Skip to main content

Advertisement

SpringerLink
Log in

Cholinergic dysfunction in vascular dementia

  • Published:
Current Psychiatry Reports Aims and scope Submit manuscript

Abstract

Vascular dementia (VaD) is the second most common type of dementia in the elderly after Alzheimer’s disease (AD). Evidence is presented indicating the occurrence of cholinergic dysfunction in VaD, independent from AD. Controlled clinical trials of cholinesterase inhibitors (ChEIs) in VaD and in patients with AD plus cerebrovascular disease are reviewed. Compared with placebo, ChEI treatment improves cognition, behavior, and activities of daily living. Cholinergic deficits in patients with VaD may result from ischemia of basal forebrain cholinergic nuclei that are irrigated by penetrating arteries that are highly susceptible to arterial hypertension, or from ischemic lesions in basal ganglia or white matter that sever the extensive cholinergic cortical projections. Cholinergic stimulation produces increases in cortical cerebral blood flow that may be relevant to the therapeutic effect of ChEIs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Lobo A, Launer LJ, Fratiglioni L, et al. for the Neurologic Diseases in the Elderly Research Group: Prevalence of dementia and major subtypes in Europe: a collaborative study of population-based cohorts. Neurology 2000, 54(Suppl 5): S4-S9.

    PubMed  CAS  Google Scholar 

  2. Dubois MF, Herbert R: The incidence of vascular dementia in Canada: a comparison with Europe and East Asia. Neuroepidemiology 2001, 20:179–187.

    Article  PubMed  CAS  Google Scholar 

  3. Ikeda M, Hokoishi K, Maki N, et al.: Increased prevalence of vascular dementia in Japan: a community-based epidemiological study. Neurology 2001, 57:839–844. This epidemiological study demonstrates that the use of brain imaging increases the prevalence of VaD cases, compared with AD.

    PubMed  CAS  Google Scholar 

  4. Chen CPL-H: Transcultural expression of subcortical vascular disease. J Neurol Sci 2004, 226:45–47. A recent review of important ethnic and cultural factors that impact epidemiological studies of dementia.

    Article  PubMed  Google Scholar 

  5. Román GC: Stroke, cognitive decline and vascular dementia: the silent epidemic of the 21st century. Neuroepidemiology 2003, 22:161–164.

    Article  PubMed  Google Scholar 

  6. Gorelick PB: Can we save the brain from the ravages of midlife cardiovascular risk factors? Neurology 1999, 52:1114–1115.

    PubMed  CAS  Google Scholar 

  7. Gorelick PB: Stroke prevention therapy beyond antithrombotics: unifying mechanisms in ischemic stroke pathogenesis and implications for therapy. Stroke 2002, 33:862–875.

    Article  PubMed  Google Scholar 

  8. O’Brien JT, Erkinjuntti T, Reisberg B, et al.: Vascular cognitive impairment. Lancet Neurol 2003, 2:89–98.

    Article  PubMed  Google Scholar 

  9. Román GC: Historical evolution of the concept of vascular dementia. In Vascular Cognitive Impairment: Preventable dementia. Edited by Bowler JV, Hachinski V. Oxford: Oxford University Press; 2003:12–20.

    Google Scholar 

  10. Román GC: On the history of lacunes, état criblé, and the white matter lesions of vascular dementia. Cerebrovasc Dis 2002, 13(Suppl 2):1–6.

    PubMed  Google Scholar 

  11. Román GC: A historical review of the concept of vascular dementia: Lessons from the past for the future. Alzheimer Dis Assoc Disord 1999, 13(Suppl 3):S4-S8.

    Article  PubMed  Google Scholar 

  12. Royall DR: The new "silent" epidemic. J Am Geriatr Soc 2004, 52:1212–1213.

    Article  PubMed  Google Scholar 

  13. Royall DR, Lauterbach EC, Cummings JL, et al.: Executive control function: a review of its promise and challenges for clinical research. A report from the Committee on Research of the American Neuropsychiatric Association. J Neuropsychiatry Clin Neurosci 2002, 14:377–405. One of the first comprehensive reviews on the importance of executive dysfunction in dementia.

    PubMed  Google Scholar 

  14. Román GC, Erkinjuntti T, Wallin A, et al.: Subcortical ischaemic vascular dementia. Lancet Neurol 2002, 1:426–436. Comprehensive review of subcortical vascular lesions leading to behavioral and cognitive manifestations, including vascular dementia and vascular depression.

