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Theme: Alzheimer's Disease - Review

New and emerging treatments for Alzheimer’s disease

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Pages 535-543 | Published online: 09 Jan 2014

References

  • Wimo A, Prince M. World Alzheimer Report 2010. Alzheimer’s Disease International, London, UK (2010).
  • Cappai R, Barnham KJ. Delineating the mechanism of Alzheimer’s disease A beta peptide neurotoxicity. Neurochem. Res.33(3), 526–532 (2008).
  • Pimplikar SW. Reassessing the amyloid cascade hypothesis of Alzheimer’s disease. Int. J. Biochem. Cell Biol.41(6), 1261–1268 (2009).
  • Perry EK, Perry RH, Blessed G, Tomlinson BE. Necropsy evidence of central cholinergic deficits in senile dementia. Lancet1(8004), 189 (1977).
  • Loy C, Schneider L. Galantamine for Alzheimer’s disease and mild cognitive impairment. Cochrane Database Syst. Rev.1, CD001747 (2006).
  • Birks J, Grimley Evans J, Iakovidou V, Tsolaki M. Rivastigmine for Alzheimer’s disease. Cochrane Database Syst. Rev.2, CD001191 (2009).
  • Birks J, Harvey RJ. Donepezil for dementia due to Alzheimer’s disease. Cochrane Database Syst. Rev.1, CD001190 (2006).
  • Rodda J, Morgan S, Walker Z. Are cholinesterase inhibitors effective in the management of the behavioral and psychological symptoms of dementia in Alzheimer’s disease? A systematic review of randomized, placebo-controlled trials of donepezil, rivastigmine and galantamine. Int. Psychogeriatr.21(5), 813–824 (2009).
  • Gauthier S, Feldman H, Hecker J et al. Efficacy of donepezil on behavioral symptoms in patients with moderate to severe Alzheimer’s disease. Donepezil MSAD Study Investigators Group. Int. Psychogeriatr.14(4), 389–404 (2002).
  • Ballard C, Sorensen S, Sharp S. Pharmacological therapy for people with Alzheimer’s disease: the balance of clinical effectiveness, ethical issues and social and healthcare costs. J. Alzheimer’s Dis.12(1), 53–59 (2007).
  • Ballard CG, Chalmers KA, Todd C et al. Cholinesterase inhibitors reduce cortical Abeta in dementia with Lewy bodies. Neurology68(20), 1726–1729 (2007).
  • Chalmers KA, Wilcock GK, Vinters HV et al. Cholinesterase inhibitors may increase phosphorylated tau in Alzheimer’s disease. J. Neurol.256(5), 717–720 (2009).
  • Lawlor BA, Davis KL. Does modulation of glutamatergic function represent a viable therapeutic strategy in Alzheimer’s disease? Biological Psych.31(4), 337–350 (1992).
  • Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA291(3), 317–324 (2004).
  • Atri A, Shaughnessy LW, Locascio JJ, Growdon JH. Long-term course and effectiveness of combination therapy in Alzheimer disease. Alzheimer Dis. Assoc. Disord.22(3), 209–221 (2008).
  • Wilcock GK, Ballard CG, Cooper JA, Loft H. Memantine for agitation/aggression and psychosis in moderately severe to severe Alzheimer’s disease: a pooled analysis of 3 studies. J. Clin. Psych.69(3), 341–348 (2008).
  • Doody RS, Tariot PN, Pfeiffer E, Olin JT, Graham SM. Meta-analysis of six-month memantine trials in Alzheimer’s disease. Alzheimers Dement.3(1), 7–17 (2007).
  • Howard R, McShane R, Lindesay J et al. Donepezil and memantine for moderate-to-severe Alzheimer’s disease. N. Engl. J. Med.366, 893–903 (2012).
  • Hock C, Maddalena A, Raschig A et al. Treatment with the selective muscarinic m1 agonist talsaclidine decreases cerebrospinal fluid levels of A beta 42 in patients with Alzheimer’s disease. Amyloid10, 1–6 (2003).
  • Bodick NC, Offen WW, Levey AI et al. Effects of xanomeline, a selective muscarinic receptor agonist, on cognitive function and behavioral symptoms in Alzheimer disease. Arch. Neurol.54(4), 465–473 (1997).
  • Sarazin M, de Souza LC, Lehéricy S, Dubois B. Clinical and Research diagnostic Criteria for Alzheimer’s Disease. Neuroimaging Clin. N. Am.22(1), 23–32 (2012).
