Skip to main content
Erschienen in: Drugs 15/2011

01.10.2011 | Review Article

Current and Emerging Drug Treatment Options for Alzheimer’s Disease

A Systematic Review

verfasst von: Nathan Herrmann, Sarah A. Chau, Ida Kircanski, Dr Krista L. Lanctôt

Erschienen in: Drugs | Ausgabe 15/2011

Einloggen, um Zugang zu erhalten

Abstract

Alzheimer’s disease (AD) is a progressive and ultimately fatal condition that causes debilitating memory loss and extensive deterioration of cognitive and functional abilities. Currently available treatments for AD (donepezil, rivastigmine, galantamine and memantine) are symptomatic and do not decelerate or prevent the progression of the disease. These therapies demonstrate modest, but particularly consistent, benefit for cognition, global status and functional ability. The search for disease-modifying interventions has focused largely on compounds targeting the amyloid-β pathway. To date, the treatments targeting this pathway, such as tramiprosate and semagacestat, have been unsuccessful in demonstrating efficacy in clinical stages of testing. At this point, it is likely that not only amyloid-β aggregation but other possible neuronal mechanisms — such as hyperphosphorylated tau, neuro-inflammation and other processes — play important roles in the pathophysiology of this multifactorial disorder. Development of better disease models and biomarkers is essential for the advancement of knowledge of the disease mechanisms. This systematic review critically examines the efficacy and safety data for currently approved drugs and emerging treatments in AD, as well as discussing the present and future directions of innovation in this field.
Literatur
1.
Zurück zum Zitat Alzheimer’s Association. 2011 Alzheimer’s disease facts and figures. Alzheimers Dement 2011 Mar; 7(2): 208–44CrossRef Alzheimer’s Association. 2011 Alzheimer’s disease facts and figures. Alzheimers Dement 2011 Mar; 7(2): 208–44CrossRef
2.
Zurück zum Zitat Birks J, Grimley E, Iakovidou V, et al. Rivastigmine for Alzheimer’s disease. Cochrane Database Syst Rev 2009 Apr; (2): CD001191 Birks J, Grimley E, Iakovidou V, et al. Rivastigmine for Alzheimer’s disease. Cochrane Database Syst Rev 2009 Apr; (2): CD001191
3.
Zurück zum Zitat Brookmeyer R, Johnson E, Ziegler-Graham K, et al. Forecasting the global burden of Alzheimer’s disease. Alzheimers Dement 2007 Jul; 3(3): 186–91PubMedCrossRef Brookmeyer R, Johnson E, Ziegler-Graham K, et al. Forecasting the global burden of Alzheimer’s disease. Alzheimers Dement 2007 Jul; 3(3): 186–91PubMedCrossRef
4.
Zurück zum Zitat Ferri CP, Prince M, Brayne C, et al. Global prevalence of dementia: a Delphi consensus study. Lancet 2005 Dec 17; 366(9503): 2112–7PubMedCrossRef Ferri CP, Prince M, Brayne C, et al. Global prevalence of dementia: a Delphi consensus study. Lancet 2005 Dec 17; 366(9503): 2112–7PubMedCrossRef
6.
7.
Zurück zum Zitat Jost BC, Grossberg GT. The natural history of Alzheimer’s disease: a brain bank study. J Am Geriatr Soc 1995 Nov; 43(11): 1248–55PubMed Jost BC, Grossberg GT. The natural history of Alzheimer’s disease: a brain bank study. J Am Geriatr Soc 1995 Nov; 43(11): 1248–55PubMed
8.
Zurück zum Zitat Cappell J, Herrmann N, Cornish S, et al. The pharmaco-economics of cognitive enhancers in moderate to severe Alzheimer’s disease. CNS Drugs 2010 Nov 1; 24(11): 909–27PubMedCrossRef Cappell J, Herrmann N, Cornish S, et al. The pharmaco-economics of cognitive enhancers in moderate to severe Alzheimer’s disease. CNS Drugs 2010 Nov 1; 24(11): 909–27PubMedCrossRef
9.
Zurück zum Zitat Knapp M, Knopman D, Solomon P, et al. A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer’s disease. The Tacrine Study Group. JAMA 1994 Apr 6; 271(13): 985–91 Knapp M, Knopman D, Solomon P, et al. A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer’s disease. The Tacrine Study Group. JAMA 1994 Apr 6; 271(13): 985–91
10.
Zurück zum Zitat Watkins P, Zimmerman H, Knapp M, et al. Hepatotoxic effects of tacrine administration in patients with Alzheimer’s disease. JAMA 1994 Apr; 271(13): 992–8PubMedCrossRef Watkins P, Zimmerman H, Knapp M, et al. Hepatotoxic effects of tacrine administration in patients with Alzheimer’s disease. JAMA 1994 Apr; 271(13): 992–8PubMedCrossRef
11.
Zurück zum Zitat Blackard WJ, Sood G, Crowe D, et al. Tacrine: a cause of fatal hepatotoxicity? J Clin Gastroenterol 1998 Jan; 26(1): 57–9PubMedCrossRef Blackard WJ, Sood G, Crowe D, et al. Tacrine: a cause of fatal hepatotoxicity? J Clin Gastroenterol 1998 Jan; 26(1): 57–9PubMedCrossRef
12.
Zurück zum Zitat McGleenon B, Dynan K, Passmore A. Acetylcholinesterase inhibitors in Alzheimer’s disease. Br J Clin Pharmacol 1999 Oct; 48(4): 471–80PubMedCrossRef McGleenon B, Dynan K, Passmore A. Acetylcholinesterase inhibitors in Alzheimer’s disease. Br J Clin Pharmacol 1999 Oct; 48(4): 471–80PubMedCrossRef
13.
Zurück zum Zitat Birks J. Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev 2006 Jan; (1): CD005593 Birks J. Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev 2006 Jan; (1): CD005593
14.
Zurück zum Zitat McShane R, Areosa Sastre A, Minakaran N. Memantine for dementia. Cochrane Database Syst Rev 2006 Apr 19; (2): CD003154 McShane R, Areosa Sastre A, Minakaran N. Memantine for dementia. Cochrane Database Syst Rev 2006 Apr 19; (2): CD003154
15.
Zurück zum Zitat Hogan D, Patterson C. Progress in clinical neurosciences: treatment of Alzheimer’s disease and other dementias. Review and comparison of the cholinesterase inhibitors. Can J Neurol Sci 2002 Nov; 29(4): 306–14 Hogan D, Patterson C. Progress in clinical neurosciences: treatment of Alzheimer’s disease and other dementias. Review and comparison of the cholinesterase inhibitors. Can J Neurol Sci 2002 Nov; 29(4): 306–14
16.
Zurück zum Zitat Hogan D, Goldlist B, Naglie G, et al. Comparison studies of cholinesterase inhibitors for Alzheimer’s disease. Lancet Neurol 2004 Oct; 3(10): 622–6PubMedCrossRef Hogan D, Goldlist B, Naglie G, et al. Comparison studies of cholinesterase inhibitors for Alzheimer’s disease. Lancet Neurol 2004 Oct; 3(10): 622–6PubMedCrossRef
17.
Zurück zum Zitat Modrego P, Fayed N, Errea J, et al. Memantine versus donepezil in mild to moderate Alzheimer’s disease: a randomized trial with magnetic resonance spectroscopy. Eur J Neurol 2010 Mar; 17(3): 405–12PubMedCrossRef Modrego P, Fayed N, Errea J, et al. Memantine versus donepezil in mild to moderate Alzheimer’s disease: a randomized trial with magnetic resonance spectroscopy. Eur J Neurol 2010 Mar; 17(3): 405–12PubMedCrossRef
18.
Zurück zum Zitat Terry RD, Gonatas NK, Weiss M. Ultrastructural studies in Alzheimer’s presenile dementia. Am J Pathol 1964 Feb; 44: 269–97PubMed Terry RD, Gonatas NK, Weiss M. Ultrastructural studies in Alzheimer’s presenile dementia. Am J Pathol 1964 Feb; 44: 269–97PubMed
19.
Zurück zum Zitat Blessed G, Tomlinson BE, Roth M. The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Br J Psychiatry 1968 Jul; 114(512): 797–811PubMedCrossRef Blessed G, Tomlinson BE, Roth M. The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Br J Psychiatry 1968 Jul; 114(512): 797–811PubMedCrossRef
20.
Zurück zum Zitat American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 2000 American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 2000
21.
Zurück zum Zitat McKhann G, Drachman D, Folstein M, et al. Clinical diagnosis of Alzheimer’s disease: report of the NINCDSADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984; 34: 939–44PubMedCrossRef McKhann G, Drachman D, Folstein M, et al. Clinical diagnosis of Alzheimer’s disease: report of the NINCDSADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984; 34: 939–44PubMedCrossRef
22.
Zurück zum Zitat World Health Organization. The tenth revision of the international classification of diseases and relative health problems (ICD-10). Geneva: WHO, 1992 World Health Organization. The tenth revision of the international classification of diseases and relative health problems (ICD-10). Geneva: WHO, 1992
23.
Zurück zum Zitat Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg 2010; 8(5): 336–4 [online]. Available from URL: http://www.prisma-statement.org/ statement.htm [Accessed 2011 Mar 22]PubMedCrossRef Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg 2010; 8(5): 336–4 [online]. Available from URL: http://​www.​prisma-statement.​org/​ statement.htm [Accessed 2011 Mar 22]PubMedCrossRef
25.
Zurück zum Zitat Mangialasche F, Solomon A, Winblad B, et al. Alzheimer’s disease: clinical trials and drug development. Lancet Neurol 2010 Jul; 9(7): 702–16PubMedCrossRef Mangialasche F, Solomon A, Winblad B, et al. Alzheimer’s disease: clinical trials and drug development. Lancet Neurol 2010 Jul; 9(7): 702–16PubMedCrossRef
26.
Zurück zum Zitat Perry E, Tomlinson B, Blessed G, et al. Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med J 1978 Nov; 2(6150): 1457–9PubMedCrossRef Perry E, Tomlinson B, Blessed G, et al. Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med J 1978 Nov; 2(6150): 1457–9PubMedCrossRef
27.
Zurück zum Zitat Sims N, Bowen D, Allen S, et al. Presynaptic cholinergic dysfunction in patients with dementia. J Neurochem 1983 Feb; 40(2): 503–9PubMedCrossRef Sims N, Bowen D, Allen S, et al. Presynaptic cholinergic dysfunction in patients with dementia. J Neurochem 1983 Feb; 40(2): 503–9PubMedCrossRef
28.
Zurück zum Zitat Bassil N, Grossberg G. Novel regimens and delivery systems in the pharmacological treatment of Alzheimer’s disease. CNS Drugs 2009; 23(4): 293–307PubMedCrossRef Bassil N, Grossberg G. Novel regimens and delivery systems in the pharmacological treatment of Alzheimer’s disease. CNS Drugs 2009; 23(4): 293–307PubMedCrossRef
29.
Zurück zum Zitat Kosasa T, Kuriya Y, Matsui K, et al. Inhibitory effect of orally administered donepezil hydrochloride (E2020), a novel treatment for Alzheimer’s disease, on cholinesterase activity in rats. Eur J Pharmacol 2000 Feb; 389(2–3): 173–9PubMedCrossRef Kosasa T, Kuriya Y, Matsui K, et al. Inhibitory effect of orally administered donepezil hydrochloride (E2020), a novel treatment for Alzheimer’s disease, on cholinesterase activity in rats. Eur J Pharmacol 2000 Feb; 389(2–3): 173–9PubMedCrossRef
30.
31.
Zurück zum Zitat Nordberg A. Mechanisms behind the neuroprotective actions of cholinesterase inhibitors in Alzheimer disease. Alzheimer Dis Assoc Disord 2006 Apr–Jun; 20 (2 Suppl. 1): S12–8PubMedCrossRef Nordberg A. Mechanisms behind the neuroprotective actions of cholinesterase inhibitors in Alzheimer disease. Alzheimer Dis Assoc Disord 2006 Apr–Jun; 20 (2 Suppl. 1): S12–8PubMedCrossRef
32.
Zurück zum Zitat Li J, Wu H, Zhou R, et al. Huperzine A for Alzheimer’s disease. Cochrane Database Syst Rev 2008 Apr; 16 (2): CD005592 Li J, Wu H, Zhou R, et al. Huperzine A for Alzheimer’s disease. Cochrane Database Syst Rev 2008 Apr; 16 (2): CD005592
33.
Zurück zum Zitat Rafii MS, Walsh S, Little JT, et al. A phase II trial of huperzine A in mild to moderate Alzheimer disease. Neurology 2011 Apr 19; 76(16): 1389–94PubMedCrossRef Rafii MS, Walsh S, Little JT, et al. A phase II trial of huperzine A in mild to moderate Alzheimer disease. Neurology 2011 Apr 19; 76(16): 1389–94PubMedCrossRef
35.
Zurück zum Zitat Winblad B. Donepezil in severe Alzheimer’s disease. Am J Alzheimers Dis Other Demen 2009 Jun–Jul; 24(3): 185–92PubMedCrossRef Winblad B. Donepezil in severe Alzheimer’s disease. Am J Alzheimers Dis Other Demen 2009 Jun–Jul; 24(3): 185–92PubMedCrossRef
36.
Zurück zum Zitat Pfizer Canada Inc. Aricept/AriceptRDT product monograph [online]. Available from URL: http://www.pfizer. ca/en/our_products/products/product/122 [Accessed 2011 Jun 23] Pfizer Canada Inc. Aricept/AriceptRDT product monograph [online]. Available from URL: http://​www.​pfizer.​ ca/en/our_products/products/product/122 [Accessed 2011 Jun 23]
37.
Zurück zum Zitat Farlow MR, Salloway S, Tariot PN, et al. Effectiveness and tolerability of high-dose (23 mg/d) versus standard-dose (10mg/d) donepezil in moderate to severe Alzheimer’s disease: a 24-week, randomized, double-blind study. Clin Ther 2010 Jul; 32(7): 1234–51PubMedCrossRef Farlow MR, Salloway S, Tariot PN, et al. Effectiveness and tolerability of high-dose (23 mg/d) versus standard-dose (10mg/d) donepezil in moderate to severe Alzheimer’s disease: a 24-week, randomized, double-blind study. Clin Ther 2010 Jul; 32(7): 1234–51PubMedCrossRef
38.
Zurück zum Zitat Di Stefano A, Iannitelli A, Laserra S, et al. Drug delivery strategies for Alzheimer’s disease treatment. Expert Opin Drug Deliv 2011; 8(5): 581–603PubMedCrossRef Di Stefano A, Iannitelli A, Laserra S, et al. Drug delivery strategies for Alzheimer’s disease treatment. Expert Opin Drug Deliv 2011; 8(5): 581–603PubMedCrossRef
39.
Zurück zum Zitat Mayeux R, Sano M. Treatment of Alzheimer’s disease. N Engl J Med 1999 Nov; 341(22): 1670–9PubMedCrossRef Mayeux R, Sano M. Treatment of Alzheimer’s disease. N Engl J Med 1999 Nov; 341(22): 1670–9PubMedCrossRef
40.
Zurück zum Zitat Takada Y, Yonezawa A, Kume T, et al. Nicotinic acetylcholine receptor-mediated neuroprotection by donepezil against glutamate neurotoxicity in rat cortical neurons. J Pharmacol Exp Ther 2003 Aug; 306(2): 772–7PubMedCrossRef Takada Y, Yonezawa A, Kume T, et al. Nicotinic acetylcholine receptor-mediated neuroprotection by donepezil against glutamate neurotoxicity in rat cortical neurons. J Pharmacol Exp Ther 2003 Aug; 306(2): 772–7PubMedCrossRef
41.
Zurück zum Zitat Birks J, Harvey R. Donepezil for dementia due to Alzheimer’s disease. Cochrane Database Syst Rev 2006 Jan; 25 (1): CD001190 Birks J, Harvey R. Donepezil for dementia due to Alzheimer’s disease. Cochrane Database Syst Rev 2006 Jan; 25 (1): CD001190
42.
Zurück zum Zitat Raina P, Santaguida P, Ismaila A, et al. Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline. Ann Intern Med 2008 Mar; 148(5): 379–97PubMed Raina P, Santaguida P, Ismaila A, et al. Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline. Ann Intern Med 2008 Mar; 148(5): 379–97PubMed
43.
Zurück zum Zitat Hansen R, Gartlehner G, Webb A, et al. Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer’s disease: a systematic review and meta-analysis. Clin Interv Aging 2008; 3(2): 211–25PubMed Hansen R, Gartlehner G, Webb A, et al. Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer’s disease: a systematic review and meta-analysis. Clin Interv Aging 2008; 3(2): 211–25PubMed
