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Neuroprotection in vascular dementia: A future path

Published:April 03, 2012DOI:https://doi.org/10.1016/j.jns.2012.02.013

      Abstract

      The burden of cognitive disorders is likely to increase over the coming years due to both increased longevity and altered risk factor patterns, arising from changes in lifestyle, healthcare and society. Vascular dementia with its underlying heterogeneous pathology, is a challenge for clinicians, and is frequently further aggravated by overlap with other neurodegenerative processes. Current Alzheimer's disease drugs have had limited clinical efficacy in treating vascular dementia and none have been approved by major regulatory authorities specifically for this disease. Moving forward, a valid choice may be a multimodal therapy, as has already been successfully proven in Alzheimer's disease. Actovegin, a hemodialysate derived from calf blood, has been shown to have effects on a variety of cellular processes and a recent experimental study has revealed its neuroprotective mechanisms of action. These data, coupled with positive results from clinical trials in mixed dementia populations, have served as a foundation for the design of a new trial investigating the efficacy and disease-modifying effects of Actovegin in post-stroke cognitive impairment.

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      References

        • Sacuiu S.
        • Gustafson D.
        • Sjogren M.
        • Guo X.
        • Ostling S.
        • Johansson B.
        • et al.
        Secular changes in cognitive predictors of dementia and mortality in 70-year-olds.
        Neurology. Aug. 31 2010; 75: 779-785
        • Gustafson D.
        • Rothenberg E.
        • Blennow K.
        • Steen B.
        • Skoog I.
        An 18-year follow-up of overweight and risk of Alzheimer disease.
        Arch Intern Med. Jul. 14 2003; 163: 1524-1528
        • Skoog I.
        • Lernfelt B.
        • Landahl S.
        • Palmertz B.
        • Andreasson L.A.
        • Nilsson L.
        • et al.
        15-year longitudinal study of blood pressure and dementia.
        Lancet. Apr. 27 1996; 347: 1141-1145
        • Seliger S.L.
        • Siscovick D.S.
        • Stehman-Breen C.O.
        • Gillen D.L.
        • Fitzpatrick A.
        • Bleyer A.
        • et al.
        Moderate renal impairment and risk of dementia among older adults: the Cardiovascular Health Cognition Study.
        J Am Soc Nephrol. Jul. 2004; 15: 1904-1911
        • Newman A.B.
        • Fitzpatrick A.L.
        • Lopez O.
        • Jackson S.
        • Lyketsos C.
        • Jagust W.
        • et al.
        Dementia and Alzheimer's disease incidence in relationship to cardiovascular disease in the Cardiovascular Health Study cohort.
        J Am Geriatr Soc. Jul. 2005; 53: 1101-1107
        • Mehlig K.
        • Skoog I.
        • Guo X.
        • Schutze M.
        • Gustafson D.
        • Waern M.
        • et al.
        Alcoholic beverages and incidence of dementia: 34-year follow-up of the prospective population study of women in Goteborg.
        Am J Epidemiol. Mar. 15 2008; 167: 684-691
        • Treves T.A.
        • Korczyn A.D.
        Modeling the dementia epidemic.
        CNS Neurosci Ther. Feb. 2012; 18: 175-178
        • United Nations, Department of Economic and Social Affairs, Population Division
        World Population Prospects: The 2010 Revision.
        2011 (2010)
        • Danaei G.
        • Finucane M.M.
        • Lu Y.
        • Singh G.M.
        • Cowan M.J.
        • Paciorek C.J.
        • et al.
        National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants.
        Lancet. Jul. 2 2011; 378: 31-40
        • Danaei G.
        • Finucane M.M.
        • Lin J.K.
        • Singh G.M.
        • Paciorek C.J.
        • Cowan M.J.
        • et al.
        National, regional, and global trends in systolic blood pressure since 1980: systematic analysis of health examination surveys and epidemiological studies with 786 country-years and 5.4 million participants.
        Lancet. Feb. 12 2011; 377: 568-577
        • Farzadfar F.
        • Finucane M.M.
        • Danaei G.
        • Pelizzari P.M.
        • Cowan M.J.
        • Paciorek C.J.
        • et al.
