Treatment of Vascular Cognitive Impairment

  • Aaron Ritter
  • Jagan A. PillaiEmail author
Dementia (E McDade, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Dementia

Opinion statement

Cerebrovascular disease (CVD) is an important cause of cognitive dysfunction and dementia. The term vascular cognitive impairment (VCI) is used to describe the entire spectrum of cognitive dysfunction—ranging from mild impairment to dementia—attributable to all forms of cerebrovascular disease. Accurate assessment and management of vascular risk factors are a top priority in the treatment of VCI, particularly early in the disease when prevention strategies may prove to be more effective. There are limited treatment options to improve cognition and function in VCI. Several acetylcholinesterase inhibitors and the NMDA receptor antagonist memantine have been studied in large, well-designed trials. These agents are safe and provide modest cognitive benefits in vascular dementia (VaD) but have demonstrated inconsistent efficacy on functional measures. Other therapies, such as aspirin, calcium channel blockers, and vitamin supplementation, have less evidence to support their use in improving cognition in VCI. Although primary prevention trials suggest that treatment of hypertension, adherence to a Mediterranean diet, physical activity, and smoking cessation may reduce the risk of cognitive decline, there is limited evidence regarding these interventions in helping improve cognition in VCI. The pathophysiology and treatment of cerebral autosomal dominant arteriopathy with subcortical infarcts (CADASIL), cerebral amyloid angiopathy (CAA), and subcortical white matter disease (SWMD) deserves special consideration.


Cerebrovascular disease (CVD) Cognitive dysfunction Dementia Vascular cognitive impairment (VCI) Treatment 


Compliance with Ethics Guidelines

Conflict of Interest

Aaron Ritter and Jagan A. Pillai declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Fratiglioni L et al. Incidence of dementia and major subtypes in Europe: a collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology. 2000;54(11 Suppl 5):S10–5.PubMedGoogle Scholar
  2. 2.
    Schneider JA. High blood pressure and microinfarcts: a link between vascular risk factors, dementia, and clinical Alzheimer’s disease. J Am Geriatr Soc. 2009;57(11):2146–7.PubMedGoogle Scholar
  3. 3.
    Schneider JA, Bennett DA. Where vascular meets neurodegenerative disease. Stroke. 2010;41(10 Suppl):S144–6.PubMedCentralPubMedGoogle Scholar
  4. 4.
    Babikian V, Ropper AH. Binswanger’s disease: a review. Stroke. 1987;18(1):2–12.PubMedGoogle Scholar
  5. 5.
    Hachinski VC. Multi-infarct dementia: a reappraisal. Alzheimer Dis Assoc Disord. 1991;5(2):64–8.PubMedGoogle Scholar
  6. 6.
    van Kooten F, Koudstaal PJ. Epidemiology of post-stroke dementia. Haemostasis. 1998;28(3-4):124–33.PubMedGoogle Scholar
  7. 7.
    Hachinski V. Vascular dementia: a radical redefinition. Dementia. 1994;5(3-4):130–2.PubMedGoogle Scholar
  8. 8.
    Bowler JV, Hachinski V. Vascular cognitive impairment: a new approach to vascular dementia. Baillieres Clin Neurol. 1995;4(2):357–76.PubMedGoogle Scholar
  9. 9.
    Roman GC et al. Vascular cognitive disorder: a new diagnostic category updating vascular cognitive impairment and vascular dementia. J Neurol Sci. 2004;226(1-2):81–7.PubMedGoogle Scholar
  10. 10.
    Erkinjuntti T, Gauthier S. The concept of vascular cognitive impairment. Front Neurol Neurosci. 2009;24:79–85.PubMedGoogle Scholar
  11. 11.
    Chui H. Vascular dementia, a new beginning: shifting focus from clinical phenotype to ischemic brain injury. Neurol Clin. 2000;18(4):951–78.PubMedGoogle Scholar
  12. 12.
    Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol. 2010;9(7):689–701.PubMedGoogle Scholar
  13. 13.