44.
Zurück zum Zitat Ritchie C, Ames D, Clayton T, et al. Metaanalysis of randomized trials of the efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer disease. Am J Geriatr Psychiatry 2004 Jul–Aug; 12(4): 358–69PubMed Ritchie C, Ames D, Clayton T, et al. Metaanalysis of randomized trials of the efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer disease. Am J Geriatr Psychiatry 2004 Jul–Aug; 12(4): 358–69PubMed
45.
Zurück zum Zitat Loy C, Schneider L. Galantamine for Alzheimer’s disease and mild cognitive impairment. Cochrane Database Syst Rev 2006 Jan; 25 (1): CD001747 Loy C, Schneider L. Galantamine for Alzheimer’s disease and mild cognitive impairment. Cochrane Database Syst Rev 2006 Jan; 25 (1): CD001747
46.
Zurück zum Zitat Campbell N, Ayub A, Boustani M, et al. Impact of cholinesterase inhibitors on behavioral and psychological symptoms of Alzheimer’s disease: a meta-analysis. Clin Interv Aging 2008; 3(4): 719–28PubMed Campbell N, Ayub A, Boustani M, et al. Impact of cholinesterase inhibitors on behavioral and psychological symptoms of Alzheimer’s disease: a meta-analysis. Clin Interv Aging 2008; 3(4): 719–28PubMed
47.
Zurück zum Zitat Hansen R, Gartlehner G, Lohr K, et al. Functional outcomes of drug treatment in Alzheimer’s disease: a systematic review and meta-analysis. Drugs Aging 2007; 24(2): 155–67PubMedCrossRef Hansen R, Gartlehner G, Lohr K, et al. Functional outcomes of drug treatment in Alzheimer’s disease: a systematic review and meta-analysis. Drugs Aging 2007; 24(2): 155–67PubMedCrossRef
48.
Zurück zum Zitat Harry R, Zakzanis K. A comparison of donepezil and galantamine in the treatment of cognitive symptoms of Alzheimer’s disease: a meta-analysis. Hum Psychopharmacol 2005 Apr; 20(3): 183–7PubMedCrossRef Harry R, Zakzanis K. A comparison of donepezil and galantamine in the treatment of cognitive symptoms of Alzheimer’s disease: a meta-analysis. Hum Psychopharmacol 2005 Apr; 20(3): 183–7PubMedCrossRef
49.
Zurück zum Zitat Lanctôt K, Herrmann N, Yau K, et al. Efficacy and safety of cholinesterase inhibitors in Alzheimer’s disease: a meta-analysis. CMAJ 2003 Sep; 169(6): 557–64PubMed Lanctôt K, Herrmann N, Yau K, et al. Efficacy and safety of cholinesterase inhibitors in Alzheimer’s disease: a meta-analysis. CMAJ 2003 Sep; 169(6): 557–64PubMed
50.
Zurück zum Zitat Schneider LS, Dagerman KS, Higgins JP, et al. Lack of evidence for the efficacy of memantine in mild Alzheimer disease. Arch Neurol. Epub 2011 Apr 11 Schneider LS, Dagerman KS, Higgins JP, et al. Lack of evidence for the efficacy of memantine in mild Alzheimer disease. Arch Neurol. Epub 2011 Apr 11
51.
Zurück zum Zitat Maidment I, Fox C, Boustani M, et al. Efficacy of memantine on behavioral and psychological symptoms related to dementia: a systematic meta-analysis. Ann Pharmacother 2008 Jan; 42(1): 32–8PubMed Maidment I, Fox C, Boustani M, et al. Efficacy of memantine on behavioral and psychological symptoms related to dementia: a systematic meta-analysis. Ann Pharmacother 2008 Jan; 42(1): 32–8PubMed
52.
Zurück zum Zitat Doody R, Tariot P, Pfeiffer E, et al. Meta-analysis of six-month memantine trials in Alzheimer’s disease. Alzheimers Dement 2007 Jan; 3(1): 7–17PubMedCrossRef Doody R, Tariot P, Pfeiffer E, et al. Meta-analysis of six-month memantine trials in Alzheimer’s disease. Alzheimers Dement 2007 Jan; 3(1): 7–17PubMedCrossRef
53.
Zurück zum Zitat Winblad B, Jones R, Wirth Y, et al. Memantine in moderate to severe Alzheimer’s disease: a meta-analysis of randomised clinical trials. Dement Geriatr Cogn Disord 2007; 24(1): 20–7PubMedCrossRef Winblad B, Jones R, Wirth Y, et al. Memantine in moderate to severe Alzheimer’s disease: a meta-analysis of randomised clinical trials. Dement Geriatr Cogn Disord 2007; 24(1): 20–7PubMedCrossRef
54.
Zurück zum Zitat Wei ZH, He QB, Wang H, et al. Meta-analysis: the efficacy of nootropic agent Cerebrolysin in the treatment of Alzheimer’s disease. J Neural Transm 2007; 114(5): 629–34PubMedCrossRef Wei ZH, He QB, Wang H, et al. Meta-analysis: the efficacy of nootropic agent Cerebrolysin in the treatment of Alzheimer’s disease. J Neural Transm 2007; 114(5): 629–34PubMedCrossRef
55.
Zurück zum Zitat Wilcock G, Howe I, Coles H, et al. A long-term comparison of galantamine and donepezil in the treatment of Alzheimer’s disease. Drugs Aging 2003; 20(10): 777–89PubMedCrossRef Wilcock G, Howe I, Coles H, et al. A long-term comparison of galantamine and donepezil in the treatment of Alzheimer’s disease. Drugs Aging 2003; 20(10): 777–89PubMedCrossRef
56.
Zurück zum Zitat Jones R, Soininen H, Hager K, et al. A multinational, randomised, 12-week study comparing the effects of donepezil and galantamine in patients with mild to moderate Alzheimer’s disease. Int J Geriatr Psychiatry 2004 Jan; 19(1): 58–67PubMedCrossRef Jones R, Soininen H, Hager K, et al. A multinational, randomised, 12-week study comparing the effects of donepezil and galantamine in patients with mild to moderate Alzheimer’s disease. Int J Geriatr Psychiatry 2004 Jan; 19(1): 58–67PubMedCrossRef
57.
Zurück zum Zitat Bullock R, Touchon J, Bergman H, et al. Rivastigmine and donepezil treatment in moderate to moderately-severe Alzheimer’s disease over a 2-year period. Curr Med Res Opin 2005 Aug; 21(8): 1317–27PubMedCrossRef Bullock R, Touchon J, Bergman H, et al. Rivastigmine and donepezil treatment in moderate to moderately-severe Alzheimer’s disease over a 2-year period. Curr Med Res Opin 2005 Aug; 21(8): 1317–27PubMedCrossRef
58.
Zurück zum Zitat Wilkinson D, Passmore A, Bullock R, et al. A multinational, randomised, 12-week, comparative study of donepezil and rivastigmine in patients with mild to moderate Alzheimer’s disease. Int J Clin Pract 2002 Jul–Aug; 56(6): 441–6PubMed Wilkinson D, Passmore A, Bullock R, et al. A multinational, randomised, 12-week, comparative study of donepezil and rivastigmine in patients with mild to moderate Alzheimer’s disease. Int J Clin Pract 2002 Jul–Aug; 56(6): 441–6PubMed
59.
Zurück zum Zitat Courtney C, Farrell D, Gray R, et al. Long-term donepezil treatment in 565 patients with Alzheimer’s disease (AD2000): randomised double-blind trial. Lancet Neurol 2004 Jun; 363(9427): 2105–15 Courtney C, Farrell D, Gray R, et al. Long-term donepezil treatment in 565 patients with Alzheimer’s disease (AD2000): randomised double-blind trial. Lancet Neurol 2004 Jun; 363(9427): 2105–15
60.
Zurück zum Zitat Standridge JB. Donepezil did not reduce the rate of institutionalisation or disability in people with mild to moderate Alzheimer’s disease. Evid Based Ment Health 2004 Nov; 7(4): 112PubMedCrossRef Standridge JB. Donepezil did not reduce the rate of institutionalisation or disability in people with mild to moderate Alzheimer’s disease. Evid Based Ment Health 2004 Nov; 7(4): 112PubMedCrossRef
61.
Zurück zum Zitat Black SE, Szalai JP. Are there long-term benefits of donepezil in Alzheimer’s disease? CMAJ 2004 Nov 9; 171(10): 1174–5PubMedCrossRef Black SE, Szalai JP. Are there long-term benefits of donepezil in Alzheimer’s disease? CMAJ 2004 Nov 9; 171(10): 1174–5PubMedCrossRef
62.
Zurück zum Zitat Holmes C, Burns A, Passmore P, et al. AD2000: design and conclusions. Lancet 2004 Oct 2–8; 364(9441): 1213–4; author reply 6-7PubMedCrossRef Holmes C, Burns A, Passmore P, et al. AD2000: design and conclusions. Lancet 2004 Oct 2–8; 364(9441): 1213–4; author reply 6-7PubMedCrossRef
63.
Zurück zum Zitat Akintade L, Zaiac M, Ieni JR, et al. AD2000: design and conclusions. Lancet 2004 Oct 2–8; 364(9441): 1214; author reply 6-7PubMedCrossRef Akintade L, Zaiac M, Ieni JR, et al. AD2000: design and conclusions. Lancet 2004 Oct 2–8; 364(9441): 1214; author reply 6-7PubMedCrossRef
64.
Zurück zum Zitat Howe I. AD2000: design and conclusions. Lancet 2004 Oct 2–8; 364(9441): 1214–5; author reply 6-7PubMedCrossRef Howe I. AD2000: design and conclusions. Lancet 2004 Oct 2–8; 364(9441): 1214–5; author reply 6-7PubMedCrossRef
65.
Zurück zum Zitat Clarke N. AD2000: design and conclusions. Lancet 2004 Oct 2–8; 364(9441): 1215–6; author reply 6-7PubMedCrossRef Clarke N. AD2000: design and conclusions. Lancet 2004 Oct 2–8; 364(9441): 1215–6; author reply 6-7PubMedCrossRef
66.
Zurück zum Zitat Schneider LS. AD2000: donepezil in Alzheimer’s disease. Lancet 2004 Jun 26; 363(9427): 2100–1PubMedCrossRef Schneider LS. AD2000: donepezil in Alzheimer’s disease. Lancet 2004 Jun 26; 363(9427): 2100–1PubMedCrossRef
67.
Zurück zum Zitat Holmes C, Wilkinson D, Dean C, et al. The efficacy of donepezil in the treatment of neuropsychiatric symptoms in Alzheimer disease. Neurology 2004 Jul; 63(2): 214–9PubMedCrossRef Holmes C, Wilkinson D, Dean C, et al. The efficacy of donepezil in the treatment of neuropsychiatric symptoms in Alzheimer disease. Neurology 2004 Jul; 63(2): 214–9PubMedCrossRef
68.
Zurück zum Zitat Ballard C, Brown R, Fossey J, et al. Brief psychosocial therapy for the treatment of agitation in Alzheimer disease (the CALM-AD trial). Am J Geriatr Psychiatry 2009 Sep; 17(9): 726–33PubMedCrossRef Ballard C, Brown R, Fossey J, et al. Brief psychosocial therapy for the treatment of agitation in Alzheimer disease (the CALM-AD trial). Am J Geriatr Psychiatry 2009 Sep; 17(9): 726–33PubMedCrossRef
69.
Zurück zum Zitat Howard R, Juszczak E, Ballard C, et al. Donepezil for the treatment of agitation in Alzheimer’s disease. N Engl J Med 2007 Oct; 357(14): 1382–92PubMedCrossRef Howard R, Juszczak E, Ballard C, et al. Donepezil for the treatment of agitation in Alzheimer’s disease. N Engl J Med 2007 Oct; 357(14): 1382–92PubMedCrossRef
70.
Zurück zum Zitat Polinsky R. Clinical pharmacology of rivastigmine: a new-generation acetylcholinesterase inhibitor for the treatment of Alzheimer’s disease. Clin Ther 1998 Jul–Aug; 20(4): 634–47PubMedCrossRef Polinsky R. Clinical pharmacology of rivastigmine: a new-generation acetylcholinesterase inhibitor for the treatment of Alzheimer’s disease. Clin Ther 1998 Jul–Aug; 20(4): 634–47PubMedCrossRef
71.
Zurück zum Zitat Farlow M, Small G, Quarg P, et al. Efficacy of rivastigmine in Alzheimer’s disease patients with rapid disease progression: results of a meta-analysis. Dement Geriatr Cogn Disord 2005; 20(2–3): 192–7PubMedCrossRef Farlow M, Small G, Quarg P, et al. Efficacy of rivastigmine in Alzheimer’s disease patients with rapid disease progression: results of a meta-analysis. Dement Geriatr Cogn Disord 2005; 20(2–3): 192–7PubMedCrossRef
72.
Zurück zum Zitat Crawford J. Alzheimer’s disease risk factors as related to cerebral blood flow: additional evidence. Med Hypotheses 1998 Jan; 50(1): 25–36PubMedCrossRef Crawford J. Alzheimer’s disease risk factors as related to cerebral blood flow: additional evidence. Med Hypotheses 1998 Jan; 50(1): 25–36PubMedCrossRef
74.
Zurück zum Zitat Cummings JL, Farlow MR, Meng X, et al. Rivastigmine transdermal patch skin tolerability: results of a 1-year clinical trial in patients with mild-to-moderate Alzheimer’s disease. Clin Drug Invest 2010; 30(1): 41–9CrossRef Cummings JL, Farlow MR, Meng X, et al. Rivastigmine transdermal patch skin tolerability: results of a 1-year clinical trial in patients with mild-to-moderate Alzheimer’s disease. Clin Drug Invest 2010; 30(1): 41–9CrossRef
75.
Zurück zum Zitat Emre M, Bernabei R, Blesa R, et al. Drug profile: transdermal rivastigmine patch in the treatment of Alzheimer disease. CNS Neurosci Ther 2010 Aug; 16(4): 246–53PubMedCrossRef Emre M, Bernabei R, Blesa R, et al. Drug profile: transdermal rivastigmine patch in the treatment of Alzheimer disease. CNS Neurosci Ther 2010 Aug; 16(4): 246–53PubMedCrossRef
76.
Zurück zum Zitat Shimohama S. Nicotinic receptor-mediated neuroprotection in neurodegenerative disease models. Biol Pharm Bull 2009 Mar; 32(3): 332–6PubMedCrossRef Shimohama S. Nicotinic receptor-mediated neuroprotection in neurodegenerative disease models. Biol Pharm Bull 2009 Mar; 32(3): 332–6PubMedCrossRef
77.
Zurück zum Zitat Razay G, Wilcock G. Galantamine in Alzheimer’s disease. Expert Rev Neurother 2008 Jan; 8(1): 9–17PubMedCrossRef Razay G, Wilcock G. Galantamine in Alzheimer’s disease. Expert Rev Neurother 2008 Jan; 8(1): 9–17PubMedCrossRef
78.
Zurück zum Zitat Seltzer B. Galantamine-ER for the treatment of mild-to-moderate Alzheimer’s disease. Clin Interv Aging 2010 Feb 5: 1–6PubMed Seltzer B. Galantamine-ER for the treatment of mild-to-moderate Alzheimer’s disease. Clin Interv Aging 2010 Feb 5: 1–6PubMed
79.
Zurück zum Zitat Kaduszkiewicz H, Zimmermann T, Beck-Bornholdt H, et al. Cholinesterase inhibitors for patients with Alzheimer’s disease: systematic review of randomised clinical trials. BMJ 2005 Aug; 331(7512): 321–7PubMedCrossRef Kaduszkiewicz H, Zimmermann T, Beck-Bornholdt H, et al. Cholinesterase inhibitors for patients with Alzheimer’s disease: systematic review of randomised clinical trials. BMJ 2005 Aug; 331(7512): 321–7PubMedCrossRef
80.
Zurück zum Zitat Herrmann N. Trials and tribulations of evidence-based medicine: the case of Alzheimer disease therapeutics. Can J Psychiatry 2007 Oct; 52(10): 617–9PubMed Herrmann N. Trials and tribulations of evidence-based medicine: the case of Alzheimer disease therapeutics. Can J Psychiatry 2007 Oct; 52(10): 617–9PubMed
81.
Zurück zum Zitat Luckmann R. Cholinesterase inhibitors may be effective in Alzheimer’s disease [review]. Evid Based Med 2006 Feb; 11(1): 23PubMedCrossRef Luckmann R. Cholinesterase inhibitors may be effective in Alzheimer’s disease [review]. Evid Based Med 2006 Feb; 11(1): 23PubMedCrossRef
82.
Zurück zum Zitat Birks J. The evidence for the efficacy of cholinesterase inhibitors in the treatment of Alzheimer’s disease is convincing. Int Psychogeriatr 2008 Feb; 6 (1–7). Epub ahead of print Birks J. The evidence for the efficacy of cholinesterase inhibitors in the treatment of Alzheimer’s disease is convincing. Int Psychogeriatr 2008 Feb; 6 (1–7). Epub ahead of print
83.