        National, regional, and global trends in serum total cholesterol since 1980: systematic analysis of health examination surveys and epidemiological studies with 321 country-years and 3.0 million participants.
        Lancet. Feb. 12 2011; 377: 578-586
        • Finucane M.M.
        • Stevens G.A.
        • Cowan M.J.
        • Danaei G.
        • Lin J.K.
        • Paciorek C.J.
        • et al.
        National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants.
        Lancet. Feb. 12 2011; 377: 557-567
        • Guo X.
        • Waern M.
        • Sjogren K.
        • Lissner L.
        • Bengtsson C.
        • Bjorkelund C.
        • et al.
        Midlife respiratory function and incidence of Alzheimer's disease: a 29-year longitudinal study in women.
        Neurobiol Aging. Mar. 2007; 28: 343-350
        • Skoog I.
        • Olesen P.J.
        • Blennow K.
        • Palmertz B.
        • Johnson S.C.
        • Bigler E.D.
        Head size may modify the impact of white matter lesions on dementia.
        Neurobiol Aging. Mar. 17 2011; ([Electronic publication ahead of print])
        • Wiederkehr S.
        • Simard M.
        • Fortin C.
        • van Reekum R.
        Comparability of the clinical diagnostic criteria for vascular dementia: a critical review. Part I.
        J Neuropsychiatry Clin Neurosci. 2008; 20: 150-161
        • Hayden K.M.
        • Zandi P.P.
        • Lyketsos C.G.
        • Khachaturian A.S.
        • Bastian L.A.
        • Charoonruk G.
        • et al.
        Vascular risk factors for incident Alzheimer disease and vascular dementia: the Cache County study.
        Alzheimer Dis Assoc Disord. Apr. 2006; 20: 93-100
        • Korczyn A.D.
        • Vakhapova V.
        Is vascular cognitive impairment a useful concept?.
        J Neurol Sci. Dec. 15 2010; 299: 2-4
        • Snowdon D.A.
        • Greiner L.H.
        • Mortimer J.A.
        • Riley K.P.
        • Greiner P.A.
        • Markesbery W.R.
        Brain infarction and the clinical expression of Alzheimer disease. The Nun Study.
        JAMA. Mar. 12 1997; 277: 813-817
        • Barber R.
        • Gholkar A.
        • Scheltens P.
        • Ballard C.
        • McKeith I.G.
        • O'Brien J.T.
        Medial temporal lobe atrophy on MRI in dementia with Lewy bodies.
        Neurology. Apr. 12 1999; 52: 1153-1158
        • Barber R.
        • Scheltens P.
        • Gholkar A.
        • Ballard C.
        • McKeith I.
        • Ince P.
        • et al.
        White matter lesions on magnetic resonance imaging in dementia with Lewy bodies, Alzheimer's disease, vascular dementia, and normal aging.
        J Neurol Neurosurg Psychiatry. Jul. 1999; 67: 66-72
        • Victoroff J.
        • Mack W.J.
        • Lyness S.A.
        • Chui H.C.
        Multicenter clinicopathological correlation in dementia.
        Am J Psychiatry. Oct. 1995; 152: 1476-1484
        • Korczyn A.D.
        Mixed dementia—the most common cause of dementia.
        Ann N Y Acad Sci. Nov. 2002; 977: 129-134
        • Baskys A.
        • Hou A.C.
        Vascular dementia: pharmacological treatment approaches and perspectives.
        Clin Interv Aging. 2007; 2: 327-335
        • Black S.
        • Roman G.C.
        • Geldmacher D.S.
        • Salloway S.
        • Hecker J.
        • Burns A.
        • et al.
        Efficacy and tolerability of donepezil in vascular dementia: positive results of a 24-week, multicenter, international, randomized, placebo-controlled clinical trial.
        Stroke. Oct. 2003; 34: 2323-2330
        • Wilkinson D.
        • Doody R.
        • Helme R.
        • Taubman K.
        • Mintzer J.
        • Kertesz A.
        • et al.
        Donepezil in vascular dementia: a randomized, placebo-controlled study.
        Neurology. Aug. 26 2003; 61: 479-486
        • Roman G.C.
        • Salloway S.
        • Black S.E.
        • Royall D.R.
        • DeCarli C.
        • Weiner M.W.
        • et al.
        Randomized, placebo-controlled, clinical trial of donepezil in vascular dementia: differential effects by hippocampal size.
        Stroke. Jun. 2010; 41: 1213-1221
        • Erkinjuntti T.
        • Kurz A.
        • Gauthier S.
        • Bullock R.
        • Lilienfeld S.
        • Damaraju C.V.
        Efficacy of galantamine in probable vascular dementia and Alzheimer's disease combined with cerebrovascular disease: a randomised trial.
