older women without diabetes mellitus. Arch Intern Med. 2005;165:1651–1656.16043685
   PubMedGoogle Scholar
• Luchsinger JA, Tang MX, Shea S, Mayeux R. Hyper-insulinemia and risk of Alzheimer disease. Neurology. 2004;63:1187–1192.15477536
   PubMed Web of Science ®Google Scholar
• Morris MC, Scherr PA, Hebert LE, Glynn RJ, Bennett DA, Evans DA. Association of incident Alzheimer disease and blood pressure measured from 13 years before to 2 years after diagnosis in a large community study. Arch Neurol. 2001;58:1640–1646.11594923
   PubMedGoogle Scholar
• Moretti R, Esposito F, Torre P, Antonello RM, Bellini G. Hypotension in subcortical vascular dementia, a new risk factor. Wasn’t it hypertension?. In: De La Monte S, editor. Alzheimer’s Disease Pathogenesis-Core Concepts, Shifting Paradigms and Therapeutic Targets Rijeka: InTech; 2011. doi:10.5772/18358
   Google Scholar
• Kennelly SP, Lawlor BA, Kenny RA. Blood pressure and dementia - a comprehensive review. Ther Adv Neurol Disord. 2009;2(4):241–260. doi: 10.11177/175628560910348321179532
   PubMedGoogle Scholar
• Whitmer RA, Sidney S, Selby J, Johnsoton SC, Yaffe K. Midlife cardiovascular risk factors and risk of dementia in late life. Neurology. 2005;64:277–281.15668425
   PubMed Web of Science ®Google Scholar
• Yamada M, Kasagi F, Sasaki H, Masunari N, Mimori Y, Suzuki G. Association between dementia and midlife risk factors: the radiation effects research foundation adult health study. J Am Ger Soc. 2003;51:410–414.
   PubMed Web of Science ®Google Scholar
• Kivipelto M, Helkala EL, Laakso MP, et al. Apolipoprotein E epsilo4 allele, elevated midlife total cholesterol level and high midlife systolic blood pressure are independent risk factors for late life Alzheimer disease. Ann Intern Med. 2002;137:149–155.12160362
   PubMed Web of Science ®Google Scholar
• Lindsay J, Laurin D, Verrault R, et al. Risk factors for Alzheimer’s disease: a prospective analysis form the Canadian Study of health and aging. Am J Epidemiol. 2002;156:445–453.12196314
   PubMed Web of Science ®Google Scholar
• van Dijck EJ, Breteler M, Schmidt R, et al. The association between blood pressure, hypertension, and cerebral white matter lesions. Hypertension. 2004;44:625–650.15466662
   PubMed Web of Science ®Google Scholar
• Kruyer A, Soplop N, Strickland S, Norris EH. Chronic hypertension leads to neurodegeneration in the TgSwDI mouse model of Alzheimer’s disease. Hypertension. 2015;66(1):175–182. Epub 2015 May 4. doi: 10.1161/HYPERTENSIONAHA.115.0552425941345
   PubMed Web of Science ®Google Scholar
• Verhaaren BF, Vernooij MW, de Boer R, et al. High blood pressure and cerebral white matter lesion progressions in the general population. Hypertension. 2013;61(6):1354–1359. doi:10.1161/HYPERTENSIONAHA.111.0043023529163
   PubMed Web of Science ®Google Scholar
• Venkat P, Chopp M, Chen J Models and mechanisms of vascular dementia. Exp Neurol. 2015;272:97–10825987538
   PubMed Web of Science ®Google Scholar
• Jackson CA, Hutchinson A, Dennis MS, et al. Differing risk factor profiles of ischemic stroke subtypes: evidence for a distinctive lacunar arteriopathy. Stroke. 2010;41:624–629.20150553
   PubMed Web of Science ®Google Scholar
• Verghese J, Lipton RB, Hall CB, Kuslansky G, Katz MJ. Low blood pressure and the risk of dementia in very old individuals. Neurology. 2003;61:1667–1672.14694027
   PubMed Web of Science ®Google Scholar
• Zhu L, Viitanen M, Guo Z, Winblad B, Fratiglioni L. Blood pressure reduction, cardiovascular disease, and cognitive decline in the mini-mental state examination in a community population of normal very old people: a three year follow-up. J Clin Epidem. 1998;51(5):385–391.
   PubMed Web of Science ®Google Scholar
• Ruitenberg A, Skoog I, Ott AM, et al. Blood pressure and risk of dementia: results from the Rotterdam Study and the Gothenburg H-70 study. Dementia and Ger Cog Dis. 2001;12:33–39.
   PubMed Web of Science ®Google Scholar
• Burke WJ, Coronado PG, Schmitt CA, Gillespie KM, Chung HD. Blood pressure regulation in Alzheimer’s disease. J Auton Nerv Syst. 1994;48:65–71.8027519
   PubMedGoogle Scholar
• Guo Z, Fratiglioni L, Zhu L, Fastbom J, Winblad B, Viitanen M. Occurrence and progression of dementia in a community population aged 75 years and older: relationship of antihyperthensive medication use. Arch Neurol. 1999;59:991–996.
   Google Scholar
• Brown WD, Frackowiak RSJ. Cerebral blood flow and metabolism studies in multi-infarct dementia. Alzh Dis Assoc Dis. 1991;5:131–143.
   PubMed Web of Science ®Google Scholar
• Guo Z, Vintanen M, Winblad B, Fratiglioni L. Low blood pressure and incidence of dementia in a very old sample: dependent on initial cognition. J Am Ger Soc. 1994;47:723–726.
   Google Scholar
• Mattila K, Haavisto M, Rajala S, Heikinheimo R. Blood pressure and five year survival in the very old. Br Med J (Clin Res Ed). 1988;296:887–889.
   PubMed Web of Science ®Google Scholar
• Nilsson SE, Read S, Berg S, Johansson B, Melander A, Lindblad U. Low systolic blood pressure is associated with impaired cognitive function in the oldest old: longitudinal observations in a population-based sample 80 years and older. Aging Clin Exp Res. 2007;19(1):41–47.17332720
   PubMed Web of Science ®Google Scholar
• Qiu C, Von Strauss E, Fastblom J, Winblad B, Fratiglion L. Low blood pressure and risk of dementia in the Kungsholmen project: a 6-year follw-up study. Arch Neurol. 2003;60:223–228.12580707
   PubMed Web of Science ®Google Scholar
• In’t Veld BA, Ruitenberg A, Hofman A, Stricker BH, Bretrler MM. Antihypertensive drugs and incidence of dementia: the Rotterdam Study. Neurobiol Aging. 2001;22:407–412.11378246
   PubMed Web of Science ®Google Scholar
• Bilazarian S. Hypertension guidelines: clear as mud. theHeart.org. 2014 Available from: http://www.medscape.com/viewarticle/819629. Accessed February 12, 2014.
   Google Scholar
• Weber MA, Schiffrin EL, White WB, et al. Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Hypertens. 2014;32:3–15.24270181
   PubMed Web of Science ®Google Scholar
• ESH/ESC Task Force for the Management of Arterial Hypertension. 2014 practice guidelines for the management of arterial hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC): ESH/ESC task force for the management of arterial hypertension. J Hypertens. 2013;31:1925–1938.24107724
   PubMed Web of Science ®Google Scholar
• James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311:507–520.24352797
   PubMed Web of Science ®Google Scholar
• Murthy VL, Shah RV, Rubenfire M, Brook RD. A comparison of the treatment implications of American Society of Hypertension and International Society of Hypertension 2013 and Eighth Joint National Committee Guidelines: an analysis of National Health and Nutrition Examination Survey. Hypertension. 2014;64:275–280.24821946
   PubMed Web of Science ®Google Scholar
• Rakugi H. DB 02-2 Strict control of hypertension in the frail elderly: is it beneficial? J Hypertens. 2016;34 Suppl 1 – ISH 2016 Abstract Book: e190.