Zurück zum Zitat Gauthier S, Wirth Y, Möbius H. Effects of memantine on behavioural symptoms in Alzheimer’s disease patients: an analysis of the Neuropsychiatric Inventory (NPI) data of two randomised, controlled studies. Int J Geriatr Psychiatry 2005 May; 20(5): 459–64PubMedCrossRef Gauthier S, Wirth Y, Möbius H. Effects of memantine on behavioural symptoms in Alzheimer’s disease patients: an analysis of the Neuropsychiatric Inventory (NPI) data of two randomised, controlled studies. Int J Geriatr Psychiatry 2005 May; 20(5): 459–64PubMedCrossRef
84.
Zurück zum Zitat Witt A, Macdonald N, Kirkpatrick P. Memantine hydrochloride. Nat Rev Drug Discov 2004 Feb; 3(2): 109–10PubMedCrossRef Witt A, Macdonald N, Kirkpatrick P. Memantine hydrochloride. Nat Rev Drug Discov 2004 Feb; 3(2): 109–10PubMedCrossRef
85.
Zurück zum Zitat Wenk GL, Parsons CG, Danysz W. Potential role of N-methyl-D-aspartate receptors as executors of neurode-generation resulting from diverse insults: focus on memantine. Behav Pharmacol 2006 Sep; 17(5–6): 411–24PubMedCrossRef Wenk GL, Parsons CG, Danysz W. Potential role of N-methyl-D-aspartate receptors as executors of neurode-generation resulting from diverse insults: focus on memantine. Behav Pharmacol 2006 Sep; 17(5–6): 411–24PubMedCrossRef
86.
Zurück zum Zitat Bassil N, Thaipisuttikul P, Grossberg GT. Memantine ER, a once-daily formulation for the treatment of Alzheimer’s disease. Expert Opin Pharmacother 2010 Jul; 11(10): 1765–71PubMedCrossRef Bassil N, Thaipisuttikul P, Grossberg GT. Memantine ER, a once-daily formulation for the treatment of Alzheimer’s disease. Expert Opin Pharmacother 2010 Jul; 11(10): 1765–71PubMedCrossRef
88.
Zurück zum Zitat Bakchine S, Pascual-Gangnant L, Loft H. Results of a placebo-controlled 6-month study in the treatment of mild-to-moderate Alzheimer’s Disease in Europe [poster no. P2087]. 9th Congress of the European Federation of Neurological Societies; 2005 Sep 17–20; Athens Bakchine S, Pascual-Gangnant L, Loft H. Results of a placebo-controlled 6-month study in the treatment of mild-to-moderate Alzheimer’s Disease in Europe [poster no. P2087]. 9th Congress of the European Federation of Neurological Societies; 2005 Sep 17–20; Athens
89.
Zurück zum Zitat Peskind ER, Potkin SG, Pomara N, et al. Memantine treatment in mild to moderate Alzheimer disease: a 24-week randomized, controlled trial. Am J Geriatr Psychiatry 2006 Aug; 14(8): 704–15PubMedCrossRef Peskind ER, Potkin SG, Pomara N, et al. Memantine treatment in mild to moderate Alzheimer disease: a 24-week randomized, controlled trial. Am J Geriatr Psychiatry 2006 Aug; 14(8): 704–15PubMedCrossRef
90.
Zurück zum Zitat Reisberg B, Doody R, Stoffler A, et al. Memantine in moderate-to-severe Alzheimer’s disease. N Engl J Med 2003 Apr 3; 348(14): 1333–41PubMedCrossRef Reisberg B, Doody R, Stoffler A, et al. Memantine in moderate-to-severe Alzheimer’s disease. N Engl J Med 2003 Apr 3; 348(14): 1333–41PubMedCrossRef
92.
Zurück zum Zitat Tariot PN, Farlow MR, Grossberg GT, et al. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA 2004 Jan 21; 291(3): 317–24PubMedCrossRef Tariot PN, Farlow MR, Grossberg GT, et al. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA 2004 Jan 21; 291(3): 317–24PubMedCrossRef
93.
Zurück zum Zitat Knopman D. Commentary on “Meta-analysis of six-month memantine trials in Alzheimer’s disease”: memantine has negligible benefits in mild to moderate Alzheimer’s disease. Alzheimers Dement 2007 Jan; 3(1): 21–2PubMedCrossRef Knopman D. Commentary on “Meta-analysis of six-month memantine trials in Alzheimer’s disease”: memantine has negligible benefits in mild to moderate Alzheimer’s disease. Alzheimers Dement 2007 Jan; 3(1): 21–2PubMedCrossRef
94.
Zurück zum Zitat Schneider L. Commentary on “Meta-analysis of six-month memantine trials in Alzheimer’s disease”: wuthering forest plots — distinguishing the forest from the plots. Alzheimers Dement 2007 Jan; 3(1): 18–20PubMedCrossRef Schneider L. Commentary on “Meta-analysis of six-month memantine trials in Alzheimer’s disease”: wuthering forest plots — distinguishing the forest from the plots. Alzheimers Dement 2007 Jan; 3(1): 18–20PubMedCrossRef
95.
Zurück zum Zitat Herrmann N, Li A, Lanctôt K. Memantine in dementia: a review of the current evidence. Expert Opin Pharmacother 2011 Apr; 12(5): 787–800PubMedCrossRef Herrmann N, Li A, Lanctôt K. Memantine in dementia: a review of the current evidence. Expert Opin Pharmacother 2011 Apr; 12(5): 787–800PubMedCrossRef
96.
Zurück zum Zitat Veinbergs I, Mallory M, Sagara Y, et al. Vitamin E supplementation prevents spatial learning deficits and dendritic alterations in aged apolipoprotein E-deficient mice. Eur J Neurosci 2000 Dec; 12(12): 4541–6PubMed Veinbergs I, Mallory M, Sagara Y, et al. Vitamin E supplementation prevents spatial learning deficits and dendritic alterations in aged apolipoprotein E-deficient mice. Eur J Neurosci 2000 Dec; 12(12): 4541–6PubMed
97.
Zurück zum Zitat Veinbergs I, Mante M, Mallory M, et al. Neurotrophic effects of Cerebrolysin in animal models of excitotoxicity. J Neural Transm 2000; 59: 273–80 Veinbergs I, Mante M, Mallory M, et al. Neurotrophic effects of Cerebrolysin in animal models of excitotoxicity. J Neural Transm 2000; 59: 273–80
98.
Zurück zum Zitat Rockenstein E, Mallory M, Mante M, et al. Effects of Cerebrolysin on amyloid-beta deposition in a transgenic model of Alzheimer’s disease. J Neural Transm Suppl 2002; (62): 327–36 Rockenstein E, Mallory M, Mante M, et al. Effects of Cerebrolysin on amyloid-beta deposition in a transgenic model of Alzheimer’s disease. J Neural Transm Suppl 2002; (62): 327–36
99.
Zurück zum Zitat Rockenstein E, Mante M, Adame A, et al. Effects of Cerebrolysin on neurogenesis in an APP transgenic model of Alzheimer’s disease. Acta Neuropathol 2007 Mar; 113(3): 265–75PubMedCrossRef Rockenstein E, Mante M, Adame A, et al. Effects of Cerebrolysin on neurogenesis in an APP transgenic model of Alzheimer’s disease. Acta Neuropathol 2007 Mar; 113(3): 265–75PubMedCrossRef
100.
Zurück zum Zitat Xiong H, Baskys A, Wojtowicz JM. Brain-derived peptides inhibit synaptic transmission via presynaptic GABAB receptors in CA1 area of rat hippocampal slices. Brain Res 1996 Oct 21; 737(1–2): 188–94PubMedCrossRef Xiong H, Baskys A, Wojtowicz JM. Brain-derived peptides inhibit synaptic transmission via presynaptic GABAB receptors in CA1 area of rat hippocampal slices. Brain Res 1996 Oct 21; 737(1–2): 188–94PubMedCrossRef
101.
Zurück zum Zitat Xiong H, Wojtowicz JM, Baskys A. Brain tissue hydrolysate acts on presynaptic adenosine receptors in the rat hippocampus. Can J Physiol Pharmacol 1995 Aug; 73(8): 1194–7PubMedCrossRef Xiong H, Wojtowicz JM, Baskys A. Brain tissue hydrolysate acts on presynaptic adenosine receptors in the rat hippocampus. Can J Physiol Pharmacol 1995 Aug; 73(8): 1194–7PubMedCrossRef
102.
Zurück zum Zitat Alvarez XA, Lombardi VR, Fernandez-Novoa L, et al. Cerebrolysin reduces microglial activation in vivo and in vitro: a potential mechanism of neuroprotection. J Neural Transm 2000; 59: 281–92 Alvarez XA, Lombardi VR, Fernandez-Novoa L, et al. Cerebrolysin reduces microglial activation in vivo and in vitro: a potential mechanism of neuroprotection. J Neural Transm 2000; 59: 281–92
103.
Zurück zum Zitat Rockenstein E, Torrance M, Mante M, et al. Cerebrolysin decreases amyloid-beta production by regulating amyloid protein precursor maturation in a transgenic model of Alzheimer’s disease. J Neurosci Res 2006 May 15; 83(7): 1252–61PubMedCrossRef Rockenstein E, Torrance M, Mante M, et al. Cerebrolysin decreases amyloid-beta production by regulating amyloid protein precursor maturation in a transgenic model of Alzheimer’s disease. J Neurosci Res 2006 May 15; 83(7): 1252–61PubMedCrossRef
104.
Zurück zum Zitat Ubhi K, Rockenstein E, Doppler E, et al. Neurofibrillary and neurodegenerative pathology in APP-transgenic mice injected with AAV2-mutant TAU: neuroprotective effects of Cerebrolysin. Acta Neuropathol 2009 Jun; 117(6): 699–712PubMedCrossRef Ubhi K, Rockenstein E, Doppler E, et al. Neurofibrillary and neurodegenerative pathology in APP-transgenic mice injected with AAV2-mutant TAU: neuroprotective effects of Cerebrolysin. Acta Neuropathol 2009 Jun; 117(6): 699–712PubMedCrossRef
105.
Zurück zum Zitat Plosker GL, Gauthier S. Cerebrolysin: a review of its use in dementia. Drugs Aging 2009; 26(11): 893–915PubMedCrossRef Plosker GL, Gauthier S. Cerebrolysin: a review of its use in dementia. Drugs Aging 2009; 26(11): 893–915PubMedCrossRef
106.
Zurück zum Zitat Alvarez XA, Cacabelos R, Sampedro C, et al. Combination treatment in Alzheimer’s disease: results of a randomized, controlled trial with cerebrolysin and donepezil. Curr Alzheimer Res. Epub 2011 Jun 17 Alvarez XA, Cacabelos R, Sampedro C, et al. Combination treatment in Alzheimer’s disease: results of a randomized, controlled trial with cerebrolysin and donepezil. Curr Alzheimer Res. Epub 2011 Jun 17
107.
Zurück zum Zitat Muresanu DF, Rainer M, Moessler H. Improved global function and activities of daily living in patients with AD: a placebo-controlled clinical study with the neurotrophic agent Cerebrolysin. J Neural Transm Suppl 2002; 62: 277–85PubMed Muresanu DF, Rainer M, Moessler H. Improved global function and activities of daily living in patients with AD: a placebo-controlled clinical study with the neurotrophic agent Cerebrolysin. J Neural Transm Suppl 2002; 62: 277–85PubMed
108.
Zurück zum Zitat Rothwell PM. External validity of randomised controlled trials: “to whom do the results of this trial apply?” Lancet 2005 Jan 1–7; 365(9453): 82–93PubMedCrossRef Rothwell PM. External validity of randomised controlled trials: “to whom do the results of this trial apply?” Lancet 2005 Jan 1–7; 365(9453): 82–93PubMedCrossRef
109.
Zurück zum Zitat Lockhart IA, Mitchell SA, Kelly S. Safety and tolerability of donepezil, rivastigmine and galantamine for patients with Alzheimer’s disease: systematic review of the ‘real-world’ evidence. Dement Geriatr Cogn Disord 2009; 28(5): 389–403PubMedCrossRef Lockhart IA, Mitchell SA, Kelly S. Safety and tolerability of donepezil, rivastigmine and galantamine for patients with Alzheimer’s disease: systematic review of the ‘real-world’ evidence. Dement Geriatr Cogn Disord 2009; 28(5): 389–403PubMedCrossRef
110.
Zurück zum Zitat Pakrasi S, Mukaetova-Ladinska EB, McKeith IG, et al. Clinical predictors of response to acetyl cholinesterase inhibitors: experience from routine clinical use in Newcastle. Int J Geriatr Psychiatry 2003 Oct; 18(10): 879–86PubMedCrossRef Pakrasi S, Mukaetova-Ladinska EB, McKeith IG, et al. Clinical predictors of response to acetyl cholinesterase inhibitors: experience from routine clinical use in Newcastle. Int J Geriatr Psychiatry 2003 Oct; 18(10): 879–86PubMedCrossRef
111.
Zurück zum Zitat Turon-Estrada A, Lopez-Pousa S, Gelada-Batlle E, et al. Tolerance and adverse events of treatment with acetylcholinesterase inhibitors in a clinical sample of patients with very slight and mild Alzheimer’s disease over a six-month period. Rev Neurol 2003 Mar 1–15; 36(5): 421–4PubMed Turon-Estrada A, Lopez-Pousa S, Gelada-Batlle E, et al. Tolerance and adverse events of treatment with acetylcholinesterase inhibitors in a clinical sample of patients with very slight and mild Alzheimer’s disease over a six-month period. Rev Neurol 2003 Mar 1–15; 36(5): 421–4PubMed
112.
Zurück zum Zitat Sobow T, Kloszewska I. Cholinesterase inhibitors in the ‘real world’ setting: rivastigmine versus donepezil tolerability and effectiveness study. Arch Med Sci 2006; 2: 194–8 Sobow T, Kloszewska I. Cholinesterase inhibitors in the ‘real world’ setting: rivastigmine versus donepezil tolerability and effectiveness study. Arch Med Sci 2006; 2: 194–8
113.
Zurück zum Zitat Hughes A, Musher J, Thomas SK, et al. Gastrointestinal adverse events in a general population sample of nursing home residents taking cholinesterase inhibitors. Consult Pharm 2004 Aug; 19(8): 713–20PubMedCrossRef Hughes A, Musher J, Thomas SK, et al. Gastrointestinal adverse events in a general population sample of nursing home residents taking cholinesterase inhibitors. Consult Pharm 2004 Aug; 19(8): 713–20PubMedCrossRef
114.
Zurück zum Zitat Park-Wyllie LY, Mamdani MM, Li P, et al. Cholinesterase inhibitors and hospitalization for bradycardia: a population-based study. PLoS Med 2009 Sep; 6(9): e1000157PubMedCrossRef Park-Wyllie LY, Mamdani MM, Li P, et al. Cholinesterase inhibitors and hospitalization for bradycardia: a population-based study. PLoS Med 2009 Sep; 6(9): e1000157PubMedCrossRef
115.
Zurück zum Zitat Gill SS, Anderson GM, Fischer HD, et al. Syncope and its consequences in patients with dementia receiving cholinesterase inhibitors: a population-based cohort study. Arch Intern Med 2009 May 11; 169(9): 867–73PubMedCrossRef Gill SS, Anderson GM, Fischer HD, et al. Syncope and its consequences in patients with dementia receiving cholinesterase inhibitors: a population-based cohort study. Arch Intern Med 2009 May 11; 169(9): 867–73PubMedCrossRef
116.
Zurück zum Zitat Mossello E, Tonon E, Caleri V, et al. Effectiveness and safety of cholinesterase inhibitors in elderly subjects with Alzheimer’s disease: a ‘real world’ study. Arch Gerontol Geriatr Suppl 2004; (9): 297–307 Mossello E, Tonon E, Caleri V, et al. Effectiveness and safety of cholinesterase inhibitors in elderly subjects with Alzheimer’s disease: a ‘real world’ study. Arch Gerontol Geriatr Suppl 2004; (9): 297–307
117.
Zurück zum Zitat Fuschillo C, Ascoli E, Franzese G, et al. Alzheimer’s disease and acetylcholinesterase inhibitor agents: a two-year longitudinal study. Arch Gerontol Geriatr Suppl 2004; (9): 187–94 Fuschillo C, Ascoli E, Franzese G, et al. Alzheimer’s disease and acetylcholinesterase inhibitor agents: a two-year longitudinal study. Arch Gerontol Geriatr Suppl 2004; (9): 187–94
118.
Zurück zum Zitat Aguglia E, Onor ML, Saina M, et al. An open-label, comparative study of rivastigmine, donepezil and galantamine in a real-world setting. Curr Med Res Opin 2004 Nov; 20(11): 1747–52PubMedCrossRef Aguglia E, Onor ML, Saina M, et al. An open-label, comparative study of rivastigmine, donepezil and galantamine in a real-world setting. Curr Med Res Opin 2004 Nov; 20(11): 1747–52PubMedCrossRef
119.