    Bocti C, Black S, Frank C. Management of dementia with a cerebrovascular component. Alzheimers Dement. 2007;3(4):398–403.PubMedGoogle Scholar
  14. 14.
    Launer LJ, Hughes TM, White LR. Microinfarcts, brain atrophy, and cognitive function: the Honolulu Asia Aging Study Autopsy Study. Ann Neurol. 2011;70(5):774–80.PubMedCentralPubMedGoogle Scholar
  15. 15.
    Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales. Neuropathology Group of the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS). Lancet, 2001. 357(9251): p. 169-75.Google Scholar
  16. 16.
    Schneider JA et al. Relation of cerebral infarctions to dementia and cognitive function in older persons. Neurology. 2003;60(7):1082–8.PubMedGoogle Scholar
  17. 17.
    Sachdev PS et al. Progression of cognitive impairment in stroke patients. Neurology. 2004;63(9):1618–23.PubMedGoogle Scholar
  18. 18.
    Desmond DW et al. Incidence of dementia after ischemic stroke: results of a longitudinal study. Stroke. 2002;33(9):2254–60.PubMedGoogle Scholar
  19. 19.•
    Dichgans M, Zietemann V. Prevention of vascular cognitive impairment. Stroke. 2012;43(11):3137–46. Concise review of the evidence regarding strategies to prevent VCI.PubMedGoogle Scholar
  20. 20.
    O'Donnell MJ et al. Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case-control study. Lancet. 2010;376(9735):112–23.PubMedGoogle Scholar
  21. 21.••
    Douiri A et al. Long-term effects of secondary prevention on cognitive function in stroke patients. Circulation. 2013;128(12):1341–8. Large study on vascular risk management noting long-term effects (up to 16 years) on cognition.PubMedGoogle Scholar
  22. 22.•
    Gorelick PB et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011;42(9):2672–713. Comprehensive review of risk factors, pathophysiology, and treatment of VCI.Google Scholar
  23. 23.
    Gupta M et al. The profile of behavioral and psychological symptoms in vascular cognitive impairment with and without dementia. Ann Indian Acad Neurol. 2013;16(4):599–602.PubMedCentralPubMedGoogle Scholar
  24. 24.
    Staekenborg SS et al. Behavioural and psychological symptoms in vascular dementia; differences between small- and large-vessel disease. J Neurol Neurosurg Psychiatry. 2010;81(5):547–51.PubMedGoogle Scholar
  25. 25.
    Chiu PY, Liu CH, Tsai CH. Neuropsychiatric manifestations in vascular cognitive impairment patients with and without dementia. Acta Neurol Taiwan. 2007;16(2):86–91.PubMedGoogle Scholar
  26. 26.
    Hsieh CJ, Chang CC, Lin CC. Neuropsychiatric profiles of patients with Alzheimer’s disease and vascular dementia in Taiwan. Int J Geriatr Psychiatry. 2009;24(6):570–7.PubMedGoogle Scholar
  27. 27.
    Sink KM et al. Caregiver characteristics are associated with neuropsychiatric symptoms of dementia. J Am Geriatr Soc. 2006;54(5):796–803.PubMedGoogle Scholar
  28. 28.
    Herrmann N et al. The contribution of neuropsychiatric symptoms to the cost of dementia care. Int J Geriatr Psychiatry. 2006;21(10):972–6.PubMedGoogle Scholar
  29. 29.
    Scarmeas N et al. Delusions and hallucinations are associated with worse outcome in Alzheimer disease. Arch Neurol. 2005;62(10):1601–8.PubMedCentralPubMedGoogle Scholar
  30. 30.
    Aarsland D, Sharp S, Ballard C. Psychiatric and behavioral symptoms in Alzheimer’s disease and other dementias: etiology and management. Curr Neurol Neurosci Rep. 2005;5(5):345–54.PubMedGoogle Scholar
  31. 31.