   Google Scholar
• Kario K, Matsuo T, Kobayashi H, Imiya M, Mastuo M, Shimada K. Nocturnal fall of blood pressure and silent cerebrovascular damage in elderly hypertensive patients: advanced silent cerebrovascular damage in extreme dippers. Hypertension. 1996;27:130–135.8591875
   PubMed Web of Science ®Google Scholar
• Nakamura K, Oita J, Yamaguchi T. Nocturnal blood pressure dip in stroke survivors: a pilot study. Stroke. 1995;26:1373–1378.7631340
   PubMed Web of Science ®Google Scholar
• Watanabe N, Imai Y, Nagai K, et al. Nocturnal blood pressure and silent cerebrovascular lesions in elderly Japanese. Stroke. 1996;27:1319–1327.8711795
   PubMed Web of Science ®Google Scholar
• Chamorro A, Pujol J, Saiz A, et al. Periventricular white matter lucencies in patients with lacunar stroke: a marker of too high or too low blood pressure? Arch Neurol. 1997;54:1284–1288.9341575
   PubMedGoogle Scholar
• De Buyzere M, Clement DL, Duprez D. Chronic low blood pressure: a review. Cardiovasc Drugs Ther. 199812:29–35.9607130
   PubMed Web of Science ®Google Scholar
• Matsubayashi K, Okumiya K, Wada T, et al. Postural dysregulation in systolic blood pressure is associated with worsened scoring on neurobehavioral function tests and leukoaraiosis in the older elderly living in a community. Stroke. 1997;28:2169–2173.9368559
   PubMed Web of Science ®Google Scholar
• Kohara K, Jiang Y, Igase M, et al. Postprandial hypotension is associated with asymptomatic cerebrovascular damage in essential hypertensive patients. Hypertension. 1999;33:565–568.9931166
   PubMed Web of Science ®Google Scholar
• Gottesman R, Schneider A, Zhou Y ,et al. Association between midlife vascular risk factors and estimated brain amyloid deposition. JAMA. 2017. doi:10.1001/jama.2017-3090.
   PubMed Web of Science ®Google Scholar
• Wise J. Vascular risk factors show link to development of Alzheimer’s. BMJ. 2017;357:11847 Doi: 10.1136/bmj.J1847.
   Google Scholar
• Jani B, Rajkumar C. Ageing and vascular ageing. Postgrad Med J. 2006;82(968):357–362.16754702
   PubMed Web of Science ®Google Scholar
• de la Torre JC. Vascular basis of Alzheimer’s pathogenesis. Ann N Y Acad Sci. 2002;977:196–215.12480752
   PubMed Web of Science ®Google Scholar
• Mathias CJ, Kimber JR. Postural hypotension: causes, clinical features, investigation, and management. Annu Rev Med. 1999;50:317–336.10073281
   PubMed Web of Science ®Google Scholar
• Roriz-Filho JS, Bernardes Silva Filho SR, Rosset I, Roriz-Cruz M. Postural blood pressure dysregulation and dementia: evidence for a vicious circle and implications for neurocardiovascular rehabilitation In: Halliday JT ,editor. Cardiac Rehabilitation. New York: Novascience Publisher Inc.; 2009:1–37. ISBN: 987-1-60741-918-1.
   Google Scholar
• Londos E, Passant U, Gustafson L. Blood pressure and drug treatment in clinically diagnosed LBD and AD. Arch Gerontol Ger. 2000;30:35–46
   PubMed Web of Science ®Google Scholar
• Kaufman H, Biaggioni I. Autonomic failure in neurodegenerative disorders. Sem Neurol. 2003;23(4):351–363.
   PubMed Web of Science ®Google Scholar
• Puisieux F, Monaca P, Deplanque D, et al. Relationship between leuko—araiosis and blood pressure variability in the elderly. Eur Neur. 2001;46:115–120.
   PubMed Web of Science ®Google Scholar
• Burke WJ, Coronado PG, Schmitt CA, Gillespie KM, Chung HD. Blood pressure regulation in AD. J Auton Nerv Syst. 1994;48:65–718027519
   PubMedGoogle Scholar
• Englund E. A White Matter Disease in Dementia. A Study with Special Reference to AD [thesis]. Lund: Lund University; 1988:7–43.
   Google Scholar
• Weiner DE, Gaussoin SA, Nord J, et al. Cognitive function and kidney disease: baseline data from the Systolic Blood Pressure Intervention Trial (SPRINT). Am J Kidney Dis. 2017; 70(3): 357–36728606731
   PubMed Web of Science ®Google Scholar
• Fisher CM. The arterial lesions underlying lacunes. Acta Neuropathol. 1969;12:1–15. doi:10.1007/BF00685305
   Web of Science ®Google Scholar
• Pantoni L, Garcia JH, Gutierrez JA. Cerebral white matter is highly vulnerable to ischemia. Stroke. 1996;27:1641–1647.8784142
   PubMed Web of Science ®Google Scholar
• Schmidt R, Schmidt H, Haybaeck J, et al. Heterogeneity in age-related white matter changes. Acta Neuropathol. 2011;122:171–185. doi:10.1007/s00401-011-0851-x21706175
   PubMed Web of Science ®Google Scholar
• Hommet C, Mondon K, Constans T, et al. Review of cerebral microangiopathy and Alzheimer’s disease: relation between white matter hyperintensities and microbleeds. Dement Geriatr Cogn Disord. 2011;32:367–378. doi:10.1159/00033556822301385
   PubMed Web of Science ®Google Scholar
• Munoz DG, Hastak SM, Harper B, et al. Pathologic correlates of increased signals of the centrum ovale on magnetic resonance imaging. Arch Neurol. 1993;50: 492–497.8489405
   PubMedGoogle Scholar
• Jellinger KA, Attems J. Prevalence and pathology of vascular dementia in the oldest-old. J Alzheimers Dis. 2010;21:1283–1293. doi:10.3233/JAD-2010-10060321504129
   PubMed Web of Science ®Google Scholar
• Ince P. Acquired forms of vascular dementia In: Kalimo H, editor. Cerebrovascular Diseases. Basel: ISN Neuropath Press; 2005:316–323.
   Google Scholar
• Hachinski V, Iadecola C, Petersen RC, et al. National Institute of Neurological Disorders and Stroke-Canadian Stroke-Network Vascular cognitive impairment harmonization standards. Stroke. 2006;37:2220–2241. doi:10.1161/01.STR.0000237236.88823.4716917086
   PubMed Web of Science ®Google Scholar
• Attems J, Jellinger K, Thal DR, Van Nostrand W. Review: sporadic cerebral amyloid angiopathy. Neuropathol Appl Neurobiol. 2011;37:75–93. doi:10.1111/j.1365-2990.2010.01137.x20946241
   PubMed Web of Science ®Google Scholar
• Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science. 2002;297:353–356. doi:10.1126/science.107299412130773
   PubMed Web of Science ®Google Scholar
• Jiménez-Balado J, Riba-Llena I, Garde E, et al. Prevalence of hippocampal enlarged perivascular spaces in a sample of patients with hypertension and their relation with vascular risk factors and cognitive function. J Neurol Neurosurg Psychiatry. 2018;89:1–6. doi:10.1136/jnnp-2017-316724.28847793
   PubMed Web of Science ®Google Scholar
• Sweeney MD, Sagare AP, Zlokovic BV. Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders. Nat Rev Neurol. 2018. doi:10.1038/nrneurol.2017.188
   PubMed Web of Science ®Google Scholar
• Abbott NJ, Pizzo ME, Preston JE, Janigro D, Thorne RG. The role of brain barriers in fluid movement in the CNS: is there a ‘glymphatic’ system? Acta Neuropathol. 2018;135(3):387–407. doi:10.1007/s00401-018-1812-429428972
   PubMed Web of Science ®Google Scholar
• Huijts M, Duits A, Staals J, et al. Basal ganglia enlarged perivascular spaces are linked to cognitive function in patients with cerebral small vessel disease. Curr Neurovasc Res. 2014;11:136–141. doi:10.2174/156720261166614031010224824606607
   PubMed Web of Science ®Google Scholar
• Potter GM, Marlborough FJ, Wardlaw JM. Wide variation in definition, detection and description of lacunar lesions on imaging. Stroke. 2011;42:359–366. doi:10.1161/STROKEAHA.110.59475421193752
   PubMed Web of Science ®Google Scholar
• Potter GM, Doubal FN, Jackson CA, et al. Counting cavitating lacunes underestimates the burden of lacunar infarction. Stroke. 2010;41: 267–272. doi:10.1161/STROKEAHA.109.56630720044528
   PubMed Web of Science ®Google Scholar
• Shi Y, Wardlaw JM. Update on cerebral small vessel disease. A dynamic whole-brain disease. Stroke Vasc Neurology. 2016;1:e.000035.
   PubMedGoogle Scholar
• Wardlaw JM, Doubal F, Armitage P, et al. Lacunar stroke is associated with diffuse blood brain barrier dysfunction. Ann Neurol. 2009;65:194–202. doi:10.1002/ana.2154919260033
   PubMed Web of Science ®Google Scholar
• De Silva TM, Faraci FM. Microvascular dysfunction and cognitive impairment. Cell Mol Neurobiol. 2016;36(2):241–258. Doi:10.1007/s10571-015-0308-1.26988697
   PubMed Web of Science ®Google Scholar
• Joutel A, Faraci FM. Cerebral small vessel 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.113.00287824503668
   PubMed Web of Science ®Google Scholar
• Lammie AG. Small vessel disease In: Kalimo H., editor. Cerebrovascular Diseases. Basel: ISN Neuropath Press; 2005:85–91.