    Article  PubMed  Google Scholar 

  15. Boyle PE: Assessing and predicting functional impairment in Alzheimer’s disease: the emerging role of frontal system dysfunction. Curr Psychiatry Rep 2004, 6:20–24. Recent review on the importance of frontal system dysfunction as determinant of functional impairment in AD.

    Article  PubMed  Google Scholar 

  16. 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. A proposal to define dementia as executive dysfunction severe enough to produce functional loss of independence.

    Article  PubMed  Google Scholar 

  17. Fernando MS, Ince PG on behalf of the MRC Cognitive Function and Ageing Neuropathology Study Group: Vascular pathologies and cognition in a population-based cohort of elderly people. J Neurol Sci 2004, 226:13–17.

    Article  PubMed  Google Scholar 

  18. Riekse RG, Leverenz JB, McCormick W, et al.: Effect of vascular lesions on cognition in Alzheimer’s disease: a communitybased study. J Am Geriatr Soc 2004, 52:1442–1448.

    Article  PubMed  Google Scholar 

  19. Schneider JA, Wilson RS, Bienias JL, et al.: Cerebral infarctions and the likelihood of dementia from Alzheimer disease pathology. Neurology 2004, 62:1148–1155.

    PubMed  CAS  Google Scholar 

  20. Knopman DS, Parisi JE, Boeve BF, et al.: Vascular dementia in a population-based autopsy study. Arch Neurol 2003, 60:569–575.

    Article  PubMed  Google Scholar 

  21. Zekry D, Duyckaerts C, Belmin J, et al.: The vascular lesions in vascular and mixed dementia: the weight of functional neuroanatomy. Neurobiol Aging 2003, 24:213–219. Fundamental study demonstrating than location of lesions is more important for cognition than number of lesions or volume of brain tissue loss. Location of subcortical lesions such as lacunar strokes and periventricular white matter ischemia interrupt prefrontalsubcortical circuits.

    Article  PubMed  Google Scholar 

  22. Jellinger KA, Attems J: Incidence of cerebrovascular lesions in Alzheimer’s disease: a postmortem study. Acta Neuropathol (Berl) 2003, 105:14–17.

    Google Scholar 

  23. Polvikoski T, Sulkava R, Myllykangas L, et al.: Prevalence of Alzheimer’s disease in very elderly people: a prospective neuropathological study. Neurology 2001, 56:1690–1696.

    PubMed  CAS  Google Scholar 

  24. Lim A, Tsuang D, Kukull W, et al.: Clinico-neuropathological correlation of Alzheimer’s disease in a community-based case series. J Am Geriatr Soc 1999, 47:564–569.

    PubMed  CAS  Google Scholar 

  25. Snowdon DA, Greiner LH, Mortimer JA, et al.: Brain infarction and the clinical expression of Alzheimer disease. The Nun Study. JAMA 1997, 277:813–817. This classic paper demonstrated that lacunes increased 20 times the risk of dementia in elderly subjects with AD.

    Article  PubMed  CAS  Google Scholar 

  26. Braak H, Braak E: Neuropathological stageing of Alzheimerrelated changes. Acta Neuropathol. (Berl) 1991, 82:239–259.

    Article  CAS  Google Scholar 

  27. Braak H, Braak E: Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiol Aging 1997, 18:351–357.

    Article  PubMed  CAS  Google Scholar 

  28. Bierer LM, Hof PR, Purohit DP, et al.: Neocortical neurofibrillary tangles correlate with dementia severity in Alzheimer’s disease. Arch Neurol 1995, 52:81–88.

    PubMed  CAS  Google Scholar 

  29. Goulding JM, Signorini DF, Chatterjee S, et al.: Inverse relation between Braak stage and cerebrovascular pathology in Alzheimer predominant dementia. J Neurol Neurosurg Psychiatry 1999, 67:654–657.

    PubMed  CAS  Google Scholar 

  30. Royall DR, Palmer R, Mulroy A, et al.: Pathological determinants of clinical dementia in Alzheimer’s disease. Exp Aging Res 2002, 28:143–162.

    Article  PubMed  Google Scholar 

  31. Royall DR, Román GC, Delacourte A: Pathological determinants of clinical dementia in Alzheimer’s disease. [Letter to the Editor] Exp. Aging Res 2002, 29:107–110.