    Perry E et al. Acetylcholine in mind: a neurotransmitter correlate of consciousness? Trends Neurosci. 1999;22(6):273–80.PubMedGoogle Scholar
  32. 32.
    Craig LA, Hong NS, McDonald RJ. Revisiting the cholinergic hypothesis in the development of Alzheimer’s disease. Neurosci Biobehav Rev. 2011;35(6):1397–409.PubMedGoogle Scholar
  33. 33.
    Selden NR et al. Trajectories of cholinergic pathways within the cerebral hemispheres of the human brain. Brain. 1998;121(Pt 12):2249–57.PubMedGoogle Scholar
  34. 34.
    Mesulam M, Siddique T, Cohen B. Cholinergic denervation in a pure multi-infarct state: observations on CADASIL. Neurology. 2003;60(7):1183–5.PubMedGoogle Scholar
  35. 35.
    Tohgi H et al. 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(10):1211–20.PubMedGoogle Scholar
  36. 36.
    Roman GC. Facts, myths, and controversies in vascular dementia. J Neurol Sci. 2004;226(1-2):49–52.PubMedGoogle Scholar
  37. 37.
    Anand P, Singh B. A review on cholinesterase inhibitors for Alzheimer’s disease. Arch Pharm Res. 2013;36(4):375–99.PubMedGoogle Scholar
  38. 38.
    Ceravolo R et al. Cerebral perfusional effects of cholinesterase inhibitors in Alzheimer disease. Clin Neuropharmacol. 2004;27(4):166–70.PubMedGoogle Scholar
  39. 39.
    Roman GC et al. Donepezil in vascular dementia: combined analysis of two large-scale clinical trials. Dement Geriatr Cogn Disord. 2005;20(6):338–44.PubMedGoogle Scholar
  40. 40.
    Wilkinson D et al. Donepezil in vascular dementia: a randomized, placebo-controlled study. Neurology. 2003;61(4):479–86.PubMedGoogle Scholar
  41. 41.
    Roman GC et al. Randomized, placebo-controlled, clinical trial of donepezil in vascular dementia: differential effects by hippocampal size. Stroke. 2010;41(6):1213–21.PubMedCentralPubMedGoogle Scholar
  42. 42.
    Schilstrom B et al. Galantamine enhances dopaminergic neurotransmission in vivo via allosteric potentiation of nicotinic acetylcholine receptors. Neuropsychopharmacology. 2007;32(1):43–53.PubMedGoogle Scholar
  43. 43.
    Auchus AP et al. Galantamine treatment of vascular dementia: a randomized trial. Neurology. 2007;69(5):448–58.PubMedGoogle Scholar
  44. 44.
    Erkinjuntti T et al. Efficacy of galantamine in probable vascular dementia and Alzheimer’s disease combined with cerebrovascular disease: a randomised trial. Lancet. 2002;359(9314):1283–90.PubMedGoogle Scholar
  45. 45.
    Erkinjuntti T, Roman G, Gauthier S. Treatment of vascular dementia—evidence from clinical trials with cholinesterase inhibitors. J Neurol Sci. 2004;226(1-2):63–6.PubMedGoogle Scholar
  46. 46.
    Erkinjuntti T et al. An open-label extension trial of galantamine in patients with probable vascular dementia and mixed dementia. Clin Ther. 2003;25(6):1765–82.PubMedGoogle Scholar
  47. 47.
    Bartorelli L et al. Effects of switching from an AChE inhibitor to a dual AChE-BuChE inhibitor in patients with Alzheimer’s disease. Curr Med Res Opin. 2005;21(11):1809–18.PubMedGoogle Scholar
  48. 48.
    Ballard C et al. Efficacy, safety and tolerability of rivastigmine capsules in patients with probable vascular dementia: the VantagE study. Curr Med Res Opin. 2008;24(9):2561–74.PubMedGoogle Scholar
  49. 49.
    Mok V et al. Rivastigmine in Chinese patients with subcortical vascular dementia. Neuropsychiatr Dis Treat. 2007;3(6):943–8.PubMedCentralPubMedGoogle Scholar
  50. 50.