   Google Scholar
• Rosenberg GA. Neurological diseases in relation to the blood- brain barrier. J Cereb Blood Flow Metab. 2012;32:1139–1151. doi:10.1038/jcbfm.2011.19722252235
   PubMed Web of Science ®Google Scholar
• Pantoni L. Pathophysiology of age-related cerebral white matter changes. Cerebrovasc Dis. 2002;13(2):7–10. doi:10.1159/000049143
   PubMedGoogle Scholar
• Englund E. White matter pathology of vascular dementia In: Chui E editor. Vascular Dementia. London: M. Dunitz; 2004:117–130.
   Google Scholar
• Englund EA, Person B. Correlations between histopathologic white matter changes and proton MR relaxation times in dementia. Alzheimer Dis Assoc Disord. 1987;1:156–170. doi:10.1097/00002093-198701030-000083453747
   PubMedGoogle Scholar
• Román GC Senile dementia of the binswanger type: a vascular form of dementia in the elderly. JAMA. 1987;258:1782–1788. doi:10.1001/jama.1987.034001300960403625988
   PubMed Web of Science ®Google Scholar
• Moody DM, Brown WR, Challa VR, Anderson RL. Periventricular venous collagenosis: association with leukoaraiosis. Radiology. 1995;194:469–476. doi:10.1148/radiology.194.2.78247287824728
   PubMed Web of Science ®Google Scholar
• Vinters HV, Ellis WG, Zarow C, et al. Neuropathological substrate of ischemic vascular dementia. J Neuropathol Exp Neurol. 2000;59:931–945. doi:10.1093/jnen/59.11.93111089571
   PubMed Web of Science ®Google Scholar
• Garcia JH, Lassen NA, Weiller C, Sperling B, Nakagawara J. Ischemic stroke and incomplete infarction. Stroke. 1996;27:761–765.8614945
   PubMed Web of Science ®Google Scholar
• Dalkara T, Alarcon-Martinez L. Cerebral micro-vascular signaling in health and disease. Brain Res. 2015;1623:3–17. doi: 10.1016/j.brainres.2015.03.04725862573
   PubMed Web of Science ®Google Scholar
• Giannakopoulos P, Gold G, Kowaru E, et al. Assessing the cognitive impact of Alzheimer disease pathology and vascular burden in the aging brain: the Geneva experience. Acta Neuropathol. 2007;113:1–12. doi:10.1007/s00401-006-0144-y17036244
   PubMed Web of Science ®Google Scholar
• Launer LJ, Hughes TM, White LR. Microinfarcts, brain atrophy, and cognitive function: the Honolulu Asia Aging Study Autopsy Study. Ann Neurol. 2011;70:774–780. doi:10.1002/ana.2252022162060
   PubMed Web of Science ®Google Scholar
• Smallwood A, Oulhaj A, Joachim C, et al. Cerebral subcortical small vessel disease and its relation to cognition in elderly subjects: a pathological study in the Oxford Project to Investigate Memory and Ageing (OPTIMA) cohort. Neuropathol Appl Neurobiol. 2012;38:337–343. doi:10.1111/j.1365-2990.2011.01221.x21951164
   PubMed Web of Science ®Google Scholar
• Kramer JH, Reed BR, Mungas D, Weiner MW, Chui H Executive dysfunction in subcortical ischaemic vascular disease. J Neurol Neurosurg Psychiatr. 2002;72:217–220. doi:10.1136/jnnp.72.2.217
   PubMed Web of Science ®Google Scholar
• Burton E, Ballard C, Stephens S, et al. Hyperintensities and fronto-subcortical atrophy on MRI are substrates of mild cognitive deficits after stroke. Dement Geriatr Cogn Disord. 2003;16:113–118. doi:10.1159/00007068412784036
   PubMed Web of Science ®Google Scholar
• Tullberg M, Fletcher E, DeCarli C, et al. White matter lesions impair frontal lobe function regard- less of their location. Neurology. 2004;63:246–253. doi:10.1212/01.WNL.0000130530.55104.B515277616
   PubMed Web of Science ®Google Scholar
• Gold G, Kovari E, Herrmann FR, et al. Cognitive consequences of thalamic, basal ganglia, and deep white matter lacunes in brain aging and dementia. Stroke. 2005;36:1184–1188. doi:10.1161/01.STR.0000166052.89772.b515891000
   PubMed Web of Science ®Google Scholar
• Van Der Veen PH, Muller M, Vinken KL, 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.114.00803025804924
   PubMed Web of Science ®Google Scholar
• Gouw AA, van Der Flier WM, Fazekas F et al. Progression of white matter hyperintensities and incidence of new lacunes over a 3-year period: the leukoaraiosis and disability study. Stroke. 2008;39:1414–1420. doi:10.1161/STROKEAHA.107.49853518323505
   PubMed Web of Science ®Google Scholar
• Schmidt R, Seiler S, Loitfelder M. Longitudinal change of small vessel disease related brain abnormalities. J Cerebr Blood Flow Metab. 2016;36:26–39. doi:10.1038/jcbfm.2015.72
   PubMed Web of Science ®Google Scholar
• Munoz-Maniega S, Chappell FM, Valdes-Henrandez ML, et al. Integrity of normal appearing white matter: influence of age, visible lesion burden and hypertension in patients with small-vessel disease. J Cerebr Blood Flow Metab. 2016 Doi: 10.1177/027168x16635657.
   PubMed Web of Science ®Google Scholar
• Nichols WW, O’Rourke MF McDonald’s Blood Flow in Arteries: Theoretical, Experimental and Clinical Principles, 5th ed. London: Hodder Arnold;2005.
   Google Scholar
• Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises. Part I: aging arteries: a “set up” for vascular disease. Circulation. 2003;107:139–146. doi:10.1161/01.CIR.0000048892.83521.5812515756
   PubMed Web of Science ®Google Scholar
• Ganong MD, William F. Review of Medical Physiology, Twenty-Second ed. New York: The McGraw-Hill Companies, Inc; 2005:587.
   Google Scholar
• Volpe M, Scuteri A. Management of risk factors in vascular dementia: hypertension. Hot Topics Neurol Psychiatry. 2008;1:17–22.
   Google Scholar
• Najjar SS, Scuteri A, Lakatta EG. Arterial aging: is it an immutable cardiovascular risk factor? Hypertension. 2005;46:454–462. doi:10.1161/01.HYP.0000177474.06749.9816103272
   PubMed Web of Science ®Google Scholar
• O’Rourke MF, Safar ME. Relationship between aortic stiffening and microvascular disease in brain and kidney: cause and logic of therapy. Hypertension. 2005;46:200–204. doi:10.1161/01.HYP.0000184108.12155.6b15911742
   PubMed Web of Science ®Google Scholar
• Cervós-Navarro J, Matakas F, Roggendorf W, Christmann U. The morphology of spastic intracerebral arterioles. Neuropathol Appl Neurobiol. 1978;4:369–379. doi:10.1111/j.1365-2990.1978.tb01349.x724092
   PubMed Web of Science ®Google Scholar
• Laurent S, Katsahian S, Fassot C, et al. Aortic stiffness is an independent predictor of fatal stroke in essential hypertension. Stroke. 2003;34:1203–1206. doi:10.1161/01.STR.0000065428.03209.6412677025
   PubMed Web of Science ®Google Scholar
• Baumbach GL, Siems JE, Heistad DD. Effects of local reduction in pressure on distensibility and composition of cerebral arterioles. Circ Res. 1991;68:338–351. doi:10.1161/01.RES.68.2.3381991342
   PubMed Web of Science ®Google Scholar
• Liao D, Cooper L, Cai J, et al. The prevalence and severity of white matter lesions, their relationship with age, ethnicity, gender, and cardiovascular disease risk factors: the ARIC Study. Neuroepidemiology. 1997;16:149–162 doi:10.1159/0003688149159770
   PubMed Web of Science ®Google Scholar
• Paulson OB, Strandgaard S, Edvinson L. Cerebral autoregulation. Cerebrovasc Brain Metab Rev. 1990;2:161–192.2201348
   PubMedGoogle Scholar
• Dawson SL, Blake MJ, Panerai RB, Potter JF. Dynamic but not static cerebral autoregulation is impaired in acute ischemic stroke. Cerebrovasc Dis. 2000;10:126–132. doi:10.1159/00001604110686451
   PubMed Web of Science ®Google Scholar
• Novak V. Cognition and Hemodynamics. Curr Cardiovasc Risk Rep. 2012;6(5):380–396. doi:10.1007/s12170-012-0260-223050027
   PubMedGoogle Scholar
• Shim Y, Yoon B, Shim DS, Kim W, An JY, Yang DW. Cognitive correlates of cerebral vasoreactivity on transcranial doppler in older adults Journal of Stroke and Cerebrovascular Diseases, 2015:1262–1269 doi:10.1016/j.jstrokecerebrovasdis.2015.01.03125906930
   PubMed Web of Science ®Google Scholar
• Roher AE, Garami Z, Tyas SL, et al. Transcranial Doppler ultrasound blood flow velocity and pulsatility index as systemic indicators for Alzheimer’s disease. Alzheimers Dement. 2011;7(4):445–455. doi:10.1016/j.jalz.2010.08.22921388892
   PubMed Web of Science ®Google Scholar
• Wallin A, Blennow K, Gottfries CG. Neurochemical abnormalities in vascular dementia. Dementia. 1989;13:658–667.