    Article  Google Scholar 

  32. Zekry D, Duyckaerts C, Moulias R, Belmin J, Geoffre C, Herrmann F, Hauw J-J: Degenerative and vascular lesions of the brain have synergistic effects in dementia of the elderly. Acta Neuropathol. (Berl) 2002, 103:481–487.

    Article  CAS  Google Scholar 

  33. Zekry D, Hauw J-J, Gold G: Mixed dementia: epidemiology, diagnosis, and treatment. J Am Geriatr Soc 2002, 50:1431–1438.

    Article  PubMed  Google Scholar 

  34. White L, Petrovitch H, Hardman J, et al.: Cerebrovascular pathology and dementia in autopsied Honolulu-Asia Aging Study participants. Ann N Y Acad Sci 2002, 977:9–23.

    Article  PubMed  Google Scholar 

  35. Kovari E, Gold G, Herrmann FR, et al.: Cortical microinfarcts and demyelination significantly affect cognition in brain aging. Stroke 2004, 35:410–414.

    Article  PubMed  Google Scholar 

  36. Hènon H, Pasquier F, Durieu I, et al.: Pre-existing dementia in stroke patients: baseline frequency, associated factors and outcome. Stroke 1997, 28:2429–2436.

    PubMed  Google Scholar 

  37. Pohjasvaara T, Erkinjuntti T, Vataja R, Kaste M: Dementia three months after stroke. Baseline frequency and effect of different definitions of dementia in the Helsinki Stroke Aging Memory Study (SAM) cohort. Stroke 1997, 28:785–792.

    PubMed  CAS  Google Scholar 

  38. Barba R, Martinez-Espinosa S, Rodriguez-Garcia E, et al.: Poststroke dementia: clinical features and risk factors. Stroke 000, 31:1494–1501.

  39. Linden T, Skoog I, Fagerberg B, et al.: Cognitive impairment and dementia 20 months after stroke. Neuroepidemiology 2004, 23:45–52.

    Article  PubMed  Google Scholar 

  40. Longstreth Jr WT, Bernick C, Manolio TA, et al.: Lacunar infarcts defined by magnetic resonance imaging of 3660 elderly people: the Cardiovascular Health Study. Arch Neurol 1998, 55:1217–1225.

    Article  PubMed  Google Scholar 

  41. 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.

    Article  PubMed  Google Scholar 

  42. Román GC, Royall DR: A diagnostic dilemma: is "Alzheimer’s dementia" Alzheimer’s disease, vascular dementia, or both? Lancet Neurol 2004, 3:141.

    Article  PubMed  Google Scholar 

  43. Bartus RT: On neurodegenerative diseases, models and treatment strategies: lessons learned and lessons forgotten a generation following the cholinergic hypothesis. Exp Neurol 2000, 163:495–529. An update on the cholinergic hypothesis by one of the originators of the hypothesis.

    Article  PubMed  CAS  Google Scholar 

  44. Drachman DA: Memory and cognitive function in man: Does the cholinergic system have a specific role? Neurology 1977, 27:783–790.

    PubMed  CAS  Google Scholar 

  45. Drachman DA, Leavitt J: Human memory and the cholinergic system. A relationship to aging? Arch Neurol 1974, 30:113–121.

    PubMed  CAS  Google Scholar 

  46. Cummings JL: Alzheimer’s disease. N Engl J Med 2004, 351:56–67. A critical update on the pathogenesis and treatment of AD.

    Article  PubMed  CAS  Google Scholar 

  47. Davis KL, Mohs RC, Marin D, et al.: Cholinergic markers in elderly patients with early signs of Alzheimer disease. J AmMed Assoc 1999, 281:1401–1406.

    Article  CAS  Google Scholar 

  48. DeKosky ST, Ikonomovic MD, Styren SD, et al.: Up-regulation of choline acetyl transferase activity in hippocampus and frontal cortex of elderly subjects with mild cognitive impairment. Ann Neurol 2002, 51:145–155.

    Article  PubMed  CAS  Google Scholar 

  49. Selden NR, Gitelman DR, Salamon-Murayama N, et al.: Trajectories of cholinergic pathways within the cerebral hemispheres of the human brain. Brain 1998, 121:2249–2225. Original description of cholinergic pathways in the human brain.