    Kumar V et al. An efficacy and safety analysis of Exelon in Alzheimer’s disease patients with concurrent vascular risk factors. Eur J Neurol. 2000;7(2):159–69.PubMedGoogle Scholar
  51. 51.
    Jones RW. A review comparing the safety and tolerability of memantine with the acetylcholinesterase inhibitors. Int J Geriatr Psychiatry. 2010;25(6):547–53.PubMedGoogle Scholar
  52. 52.
    Orgogozo JM et al. Efficacy and safety of memantine in patients with mild to moderate vascular dementia: a randomized, placebo-controlled trial (MMM 300). Stroke. 2002;33(7):1834–9.PubMedGoogle Scholar
  53. 53.
    Wilcock G, Mobius HJ, Stoffler A. A double-blind, placebo-controlled multicentre study of memantine in mild to moderate vascular dementia (MMM500). Int Clin Psychopharmacol. 2002;17(6):297–305.PubMedGoogle Scholar
  54. 54.
    Tomassoni D et al. Nimodipine and its use in cerebrovascular disease: evidence from recent preclinical and controlled clinical studies. Clin Exp Hypertens. 2008;30(8):744–66.PubMedGoogle Scholar
  55. 55.
    Lopez-Arrieta JM, Birks J. Nimodipine for primary degenerative, mixed and vascular dementia. Cochrane Database Syst Rev. 2002;(3):p. Cd000147.Google Scholar
  56. 56.
    Wang P et al. Rationale and design of a double-blind, placebo-controlled, randomized trial to evaluate the safety and efficacy of nimodipine in preventing cognitive impairment in ischemic cerebrovascular events (NICE). BMC Neurol. 2012;12:88.PubMedCentralPubMedGoogle Scholar
  57. 57.
    Amenta F et al. Nicardipine: a hypotensive dihydropyridine-type calcium antagonist with a peculiar cerebrovascular profile. Clin Exp Hypertens. 2008;30(8):808–26.PubMedGoogle Scholar
  58. 58.
    An experimental, randomized, double-blind, placebo-controlled clinical trial to investigate the effect of nicardipine on cognitive function in patients with vascular dementia. Spanish group of nicardipine study in vascular dementia]. Rev Neurol, 1999. 28(9): p. 835-45.Google Scholar
  59. 59.
    Gonzalez-Gonzalez JA, Lozano R. A study of the tolerability and effectiveness of nicardipine retard in cognitive deterioration of vascular origin. Rev Neurol. 2000;30(8):719–28.PubMedGoogle Scholar
  60. 60.
    Price JF et al. Low dose aspirin and cognitive function in middle aged to elderly adults: randomised controlled trial. BMJ. 2008;337:a1198.PubMedCentralPubMedGoogle Scholar
  61. 61.
    Diener HC, Sacco R, Yusuf S. Rationale, design and baseline data of a randomized, double-blind, controlled trial comparing two antithrombotic regimens (a fixed-dose combination of extended-release dipyridamole plus ASA with clopidogrel) and telmisartan versus placebo in patients with strokes: the Prevention Regimen for Effectively Avoiding Second Strokes Trial (PRoFESS). Cerebrovasc Dis. 2007;23(5-6):368–80.PubMedGoogle Scholar
  62. 62.
    McIlroy SP et al. Moderately elevated plasma homocysteine, methylenetetrahydrofolate reductase genotype, and risk for stroke, vascular dementia, and Alzheimer disease in Northern Ireland. Stroke. 2002;33(10):2351–6.PubMedGoogle Scholar
  63. 63.
    Tanne D et al. Prospective study of serum homocysteine and risk of ischemic stroke among patients with preexisting coronary heart disease. Stroke. 2003;34(3):632–6.PubMedGoogle Scholar
  64. 64.
    Selhub J et al. B vitamins, homocysteine, and neurocognitive function in the elderly. Am J Clin Nutr. 2000;71(2):p. 614s–20.Google Scholar
  65. 65.
