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An overview on Alzheimer’s disease, diagnosis and treatment approach
Corresponding Author(s) : Nivetha S.R
International Journal of Allied Medical Sciences and Clinical Research,
Vol. 11 No. 4 (2023): 2023 Volume -11 - Issue 4
Abstract
Merely 40 million people suffers from dementia all-over the world which is a characteristic of Alzheimer's disease. There is no cure for Alzheimer's disease, but there are treatments which help manage symptoms and improve quality of life. The symptoms can vary from person to person, but they typically include Memory loss, Difficulties in learning new things, activities of daily living concentrating, Problems with language, Disorientation, Changes in mood and personality. The treatment for Alzheimer's disease is aimed at managing the symptoms and improving quality of life. There are two main types of medications used to treat Alzheimer's disease. It includes Cholinesterase inhibitors medications, help to improve memory and thinking skills by increasing the levels of acetylcholine in the brain and Memantine, which helps to improve cognitive function by blocking the effects of glutamate in the brain. Also, non-pharmacological therapy such as physical therapy, occupational therapy, speech therapy, support groups which provide emotional support and practical advice to people with Alzheimer's disease improves their prognosis of ailment. Early diagnosis and treatment of Alzheimer's disease can help to improve quality of life and manage symptoms.
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- Yiannopoulou KG, Papageorgiou SG. Current and future treatments in Alzheimer disease: an update. J Cent Nerv Syst Dis. 2020 Jan 1;12:1179573520907397. doi: 10.1177/1179573520907397, PMID 32165850.
- Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP. The global prevalence of dementia: A systematic review and metaanalysis. Alzheimers Dement. 2013 Jan 1;9(1):63-75.e2. doi: 10.1016/j.jalz.2012.11.007, PMID 23305823.
- Kingston A, Comas-Herrera A, Jagger C, MODEM project. Forecasting the care needs of the older population in England over the next 20 years: estimates from the Population Ageing and Care Simulation (PACSim) modelling study. Lancet Public Health. 2018 Sep 1;3(9):e447-55. doi: 10.1016/S2468-2667(18)30118-X, PMID 30174210.
- Scheltens P, Blennow K, Breteler MMB, de Strooper B, Frisoni GB, Salloway S, et al. Alzheimer’s disease. Lancet. 2016 Jul 30;388(10043):505-17. doi: 10.1016/S0140-6736(15)01124-1.
- Cummings J, Lee G, Ritter A, Sabbagh M, Zhong K. Alzheimer’s disease drug development pipeline: 2019. Alzheimers Dement (N Y). 2019 Jan 1;5(1):272-93. doi: 10.1016/j.trci.2019.05.008, PMID 31334330.
- Magalingam KB, Radhakrishnan A, Ping NS, Haleagrahara N. Current concepts of neurodegenerative mechanisms in Alzheimer’s disease. BioMed Res Int. 2018;2018:3740461. doi: 10.1155/2018/3740461, PMID 29707568.
- Dá Mesquita S, Ferreira AC, Sousa JC, Correia-Neves M, Sousa N, Marques F. Insights on the pathophysiology of Alzheimer’s disease: the crosstalk between amyloid pathology, neuroinflammation and the peripheral immune system. Neurosci Biobehav Rev. 2016;68:547-62. doi: 10.1016/j.neubiorev.2016.06.014, PMID 27328788.
- Bhushan I, Kour M, Kour G, Gupta S, Sharma S, Yadav A. Alzheimer’s disease: causes & treatment – a review. Ann Biotechnol. 2018 Feb 19;1(1). doi: 10.33582/2637-4927/1002.
- Povova J, Ambroz P, Bar M, Pavukova V, Serý O, Tomaskova H, et al. Epidemiological of and risk factors for Alzheimer’s disease: a review. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2012 Jun 1;156(2):108-14. doi: 10.5507/bp.2012.055, PMID 22837131.
- Blennow K, de Leon MJ, Zetterberg H. Alzheimer’s disease. Lancet. 2006 Jul 29;368(9533):387-403. doi: 10.1016/S0140-6736(06)69113-7.
- Burns A, Iliffe S. Alzheimer’s disease. BMJ. 2009 Feb 5;338:b158. doi: 10.1136/bmj.b158, PMID 19196745.
- Burns A, Jacoby R, Levy R. Psychiatric phenomena in Alzheimer’s disease. I: Disorders of thought content. Br J Psychiatry. 2018/01/02;157(1):72–6. doi: 10.1192/bjp.157.1.72, PMID 2397365.