   Google Scholar
• Szilagy AX, Nemeth A, Martini E, et al. Serum and CSF cholinesterase activity in various kind of dementia. Eur Arch Psych Neur Sci. 1987;236:309–311. doi:10.1007/BF00380958
   PubMedGoogle Scholar
• Sakurada I, Alufuzoff I, Winblad B, et al. Substance P like immunoreactivity, choline acetyltransferase activity and cholinergic muscarinic receptors in AD and MID. Brain Res. 1990;521(1–29):329–332. doi:10.1016/0006-8993(90)91561-t1698512
   PubMed Web of Science ®Google Scholar
• Serrador JM, Freeman R. Enhanced cholinergic activity improves cerebral blood flow during orthostatic stress. Frontiers in Neurol. 2017;8: 103 Doi:10.3389/fneur.2017.00103.
   PubMed Web of Science ®Google Scholar
• Tune L, Brandt J, Frost JJ, et al. Physstigmine in AD: effects on cognitive functioning, cerebral glucose metabolism analyzed by single photon emission tomography. Acta Psych. Scand Suppl. 1991;366:61–65. doi:10.1111/j.1600-0447.1991.tb03111.x
   PubMedGoogle Scholar
• Scremin OU, Sonneschein RR, Rubinstein EH. Cholinergic cerebral vasodilatation in the rabbit: absence of concomitant metabolic activation. J Cereb Blood Flow Metab. 1982;2(2):241–247. doi:10.1038/jcbfm.1982.246804471
   PubMed Web of Science ®Google Scholar
• Halliwell B. Role of free radicals in the neurodegenerative diseases: therapeutic implications for antioxidant treatment. Drugs Aging, 2001;18(9):685–716. doi:10.2165/00002512-200118090-0000411599635
   PubMed Web of Science ®Google Scholar
• Lin MT, Beal MF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature. 2006;443(7113):787–795. doi:10.1038/nature0529217051205
   PubMed Web of Science ®Google Scholar
• Raz N. The ageing brain: structural changes and their implications for cognitive ageing In: Dixon R, Bäckman L, Nilsson L, editors. New Frontiers in Cognitive Ageing. Telangana, India: Oxford University Press; 2004:115–134.
   Google Scholar
• Petito C. Trasnformation of postisichemic perineuronal glial cells. I. Electron microscope studies. J Cerebr Blood Flow Metabol. 1986;6:616–624. doi:10.1038/jcbfm.1986.109
   PubMedGoogle Scholar
• Petito CK, Olarte JP, Roberts B, Nowak TS, Pulsinelli WA. Selective glial vulnerability following transient global ischemia in rat brain. J Neuropath Exp Neurol. 1998;57(3):231–238. doi:10.1097/00005072-199803000-000049600215
   PubMed Web of Science ®Google Scholar
• Irving EA, Nicoll J, Graham DI, Dewar D. Increased tau immunoreactivity in oligodendrocytes following human stroke and head injury. Neurosci Lett. 1996;213:189–192. doi:10.1016/0304-3940(96)12856-18873146
   PubMed Web of Science ®Google Scholar
• Irving EA, Yatsushiro K, McCullough J, Dewar R. Rapid alteration of tau in oligodendrocytes after focal ischemic injury in the rat: involvement of free radical. J Cererb Blood Flow Metab. 1997;17:612–622.
   PubMed Web of Science ®Google Scholar
• Furukawa S, Sameshima H, Yang L, Hariskuma M, Ikenoue T. Regional differences of microglial accumulation within 72 hrs of hypoxia-ischemia and the effect of acetylcholine receptor agonist on brain damage and microglial activation in newborn rats. Brain Res. 2014;1562:52–58. doi:10.1016/j.brainres.2014.03.02824680905
   PubMed Web of Science ®Google Scholar
• Gehrmann J, Bonnekoh P, Miyazawa T. Immunoistochemical study of an early microglial activation in ischemia. J Cer Blood Flow Metab. 1992;12:257–269. doi:10.1038/jcbfm.1992.36
   PubMed Web of Science ®Google Scholar
• Rupalla K, Allegrin PR, Saver D. Time course of microglia activation and apoptosis in various brain regions after permanent focal cerebral ischemia in mice. Acta Neuropathol. 1998;96:172–178.9705133
   PubMed Web of Science ®Google Scholar
• Czeh M, Gressens P, Kaindl AM. The yin and yang of microglia. Dev Neurosci. 2011;33:199–209. doi:10.1159/00032898921757877
   PubMed Web of Science ®Google Scholar
• Yuan TH, Yu HM. Notch signaling: key role in intrauterin infection/inflammation, embryonic development and white matter damage. J Neurosci Res. 2010;88:461–468. doi:10.1002/jnr.2222919768798
   PubMed Web of Science ®Google Scholar
• Irving EA, Bentley DL, Parsons AA. Assessment of white matter injury following prolonged focal cerebral ischaemia in the rat. Acta Neuropathol. 2001;102(6):627–635.11761724
   PubMed Web of Science ®Google Scholar
• Tomimoto H, Ihara M, Wakita H, et al. Chronic cerebral hypoeprfusion induces white matter lesions and loss of oligodendroglia with DNA fragmentation in the rat. Acta Neuropathol. 2003;106(6):527–534. doi:10.1007/s00401-003-0749-313680276
   PubMed Web of Science ®Google Scholar
• Wakita H, Tomimoto H, Akiguchi I, et al. Axonal damage and demyelination in the white matter after chronic cerebral hypoperfusion in the rat. Brain Res. 2002;924(1):63–70. doi:10.1016/s0006-8993(01)03223-111743996
   PubMed Web of Science ®Google Scholar
• Wakita H, Tomimoto H, Akiguchi I, Kimura J. Glial activation and white matter changes in the rat brain induced by chronic cerebral hypoperfusion: an immunoistochemical study. Acta Neuropathol. 1994;87(5):484–492.8059601
   PubMed Web of Science ®Google Scholar
• Farkas E, Donka G, de Vous RAI, Mihaly A, Bari F, Luiten PGM. Experimental cerebral hypoeprfusion induces white matter injury and microglial activation in the rat brain. Acta Neuropathol. 2004;108: 57–64. doi:10.1007/s00401-004-0864-915138777
   PubMed Web of Science ®Google Scholar
• Zhang ZG, Bower L, Zhang RL, Chen S, Windham JP, Chopp M. Three dimensional measuremtn of cerebral microvascular plasma perfusion, glial fibrillary acid protein and microtubule associated P-2 immunoreactivity after embolic stroke in rats: a double fluorescent labeled laser scanning confocal microscopic study. Brain Res. 1999;844(1–2):55–66. doi:10.1016/s0006-8993(99)01886-710536261
   PubMed Web of Science ®Google Scholar
• Tomimoto H, Akiguchi I, Wakita H, Svenaga T, Nakamura S, Kimura J Regressive changes of astroglia in white matter lesions in cerebrovascular disease and AD patients. Acta Neuropathol. 1997;94(2): 146–152. doi:10.1007/s0040100506869255389
   PubMed Web of Science ®Google Scholar
• Iadecola C. The pathobiology of vascular dementia. Neuron. 2013;80:844–866 doi:10.1016/j.neuron.2013.10.00824267647
   PubMed Web of Science ®Google Scholar
• Iadecola C. The pathobiology of vascular dementia. Neuron. 2013;80:844–866. Doi:10.1016/jneuron.2013.10.008.24267647
   PubMed Web of Science ®Google Scholar
• Lo EH, Rosenberg GA. The neuroscience unit in health and disease introduction. Stroke. 2009;40:S2–S3. doi:10.1161/STROKEAHA.108.53440419064779
   PubMed Web of Science ®Google Scholar
• Filous AS, Silver J. Targeting astrocytes in CNS injury and disease: a translational research approach. Prog Neurobiol. 2016;144:173–187. Doi:10.1016/j.pneurobio.2016.03.009.27026202
   PubMed Web of Science ®Google Scholar
• Cai W, Zhang K, Li P, et al. Dysfunction of the neurovascular unit in ischemic stroke and neurodegenerative disease: an ageing effect. Ageing Res Rev. 2017;34:77–87. Doi: 10.1016/jar.2016.09.006.27697546
   PubMed Web of Science ®Google Scholar
• Iadecola C. The neurovascular unit coming of age: a journey through neurovascular coupling in health and disease. Neuron. 2017;98(1):17–42. Doi:10.1016/jneuron.2017.07030.