    Article  PubMed  Google Scholar 

  50. Mufson EJ, Ginsberg SD, Ikonomovic MD, DeKosky ST: Human cholinergic basal forebrain: chemoanatomy and neurologic dysfunction. J Chem Neuroanat 2003, 26:233–242.

    Article  PubMed  CAS  Google Scholar 

  51. Alonso JR, U HS, Amaral DG: Cholinergic innervation of the primate hippocampal formation: effects of fimbria/fornix transection. J Comp Neurol 1996, 375:527–551.

    Article  PubMed  CAS  Google Scholar 

  52. Alonso JR, Amaral DG: Cholinergic innervation of the primate hippocampal formation. I. Distribution of choline acetyltransferase immunoreactivity in the Macaca fascicularis and Macaca mulatta monkeys. J Comp Neurol 1995, 355:135–170.

    Article  PubMed  CAS  Google Scholar 

  53. Inglis WL, Winn P: The pedunculopontine tegmental nucleus: where the striatum meets the reticular formation. Prog Neurobiol 1995, 47:1–29.

    Article  PubMed  CAS  Google Scholar 

  54. Mesulam MM, Mash D, Hersh L, et al.: Cholinergic innervation of the human striatum, globus pallidus, subthalamic nucleus, substantia nigra, and red nucleus. J Comp Neurol 1992, 323:252–268.

    Article  PubMed  CAS  Google Scholar 

  55. Swartz RH, Black SE: How common is vascular compromise of cholinergic white matter pathways in a memory clinic sample? J Neurol Sci 2002, 331:203–204.

    Google Scholar 

  56. 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. Demonstration that ischemic lesions interrupt cholinergic pathways in human patients with resultant loss of executive function.

    Article  PubMed  Google Scholar 

  57. Mesulam M, Siddique T, Cohen B: Cholinergic denervation in a pure multi-infarct state: observations on CADASIL. Neurology 2003, 60:1183–1185. Destruction of cholinergic pathways by ischemic lesions in a young patient with pure VaD, free of AD.

    PubMed  Google Scholar 

  58. Iwasaki K, Kitamura Y, Ohgami Y, et al.: The disruption of spatial cognition and changes in brain amino acid, monoamine and acetylcholine in rats with transient cerebral ischemia. Brain Res 1996, 709:163–172.

    Article  PubMed  CAS  Google Scholar 

  59. Ni JW, Matsumoto K, Li HB, et al.: Neuronal damage and decrease of central acetylcholine level following permanent occlusion of bilateral common carotid arteries in rat. Brain Res 1995, 673:290–296.

    Article  PubMed  CAS  Google Scholar 

  60. Yamamuro Y, Iwano H, Sensui N, et al.: Acetylcholine in the Zhippocampus during the discrimination learning performance in a rat model of chronic cerebral ischaemia. Neuroreport 1996, 7:1837–1840.

    Article  PubMed  CAS  Google Scholar 

  61. Togashi H, Matsumoto M, Yoshioka M, Hirokami M, Minami M, Saito H: Neurochemical profiles in cerebrospinal fluid of stroke-prone spontaneously hypertensive rats. Neurosci Lett 1994, 166:117–120.

    Article  PubMed  CAS  Google Scholar 

  62. Togashi H, Kimura S, Matsumoto M, et al.: Cholinergic changes in the hippocampus of stroke-prone spontaneously hypertensive rats. Stroke 1996, 27:520–525.

    PubMed  CAS  Google Scholar 

  63. Tohgi H, Abe T, Kimura M, et al.: Cerebrospinal fluid acetylcholine and choline in vascular dementia of Binswanger and multiple small infarct types as compared with Alzheimertype dementia. J Neural Transm 1996, 103:1211–1220.

    Article  PubMed  CAS  Google Scholar 

  64. Gottfries CG, Blennow K, Karlsson I, Wallin A: The neurochemistry of vascular dementia. Dementia 1994, 5:163–167.

    PubMed  CAS  Google Scholar 

  65. Wallin A, Gottfries CG: Biochemical substrates in normal aging and Alzheimer’s disease. Pharmacopsychiatry 1990, 23:37–43.