    Malouf R, Grimley Evans J. Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people. Cochrane Database Syst Rev. 2008;(4):p. Cd004514.Google Scholar
  66. 66.
    Lewerin C et al. Significant correlations of plasma homocysteine and serum methylmalonic acid with movement and cognitive performance in elderly subjects but no improvement from short-term vitamin therapy: a placebo-controlled randomized study. Am J Clin Nutr. 2005;81(5):1155–62.PubMedGoogle Scholar
  67. 67.
    Clarke R, Harrison G, Richards S. Effect of vitamins and aspirin on markers of platelet activation, oxidative stress and homocysteine in people at high risk of dementia. J Intern Med. 2003;254(1):67–75.PubMedGoogle Scholar
  68. 68.
    McMahon JA et al. A controlled trial of homocysteine lowering and cognitive performance. N Engl J Med. 2006;354(26):2764–72.PubMedGoogle Scholar
  69. 69.
    Durga J et al. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet. 2007;369(9557):208–16.PubMedGoogle Scholar
  70. 70.
    Solfrizzi V et al. Diet and Alzheimer’s disease risk factors or prevention: the current evidence. Expert Rev Neurother. 2011;11(5):677–708.PubMedGoogle Scholar
  71. 71.
    Tangney CC et al. Adherence to a Mediterranean-type dietary pattern and cognitive decline in a community population. Am J Clin Nutr. 2011;93(3):601–7.PubMedCentralPubMedGoogle Scholar
  72. 72.
    Feart C et al. Adherence to a Mediterranean diet, cognitive decline, and risk of dementia. Jama. 2009;302(6):638–48.PubMedCentralPubMedGoogle Scholar
  73. 73.
    Morris MC. Nutritional determinants of cognitive aging and dementia. Proc Nutr Soc. 2012;71(1):1–13.PubMedGoogle Scholar
  74. 74.
    Kramer AF et al. Fitness, aging and neurocognitive function. Neurobiol Aging. 2005;26 Suppl 1:124–7.PubMedGoogle Scholar
  75. 75.
    Vona M et al. Effects of different types of exercise training followed by detraining on endothelium-dependent dilation in patients with recent myocardial infarction. Circulation. 2009;119(12):1601–8.PubMedGoogle Scholar
  76. 76.
    Angevaren M et al. Physical activity and enhanced fitness to improve cognitive function in older people without known cognitive impairment. Cochrane Database Syst Rev. 2008;(3):p. Cd005381.Google Scholar
  77. 77.
    Lautenschlager NT et al. Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial. Jama. 2008;300(9):1027–37.PubMedGoogle Scholar
  78. 78.
    Aarsland D et al. Is physical activity a potential preventive factor for vascular dementia? A systematic review. Aging Ment Health. 2010;14(4):386–95.PubMedGoogle Scholar
  79. 79.
    Verdelho A et al. Physical activity prevents progression for cognitive impairment and vascular dementia: results from the LADIS (Leukoaraiosis and Disability) study. Stroke. 2012;43(12):3331–5.PubMedGoogle Scholar
  80. 80.
    Sitzer DI, Twamley EW, Jeste DV. Cognitive training in Alzheimer’s disease: a meta-analysis of the literature. Acta Psychiatr Scand. 2006;114(2):75–90.PubMedGoogle Scholar
  81. 81.
    Bahar-Fuchs A, Clare L, Woods B. Cognitive training and cognitive rehabilitation for persons with mild to moderate dementia of the Alzheimer’s or vascular type: a review. Alzheimers Res Ther. 2013;5(4):35.PubMedCentralPubMedGoogle Scholar
  82. 82.
    Horr T, Messinger-Rapport B, Pillai JA. Systematic review of strengths and limitations of randomized controlled trials for non-pharmacological interventions in mild cognitive impairment: focus on Alzheimer’s disease. J Nutr Health Aging. 2015;19(2):141–53.PubMedGoogle Scholar
  83. 83.