Zurück zum Zitat Lopez-Pousa S, Turon-Estrada A, Garre-Olmo J, et al. Differential efficacy of treatment with acetylcholinesterase inhibitors in patients with mild and moderate Alzheimer’s disease over a 6-month period. Dement Geriatr Cogn Disord 2005; 19(4): 189–95PubMedCrossRef Lopez-Pousa S, Turon-Estrada A, Garre-Olmo J, et al. Differential efficacy of treatment with acetylcholinesterase inhibitors in patients with mild and moderate Alzheimer’s disease over a 6-month period. Dement Geriatr Cogn Disord 2005; 19(4): 189–95PubMedCrossRef
120.
Zurück zum Zitat Jones RW. A review comparing the safety and tolerability of memantine with the acetylcholinesterase inhibitors. Int J Geriatr Psychiatry 2010 Jun; 25(6): 547–53PubMed Jones RW. A review comparing the safety and tolerability of memantine with the acetylcholinesterase inhibitors. Int J Geriatr Psychiatry 2010 Jun; 25(6): 547–53PubMed
121.
Zurück zum Zitat Calabrese P, Essner U, Forstl H. Memantine (Ebixa) in clinical practice: results of an observational study. Dement Geriatr Cogn Disord 2007; 24(2): 111–7PubMedCrossRef Calabrese P, Essner U, Forstl H. Memantine (Ebixa) in clinical practice: results of an observational study. Dement Geriatr Cogn Disord 2007; 24(2): 111–7PubMedCrossRef
122.
Zurück zum Zitat Clerici F, Vanacore N, Elia A, et al. Memantine in moderately-severe-to-severe Alzheimer’s disease: a post-marketing surveillance study. Drugs Aging 2009; 26(4): 321–32PubMedCrossRef Clerici F, Vanacore N, Elia A, et al. Memantine in moderately-severe-to-severe Alzheimer’s disease: a post-marketing surveillance study. Drugs Aging 2009; 26(4): 321–32PubMedCrossRef
123.
Zurück zum Zitat Glenner GG, Wong CW. Alzheimer’s disease and Down’s syndrome: sharing of a unique cerebrovascular amyloid fibril protein. Biochem Biophys Res Commun 1984 Aug 16; 122(3): 1131–5PubMedCrossRef Glenner GG, Wong CW. Alzheimer’s disease and Down’s syndrome: sharing of a unique cerebrovascular amyloid fibril protein. Biochem Biophys Res Commun 1984 Aug 16; 122(3): 1131–5PubMedCrossRef
124.
Zurück zum Zitat Glenner GG, Wong CW. Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 1984 May 16; 120(3): 885–90PubMedCrossRef Glenner GG, Wong CW. Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 1984 May 16; 120(3): 885–90PubMedCrossRef
125.
Zurück zum Zitat Selkoe DJ. Amyloid beta-protein and the genetics of Alzheimer’s disease. J Biol Chem 1996 Aug 2; 271(31): 18295–8PubMed Selkoe DJ. Amyloid beta-protein and the genetics of Alzheimer’s disease. J Biol Chem 1996 Aug 2; 271(31): 18295–8PubMed
126.
Zurück zum Zitat Cappai R, Barnham KJ. Delineating the mechanism of Alzheimer’s disease A beta peptide neurotoxicity. Neurochem Res 2008 Mar; 33(3): 526–32PubMedCrossRef Cappai R, Barnham KJ. Delineating the mechanism of Alzheimer’s disease A beta peptide neurotoxicity. Neurochem Res 2008 Mar; 33(3): 526–32PubMedCrossRef
127.
128.
Zurück zum Zitat Hardy JA, Higgins GA. Alzheimer’s disease: the amyloid cascade hypothesis. Science 1992 Apr 10; 256(5054): 184–5PubMedCrossRef Hardy JA, Higgins GA. Alzheimer’s disease: the amyloid cascade hypothesis. Science 1992 Apr 10; 256(5054): 184–5PubMedCrossRef
129.
Zurück zum Zitat Terry RD, Masliah E, Salmon DP, et al. Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 1991 Oct; 30(4): 572–80PubMedCrossRef Terry RD, Masliah E, Salmon DP, et al. Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 1991 Oct; 30(4): 572–80PubMedCrossRef
130.
Zurück zum Zitat Holmes C, Boche D, Wilkinson D, et al. Long-term effects of Abeta42 immunisation in Alzheimer’s disease: follow-up of a randomised, placebo-controlled phase I trial. Lancet 2008 Jul 19; 372(9634): 216–23PubMedCrossRef Holmes C, Boche D, Wilkinson D, et al. Long-term effects of Abeta42 immunisation in Alzheimer’s disease: follow-up of a randomised, placebo-controlled phase I trial. Lancet 2008 Jul 19; 372(9634): 216–23PubMedCrossRef
131.
Zurück zum Zitat Kumar-Singh S, Theuns J, Van Broeck B, et al. Mean age-of-onset of familial Alzheimer disease caused by presenilin mutations correlates with both increased Abeta42 and decreased Abeta40. Hum Mutat 2006 Jul; 27(7): 686–95PubMedCrossRef Kumar-Singh S, Theuns J, Van Broeck B, et al. Mean age-of-onset of familial Alzheimer disease caused by presenilin mutations correlates with both increased Abeta42 and decreased Abeta40. Hum Mutat 2006 Jul; 27(7): 686–95PubMedCrossRef
132.
Zurück zum Zitat Suzuki N, Cheung TT, Cai XD, et al. An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor (beta APP717) mutants. Science 1994 May 27; 264(5163): 1336–40PubMedCrossRef Suzuki N, Cheung TT, Cai XD, et al. An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor (beta APP717) mutants. Science 1994 May 27; 264(5163): 1336–40PubMedCrossRef
133.
Zurück zum Zitat Younkin SG. Evidence that A beta 42 is the real culprit in Alzheimer’s disease. Ann Neurol 1995 Mar; 37(3): 287–8PubMedCrossRef Younkin SG. Evidence that A beta 42 is the real culprit in Alzheimer’s disease. Ann Neurol 1995 Mar; 37(3): 287–8PubMedCrossRef
134.
Zurück zum Zitat Pimplikar SW. Reassessing the amyloid cascade hypothesis of Alzheimer’s disease. Int J Biochem Cell Biol 2009 Jun; 41(6): 1261–8PubMedCrossRef Pimplikar SW. Reassessing the amyloid cascade hypothesis of Alzheimer’s disease. Int J Biochem Cell Biol 2009 Jun; 41(6): 1261–8PubMedCrossRef
135.
Zurück zum Zitat Pfizer. Study evaluating the safety and efficacy of bapineuzumab in Alzheimer Disease patients [ClinicalTrials.gov identifier NCT00676143]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://clinicaltrials.gov [Accessed 2011 Jan 20] Pfizer. Study evaluating the safety and efficacy of bapineuzumab in Alzheimer Disease patients [ClinicalTrials.gov identifier NCT00676143]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​clinicaltrials.​gov [Accessed 2011 Jan 20]
136.
Zurück zum Zitat Pfizer. Study evaluating the efficacy and safety of bapineuzumab in Alzheimer disease patients [ClinicalTrials.gov identifier NCT00667810]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://clinicaltrials.gov [Accessed 2010 Dec 20] Pfizer. Study evaluating the efficacy and safety of bapineuzumab in Alzheimer disease patients [ClinicalTrials.gov identifier NCT00667810]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​clinicaltrials.​gov [Accessed 2010 Dec 20]
137.
Zurück zum Zitat Eli Lilly and Company. Effect of LY2062430 on the progression of Alzheimer’s disease (EXPEDITION) [ClinicalTrials.gov identifier NCT00905372]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://clinicaltrials.gov [Accessed 2011 Feb 28] Eli Lilly and Company. Effect of LY2062430 on the progression of Alzheimer’s disease (EXPEDITION) [ClinicalTrials.gov identifier NCT00905372]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​clinicaltrials.​gov [Accessed 2011 Feb 28]
138.
Zurück zum Zitat Eli Lilly and Company. Effect of LY2062430 on the progression of Alzheimer’s disease (EXPEDITION2) [ClinicalTrials.gov identifier NCT00904683]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://clinicaltrials.gov [Accessed 2011 Jan 20] Eli Lilly and Company. Effect of LY2062430 on the progression of Alzheimer’s disease (EXPEDITION2) [ClinicalTrials.gov identifier NCT00904683]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​clinicaltrials.​gov [Accessed 2011 Jan 20]
139.
Zurück zum Zitat Baxter Healthcare Corporation. A phase 3 study evaluating safety and effectiveness of immune globulin intravenous (IGIV 10%) for the treatment of mild to moderate Alzheimer’s disease [ClinicalTrials.gov identifier NCT00818662]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://clinicaltrials.gov [Accessed 2011 Feb 18] Baxter Healthcare Corporation. A phase 3 study evaluating safety and effectiveness of immune globulin intravenous (IGIV 10%) for the treatment of mild to moderate Alzheimer’s disease [ClinicalTrials.gov identifier NCT00818662]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​clinicaltrials.​gov [Accessed 2011 Feb 18]
140.
Zurück zum Zitat Medivation, Inc. Safety and efficacy study evaluating dimebon in patients with mild to moderate Alzheimer’s disease on donepezil (CONCERT) [ClinicalTrials.gov identifier NCT00829374]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://clinicaltrials.gov [Accessed 2011 Mar 11] Medivation, Inc. Safety and efficacy study evaluating dimebon in patients with mild to moderate Alzheimer’s disease on donepezil (CONCERT) [ClinicalTrials.gov identifier NCT00829374]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​clinicaltrials.​gov [Accessed 2011 Mar 11]
141.
Zurück zum Zitat Charite University, Berlin, Germany. Sunphenon EGCg (Epigallocatechin-Gallate) in the early stage of Alzheimer’s disease (SUN-AK) [ClinicalTrials.gov identifier NCT00951834]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://clinicaltrials.gov [Accessed 2010 Dec 20] Charite University, Berlin, Germany. Sunphenon EGCg (Epigallocatechin-Gallate) in the early stage of Alzheimer’s disease (SUN-AK) [ClinicalTrials.gov identifier NCT00951834]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​clinicaltrials.​gov [Accessed 2010 Dec 20]
142.
Zurück zum Zitat Jiang Q, Heneka M, Landreth GE. The role of peroxisome proliferator-activated receptor-gamma (PPARgamma) in Alzheimer’s disease: therapeutic implications. CNS Drugs 2008; 22(1): 1–14PubMedCrossRef Jiang Q, Heneka M, Landreth GE. The role of peroxisome proliferator-activated receptor-gamma (PPARgamma) in Alzheimer’s disease: therapeutic implications. CNS Drugs 2008; 22(1): 1–14PubMedCrossRef
143.
Zurück zum Zitat Profenno LA, Porsteinsson AP, Faraone SV. Meta-analysis of Alzheimer’s disease risk with obesity, diabetes, and related disorders. Biol Psychiatry 2010 Mar 15; 67(6): 505–12PubMedCrossRef Profenno LA, Porsteinsson AP, Faraone SV. Meta-analysis of Alzheimer’s disease risk with obesity, diabetes, and related disorders. Biol Psychiatry 2010 Mar 15; 67(6): 505–12PubMedCrossRef
144.
Zurück zum Zitat Forti P, Pisacane N, Rietti E, et al. Metabolic syndrome and risk of dementia in older adults. J Am Geriatr Soc 2010 Mar; 58(3): 487–92PubMedCrossRef Forti P, Pisacane N, Rietti E, et al. Metabolic syndrome and risk of dementia in older adults. J Am Geriatr Soc 2010 Mar; 58(3): 487–92PubMedCrossRef
145.
Zurück zum Zitat Watson GS, Craft S. The role of insulin resistance in the pathogenesis of Alzheimer’s disease: implications for treatment. CNS Drugs 2003; 17(1): 27–45PubMedCrossRef Watson GS, Craft S. The role of insulin resistance in the pathogenesis of Alzheimer’s disease: implications for treatment. CNS Drugs 2003; 17(1): 27–45PubMedCrossRef
146.
Zurück zum Zitat Craft S. Insulin resistance and Alzheimer’s disease pathogenesis: potential mechanisms and implications for treatment. Curr Alzheimer Res 2007 Apr; 4(2): 147–52PubMedCrossRef Craft S. Insulin resistance and Alzheimer’s disease pathogenesis: potential mechanisms and implications for treatment. Curr Alzheimer Res 2007 Apr; 4(2): 147–52PubMedCrossRef
147.
Zurück zum Zitat Landreth G, Jiang Q, Mandrekar S, et al. PPARgamma agonists as therapeutics for the treatment of Alzheimer’s disease. Neurotherapeutics 2008 Jul; 5(3): 481–9PubMedCrossRef Landreth G, Jiang Q, Mandrekar S, et al. PPARgamma agonists as therapeutics for the treatment of Alzheimer’s disease. Neurotherapeutics 2008 Jul; 5(3): 481–9PubMedCrossRef
148.
Zurück zum Zitat Watson GS, Cholerton BA, Reger MA, et al. Preserved cognition in patients with early Alzheimer disease and amnestic mild cognitive impairment during treatment with rosiglitazone: a preliminary study. Am J Geriatr Psychiatry 2005 Nov; 13(11): 950–8PubMed Watson GS, Cholerton BA, Reger MA, et al. Preserved cognition in patients with early Alzheimer disease and amnestic mild cognitive impairment during treatment with rosiglitazone: a preliminary study. Am J Geriatr Psychiatry 2005 Nov; 13(11): 950–8PubMed
149.
Zurück zum Zitat Risner ME, Saunders AM, Altman JF, et al. Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer’s disease. Pharmacogenomics J 2006 Jul–Aug; 6(4): 246–54PubMed Risner ME, Saunders AM, Altman JF, et al. Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer’s disease. Pharmacogenomics J 2006 Jul–Aug; 6(4): 246–54PubMed
150.
Zurück zum Zitat Gold M, Alderton C, Zvartau-Hind M, et al. Rosiglitazone monotherapy in mild-to-moderate Alzheimer’s disease: results from a randomized, double-blind, placebo-controlled phase III study. Dement Geriatr Cogn Disord 2010; 30(2): 131–46PubMedCrossRef Gold M, Alderton C, Zvartau-Hind M, et al. Rosiglitazone monotherapy in mild-to-moderate Alzheimer’s disease: results from a randomized, double-blind, placebo-controlled phase III study. Dement Geriatr Cogn Disord 2010; 30(2): 131–46PubMedCrossRef
152.
Zurück zum Zitat Aisen PS, Gauthier S, Ferris S, et al. Tramiprosate in mild-to-moderate Alzheimer’s disease: a randomized, double-blind, placebo-controlled, multi-centre study (the Alphase Study). Arch Med Sci 2011; 7(1): 102–11PubMedCrossRef Aisen PS, Gauthier S, Ferris S, et al. Tramiprosate in mild-to-moderate Alzheimer’s disease: a randomized, double-blind, placebo-controlled, multi-centre study (the Alphase Study). Arch Med Sci 2011; 7(1): 102–11PubMedCrossRef
153.
Zurück zum Zitat Tariot PN, Aisen P, Cummings J, et al. The ADCS valproate neuroprotection trial: primary efficacy and safety results. Alzheimers Dement 2009; 5 (4 Suppl.): P84–5CrossRef Tariot PN, Aisen P, Cummings J, et al. The ADCS valproate neuroprotection trial: primary efficacy and safety results. Alzheimers Dement 2009; 5 (4 Suppl.): P84–5CrossRef
154.
Zurück zum Zitat Reines SA, Block GA, Morris JC, et al. Rofecoxib: no effect on Alzheimer’s disease in a 1-year, randomized, blinded, controlled study. Neurology 2004 Jan 13; 62(1): 66–71PubMedCrossRef Reines SA, Block GA, Morris JC, et al. Rofecoxib: no effect on Alzheimer’s disease in a 1-year, randomized, blinded, controlled study. Neurology 2004 Jan 13; 62(1): 66–71PubMedCrossRef
155.
Zurück zum Zitat Aisen PS, Schafer KA, Grundman M, et al. Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. JAMA 2003 Jun 4; 289(21): 2819–26PubMedCrossRef Aisen PS, Schafer KA, Grundman M, et al. Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. JAMA 2003 Jun 4; 289(21): 2819–26PubMedCrossRef
156.