    PubMed  Google Scholar 

  66. Wallin A, Blennow K, Gottfries CG: Neurochemical abnormalities in vascular dementia. Dementia 1989, 1:120–130.

    Google Scholar 

  67. Wallin A, Sjögren M, Blennow K, Davidsson P: Decreased cerebrospinal fluid acetylcholinesterase activity in patients with subcortical vascular dementia [abstract]. J Neurol Sci 2004, 222:105.

    Article  Google Scholar 

  68. Sato A, Sato Y, Uchida S: Regulation of regional cerebral blood flow by cholinergic fibers originating in the basal forebrain. Int J Dev Neurosci 2001, 19:327–237. Important review of vasoactive cortical effects of cholinergic innervation.

    Article  PubMed  CAS  Google Scholar 

  69. Biesold D, Inanami O, Sato A, Sato Y: Stimulation of the nucleus basalis of Meynert increases cerebral cortical blood flow in rats. Neurosci Lett 1989, 98:39–44.

    Article  PubMed  CAS  Google Scholar 

  70. Sato A, Sato Y, Uchida S: Activation of the intracerebral cholinergic nerve fibers originating in the basal forebrain increases regional cerebral blood flow in the rat’s cortex and hippocampus. Neurosci Lett 2004, 361:90–93.

    Article  PubMed  CAS  Google Scholar 

  71. Hamel E: Cholinergic modulation of the cortical microvascular bed. Prog Brain Res 2004, 145:171–178.

    Article  PubMed  CAS  Google Scholar 

  72. Cauli B, Tong XK, Rancillac A, et al.: Cortical GABA interneurons in neurovascular coupling: relays for subcortical vasoactive pathways. J Neurosci 2004, 24:8940–8949.

    Article  PubMed  CAS  Google Scholar 

  73. Lacombe P, Sercombe R, Vaucher E, Seylaz J: Reduced cortical vasodilatory response to stimulation of the nucleus basalis of Meynert in the aged rat and evidence for a control of the cerebral circulation. Ann N Y Acad Sci 1997, 826:410–415.

    Article  PubMed  CAS  Google Scholar 

  74. Uchida S, Suzuki A, Kagitani F, Hotta H: Effects of age on cholinergic vasodilation of cortical cerebral blood vessels in rats. Neurosci Lett 2000, 294:109–112.

    Article  PubMed  CAS  Google Scholar 

  75. Lojkowska W, Ryglewicz D, Jedrzejczak T, et al.: The effect of cholinesterase inhibitors on the regional blood flow in patients with Alzheimer’s disease and vascular dementia. J Neurol Sci 2003, 216:119–126.

    Article  PubMed  CAS  Google Scholar 

  76. Erkinjuntti T, Román GC, Gauthier S, et al.: Emerging therapies for vascular dementia and vascular cognitive impairment. Stroke 2004, 35:1010–1017. Recent review of clinical trials using cholinergic agents for the 7symptomatic treatment of VaD.

    Article  PubMed  CAS  Google Scholar 

  77. Román GC, Rogers SJ: Donepezil: a clinical review of current and emerging indications. Expert Opin Pharmacother 2004, 5:161–180.

    Article  PubMed  Google Scholar 

  78. Black S, Román GC, Geldmacher DS, et al.; for the Donepezil 307 Vascular Dementia Study Group: Efficacy and tolerability of donepezil in vascular dementia. Positive results of a 24-week, multicenter, international, randomized, placebocontrolled clinical trial. Stroke 2003, 34:2323–2332.

    Article  PubMed  CAS  Google Scholar 

  79. Wilkinson D, Doody R, Helme R, et al.; for the Donepezil 308 Vascular Dementia Study Group: Donepezil in vascular dementia. A randomized, placebo-controlled study. Neurology 2003, 61:479–486.

    PubMed  CAS  Google Scholar 

  80. Román GC, Tatemichi TK, Erkinjuntti T, et al.: Vascular dementia: diagnostic criteria for research studies. Report of the NINDSAIREN International Workshop. Neurology 1993, 43:250–260.

    PubMed  Google Scholar 

  81. Román GC, Perdomo CA, Pratt RD: Patients with vascular dementia differ from patients with Alzheimer’s disease with respect to population characteristics and pattern of cognitive decline [abstract]. J Gen Int Med 2003, 18(Suppl 1):198–199.