  • Clare L, Linden DE, Woods RT et al. Goal-oriented cognitive rehabilitation for people with early-stage Alzheimer disease: a single-blind randomized controlled trial of clinical efficacy. Am. J. Geriatric Psych.18(10), 928–939 (2010).
  • Yu F, Rose KM, Burgener SC et al. Cognitive training for early-stage Alzheimer’s disease and dementia. J. Gerontological Nursing35, 23–29 (2009).
  • Spector A, Thorgrimsen L, Woods B et al. Efficacy of an evidence-based cognitive stimulation therapy programme for people with dementia: randomised controlled trial. Br. J. Psych.183, 248–254 (2003).
  • Owen AM, Hampshire A, Grahn JA et al. Putting brain training to the test. Nature465(7299), 775–778 (2010).
  • Erickson KI, Voss MW, Prakash RS et al. Exercise training increases size of hippocampus and improves memory. Proc. Natl Acad. Sci. USA108(7), 3017–3022 (2011).
  • Baker LD, Frank LL, Foster-Schubert K et al. Effects of aerobic exercise on mild cognitive impairment: a controlled trial. Arch. Neurol.67(1), 71–79 (2010).
  • Lautenschlager NT, Cox KL, Flicker L et al. Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial. JAMA300(9), 1027–1037 (2008).
  • Tomita T. Secretase inhibitors and modulators for Alzheimer’s disease treatment. Expert Rev. Neurother.9(5), 661–679 (2009).
  • Landreth G, Jiang Q, Mandrekar S, Heneka M. PPARgamma agonists as therapeutics for the treatment of Alzheimer’s disease. Neurotherapeutics5(3), 481–489 (2008).
  • Gold M, Alderton C, Zvartau-Hind ME et al. Effects of rosiglitazone as monotherapy in apoE4-stratified subjects with mild-to-moderate Alzheimer’s disease. Alzheimers Dement.5(4), 86 (2009).
  • Henley DB, May PC, Dean RA, Siemers ER. Development of semagacestat (LY450139), a functional gamma-secretase inhibitor, for the treatment of Alzheimer’s disease. Expert Opin. Pharmacother.10(10), 1657–1664 (2009).
  • 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. JAMA302(23), 2557–2564 (2009).
  • Tariot PN, Schneider LS, Cummings J et al. Chronic divalproex sodium to attenuate agitation and clinical progression of Alzheimer disease. Arch. General Psych.68(8), 853–861 (2011).
  • Mudher A, Shepherd D, Newman TA et al. GSK-3beta inhibition reverses axonal transport defects and behavioural phenotypes in Drosophila. Mol. Psych.9(5), 522–530 (2004).
  • Leroy K, Ando K, Heraud C et al. Lithium treatment arrests the development of neurofibrillary tangles in mutant tau transgenic mice with advanced neurofibrillary pathology. J. Alzheimer’s Dis.19(2), 705–719 (2010).
  • Macdonald A, Briggs K, Poppe M, Higgins A, Velayudhan L, Lovestone S. Feasibility and tolerability study of lithium in Alzheimer’s disease. Int. J. Geriatric Psych.23(7), 704–711 (2008).
  • Gura T. Hope in Alzheimer’s fight emerges from unexpected places. Nat. Med.14(9), 894 (2008).
  • Griffiths HH, Morten IJ, Hooper NM. Emerging and potential therapies for Alzheimer’s disease. Expert Opin. Ther. Targets12(6), 693–704 (2008).
  • Marcade M, Bourdin J, Loiseau N et al. Etazolate, a neuroprotective drug linking GABA(A) receptor pharmacology to amyloid precursor protein processing. J. Neurochem.106(1), 392–404 (2008).
  • Desire L, Marcade M, Peillon H, Drouin D, Sol O. Clinical trials of EHT 0202, a neuroprotective and procognitive alpha-secretase stimulator for Alzheimer’s disease. Alzheimers Dement.5(4), 255 (2009).
  • Jones RW. Dimebon disappointment. Alzheimers Res. Ther.2(5), 25 (2010).
  • McClean PL, Parthsarathy V, Faivre E, Holscher C. The diabetes drug liraglutide prevents degenerative processes in a mouse model of Alzheimer’s disease. J. Neurosci.31(17), 6587–6594 (2011).
  • Li Y, Duffy KB, Ottinger MA, Ray B et al. GLP-1 receptor stimulation reduces amyloid-beta peptide accumulation and cytotoxicity in cellular and animal models of Alzheimer’s disease. J. Alzheimer’s Dis.19(4), 1205–1219 (2010).