   Google Scholar
• Raichle ME, Mintun MA. Brain work and brain imaging. Annu Rev Neurosci. 2006;29:449–476. doi:10.1146/annurev.neuro.29.051605.11281916776593
   PubMed Web of Science ®Google Scholar
• Uhurovoa H, Kilic K, Tian P, et al. Cell-type specificity of neurovascular coupling in cerebral cortex. ELife. 2016;5:155 Doi.10.7554/elife.14315.
   Web of Science ®Google Scholar
• Longden TA, Dabertrand F, Koide M, et al. Capillary K+ sensing initiates retrograde hyperpolarization to increase local cerebral blood flow. Nat Neurosci. 2017: 275: A1489–14812.doi.10.1038/nm.4533.
   Google Scholar
• Payabavash S, Souza LCS, Wang Y, et al. Regional ischemic vulnerability of the brain to hypoperfusion: the need for location specific CT perfusion thresholds in acute stroke patients. Stroke. 2011;42(5):1255–1260. doi: 10.1161/STROKEAHA.110.60094021493917
   PubMed Web of Science ®Google Scholar
• Cheng B, Golsari A, Fiehler J, Rosenkranz M, Gerloff C, Thomalla G. Dynamics of regional distribution of ischemic lesions in middle cerebral artery trunk occlusion relates to collateral circulation.J Cereb Blood Flow Metab. 2010. doi: 10.1038/jcbfm.2010.185.
   Web of Science ®Google Scholar
• Dijkhuizen RM, Knollema S, van der Worp HB, et al. Dynamics of cerebral tissue injury and perfusion after temporary hypoxia-ischemia in the rat: evidence for region-specific sensitivity and delayed damage. Stroke. 1998;29:695–7049506615
   PubMed Web of Science ®Google Scholar
• Garcia JH, Liu KF, Ye ZR, Gutierrez JA. Incomplete infarct and delayed neuronal death after transient middle cerebral artery occlusion in rats. Stroke. 1997;28:2303–2309.9368580
   PubMed Web of Science ®Google Scholar
• Konaka K, Miyashita K, Naritomi H. Changes in diffusion-weighted magnetic resonance imaging findings in the acute and subacute phases of anoxic encephalopathy. J Stroke Cerebrovasc Dis. 2007;16:82–83. doi:10.1016/j.jstrokecerebrovasdis.2006.10.00717689399
   PubMedGoogle Scholar
• Ravens JR. Vascular changes in the human senile brain. Adv Neurol. 1978;20:487–501676912
   PubMedGoogle Scholar
• Klassen AC, Sung JH, Stadlan EM. Histological changes in cerebral arteries with increasing age. J Neuropathol Exp Neurol. 1968;27:607–623. doi:10.1097/00005072-196810000-000065687757
   PubMed Web of Science ®Google Scholar
• Mega MS, Cummings JL. Frontal-subcortical circuits and neuropsychiatric disorders. J Neuropsychiatry Clin Neurosci. 1994;6:358–370. doi:10.1176/jnp.6.4.3587841807
   PubMed Web of Science ®Google Scholar
• Yao H, Sadoshima S, Kuwabara Y, et al. Cerebral blood flow and oxygen metabolism in patients with vascular dementia of the Binswanger type. Stroke. 1990;21:1694–1699. doi:10.1161/01.STR.21.12.16942264076
   PubMed Web of Science ®Google Scholar
• Furuta A, Ishii N, Nishihara Y, Horie A. Medullary arteries in aging and dementia. Stroke. 1991;22:442–446. doi:10.1161/01.STR.22.4.4422024272
   PubMed Web of Science ®Google Scholar
• Tak S, Yoon SJ, Jang J, Yoo K, Jeong Y, Ye JC. Quantitative analysis of hemodynamic and metabolic changes in subcortical vascular dementia using simulataneous near-infrared spectroscopy and FMRI measurements. Neuroimage. 2011;55:176–184. doi:10.1016/j.neuroimage.2010.11.04621094685
   PubMed Web of Science ®Google Scholar
• Schroeter M, Cutini S, Wahl M, Scheid R, Yves von Cramon D. Neurovascualr coupling is impaired in cerebral microangiopathy an event related stroop study. Neuroimage. 2007;34(1):26–34. doi:10.1016/j.neuroimage.2006.09.00117070070
   PubMed Web of Science ®Google Scholar
• Bar K, Boettger M, Seidler N, Mentzelh TC, Sauer H. Influence of galantamine on vasomotor reactivity in AD and vascular dementia due to microangiopathy. Stroke. 2007;38(12):3186–3192. doi:10.1161/STROKEAHA.107.49203317962592
   PubMed Web of Science ®Google Scholar
• De Reuck J, Decoo D, MArchau M, Santens P, Lemahieu I, Strijckmans K. Positron emission tomography in vascular dementia. J Neurol Sci. 1998;154(1):55–61.9543322
   PubMed Web of Science ®Google Scholar
• Yoshikawa T, Murase K, Oku N, et al. Statistical image analysis of cerebral blood flow in vascular dementia with small-vessel disease. J Nucl Med. 2003;44(4):505–511.12679392
   PubMed Web of Science ®Google Scholar
• Yang D, Kim B, Park J, Kim S, Kim E, Sohn H. Analysis of cerebral blood flow of subcortical vascular dementia with single photon emission computed tomography: adaptation of statistical aprametric mapping. J Neurol Sci J Biomed. 2002;203:199–205. doi:10.1016/S0022-510X(02)00291-5
   PubMed Web of Science ®Google Scholar
• Ginsberg S, Martin L. Axonal transection in adult rat brain induces transynaptic apoptosis and persistent atrophy of target neurons. J Neurotrauma. 2002;19(1):99–109. doi:10.1089/08977150275346027711852982
   PubMed Web of Science ®Google Scholar
• Heiss W, Podreka I. Role of the PET and sPECT in the assessment of ischemic cererbovascular disease. Cerebrovasc Brain Metab Rev. 1993;5(4):235–263.8110593
   PubMedGoogle Scholar
• Chui H. Subcortical ischemic vascular dementia (SIVD). Neurol Clin. 2007;25(3):717. doi: 10.1016/j.ncl.2007.04.00317659187
   PubMed Web of Science ®Google Scholar
• Perry EK, Tomlinson BE, Blessed G, Bergmann K, Gibson PH, Perry RH. Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. BMJ. 1978;2:1457–1459. doi:10.1136/bmj.2.6150.1457719462
   PubMed Web of Science ®Google Scholar
• Erkinjuntti T, Kurz A, Gauthier S, Bullock R, Lilienfeld S, Damaraju CV. Efficacy of galantamine in probable vascular dementia and Alzheimer’s disease combined with cerebrovascular disease: a randomized trial. Lancet. 2002;359:1283–1290. doi:10.1016/S0140-6736(02)07571-211965273
   PubMed Web of Science ®Google Scholar
• Wilkinson D, Doody R, Helme R, et al. Donepezil in vascular dementia A randomized, placebo-controlled study. NEUROLOGY. 2003;61:479–486. doi:10.1212/01.WNL.0000078943.50032.FC12939421
   PubMed Web of Science ®Google Scholar
• Pratt RD, Perdomo CA, Surick IW, Ieni JR. Donepezil: tolerability and safety in Alzheimer’s disease. Int J Clin Pract. 2002;56:710–717.12469988
   PubMed Web of Science ®Google Scholar
• Auchus AP, Brashear HR, Salloway S, et al. Galantamine treatment of vascular dementia: a randomized trial. Neurology. 2007; 69: 448–458. doi:10.1212/01.wnl.0000266625.31615.f617664404
   PubMed Web of Science ®Google Scholar
• Ballard C, Sauter M, Scheltens P, et al. Efficacy, safety and tolerability of rivastigmine capsules in patients with probable vascular dementia: the VantagE study. Curr Med Res Opin. 2008; 24: 2561–2574. doi:10.1185/0300799080232814218674411
   PubMed Web of Science ®Google Scholar
• Borovikova LV, Ivanova S, Zhang M, et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature. 2000;405:458–462. doi:10.1038/3501307010839541
   PubMed Web of Science ®Google Scholar