    Google Scholar 

  82. Román GC, Perdomo CA, Pratt RD: Donepezil improves cognition, global function and ability to perform activities of daily living in patients with vascular dementia [abstract]. J Gen Int Med 2003, 18 (Suppl 1):198.

    Google Scholar 

  83. Salloway S, Pratt RD, Perdomo CA, for the Donepezil 307 and 308 Study Groups: A comparison of the cognitive benefits of donepezil in patients with cortical versus subcortical vascular dementia: a subanalysis of two 24-week, randomized, doubleblind, placebo-controlled trials [abstract]. Neurology 2003, 60(Suppl 1):A141-A142.

    Google Scholar 

  84. Malouf R, Birks J: Donepezil for vascular cognitive impairment. Cochrane Database Syst Rev 2004, 1:CD004395. This recent Cochrane review of controlled trials of donepezil in VaD concluded that there is evidence that donepezil improves cognitive function, clinical global impression and activities of daily living in patients with probable or possible mild to moderate VaD after 6 months of treatment.

    PubMed  Google Scholar 

  85. Loy C, Schneider L: Galantamine for Alzheimer’s disease. Cochrane Database Syst Rev 2004, 18:CD001747.

    Google Scholar 

  86. Corey-Bloom J: Galantamine: a review of its use in Alzheimer’s disease and vascular dementia. Int J Clin Practice 2003, 57:219–223.

    CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  88. McKhann G, Drachman D, Folstein M, et al.: Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984, 34:939–944.

    PubMed  CAS  Google Scholar 

  89. Erkinjuntti T, Kurz A, Small GW, et al. for the GAL-INT-6 Study Group: An open-label extension trial of galantamine in patients with probable vascular dementia and mixed dementia. Clin Ther 2003, 25:1765–1782.

    Article  PubMed  CAS  Google Scholar 

  90. 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.

    Article  PubMed  CAS  Google Scholar 

  91. Finkel SI: Effects of rivastigmine on behavioral and psychological symptoms of dementia in Alzheimer’s disease. Clin Ther 2004, 26:980–990.

    Article  PubMed  CAS  Google Scholar 

  92. Darreh-Shori T, Hellstrom-Lindahl E, Flores-Flores C, et al.: Sustained cholinesterase inhibition in AD patients receiving rivastigmine for 12 months. Neurology 2002, 59:563–572.

    PubMed  CAS  Google Scholar 

  93. Moretti R, Torre P, Antonello RM, et al.: Rivastigmine in vascular dementia. Exp Opin Pharmacother 2004, 5:1399–1410.

    Article  CAS  Google Scholar 

  94. Moretti R, Torre P, Antonello RM, Cazzato G: Rivastigmine in subcortical vascular dementia: a comparison trial on efficacy and tolerability for 12 months follow-up. Eur J Neurol 2001, 8:361–362.

    Article  PubMed  CAS  Google Scholar 

  95. Moretti R, Torre P, Antonello RM, et al.: Rivastigmine in subcortical vascular dementia: an open 22-month study. J Neurol Sci 2002, 203:141–146.

    Article  PubMed  Google Scholar 

  96. Kumar V, Anand R, Messina J, et al.: An efficacy and safety analysis of Exelon in Alzheimer’s disease patients with concurrent vascular risk factors. Eur J Neurol 2000, 7:159–169.

    Article  PubMed  CAS  Google Scholar 

  97. Erkinjuntti T, Skoog I, Lane R, Andrews C: Rivastigmine in patients with Alzheimer’s disease and concurrent hypertension. Int J Clin Practice 2002, 56:791–796.

    CAS  Google Scholar 

  98. Erkinjuntti T, Skoog I, Lane R, Andrews C: Potential long-term effects of rivastigmine on disease progression may be linked to drug effects on vascular changes in Alzheimer brains. Int J Clin Practice 2003, 57:756–760.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, University of Texas Health Science Center at San Antonio, 78232, San Antonio, TX, USA

    Gustavo C. Román MD

  2. Department of Neurology, Audie Murphy Veterans Administration Hospital, 78232, San Antonio, TX, USA

    Gustavo C. Román MD

Authors
  1. Gustavo C. Román MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Román, G.C. Cholinergic dysfunction in vascular dementia. Curr Psychiatry Rep 7, 18–26 (2005). https://doi.org/10.1007/s11920-005-0019-2

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11920-005-0019-2

Keywords

Search

Navigation