  • Hemming ML, Selkoe DJ, Farris W. Effects of prolonged angiotensin-converting enzyme inhibitor treatment on amyloid beta-protein metabolism in mouse models of Alzheimer disease. Neurobiol. Dis.26(1), 273–281 (2007).
  • Khachaturian AS, Zandi PP, Lyketsos CG et al. Antihypertensive medication use and incident Alzheimer disease: the Cache County Study. Arch. Neurol.63(5), 686–692 (2006).
  • Li NC, Lee A, Whitmer RA et al. Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis. BMJ340, b5465 (2010).
  • Domercq M, Matute C. Neuroprotection by tetracyclines. Trends Pharmacol. Sci.25(12), 609–612 (2004).
  • Loeb MB, Molloy DW, Smieja M et al. A randomized, controlled trial of doxycycline and rifampin for patients with Alzheimer’s disease. J. Am. Geriatrics Soc.52(3), 381–387 (2004).
  • Dubois B, Feldman HH, Jacova C et al. Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS-ADRDA criteria. Lancet Neurol.6(8), 734–746 (2007).
  • Gilman S, Koller M, Black RS et al. Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial. Neurology64(9), 1553–1562 (2005).
  • 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. Lancet372(9634), 216–223 (2008).
  • Schneeberger A, Mandler M, Otawa O, Zauner W, Mattner F, Schmidt W. Development of affitope vaccines for Alzheimer’s disease (AD) – from concept to clinical testing. J. Nutr Health Aging13(3), 264–267 (2009).
  • Winblad B, Minthon L, Floesser A et al. Results of the first-in-man study with the active Aβ immunotherapy CAD106 in Alzheimer patients. Alzheimers Dement.5(4), 113 (2009).
  • Wilcock DM, Colton CA. Anti-amyloid-beta immunotherapy in Alzheimer’s disease: relevance of transgenic mouse studies to clinical trials. J. Alzheimers Dis.15(4), 555–569 (2008).
  • Relkin NR, Szabo P, Adamiak B et al. 18-month study of intravenous immunoglobulin for treatment of mild Alzheimer disease. Neurobiol. Aging30(11), 1728–1736 (2009).
  • 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. Alzheimers Dement.4(4), 774 (2008).
  • Salloway S, Sperling R, Gilman S et al. A Phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease. Neurology73(24), 2061–2070 (2009).
  • Haass C, Selkoe DJ. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid beta-peptide. Nat. Rev. Mol. Cell Biol.8(2), 101–112 (2007).
  • 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.14(8), 837–842 (2008).
  • Aisen PS, Saumier D, Briand R et al. A Phase II study targeting amyloid-beta with 3APS in mild-to-moderate Alzheimer disease. Neurology67(10), 1757–1763 (2006).
  • Aisen P, Gauthier S, Ferris S et al. A Phase III, placebo-controlled, double-blind, randomized trial of tramiprosate in the clinical management of patients with mild-to-moderate Alzheimer’s disease (the Alphase study). Presented at: 61st American Academy of Neurology Annual Meeting. WA, USA, 25 April–2 May 2009 (Abstract S32.003).
  • McLaurin J, Kierstead ME, Brown ME et al. Cyclohexanehexol inhibitors of Abeta aggregation prevent and reverse Alzheimer phenotype in a mouse model. Nat. Med.12(7), 801–808 (2006).
  • Garzone P, Koller M, Pastrak A et al. Oral amyloid anti-aggregating agent ELND005 is measurable in CSF and brain of healthy adult men. Alzheimers Dement.5(4), 323 (2009).
  • Ritchie CW, Bush AI, Mackinnon A, et al. Metal-protein attenuation with iodochlorhydroxyquin (clioquinol) targeting Abeta amyloid deposition and toxicity in Alzheimer disease: a pilot Phase 2 clinical trial. Arch. Neurol.60(12), 1685–1691 (2003).
  • 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.7(9), 779–786 (2008).
  • Wilcock DM, Colton CA. Anti-Aβ immunotherapy in Alzheimer’s disease; relevance of transgenic mouse studies to clinical trials J. Alzheimers Dis.15(4), 555–569 (2008).
  • Weinreb O, Amit T, Bar-Am O, Youdim MB. A novel anti-Alzheimer’s disease drug, ladostigil neuroprotective, multimodal brain-selective monoamine oxidase and cholinesterase inhibitor. Int. Rev. Neurobiol.100, 191–215 (2011).
  • Maher-Edwards G, Zvartau-Hind M, Hunter AL et al. Double-blind, controlled Phase II study of a 5-HT6 receptor antagonist, SB-742457, in Alzheimer’s disease. Curr. Alzheimer Res.7(5), 374–385 (2010).