• Wang H, Yu M, Ochani M, et al. Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature. 2003;421:384–388. doi:10.1038/nature0133912508119
   PubMed Web of Science ®Google Scholar
• Conejero-Goldberg C, Davies P, Ulloa L. Alpha7 nicotinic acetylcholine receptor: a link between inflammation and neurodegeneration. Neurosci Biobehav Rev. 2008;32:693–706. doi:10.1016/j.neubiorev.2007.10.00718180036
   PubMed Web of Science ®Google Scholar
• Pavlov VA, Tracey KJ. Controlling inflammation: the cholinergic anti-inflammatory pathway. Biochem Soc Trans. 2006;34:1037–1040. doi:10.1042/BST034103717073745
   PubMed Web of Science ®Google Scholar
• Maelicke A. Allosteric modulation of nicotinic receptors as a treatment strategy for Alzheimer’s disease. Dement Geriatr Cogn Disord. 2000;11 Suppl 1: 11–18. doi:10.1159/000051227
   PubMed Web of Science ®Google Scholar
• Tohgi H, Abe T, Kimura M, Saheki M, Takahashi S. Cerebrospinal fluid acetylcholine and choline in vascular dementia of Binswanger and multiple small infarct types as compared with Alzheimer-type dementia. J Neural Transm. 1996;103:1211–1220. doi:10.1007/BF012712069013408
   PubMed Web of Science ®Google Scholar
• Wallin A, Sjogren M, Blennow K, Davidsson P. Decreased cerebrospinal fluid acetylcholinesterase in patients with subcortical ischemic vascular dementia. Dement Geriatr Cogn Disord. 2003;16:200–207. doi:10.1159/00007280314512714
   PubMed Web of Science ®Google Scholar
• Yamada M, Lamping KG, Duttaroy A, et al. Cholinergic dilatation of cerebral blood vessels is abolished in M5 muscarinic acetylcoline receptor knockout mice. Prc Natl Ac Sci USA. 2001;98:14096–14101. doi:10.1073/pnas.251542998
   PubMedGoogle Scholar
• Togashi H, Matsumoto M, Yoshioka M, et al. Neurochemical profiles in cerebrospinal fluid of stroke-prone spontaneously hypertensive rats. Behav Lett. 1994;166:117–120.
   Google Scholar
• Togashi H, Kimura S, Matsumoto M, et al. Cholinergic changes in the hippocampus of stroke-prone spontaneously hypertensive rats. Stroke. 1996;27:520–526.8610323
   PubMed Web of Science ®Google Scholar
• Scremin OU, Li MG, Scremin AM, Jenden DJ. Cholinesterase inhibition improves blood flow in the ischemic cerebral cortex. Brain Res Bull. 1997;42:59–70. doi:10.1016/S0361-9230(96)00207-98978935
   PubMed Web of Science ®Google Scholar
• Furukawa S, Sameshima H, Yang L, Ikenove T. Activation of acetylcholine receptros and microglia in hypoxic-ischemic brain damage in newborn rats. Brain and Develop. 2013;35:607–613. doi:10.1016/j.braindev.2012.10.006
   PubMed Web of Science ®Google Scholar
• Hejmadi MV, Dajas-BAilador F, Barns SM, Jones B, Wonnacott S. Neuroprotection by nicotine against hypoxia-induced apopotosis in cortical cultures involves activation of multiple nicotinic acethylcholine receptor subtypes. Mol Cell Neurosci. 2003;24:779–786.14664825
   PubMedGoogle Scholar
• Albuquerque EX, Pereira EF, Alkondon M, Rogers SW. Mammalian nicotinic acetylcholine receptors: from structure to function. Physiol Rev. 2009;89:73–120. doi:10.1152/physrev.00015.200819126755
   PubMed Web of Science ®Google Scholar
• Alkondon M, Pereira EF, Eisenberg HM, Albuquerque EX. Choline and selective antagonists identify two subtypes of nicotinic acetylcholine receptors that modulate GABA release from CA1 interneurons in rat hippocampal slices. J Neurosci. 1999;19:2693–2705.10087082
   PubMed Web of Science ®Google Scholar
• Alkondon M, Albuquerque EX. The nicotinic acetylcholine receptor subtypes and their function in the hippocampus and cerebral cortex. Prog Brain Res. 2004;145:109–120. doi:10.1016/S0079-6123(03)45007-314650910
   PubMed Web of Science ®Google Scholar
• Court J, Perry E, Kalaria R. Neurotransmitter control of the cerebral vasculature and abnormalities in vascular dementia In: Erkinjuntti T, Gauthier S, editors. Vascular Cognitive Impairment. Martin Dunitz: London; 2002:167–185.
   Google Scholar
• Roman GC, Kalaria RN. Vascular determinants of cholinergic deficits in AD and vascular dementia. Neurobiol Aging. 2006;27:1769–1785.16300856
   PubMed Web of Science ®Google Scholar
• Roman GC. Brain Hypoperfusion: a critical factor in vascular dementia. Neurol Res. 2004;26:454–458 doi:10.1179/01616410422501768615265263
   PubMed Web of Science ®Google Scholar
• Scarr E. Muscarinc receptors: their roles in disorders of the central nervous system and potential therapeutic targets. CNS Neurosci Ther. 2012;18:369–379. Doi 10.1111/j.1755-5949.201100249.x22070219
   PubMed Web of Science ®Google Scholar
• Perry E, Walker M, Grace J, Perry R. Acetylcholine in mind: a neurotransmitter correlate of consciousness? Trends Neurosci. 1999;22:273–28010354606
   PubMed Web of Science ®Google Scholar
• Vasquez J, Purve MJ. The cholinergic pathway to cerebral blood vessels. I. Morphological Studies. Pflugers Arch. 1979;379:157–163. doi:10.1007/BF00586942571110
   PubMed Web of Science ®Google Scholar
• Tong XK, Hamel E. Regional cholinergic denervation of cortical microvessels and nitric oxid synthase-containing neurons in AD. Neuroscience. 1999;92:163–175.10392839
   PubMed Web of Science ®Google Scholar
• Cauli B, Tong XK, Rancillac A, et al. Cortical GABA interneurons in neurovascular coupling: relays for the subcortical vasoactive pathways. J Neurosci. 2004;24:8940–8949. doi:10.1523/JNEUROSCI.3065-04.200415483113
   PubMed Web of Science ®Google Scholar
• Vanhoutte PM. Endothelium and control of vascular function. State of the art lecture. Hypertension. 1989;13:658–667.2661425
   PubMed Web of Science ®Google Scholar
• Kocharyan A, Fernandes P, Tong XP, Vaucher E, Hamel E. Specific subtypes of cortical GABA interneurons contribute to the neurovascular coupling response to basal forebrain stimulation. J Cerebr Blood Flow Metab. 2008;28:221–231. doi:10.1038/sj.jcbfm.9600558
   PubMed Web of Science ®Google Scholar
• Lacombe P, Sercombe R, Vaucher E, Seylaz J. reduced cortical vasodilatory response to stimulation of the nucleus basalis of Meynert in the aged rats and evidence for a control of the cerebral circulation. Ann Ny Acad Sci. 1997;826:410–415. doi:10.1111/j.1749-6632.1997.tb48494.x9329714
   PubMedGoogle Scholar
• Elhusseiny A, Hamel E. Muscarinic but not nicotinic acetylcholine receptros mediated nitric oxide dependent dilatation in brain cortical arterioles: a possible role for the M5 receptor subtype. J Cerebr Blood Flow Metab. 2000:298–305. doi:10.1097/00004647-200002000-00011
   PubMed Web of Science ®Google Scholar
• Yamada M, Lamping KG, Duttaroy A, et al. Cholinergic dilation of cerebral blood vessels is abolished in M5 muscarinic acetylcholine receptor knockout mice. PNAS. 2001;98(24):14096–14101. doi:10.1073/pnas.25154299811707605
   PubMed Web of Science ®Google Scholar
• Salloway S. Subcortical Vascular Dementia: Binswanger’s and CADASIL. Honolulu: American Academy of Neurology (AAN); 2003:(CD 8AC.006-2):1–29.