Zurück zum Zitat Aisen PS, Davis KL, Berg JD, et al. A randomized controlled trial of prednisone in Alzheimer’s disease. Alzheimer’s Disease Cooperative Study. Neurology 2000 Feb 8; 54(3): 588–93 Aisen PS, Davis KL, Berg JD, et al. A randomized controlled trial of prednisone in Alzheimer’s disease. Alzheimer’s Disease Cooperative Study. Neurology 2000 Feb 8; 54(3): 588–93
157.
Zurück zum Zitat Van Gool WA, Weinstein HC, Scheltens P, et al. Effect of hydroxychloroquine on progression of dementia in early Alzheimer’s disease: an 18-month randomised, double-blind, placebo-controlled study. Lancet 2001 Aug 11; 358(9280): 455–60PubMedCrossRef Van Gool WA, Weinstein HC, Scheltens P, et al. Effect of hydroxychloroquine on progression of dementia in early Alzheimer’s disease: an 18-month randomised, double-blind, placebo-controlled study. Lancet 2001 Aug 11; 358(9280): 455–60PubMedCrossRef
158.
Zurück zum Zitat de Jong D, Jansen R, Hoefnagels W, et al. No effect of one-year treatment with indomethacin on Alzheimer’s disease progression: a randomized controlled trial. PLoS One 2008; 3(1): e1475PubMedCrossRef de Jong D, Jansen R, Hoefnagels W, et al. No effect of one-year treatment with indomethacin on Alzheimer’s disease progression: a randomized controlled trial. PLoS One 2008; 3(1): e1475PubMedCrossRef
159.
Zurück zum Zitat Green RC, Schneider LS, Amato DA, et al. Effect of tarenflurbil on cognitive decline and activities of daily living in patients with mild Alzheimer disease: a randomized controlled trial. JAMA 2009 Dec 16; 302(23): 2557–64PubMedCrossRef Green RC, Schneider LS, Amato DA, et al. Effect of tarenflurbil on cognitive decline and activities of daily living in patients with mild Alzheimer disease: a randomized controlled trial. JAMA 2009 Dec 16; 302(23): 2557–64PubMedCrossRef
161.
Zurück zum Zitat Freund-Levi Y, Eriksdotter-Jonhagen M, Cederholm T, et al. Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study — a randomized double-blind trial. Arch Neurol 2006 Oct; 63(10): 1402–8PubMedCrossRef Freund-Levi Y, Eriksdotter-Jonhagen M, Cederholm T, et al. Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study — a randomized double-blind trial. Arch Neurol 2006 Oct; 63(10): 1402–8PubMedCrossRef
162.
Zurück zum Zitat Quinn JF, Raman R, Thomas RG, et al. Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial. JAMA 2010 Nov 3; 304(17): 1903–11PubMedCrossRef Quinn JF, Raman R, Thomas RG, et al. Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial. JAMA 2010 Nov 3; 304(17): 1903–11PubMedCrossRef
163.
Zurück zum Zitat Sparks DL, Connor DJ, Sabbagh MN, et al. Circulating cholesterol levels, apolipoprotein E genotype and dementia severity influence the benefit of atorvastatin treatment in Alzheimer’s disease: results of the Alzheimer’s Disease Cholesterol-Lowering Treatment (ADCLT) trial. Acta Neurol Scand Suppl 2006; 185: 3–7PubMedCrossRef Sparks DL, Connor DJ, Sabbagh MN, et al. Circulating cholesterol levels, apolipoprotein E genotype and dementia severity influence the benefit of atorvastatin treatment in Alzheimer’s disease: results of the Alzheimer’s Disease Cholesterol-Lowering Treatment (ADCLT) trial. Acta Neurol Scand Suppl 2006; 185: 3–7PubMedCrossRef
164.
Zurück zum Zitat Feldman HH, Doody RS, Kivipelto M, et al. Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe. Neurology 2010 Mar 23; 74(12): 956–64PubMedCrossRef Feldman HH, Doody RS, Kivipelto M, et al. Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe. Neurology 2010 Mar 23; 74(12): 956–64PubMedCrossRef
165.
Zurück zum Zitat National Institute on Aging (NIA). Cholesterol Lowering Agent to Slow Progression (CLASP) of Alzheimer’s disease study [ClinicalTrials.gov identifier NCT00053599]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://clinicaltrials.gov [Accessed 2010 Dec 20] National Institute on Aging (NIA). Cholesterol Lowering Agent to Slow Progression (CLASP) of Alzheimer’s disease study [ClinicalTrials.gov identifier NCT00053599]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​clinicaltrials.​gov [Accessed 2010 Dec 20]
166.
Zurück zum Zitat Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007 Jun 14; 356(24): 2457–71PubMedCrossRef Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007 Jun 14; 356(24): 2457–71PubMedCrossRef
167.
Zurück zum Zitat Festuccia WT, Oztezcan S, Laplante M, et al. Peroxisome proliferator-activated receptor-gamma-mediated positive energy balance in the rat is associated with reduced sympathetic drive to adipose tissues and thyroid status. Endocrinology 2008 May; 149(5): 2121–30PubMedCrossRef Festuccia WT, Oztezcan S, Laplante M, et al. Peroxisome proliferator-activated receptor-gamma-mediated positive energy balance in the rat is associated with reduced sympathetic drive to adipose tissues and thyroid status. Endocrinology 2008 May; 149(5): 2121–30PubMedCrossRef
168.
Zurück zum Zitat Heneka MT, Sastre M, Dumitrescu-Ozimek L, et al. Acute treatment with the PPARgamma agonist pioglitazone and ibuprofen reduces glial inflammation and Abeta1-42 levels in APPV717I transgenic mice. Brain 2005 Jun; 128(Pt 6): 1442–53PubMedCrossRef Heneka MT, Sastre M, Dumitrescu-Ozimek L, et al. Acute treatment with the PPARgamma agonist pioglitazone and ibuprofen reduces glial inflammation and Abeta1-42 levels in APPV717I transgenic mice. Brain 2005 Jun; 128(Pt 6): 1442–53PubMedCrossRef
169.
Zurück zum Zitat Maeshiba Y, Kiyota Y, Yamashita K, et al. Disposition of the new antidiabetic agent pioglitazone in rats, dogs, and monkeys. Arzneimittelforschung 1997; 47(1): 29–35PubMed Maeshiba Y, Kiyota Y, Yamashita K, et al. Disposition of the new antidiabetic agent pioglitazone in rats, dogs, and monkeys. Arzneimittelforschung 1997; 47(1): 29–35PubMed
170.
Zurück zum Zitat Geldmacher DS, Fritsch T, McClendon MJ, et al. A randomized pilot clinical trial of the safety of pioglitazone in treatment of patients with Alzheimer disease. Arch Neurol 2011 Jan; 68(1): 45–50PubMedCrossRef Geldmacher DS, Fritsch T, McClendon MJ, et al. A randomized pilot clinical trial of the safety of pioglitazone in treatment of patients with Alzheimer disease. Arch Neurol 2011 Jan; 68(1): 45–50PubMedCrossRef
171.
Zurück zum Zitat Lewis HD, Perez Revuelta BI, Nadin A, et al. Catalytic site-directed gamma-secretase complex inhibitors do not discriminate pharmacologically between Notch S3 and beta-APP cleavages. Biochemistry 2003 Jun 24; 42(24): 7580–6PubMedCrossRef Lewis HD, Perez Revuelta BI, Nadin A, et al. Catalytic site-directed gamma-secretase complex inhibitors do not discriminate pharmacologically between Notch S3 and beta-APP cleavages. Biochemistry 2003 Jun 24; 42(24): 7580–6PubMedCrossRef
172.
Zurück zum Zitat Hartmann D, Tournoy J, Saftig P, et al. Implication of APP secretases in notch signaling. J Mol Neurosci 2001 Oct; 17(2): 171–81PubMedCrossRef Hartmann D, Tournoy J, Saftig P, et al. Implication of APP secretases in notch signaling. J Mol Neurosci 2001 Oct; 17(2): 171–81PubMedCrossRef
173.
Zurück zum Zitat Bateman RJ, Siemers ER, Mawuenyega KG, et al. A gamma-secretase inhibitor decreases amyloid-beta production in the central nervous system. Ann Neurol 2009 Jul; 66(1): 48–54PubMedCrossRef Bateman RJ, Siemers ER, Mawuenyega KG, et al. A gamma-secretase inhibitor decreases amyloid-beta production in the central nervous system. Ann Neurol 2009 Jul; 66(1): 48–54PubMedCrossRef
174.
Zurück zum Zitat Siemers ER, Quinn JF, Kaye J, et al. Effects of a gamma-secretase inhibitor in a randomized study of patients with Alzheimer disease. Neurology 2006 Feb 28; 66(4): 602–4PubMedCrossRef Siemers ER, Quinn JF, Kaye J, et al. Effects of a gamma-secretase inhibitor in a randomized study of patients with Alzheimer disease. Neurology 2006 Feb 28; 66(4): 602–4PubMedCrossRef
175.
Zurück zum Zitat Fleisher AS, Raman R, Siemers ER, et al. Phase 2 safety trial targeting amyloid beta production with a gamma-secretase inhibitor in Alzheimer disease. Arch Neurol 2008 Aug; 65(8): 1031–8PubMedCrossRef Fleisher AS, Raman R, Siemers ER, et al. Phase 2 safety trial targeting amyloid beta production with a gamma-secretase inhibitor in Alzheimer disease. Arch Neurol 2008 Aug; 65(8): 1031–8PubMedCrossRef
176.
Zurück zum Zitat Bateman RJ, Munsell LY, Morris JC, et al. Human amyloid-beta synthesis and clearance rates as measured in cerebrospinal fluid in vivo. Nat Med 2006 Jul; 12(7): 856–61PubMedCrossRef Bateman RJ, Munsell LY, Morris JC, et al. Human amyloid-beta synthesis and clearance rates as measured in cerebrospinal fluid in vivo. Nat Med 2006 Jul; 12(7): 856–61PubMedCrossRef
177.
Zurück zum Zitat Imbimbo BP, Peretto I. Semagacestat, a gamma-secretase inhibitor for the potential treatment of Alzheimer’s disease. Curr Opin Investig Drugs 2009 Jul; 10(7): 721–30PubMed Imbimbo BP, Peretto I. Semagacestat, a gamma-secretase inhibitor for the potential treatment of Alzheimer’s disease. Curr Opin Investig Drugs 2009 Jul; 10(7): 721–30PubMed
178.
Zurück zum Zitat Jacobsen S, Comery T, Kreft A, et al. GSI-953 is a potent APP-selective gamma-secretase inhibitor for the treatment of Alzheimer’s disease [abstract]. Alzheimers Dement 2009; 5 Suppl. 1 (4): P139CrossRef Jacobsen S, Comery T, Kreft A, et al. GSI-953 is a potent APP-selective gamma-secretase inhibitor for the treatment of Alzheimer’s disease [abstract]. Alzheimers Dement 2009; 5 Suppl. 1 (4): P139CrossRef
179.
Zurück zum Zitat Soares H, Raha N, Sikpi M, et al. b variability and effect of gamma secretase inhibition on cerebrospinal fluid levels of Ab in healthy volunteers. Alzheimers Dement 2009; 5 (1 Suppl. 4): P252–3CrossRef Soares H, Raha N, Sikpi M, et al. b variability and effect of gamma secretase inhibition on cerebrospinal fluid levels of Ab in healthy volunteers. Alzheimers Dement 2009; 5 (1 Suppl. 4): P252–3CrossRef
180.
Zurück zum Zitat Grossman H, Marzloff G, Luo X, et al. NIC5-15 as a treatment for Alzheimer’s: safety, pharmacokinetics and clinical variables [abstract]. Alzheimers Dement 2009; 5 (1 Suppl. 4): P259CrossRef Grossman H, Marzloff G, Luo X, et al. NIC5-15 as a treatment for Alzheimer’s: safety, pharmacokinetics and clinical variables [abstract]. Alzheimers Dement 2009; 5 (1 Suppl. 4): P259CrossRef
181.
Zurück zum Zitat Furukawa K, Sopher BL, Rydel RE, et al. Increased activity-regulating and neuroprotective efficacy of alpha-secretase-derived secreted amyloid precursor protein conferred by a C-terminal heparin-binding domain. J Neurochem 1996 Nov; 67(5): 1882–96PubMedCrossRef Furukawa K, Sopher BL, Rydel RE, et al. Increased activity-regulating and neuroprotective efficacy of alpha-secretase-derived secreted amyloid precursor protein conferred by a C-terminal heparin-binding domain. J Neurochem 1996 Nov; 67(5): 1882–96PubMedCrossRef
182.
Zurück zum Zitat Meziane H, Dodart JC, Mathis C, et al. Memory-enhancing effects of secreted forms of the beta-amyloid precursor protein in normal and amnestic mice. Proc Natl Acad Sci U S A 1998 Oct 13; 95(21): 12683–8PubMedCrossRef Meziane H, Dodart JC, Mathis C, et al. Memory-enhancing effects of secreted forms of the beta-amyloid precursor protein in normal and amnestic mice. Proc Natl Acad Sci U S A 1998 Oct 13; 95(21): 12683–8PubMedCrossRef
183.
Zurück zum Zitat Turner PR, O’Connor K, Tate WP, et al. Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory. Prog Neurobiol 2003 May; 70(1): 1–32PubMedCrossRef Turner PR, O’Connor K, Tate WP, et al. Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory. Prog Neurobiol 2003 May; 70(1): 1–32PubMedCrossRef
184.
Zurück zum Zitat Marcade M, Bourdin J, Loiseau N, et al. Etazolate, a neuroprotective drug linking GABA(A) receptor pharmacology to amyloid precursor protein processing. J Neurochem 2008 Jul; 106(1): 392–404PubMedCrossRef Marcade M, Bourdin J, Loiseau N, et al. Etazolate, a neuroprotective drug linking GABA(A) receptor pharmacology to amyloid precursor protein processing. J Neurochem 2008 Jul; 106(1): 392–404PubMedCrossRef
185.
Zurück zum Zitat Etcheberrigaray R, Tan M, Dewachter I, et al. Therapeutic effects of PKC activators in Alzheimer’s disease transgenic mice. Proc Natl Acad Sci U S A 2004 Jul 27; 101(30): 11141–6PubMedCrossRef Etcheberrigaray R, Tan M, Dewachter I, et al. Therapeutic effects of PKC activators in Alzheimer’s disease transgenic mice. Proc Natl Acad Sci U S A 2004 Jul 27; 101(30): 11141–6PubMedCrossRef
186.
Zurück zum Zitat Griffiths HH, Morten IJ, Hooper NM. Emerging and potential therapies for Alzheimer’s disease. Expert Opin Ther Targets 2008 Jun; 12(6): 693–704PubMedCrossRef Griffiths HH, Morten IJ, Hooper NM. Emerging and potential therapies for Alzheimer’s disease. Expert Opin Ther Targets 2008 Jun; 12(6): 693–704PubMedCrossRef
187.
Zurück zum Zitat Haass C, Selkoe DJ. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid beta-peptide. Nat Rev Mol Cell Biol 2007 Feb; 8(2): 101–12PubMedCrossRef Haass C, Selkoe DJ. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid beta-peptide. Nat Rev Mol Cell Biol 2007 Feb; 8(2): 101–12PubMedCrossRef
188.
Zurück zum Zitat Shankar GM, Li S, Mehta TH, et al. Amyloid-beta protein dimers isolated directly from Alzheimer’s brains impair synaptic plasticity and memory. Nat Med 2008 Aug; 14(8): 837–42PubMedCrossRef Shankar GM, Li S, Mehta TH, et al. Amyloid-beta protein dimers isolated directly from Alzheimer’s brains impair synaptic plasticity and memory. Nat Med 2008 Aug; 14(8): 837–42PubMedCrossRef
189.
Zurück zum Zitat Gong Y, Chang L, Viola KL, et al. Alzheimer’s disease-affected brain: presence of oligomeric A beta ligands (ADDLs) suggests a molecular basis for reversible memory loss. Proc Natl Acad Sci U S A 2003 Sep 2; 100(18): 10417–22PubMedCrossRef Gong Y, Chang L, Viola KL, et al. Alzheimer’s disease-affected brain: presence of oligomeric A beta ligands (ADDLs) suggests a molecular basis for reversible memory loss. Proc Natl Acad Sci U S A 2003 Sep 2; 100(18): 10417–22PubMedCrossRef
190.
Zurück zum Zitat Gervais F, Paquette J, Morissette C, et al. Targeting soluble Abeta peptide with Tramiprosate for the treatment of brain amyloidosis. Neurobiol Aging 2007 Apr; 28(4): 537–47PubMedCrossRef Gervais F, Paquette J, Morissette C, et al. Targeting soluble Abeta peptide with Tramiprosate for the treatment of brain amyloidosis. Neurobiol Aging 2007 Apr; 28(4): 537–47PubMedCrossRef
191.
