Treatment of vascular cognitive impairment


  • Permphan Dharmasaroja Department of Anatomy, Faculty of Science, Mahidol University


vascular dementia, vascular cognitive impairment, clinical trial, treatment, prevention


Vascular cognitive impairment is spectrum of cognitive change related to vascular pathology from early cognitive decline to dementia. Management of risk factors that may increase damage to the brain vasculature is an important treatment strategy. There is substantial evidence that treating risk factors may improve outcomes and help delay further decline. Thus, pharmacological therapy primarily helps to prevent worsening of vascular dementia by controlling the underlying disease, such as hypertension, hyperlipidemia or diabetes mellitus. To date, there is no approved drug for vascular dementia, and the use of acetylcholinesterase inhibitors should not be routinely prescribed.


Knopman D, Boland LL, Mosley T, et al. Cardiovascular risk factors and cognitive decline in middleaged adults. Neurology 2001; 56: 42–48.

Yaffe K, Kanaya A, Lindquist K, et al. The metabolic syndrome, inflammation, and rise of cognitive decline. JAMA 2004; 292: 2237–2242.

Solomon A, Kareholt I, Ngandu T. Serum cholesterol changes after mid-life and late-life cognition: twenty-one-year follow-up. Neurology 2007; 68:

Vermeer SE, Prins ND, den Heijer T, et al. Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med 2003; 348: 1215–1222.

Boyle PA, Yang J, Yu L, et al. Varied effects of age-related neuropathologies on the trajectory of late life cognitive decline. Brain 2017 Jan 12. pii: aww341.

Reed BR, Mungas DM, Kramer JH, et al. Profiles of neuropsychological impairment in autopsy-defined Alzheimer’s disease and cerebrovascular disease.
Brain 2007; 130(Pt 3): 731-739.

Gorelick PB, Scuteri A, Black SE, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from
the american heart association/american stroke association. Stroke 2011; 42: 2672-713.

Vagnucci AH Jr, Li WW. Alzheimer’s disease and angiogenesis. Lancet 2003; 361: 605–608.

Wu Z, Guo H, Chow N, et al. Role of the MEOX2 homeobox gene in neurovascular dysfunction in Alzheimer’s disease. Nat Med 2005; 11: 899–904.

American Academy of Neurology. Clinical Practice Guideline Process Manual. 2011; 2011 ed. St. Paul, MN: The American Academy of Neurology.

Peters R, Beckett N, Forette F, 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: 683-689.

Williamson JD, Miller ME, Bryan RN, et al. The action to control cardiovascular risk in diabetes memory in diabetes study (ACCORD-MIND): rationale, design, and methods. Am J Cardiol 2007; 99: S112-S122.

Bonds DE, Miller ME, Bergenstal RM, et al. The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. BMJ 2010; 340: b4909.

McGuiness B, Craig D, Bullock R, Passmore P. Statins for the prevention of dementia. Cochrane Database Syst Rev 2009; 15: CD003160.

McGuiness B, OHare J, Craig D, et al. Statins for the treatment of dementia. Cochrane Database Syst Rev 2010; 4: CD007514.

Zuccala G, Onder G, Marzetti E, et al. Use of angiotensin-converting enzyme inhibitors and variations in cognitive performance among patients with heart failure. Eur Heart J 2005; 26: 226-233.

Bo M, Massaia M, Speme S, et al. Risk of cognitive decline in older patients after carotid endarterectomy: an observational study. J Am Geriatr Soc 2006; 54:

Crawley F, Stygall J, Lunn S, Harrison M, Brown MM, Newman S. Comparison of microembolism detected by transcranial Doppler and neuropsychological sequelae of carotid surgery and percutaneous transluminal angioplasty. Stroke 2000; 31: 1329-1334.

Grunwald IQ, Supprian T, Politi M, et al. Cognitive changes after carotid artery stenting. Neuroradiology 2006; 48: 319-323.

Kishikawa K, Kamouchi M, Okada Y, et al. Effects of carotid endarterectomy on cerebral blood flow and neuropsychological test performance in patients with
high-grade carotid stenosis. J Neurol Sci 2003; 213: 19-24.

Lunn S, Crawley F, Harrison MJG, Brown MM, Newman SP. Impact of carotid endarterectomy upon cognitive functioning. a systematic review of the
literature. Cerebrovasc Dis 1999; 9: 74-81.

Price JF, Stewart MC, Deary IJ, et al. Low dose aspirin and cognitive function in middle aged to elderly adults: randomized controlled trial. BMJ 2008;
337: a1198.