    Qiu C, Winblad B, Fratiglioni L. The age-dependent relation of blood pressure to cognitive function and dementia. Lancet Neurol. 2005;4(8):487–99.PubMedGoogle Scholar
  84. 84.
    Nation DA et al. Pulse pressure in relation to tau-mediated neurodegeneration, cerebral amyloidosis, and progression to dementia in very old adults. JAMA Neurol. 2015;72(5):546–53.PubMedCentralPubMedGoogle Scholar
  85. 85.
    Kennelly SP, Lawlor BA, Kenny RA. Blood pressure and the risk for dementia: a double edged sword. Ageing Res Rev. 2009;8(2):61–70.PubMedGoogle Scholar
  86. 86.
    In't Veld BA et al. Antihypertensive drugs and incidence of dementia: the Rotterdam Study. Neurobiol Aging. 2001;22(3):p. 407–12.PubMedGoogle Scholar
  87. 87.
    Peila R et al. Reducing the risk of dementia: efficacy of long-term treatment of hypertension. Stroke. 2006;37(5):1165–70.PubMedGoogle Scholar
  88. 88.
    Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. Jama, 1991. 265(24): p. 3255-64.Google Scholar
  89. 89.
    Lithell H et al. The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial. J Hypertens. 2003;21(5):875–86.PubMedGoogle Scholar
  90. 90.
    Peters R et al. Incident dementia and blood pressure lowering in the Hypertension in the Very Elderly Trial cognitive function assessment (HYVET-COG): a double-blind, placebo controlled trial. Lancet Neurol. 2008;7(8):683–9.PubMedGoogle Scholar
  91. 91.
    Forette F et al. Prevention of dementia in randomised double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial. Lancet. 1998;352(9137):1347–51.PubMedGoogle Scholar
  92. 92.
    Forette F 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(18):2046–52.PubMedGoogle Scholar
  93. 93.
    Tzourio C et al. Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease. Arch Intern Med. 2003;163(9):1069–75.PubMedGoogle Scholar
  94. 94.
    Dufouil C et al. Effects of blood pressure lowering on cerebral white matter hyperintensities in patients with stroke: the PROGRESS (Perindopril Protection Against Recurrent Stroke Study) Magnetic Resonance Imaging Substudy. Circulation. 2005;112(11):1644–50.PubMedGoogle Scholar
  95. 95.
    van Vliet P et al. The influence of age on the association between cholesterol and cognitive function. Exp Gerontol. 2009;44(1-2):112–22.PubMedGoogle Scholar
  96. 96.
    Solomon A et al. Midlife serum cholesterol and increased risk of Alzheimer’s and vascular dementia three decades later. Dement Geriatr Cogn Disord. 2009;28(1):75–80.PubMedCentralPubMedGoogle Scholar
  97. 97.
    Giannopoulos S et al. Statins and vascular dementia: a review. J Alzheimers Dis. 2014;42 Suppl 3:S315–20.PubMedGoogle Scholar
  98. 98.
    Feldman HH et al. Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe. Neurology. 2010;74(12):956–64.PubMedGoogle Scholar
  99. 99.
    MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360(9326):7–22.Google Scholar
  100. 100.
    Trompet S et al. Pravastatin and cognitive function in the elderly. Results of the PROSPER study. J Neurol. 2010;257(1):85–90.PubMedGoogle Scholar
  101. 101.
    Lu FP, Lin KP, Kuo HK. Diabetes and the risk of multi-system aging phenotypes: a systematic review and meta-analysis. PLoS One. 2009;4(1), e4144.PubMedCentralPubMedGoogle Scholar
  102. 102.
    Saczynski JS et al. Cognitive impairment: an increasingly important complication of type 2 diabetes: the age, gene/environment susceptibility—Reykjavik study. Am J Epidemiol. 2008;168(10):1132–9.PubMedCentralPubMedGoogle Scholar
  103. 103.
    Abbatecola AM et al. Postprandial plasma glucose excursions and cognitive functioning in aged type 2 diabetics. Neurology. 2006;67(2):235–40.PubMedGoogle Scholar
  104. 104.