Zurück zum Zitat Aisen PS, Saumier D, Briand R, et al. A phase II study targeting amyloid-beta with 3APS in mild-to-moderate Alzheimer disease. Neurology 2006 Nov 28; 67(10): 1757–63PubMedCrossRef Aisen PS, Saumier D, Briand R, et al. A phase II study targeting amyloid-beta with 3APS in mild-to-moderate Alzheimer disease. Neurology 2006 Nov 28; 67(10): 1757–63PubMedCrossRef
192.
Zurück zum Zitat Saumier D, Duong A, Haine D, et al. Domain-specific cognitive effects of tramiprosate in patients with mild to moderate Alzheimer’s disease: ADAS-cog subscale results from the Alphase Study. J Nutr Health Aging 2009 Nov; 13(9): 808–12PubMedCrossRef Saumier D, Duong A, Haine D, et al. Domain-specific cognitive effects of tramiprosate in patients with mild to moderate Alzheimer’s disease: ADAS-cog subscale results from the Alphase Study. J Nutr Health Aging 2009 Nov; 13(9): 808–12PubMedCrossRef
193.
Zurück zum Zitat Guo JP, Yu S, McGeer PL. Simple in vitro assays to identify amyloid-beta aggregation blockers for Alzheimer’s disease therapy. J Alzheimers Dis 2010; 19(4): 1359–70PubMed Guo JP, Yu S, McGeer PL. Simple in vitro assays to identify amyloid-beta aggregation blockers for Alzheimer’s disease therapy. J Alzheimers Dis 2010; 19(4): 1359–70PubMed
194.
Zurück zum Zitat Bastianetto S, Yao ZX, Papadopoulos V, et al. Neuroprotective effects of green and black teas and their catechin gallate esters against beta-amyloid-induced toxicity. Eur J Neurosci 2006 Jan; 23(1): 55–64PubMedCrossRef Bastianetto S, Yao ZX, Papadopoulos V, et al. Neuroprotective effects of green and black teas and their catechin gallate esters against beta-amyloid-induced toxicity. Eur J Neurosci 2006 Jan; 23(1): 55–64PubMedCrossRef
195.
Zurück zum Zitat Levites Y, Amit T, Mandel S, et al. Neuroprotection and neurorescue against Abeta toxicity and PKC-dependent release of nonamyloidogenic soluble precursor protein by green tea polyphenol (−)-epigallocatechin-3-gallate. FASEB J 2003 May; 17(8): 952–4PubMed Levites Y, Amit T, Mandel S, et al. Neuroprotection and neurorescue against Abeta toxicity and PKC-dependent release of nonamyloidogenic soluble precursor protein by green tea polyphenol (−)-epigallocatechin-3-gallate. FASEB J 2003 May; 17(8): 952–4PubMed
196.
Zurück zum Zitat Choi YT, Jung CH, Lee SR, et al. The green tea polyphenol (−)-epigallocatechin gallate attenuates beta-amyloid-induced neurotoxicity in cultured hippocampal neurons. Life Sci 2001 Dec 21; 70(5): 603–14PubMedCrossRef Choi YT, Jung CH, Lee SR, et al. The green tea polyphenol (−)-epigallocatechin gallate attenuates beta-amyloid-induced neurotoxicity in cultured hippocampal neurons. Life Sci 2001 Dec 21; 70(5): 603–14PubMedCrossRef
197.
Zurück zum Zitat Lee JW, Lee YK, Ban JO, et al. Green tea (−)-epigallocatechin-3-gallate inhibits beta-amyloid-induced cognitive dysfunction through modification of secretase activity via inhibition of ERK and NF-kappaB pathways in mice. J Nutr 2009 Oct; 139(10): 1987–93PubMedCrossRef Lee JW, Lee YK, Ban JO, et al. Green tea (−)-epigallocatechin-3-gallate inhibits beta-amyloid-induced cognitive dysfunction through modification of secretase activity via inhibition of ERK and NF-kappaB pathways in mice. J Nutr 2009 Oct; 139(10): 1987–93PubMedCrossRef
198.
Zurück zum Zitat Rezai-Zadeh K, Arendash GW, Hou H, et al. Green tea epigallocatechin-3-gallate (EGCG) reduces beta-amyloid mediated cognitive impairment and modulates tau pathology in Alzheimer transgenic mice. Brain Res 2008 Jun 12; 1214: 177–87PubMedCrossRef Rezai-Zadeh K, Arendash GW, Hou H, et al. Green tea epigallocatechin-3-gallate (EGCG) reduces beta-amyloid mediated cognitive impairment and modulates tau pathology in Alzheimer transgenic mice. Brain Res 2008 Jun 12; 1214: 177–87PubMedCrossRef
199.
Zurück zum Zitat Lannfelt L, Blennow K, Zetterberg H, et al. Safety, efficacy, and biomarker findings of PBT2 in targeting Abeta as a modifying therapy for Alzheimer’s disease: a phase IIa, double-blind, randomised, placebo-controlled trial. Lancet Neurol 2008 Sep; 7(9): 779–86PubMedCrossRef Lannfelt L, Blennow K, Zetterberg H, et al. Safety, efficacy, and biomarker findings of PBT2 in targeting Abeta as a modifying therapy for Alzheimer’s disease: a phase IIa, double-blind, randomised, placebo-controlled trial. Lancet Neurol 2008 Sep; 7(9): 779–86PubMedCrossRef
200.
Zurück zum Zitat Garzone P, Koller M, Pastrak A, et al. Oral amyloid anti-aggregating agent ELND005 is measurable in CSF and brain of healthy adult men [abstract]. Alzheimers Dement 2009; 5 (1 Suppl. 4): P323CrossRef Garzone P, Koller M, Pastrak A, et al. Oral amyloid anti-aggregating agent ELND005 is measurable in CSF and brain of healthy adult men [abstract]. Alzheimers Dement 2009; 5 (1 Suppl. 4): P323CrossRef
201.
Zurück zum Zitat Schenk D, Barbour R, Dunn W, et al. Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 1999 Jul 8; 400(6740): 173–7PubMedCrossRef Schenk D, Barbour R, Dunn W, et al. Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 1999 Jul 8; 400(6740): 173–7PubMedCrossRef
202.
Zurück zum Zitat Bard F, Cannon C, Barbour R, et al. Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Nat Med 2000 Aug; 6(8): 916–9PubMedCrossRef Bard F, Cannon C, Barbour R, et al. Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Nat Med 2000 Aug; 6(8): 916–9PubMedCrossRef
203.
Zurück zum Zitat Frenkel D, Solomon B, Benhar I. Modulation of Alzheimer’s beta-amyloid neurotoxicity by site-directed single-chain antibody. J Neuroimmunol 2000 Jul 1; 106(1–2): 23–31PubMedCrossRef Frenkel D, Solomon B, Benhar I. Modulation of Alzheimer’s beta-amyloid neurotoxicity by site-directed single-chain antibody. J Neuroimmunol 2000 Jul 1; 106(1–2): 23–31PubMedCrossRef
204.
Zurück zum Zitat Bacskai BJ, Kajdasz ST, McLellan ME, et al. Non-Fcmediated mechanisms are involved in clearance of amyloid-beta in vivo by immunotherapy. J Neurosci 2002 Sep 15; 22(18): 7873–8PubMed Bacskai BJ, Kajdasz ST, McLellan ME, et al. Non-Fcmediated mechanisms are involved in clearance of amyloid-beta in vivo by immunotherapy. J Neurosci 2002 Sep 15; 22(18): 7873–8PubMed
205.
Zurück zum Zitat DeMattos RB, Bales KR, Cummins DJ, et al. Peripheral anti-A beta antibody alters CNS and plasma A beta clearance and decreases brain A beta burden in a mouse model of Alzheimer’s disease. Proc Natl Acad Sci U S A 2001 Jul 17; 98(15): 8850–5PubMedCrossRef DeMattos RB, Bales KR, Cummins DJ, et al. Peripheral anti-A beta antibody alters CNS and plasma A beta clearance and decreases brain A beta burden in a mouse model of Alzheimer’s disease. Proc Natl Acad Sci U S A 2001 Jul 17; 98(15): 8850–5PubMedCrossRef
206.
Zurück zum Zitat Dodart JC, Bales KR, Gannon KS, et al. Immunization reverses memory deficits without reducing brain Abeta burden in Alzheimer’s disease model. Nat Neurosci 2002 May; 5(5): 452–7PubMed Dodart JC, Bales KR, Gannon KS, et al. Immunization reverses memory deficits without reducing brain Abeta burden in Alzheimer’s disease model. Nat Neurosci 2002 May; 5(5): 452–7PubMed
207.
Zurück zum Zitat Gilman S, Koller M, Black RS, et al. Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial. Neurology 2005 May 10; 64(9): 1553–62PubMedCrossRef Gilman S, Koller M, Black RS, et al. Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial. Neurology 2005 May 10; 64(9): 1553–62PubMedCrossRef
208.
Zurück zum Zitat Wang CY, Finstad CL, Walfield AM, et al. Site-specific UBITh amyloid-beta vaccine for immunotherapy of Alzheimer’s disease. Vaccine 2007 Apr 20; 25(16): 3041–52PubMedCrossRef Wang CY, Finstad CL, Walfield AM, et al. Site-specific UBITh amyloid-beta vaccine for immunotherapy of Alzheimer’s disease. Vaccine 2007 Apr 20; 25(16): 3041–52PubMedCrossRef
209.
Zurück zum Zitat Schneeberger A, Mandler M, Otawa O, et al. Development of AFFITOPE vaccines for Alzheimer’s disease (AD): from concept to clinical testing. J Nutr Health Aging 2009 Mar; 13(3): 264–7PubMedCrossRef Schneeberger A, Mandler M, Otawa O, et al. Development of AFFITOPE vaccines for Alzheimer’s disease (AD): from concept to clinical testing. J Nutr Health Aging 2009 Mar; 13(3): 264–7PubMedCrossRef
210.
Zurück zum Zitat Black RS, Sperling RA, Safirstein B, et al. A single ascending dose study of bapineuzumab in patients with Alzheimer disease. Alzheimer Dis Assoc Disord 2010 Apr–Jun; 24(2): 198–203PubMedCrossRef Black RS, Sperling RA, Safirstein B, et al. A single ascending dose study of bapineuzumab in patients with Alzheimer disease. Alzheimer Dis Assoc Disord 2010 Apr–Jun; 24(2): 198–203PubMedCrossRef
211.
Zurück zum Zitat Salloway S, Sperling R, Gilman S, et al. A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease. Neurology 2009 Dec 15; 73(24): 2061–70PubMedCrossRef Salloway S, Sperling R, Gilman S, et al. A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease. Neurology 2009 Dec 15; 73(24): 2061–70PubMedCrossRef
212.
Zurück zum Zitat Pfizer. A long-term safety and tolerability study of bapineuzumab in Alzheimer disease patients [ClinicalTrials.gov identifier NCT00996918]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://clinicaltrials.gov [Accessed 2010 Dec 20] Pfizer. A long-term safety and tolerability study of bapineuzumab in Alzheimer disease patients [ClinicalTrials.gov identifier NCT00996918]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​clinicaltrials.​gov [Accessed 2010 Dec 20]
213.
Zurück zum Zitat Pfizer. A long-term safety and tolerability extension study of bapineuzumab in Alzheimer disease patients [ClinicalTrials.gov identifier NCT00998764]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://clinicaltrials.gov [Accessed 2010 Dec 20] Pfizer. A long-term safety and tolerability extension study of bapineuzumab in Alzheimer disease patients [ClinicalTrials.gov identifier NCT00998764]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​clinicaltrials.​gov [Accessed 2010 Dec 20]
214.
Zurück zum Zitat Siemers ER, Friedrich S, Dean RA, et al. Safety and changes in plasma and cerebrospinal fluid amyloid beta after a single administration of an amyloid beta monoclonal antibody in subjects with Alzheimer disease. Clin Neuropharmacol 2010 Mar–Apr; 33(2): 67–73PubMedCrossRef Siemers ER, Friedrich S, Dean RA, et al. Safety and changes in plasma and cerebrospinal fluid amyloid beta after a single administration of an amyloid beta monoclonal antibody in subjects with Alzheimer disease. Clin Neuropharmacol 2010 Mar–Apr; 33(2): 67–73PubMedCrossRef
215.
Zurück zum Zitat Siemers ER, Friedrich S, Dean RA, et al. Safety, tolerability and biomarker effects of an Abeta monoclonal antibody administered to patients with Alzheimer’s disease [abstract]. Alzheimers Dement 2008; 4 (1 Suppl. 4): T774CrossRef Siemers ER, Friedrich S, Dean RA, et al. Safety, tolerability and biomarker effects of an Abeta monoclonal antibody administered to patients with Alzheimer’s disease [abstract]. Alzheimers Dement 2008; 4 (1 Suppl. 4): T774CrossRef
216.
Zurück zum Zitat Goto T, Fujikoshi S, Uenaka K, et al. Solanezumab was safe and well-tolerated for Asian patients with mild-to-moderate Alzheimer’s disease in a multicenter, randomized, open-label, multi-dose study [abstract]. Alzheimers Dement 2010; 6 (1 Suppl. 4): S308CrossRef Goto T, Fujikoshi S, Uenaka K, et al. Solanezumab was safe and well-tolerated for Asian patients with mild-to-moderate Alzheimer’s disease in a multicenter, randomized, open-label, multi-dose study [abstract]. Alzheimers Dement 2010; 6 (1 Suppl. 4): S308CrossRef
217.
Zurück zum Zitat Eli Lilly and Company. Continued safety monitoring of solanezumab in Alzheimer’s disease (EXPEDITION EXT) [ClinicalTrials.gov identifier NCT01127633]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://clinicaltrials.gov [Accessed 2011 Mar 14] Eli Lilly and Company. Continued safety monitoring of solanezumab in Alzheimer’s disease (EXPEDITION EXT) [ClinicalTrials.gov identifier NCT01127633]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​clinicaltrials.​gov [Accessed 2011 Mar 14]
218.
Zurück zum Zitat Dodel RC, Du Y, Depboylu C, et al. Intravenous immunoglobulins containing antibodies against beta-amyloid for the treatment of Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2004 Oct; 75(10): 1472–4PubMedCrossRef Dodel RC, Du Y, Depboylu C, et al. Intravenous immunoglobulins containing antibodies against beta-amyloid for the treatment of Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2004 Oct; 75(10): 1472–4PubMedCrossRef
219.
Zurück zum Zitat Relkin NR, Szabo P, Adamiak B, et al. 18-Month study of intravenous immunoglobulin for treatment of mild Alzheimer disease. Neurobiol Aging 2009 Nov; 30(11): 1728–36PubMedCrossRef Relkin NR, Szabo P, Adamiak B, et al. 18-Month study of intravenous immunoglobulin for treatment of mild Alzheimer disease. Neurobiol Aging 2009 Nov; 30(11): 1728–36PubMedCrossRef
220.
Zurück zum Zitat Tsakanikas D, Shah K, Flores C, et al. Effects of uninterrupted intravenous immunoglobin treatment of Alzheimer’s Disease for nine months [abstract]. Alzheimers Dement 2008; 4 (1 Suppl. 4): T776CrossRef Tsakanikas D, Shah K, Flores C, et al. Effects of uninterrupted intravenous immunoglobin treatment of Alzheimer’s Disease for nine months [abstract]. Alzheimers Dement 2008; 4 (1 Suppl. 4): T776CrossRef
221.
Zurück zum Zitat Goedert M, Klug A, Crowther RA. Tau protein, the paired helical filament and Alzheimer’s disease. J Alzheimers Dis 2006; 9 (3 Suppl.): 195–207PubMed Goedert M, Klug A, Crowther RA. Tau protein, the paired helical filament and Alzheimer’s disease. J Alzheimers Dis 2006; 9 (3 Suppl.): 195–207PubMed
222.
Zurück zum Zitat Thal DR, Holzer M, Rub U, et al. Alzheimer-related taupathology in the perforant path target zone and in the hippocampal stratum oriens and radiatum correlates with onset and degree of dementia. Exp Neurol 2000 May; 163(1): 98–110PubMedCrossRef Thal DR, Holzer M, Rub U, et al. Alzheimer-related taupathology in the perforant path target zone and in the hippocampal stratum oriens and radiatum correlates with onset and degree of dementia. Exp Neurol 2000 May; 163(1): 98–110PubMedCrossRef
223.
Zurück zum Zitat Schneider A, Mandelkow E. Tau-based treatment strategies in neurodegenerative diseases. Neurotherapeutics 2008 Jul; 5(3): 443–57PubMedCrossRef Schneider A, Mandelkow E. Tau-based treatment strategies in neurodegenerative diseases. Neurotherapeutics 2008 Jul; 5(3): 443–57PubMedCrossRef