Diener H-C, Sacco RL, Yusuf S, et al. Effects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial: a double-blind, active and placebo-controlled study. Lancet Neurol 2008; 7: 875-884.

AD2000 Collaborative Group. Bentham P, Gray R, et al. Aspirin in Alzheimer’s disease (AD2000): a randomized open-label trial. Lancet Neurol 2008;
7: 41-49.

Thoonsen H, Richard E, Bentham P, et al. Aspirin in Alzheimer’s disease. Increased risks of intracerebral hemorrhage: cause for concern? Stroke 2010; 41:

Rusanen M, Kivipelto M, Quesenberry CP Jr, et al. Heavy smoking in midlife and long-term risk of Alzheimer and vascular dementia. Arch Intern Med
2011; 171: 333-339.

Anstey KJ, Holly MA, Cherbuin N. Alcohol consumption as a risk factor for dementia and cognitive decline: meta-analysis of prospective studies. Am J Geriatr Psychiatr 2009; 17: 542-555.

Hughes TF, Ganguli M. Modifiable midlife risk factors for late-life cognitive impairment and dementia. Curr Psychiatr Rev 2009; 5: 73-92.

Whitmer RA, Gunderson EP, Quesenberry Jr CP, et al. Body mass index in midlife and risk of Alzheimer disease and vascular dementia. Curr
Alzheimer Res 2007; 4: 103-109.

Scarmeas N, Stern Y, Tang MX, et al. Mediterranean diet and risk for Alzheimer’s disease. Ann Neurol 2006; 59: 922-927.

Scarmeas N, Sterm Y, Mayeux R, et al. Mediterranean diet and mild cognitive impairment. Arch Neurol 2009; 66: 216-225.

van de Rest O, Geleijnse JM, Kok FJ, et al. Effect of fish oil on cognitive performance in older subjects: a randomized, controlled trial. Neurology 2008; 71:

Kang JH, Cook N, Manson J et al. A trial of B vitamins and cognitive function among women at high risk of cardiovascular disease. Am J Clin Nutr
2008; 88: 1602-1610.

Kang JH, Cook NR, Manson JE, et al. Vitamin E, Vitamin C, Beta Carotene, and cognitive function among women with or at risk of cardiovascular
disease: the women antioxidant and cardiovascular study. Circulation 2009; 119: 2772-2780.

Sofi F, Valecchi D, Bacci D, et al. Physical activity and risk of cognitive decline: a meta-analysis of prospective studies. J Intern Med 2011; 269: 107-117.

Lautenschlager NT, Cox KL, Flicker L, et al. Effect of physical activity on cognitive function in older adults at risk for Alzheimer’s disease. A randomized
trial. JAMA 2008; 300: 1027-1037.

Ancoli-Israel S, Palmer BW, Cooke JR, et al. Cognitive effects of treating obstructive sleep apnea in Alzheimer’s disease: a randomized controlled
study. J Am Geriatr Soc 2008; 56: 2076-2081.

Black S, Roman GC, Geldmacher DS, et al. Efficacy and tolerability of donepezil in vascular dementia: positive results of a 24-week, multicenter, international,
randomized, placebo-controlled clinical trial. Stroke 2003; 34: 2323–2330.

Wilkinson D, Doody R, Helme R, et al. Donepezil in vascular dementia: a randomized, placebocontrolled study. Neurology 2003; 61: 479–486.

Pratt RD, Perdomo CA. Donepezil-treated patients with probable vascular dementia demonstrate cognitive benefits. Ann NY Acad Sci 2002; 977: 513-522.

Salloway SP, Pratt RD, Perdomo CA. Donepezil is well tolerated in patients with vascular dementia: a comparison of tolerability in vascular dementia
patients and Alzheimer’s disease patients. Eur J Neurol 2002; 9: 165-224.

Meyer JS, Chowdhury MH, Xu G, Li YS, Quach M. Donepezil treatment of vascular dementia. Ann NY Acad Sci 2002; 977: 482-486.

Erkinjuntti T, Kurz A, Gauthier S, et al. Efficacy of galantamine in probable vascular dementia and Alzheimer’s disease combined with cerebrovascular
disease: a randomized trial. Lancet 2002; 359: 1283–1290.

Bullock R, Erkinjuntti T, Lilienfeld S. Management of patients with Alzheimer’s disease plus cerebrovascular disease: 12-month treatment with
galantamine. Dem Geriatr Cogn Dis 2004; 17: 29-34.