    Areosa SA, Grimley EV. Effect of the treatment of type II diabetes mellitus on the development of cognitive impairment and dementia. Cochrane Database Syst Rev. 2002;(4):p. Cd003804.Google Scholar
  105. 105.
    Launer LJ et al. Effects of intensive glucose lowering on brain structure and function in people with type 2 diabetes (ACCORD MIND): a randomised open-label substudy. Lancet Neurol. 2011;10(11):969–77.PubMedCentralPubMedGoogle Scholar
  106. 106.
    Patel A et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358(24):2560–72.PubMedGoogle Scholar
  107. 107.
    Whitmer RA et al. Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. Jama. 2009;301(15):1565–72.PubMedCentralPubMedGoogle Scholar
  108. 108.
    Sabia S et al. Impact of smoking on cognitive decline in early old age: the Whitehall II cohort study. Arch Gen Psychiatry. 2012;69(6):627–35.PubMedCentralPubMedGoogle Scholar
  109. 109.
    Galanis DJ et al. Smoking history in middle age and subsequent cognitive performance in elderly Japanese-American men. The Honolulu-Asia Aging Study. Am J Epidemiol. 1997;145(6):507–15.PubMedGoogle Scholar
  110. 110.
    Ott A et al. Effect of smoking on global cognitive function in nondemented elderly. Neurology. 2004;62(6):920–4.PubMedGoogle Scholar
  111. 111.
    Almeida OP et al. 24-month effect of smoking cessation on cognitive function and brain structure in later life. Neuroimage. 2011;55(4):1480–9.PubMedGoogle Scholar
  112. 112.
    Auriel E, Greenberg SM. The pathophysiology and clinical presentation of cerebral amyloid angiopathy. Curr Atheroscler Rep. 2012;14(4):343–50.PubMedGoogle Scholar
  113. 113.
    Aguilar MI, Freeman WD. Spontaneous intracerebral hemorrhage. Semin Neurol. 2010;30(5):555–64.PubMedGoogle Scholar
  114. 114.
    Attems J, Jellinger KA. Only cerebral capillary amyloid angiopathy correlates with Alzheimer pathology—a pilot study. Acta Neuropathol. 2004;107(2):83–90.PubMedGoogle Scholar
  115. 115.
    Greenberg SM. Cerebral amyloid angiopathy and vessel dysfunction. Cerebrovasc Dis. 2002;13 Suppl 2:42–7.PubMedGoogle Scholar
  116. 116.•
    Charidimou A, Gang Q, Werring DJ. Sporadic cerebral amyloid angiopathy revisited: recent insights into pathophysiology and clinical spectrum. J Neurol Neurosurg Psychiatry. 2012;83(2):124–37. Excellent review of pathophysiology, diagnosis, and treatment of CAA.PubMedGoogle Scholar
  117. 117.
    O'Donnell HC et al. Apolipoprotein E genotype and the risk of recurrent lobar intracerebral hemorrhage. N Engl J Med. 2000;342(4):240–5.PubMedGoogle Scholar
  118. 118.
    Biffi A et al. Aspirin and recurrent intracerebral hemorrhage in cerebral amyloid angiopathy. Neurology. 2010;75(8):693–8.PubMedCentralPubMedGoogle Scholar
  119. 119.
    Biffi A et al. Warfarin-related intraventricular hemorrhage: imaging and outcome. Neurology. 2011;77(20):1840–6.PubMedCentralPubMedGoogle Scholar
  120. 120.
    Arima H et al. Effects of perindopril-based lowering of blood pressure on intracerebral hemorrhage related to amyloid angiopathy: the PROGRESS trial. Stroke. 2010;41(2):394–6.PubMedGoogle Scholar
  121. 121.
    Goldstein LB et al. Hemorrhagic stroke in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels study. Neurology. 2008;70(24 Pt 2):2364–70.PubMedGoogle Scholar
  122. 122.