  • Kurakhmaeva KB, Djindjikhashvili IA, Petrov VE et al. Brain targeting of nerve growth factor using poly(butyl cyanoacrylate) nanoparticles. J. Drug Targeting17(8), 564–574 (2009).
  • Blurton-Jones M, Kitazawa M, Martinez-Coria H et al. Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer disease. Proc. Natl Acad. Sci. USA106(32), 13594–13599 (2009).
  • Yurko-Mauro K, McCarthy D, Rom D et al. Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline. Alzheimers Dement.6(6), 456–464 (2010).
  • Kotani S, Sakaguchi E, Warashina S et al. Dietary supplementation of arachidonic and docosahexaenoic acids improves cognitive dysfunction. Neurosci. Res.56(2), 159–164 (2006).
  • Quinn JF, Raman R, Thomas RG et al. Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial. JAMA304(17), 1903–1911 (2010).
  • Freund-Levi Y, Eriksdotter-Jönhagen 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.63(10), 1402–1408 (2006).
  • Freund-Levi Y, Basun H, Cederholm T et al. Omega-3 supplementation in mild to moderate Alzheimer’s disease: effects on neuropsychiatric symptoms. Int. J. Geriatr. Psychiatry23(2), 161–169 (2008).
  • Lloret A, Badía MC, Mora NJ et al. Vitamin E paradox in Alzheimer’s disease: it does not prevent loss of cognition and may even be detrimental. J. Alzheimers Dis.17(1), 143–149 (2009).
  • Remington R, Chan A, Paskavitz J et al. Efficacy of a vitamin/nutriceutical formulation for moderate-stage to later-stage Alzheimer’s disease: a placebo-controlled pilot study. Am. J. Alzheimers Dis. Other Demen.24(1), 27–33 (2009).
  • Tong XK, Nicolakakis N, Fernandes P et al. Simvastatin improves cerebrovascular function and counters soluble amyloid-beta, inflammation and oxidative stress in aged APP mice. Neurobiol. Dis.35(3), 406–414 (2009)
  • Feldman HH, Doody RS, Kivipelto M et al. Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe. Neurology74(12), 956–964 (2010).
  • Aisen PS, Schafer KA, Grundman M et al. Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. JAMA289(21), 2819–2826 (2003).
  • Reines SA, Block GA, Morris JC et al. Rofecoxib: no effect on Alzheimer’s disease in a 1-year, randomized, blinded, controlled study. Neurology62(1), 66–71 (2004).
  • Rogers J, Kirby LC, Hempelman SR et al. Clinical trial of indomethacin in Alzheimer’s disease. Neurology43(8), 1609–1611 (1993).
  • Tabet N, Feldman H. Indomethacin for the treatment of Alzheimer’s disease patients. Cochrane Database Syst. Rev.2, CD003673 (2002).
  • 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 ONE3(1), e1475 (2008).
  • Schmidt AM, Sahagan B, Nelson RB et al. The role of RAGE in amyloid-beta peptide-mediated pathology in Alzheimer’s disease. Curr. Opin. Investig Drugs10(7), 672–680 (2009).
  • Bates KA, Verdile G, Li QX et al. Clearance mechanisms of Alzheimer’s amyloid-beta peptide: implications for therapeutic design and diagnostic tests. Mol. Psych.14(5), 469–486 (2009).
  • Deane R, Wu Z, Zlokovic BV. RAGE (yin) versus LRP (yang) balance regulates alzheimer amyloid beta-peptide clearance through transport across the blood–brain barrier. Stroke35(11 Suppl. 1), 2628–2631 (2004).
  • Shi JQ, Shen W, Chen J et al. Anti-TNF-α reduces amyloid plaques and tau phosphorylation and induces CD11c-positive dendritic-like cell in the APP/PS1 transgenic mouse brains. Brain Res.1368, 239–247 (2011).
  • Rockwood K, Fay S, Song X, MacKnight C, Gorman M. Attainment of treatment goals by people with Alzheimer’s disease receiving galantamine: a randomized controlled trial. Video-Imaging Synthesis of Treating Alzheimer’s Disease (VISTA) Investigators. CMAJ174(8), 1099–1105 (2006).
  • Rockwood K, Fay S, Gorman M, Carver D, Graham JE. The clinical meaningfulness of ADAS-Cog changes in Alzheimer’s disease patients treated with donepezil in an open-label trial. BMC Neurol.7, 26 (2007).

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