        Lancet. Apr. 13 2002; 359: 1283-1290
        • Auchus A.P.
        • Brashear H.R.
        • Salloway S.
        • Korczyn A.D.
        • De Deyn P.P.
        • Gassmann-Mayer C.
        Galantamine treatment of vascular dementia: a randomized trial.
        Neurology. Jul. 31 2007; 69: 448-458
        • Orgogozo J.M.
        • Rigaud A.S.
        • Stoffler A.
        • Mobius H.J.
        • Forette F.
        Efficacy and safety of memantine in patients with mild to moderate vascular dementia: a randomized, placebo-controlled trial (MMM 300).
        Stroke. Jul. 2002; 33: 1834-1839
        • Wilcock G.
        • Mobius H.J.
        • Stoffler A.
        A double-blind, placebo-controlled multicentre study of memantine in mild to moderate vascular dementia (MMM500).
        Int Clin Psychopharmacol. Nov. 2002; 17: 297-305
        • Jones R.W.
        Dimebon disappointment.
        Alzheimers Res Ther. 2010; 2: 25
        • Samadi H.
        • Sultzer D.
        Solanezumab for Alzheimer's disease.
        Expert Opin Biol Ther. Jun. 2011; 11: 787-798
        • Kerchner G.A.
        • Boxer A.L.
        Bapineuzumab.
        Expert Opin Biol Ther. Jul. 2010; 10: 1121-1130
        • Tariot P.N.
        • Farlow M.R.
        • Grossberg G.T.
        • Graham S.M.
        • McDonald S.
        • Gergel I.
        Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial.
        JAMA. Jan. 21 2004; 291: 317-324
        • Guekht A.B.
        • Moessler H.
        • Novak P.H.
        • Gusev E.I.
        Cerebrolysin in vascular dementia: improvement of clinical outcome in a randomized, double-blind, placebo-controlled multicenter trial.
        J Stroke Cerebrovasc Dis. Jul. 2011; 20: 310-318
        • Ortega G.
        • Jacas C.
        • Quintana M.
        • Ribó M.
        • Santamarina E.
        • Maisterra O.
        • et al.
        Citicoline treatment prevents neurocognitive decline after a first ischemic stroke.
        Cerebrovasc Dis. 2010; 29
        • Herrmann W.M.
        • Bohn-Olszewsky W.J.
        • Kuntz G.
        Actovegin infusion treatment in patients with primarily degenerative dementia of the Alzheimer type and multi-infarct dementia.
        Z Geriatr. 1992; 5: 46-55
        • Kanowski S.
        • Kinzler E.
        • Lehmann E.
        • Schweizer A.
        • Kuntz G.
        Confirmed clinical efficacy of actovegin in elderly patients with organic brain syndrome.
        Pharmacopsychiatry. Jul. 1995; 28: 125-133
        • Parade D.
        • Biro G.
        • Ketti H.
        Studies on the insulin-like action of a low molecular-weight blood extract on the glucose metabolism of isolated adipose tissue of the rat in vitro.
        Arzneimittel-Forschung/Drug Res. 1968; 18: 1019-1021
        • Jaeger K.H.
        • Leybold K.
        • Mittenzwei H.
        • Staudinger H.
        • von Waldstatten L.
        Promotion of cell respiration by a blood extract.
        Arzneimittelforschung. Jul. 1965; 15: 750-754
        • de Groot H.
        • Brecht M.
        • Machicao F.
        Evidence for a factor protective against hypoxic liver parenchymal cell injury in a protein-free blood extract.
        Res Commun Chem Pathol Pharmacol. Apr. 1990; 68: 125-128
        • Mochida H.
        • Kikuchi T.
        • Tanaka H.
        • Ikeda A.
        • Fujii Y.
        • Sasamura T.
        • et al.
        Influence of actovegin containing infusion solutions on wound healing and function of the intestinal tract in rats.
        Pharmacol Ther. 1989; 17: 789-797
        • Tamou S.
        • Trott K.R.
        Modification of late radiation damage in the rectum of rats by deproteinized calf blood serum (ActoHorm) and pentoxifylline (PTX).
        Strahlenther Onkol. Jul. 1994; 170: 415-420
        • Elmlinger M.W.
        • Kriebel M.
        • Ziegler D.
        Neuroprotective and anti-oxidative effects of the hemodialysate actovegin on primary rat neurons in vitro.
        Neuromolecular Med. Dec. 2011; 13: 266-274
        • Shamalov N.A.
        • Stakhovskaia L.V.
        • Shetova I.M.
        • Efremova N.M.
        • Anisimov K.V.
        Efficacy and safety of the combined therapy with citicholine and actovegin in the acute period of ischemic stroke.
        Zh Nevrol Psikhiatr Im S S Korsakova. 2010; 110: 13-17