224.
Zurück zum Zitat Lee VM, Trojanowski JQ. Progress from Alzheimer’s tangles to pathological tau points towards more effective therapies now. J Alzheimers Dis 2006; 9 (3 Suppl.): 257–62PubMed Lee VM, Trojanowski JQ. Progress from Alzheimer’s tangles to pathological tau points towards more effective therapies now. J Alzheimers Dis 2006; 9 (3 Suppl.): 257–62PubMed
225.
Zurück zum Zitat Tariot PN, Aisen PS. Can lithium or valproate untie tangles in Alzheimer’s disease? J Clin Psychiatry 2009 Jun; 70(6): 919–21PubMedCrossRef Tariot PN, Aisen PS. Can lithium or valproate untie tangles in Alzheimer’s disease? J Clin Psychiatry 2009 Jun; 70(6): 919–21PubMedCrossRef
226.
Zurück zum Zitat Hampel H, Ewers M, Burger K, et al. Lithium trial in Alzheimer’s disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study. J Clin Psychiatry 2009 Jun; 70(6): 922–31PubMedCrossRef Hampel H, Ewers M, Burger K, et al. Lithium trial in Alzheimer’s disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study. J Clin Psychiatry 2009 Jun; 70(6): 922–31PubMedCrossRef
227.
Zurück zum Zitat Noscira SA. Efficacy, safety and tolerability of tideglusib to treat mild-to-moderate Alzheimer’s disease patients (ARGO) [ClinicalTrials.gov identifier NCT01350362]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://clinicaltrials.gov [Accessed 2011 Jun 12] Noscira SA. Efficacy, safety and tolerability of tideglusib to treat mild-to-moderate Alzheimer’s disease patients (ARGO) [ClinicalTrials.gov identifier NCT01350362]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​clinicaltrials.​gov [Accessed 2011 Jun 12]
229.
Zurück zum Zitat Wischik CM, Edwards PC, Lai RY, et al. Selective inhibition of Alzheimer disease-like tau aggregation by phenothiazines. Proc Natl Acad Sci U S A 1996 Oct 1; 93(20): 11213–8PubMedCrossRef Wischik CM, Edwards PC, Lai RY, et al. Selective inhibition of Alzheimer disease-like tau aggregation by phenothiazines. Proc Natl Acad Sci U S A 1996 Oct 1; 93(20): 11213–8PubMedCrossRef
230.
Zurück zum Zitat Oz M, Lorke DE, Petroianu GA. Methylene blue and Alzheimer’s disease. Biochem Pharmacol 2009 Oct 15; 78(8): 927–32PubMedCrossRef Oz M, Lorke DE, Petroianu GA. Methylene blue and Alzheimer’s disease. Biochem Pharmacol 2009 Oct 15; 78(8): 927–32PubMedCrossRef
231.
Zurück zum Zitat Atamna H, Kumar R. Protective role of methylene blue in Alzheimer’s disease via mitochondria and cytochrome c oxidase. J Alzheimers Dis 2010; 20 (2 Suppl.): S439–52PubMed Atamna H, Kumar R. Protective role of methylene blue in Alzheimer’s disease via mitochondria and cytochrome c oxidase. J Alzheimers Dis 2010; 20 (2 Suppl.): S439–52PubMed
232.
Zurück zum Zitat Wischik CM, Bentham P, Wischik DJ, et al. Tau aggregation inhibitor (TAI) therapy with rember™ arrests disease progression in mild and moderate Alzheimer’s disease over 50 weeks [abstract]. Alzheimers Dement 2008; 4(4): T167CrossRef Wischik CM, Bentham P, Wischik DJ, et al. Tau aggregation inhibitor (TAI) therapy with rember™ arrests disease progression in mild and moderate Alzheimer’s disease over 50 weeks [abstract]. Alzheimers Dement 2008; 4(4): T167CrossRef
234.
Zurück zum Zitat Swardfager W, Lanctot K, Rothenburg L, et al. A meta-analysis of cytokines in Alzheimer’s disease. Biol Psychiatry 2010 Nov 15; 68(10): 930–41PubMedCrossRef Swardfager W, Lanctot K, Rothenburg L, et al. A meta-analysis of cytokines in Alzheimer’s disease. Biol Psychiatry 2010 Nov 15; 68(10): 930–41PubMedCrossRef
235.
Zurück zum Zitat McGeer PL, McGeer EG. NSAIDs and Alzheimer disease: epidemiological, animal model and clinical studies. Neurobiol Aging 2007 May; 28(5): 639–47PubMedCrossRef McGeer PL, McGeer EG. NSAIDs and Alzheimer disease: epidemiological, animal model and clinical studies. Neurobiol Aging 2007 May; 28(5): 639–47PubMedCrossRef
236.
Zurück zum Zitat Cagnin A, Brooks DJ, Kennedy AM, et al. In-vivo measurement of activated microglia in dementia. Lancet 2001 Aug 11; 358(9280): 461–7PubMedCrossRef Cagnin A, Brooks DJ, Kennedy AM, et al. In-vivo measurement of activated microglia in dementia. Lancet 2001 Aug 11; 358(9280): 461–7PubMedCrossRef
237.
Zurück zum Zitat Floyd RA. Neuroinflammatory processes are important in neurodegenerative diseases: an hypothesis to explain the increased formation of reactive oxygen and nitrogen species as major factors involved in neurodegenerative disease development. Free Radic Biol Med 1999 May; 26(9–10): 1346–55PubMedCrossRef Floyd RA. Neuroinflammatory processes are important in neurodegenerative diseases: an hypothesis to explain the increased formation of reactive oxygen and nitrogen species as major factors involved in neurodegenerative disease development. Free Radic Biol Med 1999 May; 26(9–10): 1346–55PubMedCrossRef
238.
Zurück zum Zitat McGeer PL, Schulzer M, McGeer EG. Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer’s disease: a review of 17 epidemiologic studies. Neurology 1996 Aug; 47(2): 425–32PubMedCrossRef McGeer PL, Schulzer M, McGeer EG. Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer’s disease: a review of 17 epidemiologic studies. Neurology 1996 Aug; 47(2): 425–32PubMedCrossRef
239.
Zurück zum Zitat Szekely CA, Thorne JE, Zandi PP, et al. Nonsteroidal anti-inflammatory drugs for the prevention of Alzheimer’s disease: a systematic review. Neuroepidemiology 2004 Jul–Aug; 23(4): 159–69PubMedCrossRef Szekely CA, Thorne JE, Zandi PP, et al. Nonsteroidal anti-inflammatory drugs for the prevention of Alzheimer’s disease: a systematic review. Neuroepidemiology 2004 Jul–Aug; 23(4): 159–69PubMedCrossRef
240.
Zurück zum Zitat Aisen PS, Davis KL. Inflammatory mechanisms in Alzheimer’s disease: implications for therapy. Am J Psychiatry 1994 Aug; 151(8): 1105–13PubMed Aisen PS, Davis KL. Inflammatory mechanisms in Alzheimer’s disease: implications for therapy. Am J Psychiatry 1994 Aug; 151(8): 1105–13PubMed
241.
Zurück zum Zitat Hoozemans JJ, Veerhuis R, Janssen I, et al. The role of cyclo-oxygenase 1 and 2 activity in prostaglandin E(2) secretion by cultured human adult microglia: implications for Alzheimer’s disease. Brain Res 2002 Oct 4; 951(2): 218–26PubMedCrossRef Hoozemans JJ, Veerhuis R, Janssen I, et al. The role of cyclo-oxygenase 1 and 2 activity in prostaglandin E(2) secretion by cultured human adult microglia: implications for Alzheimer’s disease. Brain Res 2002 Oct 4; 951(2): 218–26PubMedCrossRef
242.
Zurück zum Zitat Weggen S, Eriksen JL, Sagi SA, et al. Evidence that nonsteroidal anti-inflammatory drugs decrease amyloid beta 42 production by direct modulation of gamma-secretase activity. J Biol Chem 2003 Aug 22; 278(34): 31831–7PubMedCrossRef Weggen S, Eriksen JL, Sagi SA, et al. Evidence that nonsteroidal anti-inflammatory drugs decrease amyloid beta 42 production by direct modulation of gamma-secretase activity. J Biol Chem 2003 Aug 22; 278(34): 31831–7PubMedCrossRef
243.
Zurück zum Zitat Beher D, Clarke EE, Wrigley JD, et al. Selected non-steroidal anti-inflammatory drugs and their derivatives target gamma-secretase at a novel site: evidence for an allosteric mechanism. J Biol Chem 2004 Oct 15; 279(42): 43419–26PubMedCrossRef Beher D, Clarke EE, Wrigley JD, et al. Selected non-steroidal anti-inflammatory drugs and their derivatives target gamma-secretase at a novel site: evidence for an allosteric mechanism. J Biol Chem 2004 Oct 15; 279(42): 43419–26PubMedCrossRef
244.
Zurück zum Zitat Rogers J, Kirby LC, Hempelman SR, et al. Clinical trial of indomethacin in Alzheimer’s disease. Neurology 1993 Aug; 43(8): 1609–11PubMedCrossRef Rogers J, Kirby LC, Hempelman SR, et al. Clinical trial of indomethacin in Alzheimer’s disease. Neurology 1993 Aug; 43(8): 1609–11PubMedCrossRef
245.
Zurück zum Zitat Tabet N, Feldman H. Indomethacin for Alzheimer’s disease. Cochrane Database of Syst Rev 2002; (2): CD003673 Tabet N, Feldman H. Indomethacin for Alzheimer’s disease. Cochrane Database of Syst Rev 2002; (2): CD003673
246.
Zurück zum Zitat Eriksen JL, Sagi SA, Smith TE, et al. NSAIDs and enantiomers of flurbiprofen target gamma-secretase and lower Abeta 42 in vivo. J Clin Invest 2003 Aug; 112(3): 440–9PubMed Eriksen JL, Sagi SA, Smith TE, et al. NSAIDs and enantiomers of flurbiprofen target gamma-secretase and lower Abeta 42 in vivo. J Clin Invest 2003 Aug; 112(3): 440–9PubMed
247.
Zurück zum Zitat Morihara T, Chu T, Ubeda O, et al. Selective inhibition of Abeta42 production by NSAID R-enantiomers. J Neurochem 2002 Nov; 83(4): 1009–12PubMedCrossRef Morihara T, Chu T, Ubeda O, et al. Selective inhibition of Abeta42 production by NSAID R-enantiomers. J Neurochem 2002 Nov; 83(4): 1009–12PubMedCrossRef
248.
Zurück zum Zitat Galasko DR, Graff-Radford N, May S, et al. Safety, tolerability, pharmacokinetics, and Abeta levels after short-term administration of R-flurbiprofen in healthy elderly individuals. Alzheimer Dis Assoc Disord 2007 Oct–Dec; 21(4): 292–9PubMedCrossRef Galasko DR, Graff-Radford N, May S, et al. Safety, tolerability, pharmacokinetics, and Abeta levels after short-term administration of R-flurbiprofen in healthy elderly individuals. Alzheimer Dis Assoc Disord 2007 Oct–Dec; 21(4): 292–9PubMedCrossRef
249.
Zurück zum Zitat Wilcock GK, Black SE, Hendrix SB, et al. Efficacy and safety of tarenflurbil in mild to moderate Alzheimer’s disease: a randomised phase II trial. Lancet Neurol 2008 Jun; 7(6): 483–93PubMedCrossRef Wilcock GK, Black SE, Hendrix SB, et al. Efficacy and safety of tarenflurbil in mild to moderate Alzheimer’s disease: a randomised phase II trial. Lancet Neurol 2008 Jun; 7(6): 483–93PubMedCrossRef
250.
Zurück zum Zitat Imbimbo BP. Why did tarenflurbil fail in Alzheimer’s disease? J Alzheimers Dis 2009; 17(4): 757–60PubMed Imbimbo BP. Why did tarenflurbil fail in Alzheimer’s disease? J Alzheimers Dis 2009; 17(4): 757–60PubMed
251.
Zurück zum Zitat Reddy PH, Beal MF. Amyloid beta, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer’s disease. Trends Mol Med 2008 Feb; 14(2): 45–53PubMedCrossRef Reddy PH, Beal MF. Amyloid beta, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer’s disease. Trends Mol Med 2008 Feb; 14(2): 45–53PubMedCrossRef
252.
Zurück zum Zitat Hansson Petersen CA, Alikhani N, Behbahani H, et al. The amyloid beta-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae. Proc Natl Acad Sci U S A 2008 Sep 2; 105(35): 13145–50PubMedCrossRef Hansson Petersen CA, Alikhani N, Behbahani H, et al. The amyloid beta-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae. Proc Natl Acad Sci U S A 2008 Sep 2; 105(35): 13145–50PubMedCrossRef
253.
Zurück zum Zitat Bachurin S, Bukatina E, Lermontova N, et al. Antihistamine agent Dimebon as a novel neuroprotector and a cognition enhancer. Ann N Y Acad Sci 2001 Jun; 939: 425–35PubMedCrossRef Bachurin S, Bukatina E, Lermontova N, et al. Antihistamine agent Dimebon as a novel neuroprotector and a cognition enhancer. Ann N Y Acad Sci 2001 Jun; 939: 425–35PubMedCrossRef
254.
Zurück zum Zitat Wu J, Li Q, Bezprozvanny I. Evaluation of Dimebon in cellular model of Huntington’s disease [abstract]. Mol Neurodegener 2008; 3: 15PubMedCrossRef Wu J, Li Q, Bezprozvanny I. Evaluation of Dimebon in cellular model of Huntington’s disease [abstract]. Mol Neurodegener 2008; 3: 15PubMedCrossRef
255.
Zurück zum Zitat Moreira PI, Santos MS, Moreno A, et al. Amyloid beta-peptide promotes permeability transition pore in brain mitochondria. Biosci Rep 2001 Dec; 21(6): 789–800PubMedCrossRef Moreira PI, Santos MS, Moreno A, et al. Amyloid beta-peptide promotes permeability transition pore in brain mitochondria. Biosci Rep 2001 Dec; 21(6): 789–800PubMedCrossRef
256.
Zurück zum Zitat Zhang S, Hedskog L, Petersen CA, et al. Dimebon (latrepirdine) enhances mitochondrial function and protects neuronal cells from death. J Alzheimers Dis 2010; 21(2): 389–402PubMed Zhang S, Hedskog L, Petersen CA, et al. Dimebon (latrepirdine) enhances mitochondrial function and protects neuronal cells from death. J Alzheimers Dis 2010; 21(2): 389–402PubMed
257.
Zurück zum Zitat Doody RS, Gavrilova SI, Sano M, et al. Effect of dimebon on cognition, activities of daily living, behaviour, and global function in patients with mild-to-moderate Alzheimer’s disease: a randomised, double-blind, placebo-controlled study. Lancet 2008 Jul 19; 372(9634): 207–15PubMedCrossRef Doody RS, Gavrilova SI, Sano M, et al. Effect of dimebon on cognition, activities of daily living, behaviour, and global function in patients with mild-to-moderate Alzheimer’s disease: a randomised, double-blind, placebo-controlled study. Lancet 2008 Jul 19; 372(9634): 207–15PubMedCrossRef
258.
Zurück zum Zitat Kalmijn S, Launer LJ, Ott A, et al. Dietary fat intake and the risk of incident dementia in the Rotterdam Study. Ann Neurol 1997 Nov; 42(5): 776–82PubMedCrossRef Kalmijn S, Launer LJ, Ott A, et al. Dietary fat intake and the risk of incident dementia in the Rotterdam Study. Ann Neurol 1997 Nov; 42(5): 776–82PubMedCrossRef
259.
Zurück zum Zitat Morris MC, Evans DA, Bienias JL, et al. Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Arch Neurol 2003 Jul; 60(7): 940–6PubMedCrossRef Morris MC, Evans DA, Bienias JL, et al. Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Arch Neurol 2003 Jul; 60(7): 940–6PubMedCrossRef
260.
Zurück zum Zitat Schaefer EJ, Bongard V, Beiser AS, et al. Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease: the Framingham Heart Study. Arch Neurol 2006 Nov; 63(11): 1545–50PubMedCrossRef Schaefer EJ, Bongard V, Beiser AS, et al. Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease: the Framingham Heart Study. Arch Neurol 2006 Nov; 63(11): 1545–50PubMedCrossRef
261.
Zurück zum Zitat Prasad MR, Lovell MA, Yatin M, et al. Regional membrane phospholipid alterations in Alzheimer’s disease. Neurochem Res 1998 Jan; 23(1): 81–8PubMedCrossRef Prasad MR, Lovell MA, Yatin M, et al. Regional membrane phospholipid alterations in Alzheimer’s disease. Neurochem Res 1998 Jan; 23(1): 81–8PubMedCrossRef
262.
Zurück zum Zitat Soderberg M, Edlund C, Kristensson K, et al. Fatty acid composition of brain phospholipids in aging and in Alzheimer’s disease. Lipids 1991 Jun; 26(6): 421–5PubMedCrossRef Soderberg M, Edlund C, Kristensson K, et al. Fatty acid composition of brain phospholipids in aging and in Alzheimer’s disease. Lipids 1991 Jun; 26(6): 421–5PubMedCrossRef