    Chung KK et al. Cerebral amyloid angiopathy related inflammation: three case reports and a review. J Neurol Neurosurg Psychiatry. 2011;82(1):20–6.PubMedGoogle Scholar
  123. 123.
    Kloppenborg RP et al. Steroid responsive encephalopathy in cerebral amyloid angiopathy: a case report and review of evidence for immunosuppressive treatment. J Neuroinflammation. 2010;7:18.PubMedCentralPubMedGoogle Scholar
  124. 124.
    Jellinger KA. The pathology of “vascular dementia”: a critical update. J Alzheimers Dis. 2008;14(1):107–23.PubMedGoogle Scholar
  125. 125.
    Roh JH, Lee JH. Recent updates on subcortical ischemic vascular dementia. J Stroke. 2014;16(1):18–26.PubMedCentralPubMedGoogle Scholar
  126. 126.
    Yoshita M et al. Extent and distribution of white matter hyperintensities in normal aging, MCI, and AD. Neurology. 2006;67(12):2192–8.PubMedCentralPubMedGoogle Scholar
  127. 127.•
    Benzinger TL. Progressive white matter abnormalities in autosomal dominant Alzheimer’s disease: results of the DIAN study. Alzheimer Dement. 2012;8(4):68–69. Notes significant white matter changes in the DIAN study (AD subjects without significant vascular comorbidities).Google Scholar
  128. 128.
    Maillard P et al. Coevolution of white matter hyperintensities and cognition in the elderly. Neurology. 2012;79(5):442–8.PubMedCentralPubMedGoogle Scholar
  129. 129.
    Verdelho A et al. White matter changes and diabetes predict cognitive decline in the elderly: the LADIS study. Neurology. 2010;75(2):160–7.PubMedGoogle Scholar
  130. 130.
    Debette S, Markus HS. The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis. Bmj. 2010;341:c3666.PubMedCentralPubMedGoogle Scholar
  131. 131.
    Inzitari D et al. Changes in white matter as determinant of global functional decline in older independent outpatients: three year follow-up of LADIS (leukoaraiosis and disability) study cohort. Bmj. 2009;339:b2477.PubMedCentralPubMedGoogle Scholar
  132. 132.
    Richard E et al. Vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of white matter lesions on MRI: the evaluation of vascular care in Alzheimer’s disease (EVA) study. Stroke. 2010;41(3):554–6.PubMedGoogle Scholar
  133. 133.
    Pantoni L et al. Efficacy and safety of nimodipine in subcortical vascular dementia: a randomized placebo-controlled trial. Stroke. 2005;36(3):619–24.PubMedGoogle Scholar
  134. 134.
    Chabriat H et al. Cadasil. Lancet Neurol. 2009;8(7):643–53.PubMedGoogle Scholar
  135. 135.
    Amberla K et al. Insidious cognitive decline in CADASIL. Stroke. 2004;35(7):1598–602.PubMedGoogle Scholar
  136. 136.
    Dichgans M et al. The phenotypic spectrum of CADASIL: clinical findings in 102 cases. Ann Neurol. 1998;44(5):731–9.PubMedGoogle Scholar
  137. 137.
    Andre C. CADASIL: pathogenesis, clinical and radiological findings and treatment. Arq Neuropsiquiatr. 2010;68(2):287–99.PubMedGoogle Scholar
  138. 138.
    Mizuno T et al. Cognitive impairment and cerebral hypoperfusion in a CADASIL patient improved during administration of lomerizine. Clin Neuropharmacol. 2009;32(2):113–6.PubMedGoogle Scholar
  139. 139.
    Dichgans M et al. Donepezil in patients with subcortical vascular cognitive impairment: a randomised double-blind trial in CADASIL. Lancet Neurol. 2008;7(4):310–8.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of Neurology, Lou Ruvo Center for Brain HealthCleveland ClinicLas VegasUSA
  2. 2.Department of Neurology, Lou Ruvo Center for Brain HealthCleveland ClinicClevelandUSA

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