   Google Scholar
• Mirski MA. Pharmacology of Blood Pressure Management during Cerebral Ischemia.Miami: American Academy of Neurology (AAN); 2005:5PC-004:456–469.
   Google Scholar
• Wallin A, Blennow K, Gottfries CG. Neurochemical abnormalities in vascular dementia. Dementia. 1989;1:120–130.
   Google Scholar
• Bohnen NI, Muller MLTM, Kuwabara H, Ocnstantien GM, Studentski SA. Age-associated leukoaraiosis and cortical cholinergic deafferentation. Neurology. 2009;72:1411–1416. doi:10.1212/WNL.0b013e3181a187c619380700
   PubMed Web of Science ®Google Scholar
• Szilagy AK, Nemeth A, Martini E, Lendvai B, Venter V. Serum and CSF cholinesterase activity in various kind of dementia. Eur Arch Psychiatry Neurol Sci. 1987;236:309–311.3653153
   PubMedGoogle Scholar
• Kimura S, Saito H, Minami M, et al. Pathogenesis of vascular dementia in stroke-prone spontaneously hypertensive rats. Toxicology. 2000;153:167–187. doi:10.1016/S0300-483X(00)00312-711090955
   PubMed Web of Science ®Google Scholar
• Tomimoto H, Ohtani R, Shibata M, Nakamura N, Ihara M Loss of cholinergic pathways in vascular dementia of the Binswanger type. Dement Geriatr Cogn Disord 2005; 19:282–288. doi:10.1159/00008455315785029
   PubMed Web of Science ®Google Scholar
• Wang J, Zhang HY, Tang XC. Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment. Acta Pharamcol Sinica. 2009;30:879–888. doi:10.1038/aps.2009.82
   PubMed Web of Science ®Google Scholar
• Mann DM, Yates PD, Marcyniuk B. The nucleus basalis of Meynert in multi-infarct dementia. Acta Neuropathol. 1986;71:332–337.3799146
   PubMed Web of Science ®Google Scholar
• Sakurada T, Alufuzoff I, Winblad B, Nordberg A. Substance P like immunoreactivity, choline acetyltransferase activity and cholinergic muscarinic receptors in Alzheimer’s disease and multi-infarct dementia. Brain Res .1990;521:329–332. doi:10.1016/0006-8993(90)91561-t1698512
   PubMed Web of Science ®Google Scholar
• Jung S, Zarow C, Mack WJ, et al. Preservation of neurons of the nucleus basalis in subcortical ischemic vascular disease. Arch Neurol. 2012;69:879–886. doi: 10.1001/archneurol.2011.287422393167
   PubMedGoogle Scholar
• Swartz RH, Sahlas DJ, Black SE. Strategic involvement of cholinergic pathways and executive dysfunction: does location of white matter signal hyperintensities matter? J Stroke Cerebrovasc Dis. 2003;12:29–36. doi:10.1053/jscd.2003.517903901
   PubMedGoogle Scholar
• Wardlaw JM, Smith C, Dichgans M. Mechanism of sporadic cerebral small vessel disease: insight from neuroimaging. Lancet Neurol. 2013;12:483–497. doi:10.1016/S1474-4422(13)70060-723602162
   PubMed Web of Science ®Google Scholar
• De Silva TM, Miller AA. Cerebral small vessel disease: targeting oxidative stress as a novel therapeutic strategy. Frontiers in Pharmacol. 2016. doi:10.3389/fpharm.2016.00061.
   PubMed Web of Science ®Google Scholar
• Chan SL, Umesalma S, Baumbach GL. Epidermal growth factor receptor is critical for angiotensin II mediated hypertrophy in cerebral arterioles. Hypertension. 2015;65:808–812. Doi: 10.1161/HYEPRTENSIONHA.114.04794;
   Web of Science ®Google Scholar
• Umesalma S, Houwen FK, Baumbach GL, Chan SL. Roles of ceveolin-1 in angiotensin-ii induced hypertrophy and inward remodeling of cerebral pial arterioles. Hypertension. 2016;67:623–629.26831194
   PubMed Web of Science ®Google Scholar
• Zhang R, Zuckerman JH, Iwasaki K, Wilson TE, Crandall CG, Levine BD.Autonomic neural control of dynamic cerebral autoregulation in humans. Circul. 2002;106:1814–1820. doi:10.1161/01.CIR.0000031798.07790.FE
   PubMed Web of Science ®Google Scholar
• Hamner JW, Tan CO, Lee K, Cohen MA, Taylor JA. Sympathetic control of the cerebral vasculature in humans. Stroke. 2010;41;102–109. doi:10.1161/STROKEAHA.109.55713220007920
   PubMed Web of Science ®Google Scholar
• Hamner JW, Tan CO, Tzeng YC, Taylor JA. Cholinergic control of the cerebral vasculature in humans. J Physiol. 2012;590(24):6343–6352. doi:10.1113/jphysiol.2012.24510023070700
   PubMed Web of Science ®Google Scholar
• Brown WR, Thore CR. Review: cerebral microvascular pathology in ageing and neurodegeneration. Neuropathol Appl NeuroBiol. 2011;37:56–74. doi:10.1111/j.1365-2990.2010.01139.x20946471
   PubMed Web of Science ®Google Scholar
• Barrett KM, Brott TG, Brown RD Jr, et al. Enhancing recovery after acute ischemic stroke with donepezil as an adjuvant therapy to standard medical care: results of a phase IIA clinical trial. J Stroke Cerebrovasc Dis. 2011;20:177–182. doi:10.1016/j.jstrokecerebrovasdis.2010.12.00921295494
   PubMed Web of Science ®Google Scholar
• Silver JM, Koumaras B, Mneg X, et al. Long term effects of rivastigmine capsules in patients with transient brain injury. Brain Inj. 2009;23:123–132. doi:10.1080/0269905080264969619191091
   PubMed Web of Science ®Google Scholar
• Gericke A, Sniatechi JJ, Mayer VG, et al. Role of the M1, M3 and M5 muscarinic Ach receptors in cholinergic dilatation of small Arteries studied with gene targeted mice. Am J Physiol Heart Circ Physiol. 2011;300; H1602–H1608. doi:10.1152/ajpheart.00982.201021335473
   PubMed Web of Science ®Google Scholar
• Elhusseiny A, Hamel E. Muscarinic, but not nicotinic acetylcholine receptors mediate nitric oxid dependent dilation in brain cortical arterioles: a possible role for the M5 receptor subtype. J Cerebr Blood Flow Metab. 2000;20;298–305. doi:10.1097/00004647-200002000-00011
   PubMed Web of Science ®Google Scholar
• Katusic ZS, Austin SA. Endothelial nitric oxide: protector of a healthy mind. Eur Heart J. 2014;35:888–894. doi:10.1093/eurheartj/eht54424357508
   PubMed Web of Science ®Google Scholar
• Joutel A. The Notch3-ECD cascade hypothesis of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy disease. Neurol Clin Neurosci. 2015;3:1–6. doi:10.1111/ncn3.2015.3.issue-1
   Google Scholar
• Ridder DA, Wenzel J, Muller K, et al. Brain endothelial TAK1 and NEMO safeguard the neurovascular unit. J Exp Med. 2015;212:1529–1549. doi:10.1084/jem.2015016526347470
   PubMed Web of Science ®Google Scholar
• Román GC. Brain hypoperfusion: a critical factor in vascular dementia. Neurol Res. 2004; 26:454–458. doi:10.1179/01616410422501768615265263
   PubMed Web of Science ®Google Scholar
• Zhan SS, Beyreuther K, Schmitt HP. Synaptophysin immunoreactivity of the cortical neuropil in vascular dementia of Binswanger type compared with the dementia of Alzheimer type and non-demented controls. Dementia. 1994;5:79–87.8038870
   PubMedGoogle Scholar
• Ishunina TA, Kamphorst W, Swaab DF. Metabolic alterations in the hypothalamus and basal forebrain in vascular dementia. J Neuropathol Exp Neurol. 2004;63(12):1243–1254. doi:10.1093/jnen/63.12.124315624761
   PubMed Web of Science ®Google Scholar
• Iadecola C, Yang G, Ebner TJ, Chen G. Local and propagated vascular responses evoked by focal synaptic activity in cerebellar cortex. J Neurophysiol. 1997;78(2):651–659. doi:10.1152/jn.1997.78.2.6519307102
   PubMed Web of Science ®Google Scholar
• Cummings JL. Frontal-subcortical circuits and human behavior. Arch Neurol. 1993;50:873–880. doi:10.1001/archneur.1993.005400800760208352676
   PubMed Web of Science ®Google Scholar
• Ahtiluoto S, Polvikoski T, Peltonen M, et al. Diabetes, Alzheimer disease, and vascular dementia: a population-based neuropathologic study. Neurology. 2010;75:1195–1202. doi:10.1212/WNL.0b013e3181ed735b20739645
   PubMed Web of Science ®Google Scholar
• Poggesi A, Pasi M, Pascini F, Pantoni L, Inzitari D. Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: a review. J Cerebr Blood Flow Metab. 2015. doi: 10.1038/jcbfm.2015.116
   Web of Science ®Google Scholar
• Gorelick PB, Scuteri A, Black SE et al. Vascular contributions to cognitive impairment and dementia a statement for healthcare professional from the American Heart Association/American Stroke Association. Stroke. 2011;42:2672–2713. doi:10.1161/STR.0b013e318229949621778438
   PubMed Web of Science ®Google Scholar
• Kivipelto M, Ngandu T, Laatikainen T, WInblad B, Soinen H, Tuomilehto J. Risk score for the prediction of dementia risk in 20 years among middle aged people: a longitudinal, population-based study. Lancet Neurol. 2006;5:735–741. doi:10.1016/S1474-4422(06)70537-316914401
   PubMed Web of Science ®Google Scholar
• Prins ND, Scheltens P. White matter hyper-intensities, cognitive impairment and dementia: an update, Nature Rev Neurol. 2015;11:157–165. doi:10.1038/nrneurol.2015.1025686760
   PubMed Web of Science ®Google Scholar
• Wallin A, Blennow K, Gottfires CG. Subcortical symptoms predominate in vascular dementia. Int J Ger Psych. 1991;6:137–146. doi:10.1002/gps.930060305
   Web of Science ®Google Scholar
• Moretti R, Cavressi M, Tomietto P. Gait and apathy as relevant symptoms of subcortical vascular dementia. Am J Alzh Dis Other Dem. 2015;30(4):390–399. Doi:10.1177/1533317514550329.