263.
Zurück zum Zitat Hoglund K, Blennow K. Effect of HMG-CoA reductase inhibitors on beta-amyloid peptide levels: implications for Alzheimer’s disease. CNS Drugs 2007; 21(6): 449–62PubMedCrossRef Hoglund K, Blennow K. Effect of HMG-CoA reductase inhibitors on beta-amyloid peptide levels: implications for Alzheimer’s disease. CNS Drugs 2007; 21(6): 449–62PubMedCrossRef
264.
Zurück zum Zitat Fassbender K, Simons M, Bergmann C, et al. Simvastatin strongly reduces levels of Alzheimer’s disease beta-amyloid peptides Abeta 42 and Abeta 40 in vitro and in vivo. Proc Natl Acad Sci U S A 2001 May 8; 98(10): 5856–61PubMedCrossRef Fassbender K, Simons M, Bergmann C, et al. Simvastatin strongly reduces levels of Alzheimer’s disease beta-amyloid peptides Abeta 42 and Abeta 40 in vitro and in vivo. Proc Natl Acad Sci U S A 2001 May 8; 98(10): 5856–61PubMedCrossRef
265.
Zurück zum Zitat Refolo LM, Pappolla MA, LaFrancois J, et al. A cholesterol-lowering drug reduces beta-amyloid pathology in a transgenic mouse model of Alzheimer’s disease. Neurobiol Dis 2001 Oct; 8(5): 890–9PubMedCrossRef Refolo LM, Pappolla MA, LaFrancois J, et al. A cholesterol-lowering drug reduces beta-amyloid pathology in a transgenic mouse model of Alzheimer’s disease. Neurobiol Dis 2001 Oct; 8(5): 890–9PubMedCrossRef
266.
Zurück zum Zitat Solomon A, Kivipelto M. Cholesterol-modifying strategies for Alzheimer’s disease. Expert Rev Neurother 2009 May; 9(5): 695–709PubMedCrossRef Solomon A, Kivipelto M. Cholesterol-modifying strategies for Alzheimer’s disease. Expert Rev Neurother 2009 May; 9(5): 695–709PubMedCrossRef
267.
Zurück zum Zitat McGuinness B, Craig D, Bullock R, et al. Statins for the prevention of dementia. Cochrane Database Syst Rev 2009; (2): CD003160 McGuinness B, Craig D, Bullock R, et al. Statins for the prevention of dementia. Cochrane Database Syst Rev 2009; (2): CD003160
268.
Zurück zum Zitat Rockwood K, Kirkland S, Hogan DB, et al. Use of lipid-lowering agents, indication bias, and the risk of dementia in community-dwelling elderly people. Arch Neurol 2002 Feb; 59(2): 223–7PubMedCrossRef Rockwood K, Kirkland S, Hogan DB, et al. Use of lipid-lowering agents, indication bias, and the risk of dementia in community-dwelling elderly people. Arch Neurol 2002 Feb; 59(2): 223–7PubMedCrossRef
269.
Zurück zum Zitat Jick H, Zornberg GL, Jick SS, et al. Statins and the risk of dementia. Lancet 2000 Nov 11; 356(9242): 1627–31PubMedCrossRef Jick H, Zornberg GL, Jick SS, et al. Statins and the risk of dementia. Lancet 2000 Nov 11; 356(9242): 1627–31PubMedCrossRef
270.
Zurück zum Zitat Arvanitakis Z, Schneider JA, Wilson RS, et al. Statins, incident Alzheimer disease, change in cognitive function, and neuropathology. Neurology 2008 May 6; 70(19 Pt 2): 1795–802PubMed Arvanitakis Z, Schneider JA, Wilson RS, et al. Statins, incident Alzheimer disease, change in cognitive function, and neuropathology. Neurology 2008 May 6; 70(19 Pt 2): 1795–802PubMed
271.
Zurück zum Zitat Tokuda T, Tamaoka A, Matsuno S, et al. Plasma levels of amyloid beta proteins did not differ between subjects taking statins and those not taking statins. Ann Neurol 2001 Apr; 49(4): 546–7PubMedCrossRef Tokuda T, Tamaoka A, Matsuno S, et al. Plasma levels of amyloid beta proteins did not differ between subjects taking statins and those not taking statins. Ann Neurol 2001 Apr; 49(4): 546–7PubMedCrossRef
272.
Zurück zum Zitat Benito-Leon J, Louis ED, Vega S, et al. Statins and cognitive functioning in the elderly: a population-based study. J Alzheimers Dis 2010; 21(1): 95–102PubMed Benito-Leon J, Louis ED, Vega S, et al. Statins and cognitive functioning in the elderly: a population-based study. J Alzheimers Dis 2010; 21(1): 95–102PubMed
273.
Zurück zum Zitat McGuinness B, O’Hare J, Craig D, et al. Statins for the treatment of dementia. Cochrane Database Syst Rev 2010; (8) CD007514 McGuinness B, O’Hare J, Craig D, et al. Statins for the treatment of dementia. Cochrane Database Syst Rev 2010; (8) CD007514
274.
Zurück zum Zitat Tsuji A, Saheki A, Tamai I, et al. Transport mechanism of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors at the blood-brain barrier. J Pharmacol Exp Ther 1993 Dec; 267(3): 1085–90PubMed Tsuji A, Saheki A, Tamai I, et al. Transport mechanism of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors at the blood-brain barrier. J Pharmacol Exp Ther 1993 Dec; 267(3): 1085–90PubMed
275.
Zurück zum Zitat Sparks DL, Connor DJ, Browne PJ, et al. HMG-CoA reductase inhibitors (statins) in the treatment of Alzheimer’s disease and why it would be ill-advised to use one that crosses the blood-brain barrier. J Nutr Health Aging 2002; 6(5): 324–31PubMed Sparks DL, Connor DJ, Browne PJ, et al. HMG-CoA reductase inhibitors (statins) in the treatment of Alzheimer’s disease and why it would be ill-advised to use one that crosses the blood-brain barrier. J Nutr Health Aging 2002; 6(5): 324–31PubMed
276.
Zurück zum Zitat Simons M, Schwarzler F, Lutjohann D, et al. Treatment with simvastatin in normocholesterolemic patients with Alzheimer’s disease: a 26-week randomized, placebo-controlled, double-blind trial. Ann Neurol 2002 Sep; 52(3): 346–50PubMedCrossRef Simons M, Schwarzler F, Lutjohann D, et al. Treatment with simvastatin in normocholesterolemic patients with Alzheimer’s disease: a 26-week randomized, placebo-controlled, double-blind trial. Ann Neurol 2002 Sep; 52(3): 346–50PubMedCrossRef
277.
Zurück zum Zitat Lewis J, Dickson DW, Lin WL, et al. Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP. Science 2001 Aug 24; 293(5534): 1487–91PubMedCrossRef Lewis J, Dickson DW, Lin WL, et al. Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP. Science 2001 Aug 24; 293(5534): 1487–91PubMedCrossRef
278.
Zurück zum Zitat Gonzalez-Martinez A, Rosado B, Pesini P, et al. Plasma beta-amyloid peptides in canine aging and cognitive dysfunction as a model of Alzheimer’s disease. Exp Gerontol 2011 Mar 3; 46(7); 590–6PubMedCrossRef Gonzalez-Martinez A, Rosado B, Pesini P, et al. Plasma beta-amyloid peptides in canine aging and cognitive dysfunction as a model of Alzheimer’s disease. Exp Gerontol 2011 Mar 3; 46(7); 590–6PubMedCrossRef
279.
Zurück zum Zitat Sarasa M, Pesini P. Natural non-transgenic animal models for research in Alzheimer’s disease. Curr Alzheimer Res 2009 Apr; 6(2): 171–8PubMedCrossRef Sarasa M, Pesini P. Natural non-transgenic animal models for research in Alzheimer’s disease. Curr Alzheimer Res 2009 Apr; 6(2): 171–8PubMedCrossRef
280.
Zurück zum Zitat Hampel H, Frank R, Broich K, et al. Biomarkers for Alzheimer’s disease: academic, industry and regulatory perspectives. Nat Rev Drug Discov 2010 Jul; 9(7): 560–74PubMedCrossRef Hampel H, Frank R, Broich K, et al. Biomarkers for Alzheimer’s disease: academic, industry and regulatory perspectives. Nat Rev Drug Discov 2010 Jul; 9(7): 560–74PubMedCrossRef
281.
Zurück zum Zitat Strozyk D, Blennow K, White LR, et al. CSF Abeta 42 levels correlate with amyloid-neuropathology in a population-based autopsy study. Neurology 2003 Feb 25; 60(4): 652–6PubMedCrossRef Strozyk D, Blennow K, White LR, et al. CSF Abeta 42 levels correlate with amyloid-neuropathology in a population-based autopsy study. Neurology 2003 Feb 25; 60(4): 652–6PubMedCrossRef
282.
Zurück zum Zitat Buerger K, Ewers M, Pirttila T, et al. CSF phosphorylated tau protein correlates with neocortical neurofibrillary pathology in Alzheimer’s disease. Brain 2006 Nov; 129(Pt 11): 3035–41PubMedCrossRef Buerger K, Ewers M, Pirttila T, et al. CSF phosphorylated tau protein correlates with neocortical neurofibrillary pathology in Alzheimer’s disease. Brain 2006 Nov; 129(Pt 11): 3035–41PubMedCrossRef
283.
Zurück zum Zitat de Jong D, Kremer BP, Olde Rikkert MG, et al. Current state and future directions of neurochemical biomarkers for Alzheimer’s disease. Clin Chem Lab Med 2007; 45(11): 1421–34PubMed de Jong D, Kremer BP, Olde Rikkert MG, et al. Current state and future directions of neurochemical biomarkers for Alzheimer’s disease. Clin Chem Lab Med 2007; 45(11): 1421–34PubMed
284.
Zurück zum Zitat Ridha BH, Anderson VM, Barnes J, et al. Volumetric MRI and cognitive measures in Alzheimer disease: comparison of markers of progression. J Neurol 2008 Apr; 255(4): 567–74PubMedCrossRef Ridha BH, Anderson VM, Barnes J, et al. Volumetric MRI and cognitive measures in Alzheimer disease: comparison of markers of progression. J Neurol 2008 Apr; 255(4): 567–74PubMedCrossRef
285.
Zurück zum Zitat Frisoni GB, Fox NC, Jack Jr CR, et al. The clinical use of structural MRI in Alzheimer disease. Nat Rev Neurol 2010 Feb; 6(2): 67–77PubMedCrossRef Frisoni GB, Fox NC, Jack Jr CR, et al. The clinical use of structural MRI in Alzheimer disease. Nat Rev Neurol 2010 Feb; 6(2): 67–77PubMedCrossRef
286.
Zurück zum Zitat Yuan X, Shan B, Ma Y, et al. Multi-center study on Alzheimer’s disease using FDG PET: group and individual analyses. J Alzheimers Dis 2010; 19(3): 927–35PubMed Yuan X, Shan B, Ma Y, et al. Multi-center study on Alzheimer’s disease using FDG PET: group and individual analyses. J Alzheimers Dis 2010; 19(3): 927–35PubMed
287.
Zurück zum Zitat Mosconi L. Brain glucose metabolism in the early and specific diagnosis of Alzheimer’s disease: FDG-PET studies in MCI and AD. Eur J Nucl Med Mol Imaging 2005 Apr; 32(4): 486–510PubMedCrossRef Mosconi L. Brain glucose metabolism in the early and specific diagnosis of Alzheimer’s disease: FDG-PET studies in MCI and AD. Eur J Nucl Med Mol Imaging 2005 Apr; 32(4): 486–510PubMedCrossRef
288.
Zurück zum Zitat Rinne JO, Brooks DJ, Rossor MN, et al. 11C-PiB PET assessment of change in fibrillar amyloid-beta load in patients with Alzheimer’s disease treated with bapineuzumab: a phase 2, double-blind, placebo-controlled, ascending-dose study. Lancet Neurol 2010 Apr; 9(4): 363–72PubMedCrossRef Rinne JO, Brooks DJ, Rossor MN, et al. 11C-PiB PET assessment of change in fibrillar amyloid-beta load in patients with Alzheimer’s disease treated with bapineuzumab: a phase 2, double-blind, placebo-controlled, ascending-dose study. Lancet Neurol 2010 Apr; 9(4): 363–72PubMedCrossRef
289.
Zurück zum Zitat Forsberg A, Almkvist O, Engler H, et al. High PIB retention in Alzheimer’s disease is an early event with complex relationship with CSF biomarkers and functional parameters. Curr Alzheimer Res 2010 Feb; 7(1): 56–66PubMedCrossRef Forsberg A, Almkvist O, Engler H, et al. High PIB retention in Alzheimer’s disease is an early event with complex relationship with CSF biomarkers and functional parameters. Curr Alzheimer Res 2010 Feb; 7(1): 56–66PubMedCrossRef
290.
Zurück zum Zitat Clark CM, Schneider JA, Bedell BJ, et al. Use of florbetapir-PET for imaging beta-amyloid pathology. JAMA 2011 Jan 19; 305(3): 275–83PubMedCrossRef Clark CM, Schneider JA, Bedell BJ, et al. Use of florbetapir-PET for imaging beta-amyloid pathology. JAMA 2011 Jan 19; 305(3): 275–83PubMedCrossRef
291.
Zurück zum Zitat Okamura N, Yanai K. Florbetapir (18F), a PET imaging agent that binds to amyloid plaques for the potential detection of Alzheimer’s disease. IDrugs 2010 Dec; 13(12): 890–9PubMed Okamura N, Yanai K. Florbetapir (18F), a PET imaging agent that binds to amyloid plaques for the potential detection of Alzheimer’s disease. IDrugs 2010 Dec; 13(12): 890–9PubMed
292.
Zurück zum Zitat Engler H, Forsberg A, Almkvist O, et al. Two-year follow-up of amyloid deposition in patients with Alzheimer’s disease. Brain 2006 Nov; 129(Pt 11): 2856–66PubMedCrossRef Engler H, Forsberg A, Almkvist O, et al. Two-year follow-up of amyloid deposition in patients with Alzheimer’s disease. Brain 2006 Nov; 129(Pt 11): 2856–66PubMedCrossRef
293.
Zurück zum Zitat Scheuner D, Eckman C, Jensen M, et al. Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer’s disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer’s disease. Nat Med 1996 Aug; 2(8): 864–70PubMedCrossRef Scheuner D, Eckman C, Jensen M, et al. Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer’s disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer’s disease. Nat Med 1996 Aug; 2(8): 864–70PubMedCrossRef
294.
Zurück zum Zitat Kauwe JS, Wang J, Mayo K, et al. Alzheimer’s disease risk variants show association with cerebrospinal fluid amyloid beta. Neurogenetics 2009 Feb; 10(1): 13–7PubMedCrossRef Kauwe JS, Wang J, Mayo K, et al. Alzheimer’s disease risk variants show association with cerebrospinal fluid amyloid beta. Neurogenetics 2009 Feb; 10(1): 13–7PubMedCrossRef
295.
Zurück zum Zitat Coon KD, Myers AJ, Craig DW, et al. A high-density whole-genome association study reveals that APOE is the major susceptibility gene for sporadic late-onset Alzheimer’s disease. J Clin Psychiatry 2007 Apr; 68(4): 613–8PubMedCrossRef Coon KD, Myers AJ, Craig DW, et al. A high-density whole-genome association study reveals that APOE is the major susceptibility gene for sporadic late-onset Alzheimer’s disease. J Clin Psychiatry 2007 Apr; 68(4): 613–8PubMedCrossRef
296.
Zurück zum Zitat Lambert JC, Amouyel P. Genetics of Alzheimer’s disease: new evidences for an old hypothesis? Curr Opin Genet Dev 2011 Mar 1; 21(3): 295–301PubMedCrossRef Lambert JC, Amouyel P. Genetics of Alzheimer’s disease: new evidences for an old hypothesis? Curr Opin Genet Dev 2011 Mar 1; 21(3): 295–301PubMedCrossRef
297.
Zurück zum Zitat DeKosky ST, Carrillo MC, Phelps C, et al. Revision of the criteria for Alzheimer’s disease: a symposium. Alzheimers Dement 2011 Jan; 7(1): e1–12PubMedCrossRef DeKosky ST, Carrillo MC, Phelps C, et al. Revision of the criteria for Alzheimer’s disease: a symposium. Alzheimers Dement 2011 Jan; 7(1): e1–12PubMedCrossRef
Metadaten
Titel
Current and Emerging Drug Treatment Options for Alzheimer’s Disease
A Systematic Review
verfasst von
Nathan Herrmann
Sarah A. Chau
Ida Kircanski
Dr Krista L. Lanctôt
Publikationsdatum
01.10.2011
Verlag
Springer International Publishing
Erschienen in
Drugs / Ausgabe 15/2011
Print ISSN: 0012-6667
Elektronische ISSN: 1179-1950
DOI
https://doi.org/10.2165/11595870-000000000-00000

Weitere Artikel der Ausgabe 15/2011

Drugs 15/2011 Zur Ausgabe

Adis Drug Profile

Abiraterone Acetate

Current Opinion

Vitamins and Cognition

R&D Insight Profile

Apixaban