Erkinjuntti T, Kurz A, Small GW, et al. An openlabel extension trial of galantamine in patients with probable vascular dementia and mixed ementia. Clin Therap 2003; 25: 1765-1782.

Kertesz A. Efficacy of galantamine in probable vascular dementia and Alzheimer’s disease combined with cerebrovascular disease: a randomized
trial. Curr Neurol Neurosc Rep 2002; 2: 503-504.

Kurz AF, Erkinjuntti T, Small GW, et al. Long-term safety and cognitive effects of galantamine in the treatment of probable vascular dementia or Alzheimer’s disease with cerebrovascular disease. Eur J Neurol 2003; 10: 633-640.

Small G, Erkinjuntti T, Kurz A, Lilienfeld S. Galantamine in the treatment of cognitive decline in patients with vascular dementia or Alzheimer’s
disease with cerebrovascular disease. CNS drugs 2003; 17: 905-914.

Aguilar M, Roman G, Black S, et al. Efficacy and safety of donepezil in vascular dementia: results from the largest double-blind trial in vascular
dementia [abstract P4-439]. Presented at the 10th International Conference on Alzheimer’s Disease and Related Disorders. Madrid, Spain, 2006; July 15–20.

Kavirajan H, Schneider LS. Efficacy and adverse effects of cholinesterase inhibitors and memantine in vascular dementia: a meta-analysis of randomized
clinical trials. Lancet Neurol 2007; 6: 782–792.

Wilcock G, Mobius HJ, Stoffler A; MMM 500 Group. A double-blind, placebo-controlled multicentre study of memantine in mild to moderate vascular
dementia (MMM 500). Int Clin Psychopharmacol 2002; 17: 297–305.

52.Orgogozo JM, Rigaud AS, Stoffler A, 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: 1834–1839.

Dichgans M, Markus HS, Salloway S, et al. Donepezil in patients with subcortical vascular cognitive impairment: a randomized double-blind
trial in CADASIL. Lancet Neurol 2008; 7: 310–318.

Pantoni L, del Ser T, Soglian AG, et al. Efficacy and safety of nimodipine in subcortical vascular dementia. A randomized placebo-controlled trial.
Stroke 2005; 36: 619-624.

Spanish Group of Nicardipine Study in Vascular Dementia. An experimental, randomized, double-blind, placebo-controlled clinical trial to investigate the effect of nicardipine on cognitive function in patients with vascular dementia. Rev Neurol 1999; 15: 835-845.

Gonzalez-Gonzalez JA, Lozano RA. Study of the tolerability and effectiveness of nicardipine retard in cognitive deterioration of vascular origin. Rev
Neurol 2000; 30: 719-728.

Sha MC, Callahan CM. The efficacy of pentoxifylline in the treatment of vascular dementia: a systematic review. Alz Dis Ass Disord 2003; 17: 46-54.

Fioravanti M, Yanagi M. Cytidinephosphocholine (CDP-choline) for cognitive and behavioural disturbances associated with chronic cerebral disorders in the elderly. Cochrane Database of Systematic Reviews 2011. In: The Cochrane Library, Issue 03, Art. No. CD000269.

Guekht AB, Moessler H, Novak PH, et al. Cerebrolysin in vascular dementia: improvement of clinical outcome in a randomized, double-blind, placebo-controlled multicenter trial. J Stroke Cerebrovasc Dis 2011; 20: 310-318.

Birks J, Grimley EJ. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database of Systematic Reviews 2011. In: The Cochrane Library,
Issue 03, Art. No. CD003120.

Schneider L, Olin JT, Novit A, Luczak S. Hydergine for dementia. Cochrane Database of Systematic Reviews 2011. In: The Cochrane Library, Issue 03,
Art. No. CD000359.

Flicker L, Grimley EJ. Piracetam for dementia or cognitive impairment. Cochrane Database of Systematic Reviews 2011. In: The Cochrane Library,
Issue 03, Art. No. CD001011.

Flaker GC, Pogue J, Yusuf S, et al. Cogntive function and anticoagulation control in patients with atrial fibrillation. Circ Cardiovasc Qual Outcomes 2010; 3: 277.




How to Cite

Dharmasaroja P. Treatment of vascular cognitive impairment. J Thai Stroke Soc [Internet]. 2019 Feb. 13 [cited 2024 Jun. 14];16(2):16-2. Available from:



Original article