   PubMed Web of Science ®Google Scholar
• Fischer P, Gaterer G, Martere A, Simanyi M, Danielcyzk W. Course characteristics in the differentiation of dementia of the Alzheimer’s type and multi-infarct dementia. Acta Psych Scand 1990;81:551–553. doi:10.1111/j.1600-0447.1990.tb05497.x
   PubMed Web of Science ®Google Scholar
• Cummings JL.Vascular subcortical dementias: clinical aspects. Dementia 1994;5:177–180.8087175
   PubMedGoogle Scholar
• Desmond D, Erkinjuntti T, Sano M, et al. The cognitive syndrome of vascular dementia: implications for clinical trials. Alzh Dis Ass Dis 1999;13:21–29.
   PubMed Web of Science ®Google Scholar
• Sachdev PS, Brodaty H, Valenzuela MJ, et al. the neuropsychological profile of vascular cognitive impairment in stroke and TIA paitents. Neurol. 2004;62(6):912–919.
   PubMedGoogle Scholar
• Traykov L, Baudic S, Thibaudet MC, Rigaud AS, Samgghe A, Boller F. Neuropsychological deficit in early subcortical vascular dementia: comparison to AD. Demen Geriatr Cogn Dis. 2002;14:26–32. doi:10.1159/000058330
   PubMed Web of Science ®Google Scholar
• Wallin A, Milo S, Sjogren M, Pantoni L, Erkinjuntti T Classification and subtypes of vascular dementia. Int PSychoger. 2003;15:27–37. doi:10.1017/S1041610203008937
   PubMed Web of Science ®Google Scholar
• Moretti R, Torre P, Antonello RM, Cazzato G. Behavioral alterations and vascular dementia. Neurologist. 2006;12(81):43–47. doi:10.1097/01.nrl.0000186806.54314.e816547446
   PubMedGoogle Scholar
• Moretti R, Signori R. Neural correlates for apathy: frontal-prefrontal and parietal cortical-subcortical circuits. Front Aging Neurosci. 2016;9:8:289. doi: 10.3389/fnagi.2106.00289.
   Google Scholar
• Ishii N, Nashihara Y, Imamura T. Why do frontal lobe symptoms predominate in vascular dementia with lacunes? Neurology. 1986; 36:340–345. doi:10.1212/wnl.36.3.3403951700
   PubMed Web of Science ®Google Scholar
• Levine B, Stuss DT, Milberg WP. Effects of aging on conditioned associative learning: process analysis and comparison with focal frontal lesions. Neupsychol. 1997;11:367–381.
   PubMed Web of Science ®Google Scholar
• Jorm AF, Jolley D. The incidence of dementia: a meta-analysis. Neurology. 1998:51(3):728–733.
   PubMedGoogle Scholar
• Meyer JS, Xu G, Thornby J, Chowdhury MH, Quach M. Is mild cognitive impairment prodromal for vascular dementia like AD? Stroke. 2002;33(8):1981-1985.
   Google Scholar
• Grau-Olivares M, Arboix A. Mild cognitive impairment in stroke patients with ischemic cerebral small vessel disease: a forerunner of vascular dementia. Exp Rev Neurotherpae. 2009;9:1201–1217.
   PubMed Web of Science ®Google Scholar
• Sabri O, Hellwig D, Schreckenberger M, et al. Correlation of neuropsychological, morphological and functional findings in cerebral microangiopathy. J Nucl Med 1998;39:147–154.9443754
   PubMed Web of Science ®Google Scholar
• Prins ND, van Dijk EJ, Den Heijer T, et al. Cerebral small-vessel disease and decline in information processing speed, executive function and memory. Brain 2005; 128: 20134–22041.
   Web of Science ®Google Scholar
• Grau-Olivares M, Arboix A, Bartres-Faz D, Junque C. Neuropsychological abnormalities associated with lacunar infarction. J Neurol Sci. 2007;257:160–165.17316693
   PubMed Web of Science ®Google Scholar
• Jokinen H, Kalska H, Ylikoski R, et al. Longitudinal cognitive decline in subcortical ischemic vascular disease-the LADIS study. Cerebrovasc Dis. 2009;27:384–391.19276621
   PubMed Web of Science ®Google Scholar
• Baker JG, Williams AJ, Ionita CC, Lee-Kwen P, Ching M, Miletich RS. Cerebral small-vessel disease: cognition, mood, daily functioning, and imaging finding from a small pilot sample. Dem Ger Cogn Disord. 2012;2:169–179. doi: 10.1159/0000333482.
   Google Scholar
• Nitkunan A, Lanfranconi S, Charlton RA, Barrick TR, Markus HS. Brain atrophy and cerebral small vessel disease. A prospective follow-up study. Stroke. 2011; 42:133–138.21148440
   PubMed Web of Science ®Google Scholar
• Kim HJ, Ye BS, Yoon CW, et al. Cortical thickness and hippocampal shape in pure vascular mild cognitive impairment and dementia of subcortical type. Eur J Neur. 2014;21:744–751. doi: 10.111/ene.123769.
   Google Scholar
• Shi Y, Tirpletton MJ, Makin SD, et al. Cerebral blood flow in small vessel disease: a systematic review and meta-analysis. J Cerebr Blood Flow Metab. 201636(10):1653-1667. doi:10.1177/0271678X166662891.
   Web of Science ®Google Scholar
• Maillard P, Fletcher E, Lockhart SN, et al. White matter hyperintensities and their penumbra lie along a continuum of injury in the aging brain. Stroke. 2014;45:1721–1726.24781079
   PubMed Web of Science ®Google Scholar
• Maniega SM, Valdes Hernandez MC, Clayden JD, et al. White matter hyperintensities and normal-appearing white matter integrity in the aging brain. Neurobiol Aging. 2015;36:909–918.25457555
   PubMed Web of Science ®Google Scholar
• Madden DJ, Bennett IJ, Burzynska A, et al. Diffusion tensor imaging of cerebral white matter integrity in cognitive aging. Biochim Biophys Acta. 2012:1822:386–400.21871957
   PubMed Web of Science ®Google Scholar
• Iliff JJ, 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(147):147ra111.
   PubMed Web of Science ®Google Scholar
• O’Brien JT, Thomas A. Vascular dementia. Lancet. 2015;386:1698–1706.26595643
   PubMed Web of Science ®Google Scholar
• O’Brien JT, Thomas A. Non-Alzheimer’s dementia 3 vascular dementia. Lancet. 2015;386:1698–1706. doi:10.1016/S0140-6736(15)00463-826595643
   PubMed Web of Science ®Google Scholar