- Snowdon DA, Greiner LH, Mortimer JA, Riley KP, Greiner PA, Markesbery WR. Brain infarction and the clinical expression of Alzheimer disease. The nun study. JAMA. 1997;277(10):813-7. doi: 10.1001/jama.277.10.813, PMID 9052711.
- Association A. 2010 Alzheimer’s disease facts and figures. Alzheimers Dem. 2010;6(2):158-94. doi: 10.1016/j.jalz.2010.01.009.
- Diagnostic and statistical manual of mental disorders: DSM-5TM. 5th ed. Diagnostic and statistical manual of mental disorders: DSM-5TM. 5th ed. Arlington, VA: American Psychiatric Publishing, Inc; 2013. 947, xliv. p. 947-xliv.
- Korolev I. Alzheimer’s disease: A clinical and basic science review. Med Student Res J. 2014 Jan 1;4:24-33.
- Mann DMA. Pyramidal nerve cell loss in Alzheimer’s disease. Neurodegeneration. 1996;5(4):423-7. doi: 10.1006/neur.1996.0057, PMID 9117557.
- Norfray JF, Provenzale JM. Alzheimer’s disease: neuropathologic findings and recent advances in imaging. AJR Am J Roentgenol. 2004;182(1):3-13. doi: 10.2214/ajr.182.1.1820003, PMID 14684506.
- Selkoe DJ. Alzheimer’s disease is a synaptic failure. Science. 2002 [internet];298(5594):789-91. doi: 10.1126/science.1074069, PMID 12399581.
- Petersen CR, Xu YC, Waring SC, O, O’Brien PC, Tangalos EG et al.';Brien PC, Tangalos EG, et alMedial temporal atrophy on MRI in normal aging and very mild Alzheimer’s disease. Neurology. 1997 Sep 1;49(3):786-94. doi: 10.1212/wnl.49.3.786, PMID 9305341.
- Holtzman DM, Morris JC, Goate AM. Alzheimer’s disease: the challenge of the second century. Sci Transl Med. 2011;3(77):77sr1. doi: 10.1126/scitranslmed.3002369, PMID 21471435.
- Bozoki AC, Korolev IO, Davis NC, Hoisington LA, Berger KL. Disruption of limbic white matter pathways in mild cognitive impairment and Alzheimer’s disease: a DTI/FDG‐PET Study. Hum Brain Mapp. 2012;33(8):1792-802. doi: 10.1002/hbm.21320, PMID 21674695.
- Querfurth HW, LaFerla FM. Alzheimer’s disease. N Engl J Med. 2010 Jan 28;362(4):329-44. doi: 10.1056/NEJMra0909142, PMID 20107219.
- Braak H, Thal DR, Ghebremedhin E, Del Tredici K. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J Neuropathol Exp Neurol. 2011 Nov 1;70(11):960-9. doi: 10.1097/NEN.0b013e318232a379, PMID 22002422.
- Khan M, Ahsan F, Ahmad U, Akhtar J, Badruddeen MM. Alzheimer disease: a review. World J Pharm Pharm Sci. 2016 May 24;5:649-66.
- Chandrashekar K, Meti V, Saritha MK. Recent advances in the management of Alzheimer’s disease. Int J Pharm Biol Sci. 2013 Jan 1;4:519-23.
- Dickson DW, Crystal HA, Bevona C, Honer W, Vincent I, Davies P. Correlations of synaptic and pathological markers with cognition of the elderly. Neurobiol Aging. 1995;16(3):285-98; discussion 298. doi: 10.1016/0197-4580(95)00013-5, PMID 7566338.
- Krishnan KRR. Organic bases of depression in the elderly. Annu Rev Med. 1991;42:261-6. doi: 10.1146/annurev.me.42.020191.001401, PMID 2035971.
- Hu X, Crick SL, Bu G, Frieden C, Pappu RV, Lee JM. Amyloid seeds formed by cellular uptake, concentration, and aggregation of the amyloid-beta peptide. Proc Natl Acad Sci U S A. 2009;106(48):20324-9. doi: 10.1073/pnas.0911281106, PMID 19910533.
- Schneck MK, Reisberg B, Ferris SH. An overview of current concepts of Alzheimer’s disease. Am J Psychiatry. 1982 Mar 1;139(2):165-73. doi: 10.1176/ajp.139.2.165, PMID 6119911.
- Goldblum MC, Gomez CM, Dalla Barba GD, Boller F, Deweer B, Hahn V, et al. The influence of semantic and perceptual encoding on recognition memory in Alzheimer’s disease. Neuropsychologia. 1998;36(8):717-29. doi: 10.1016/s0028-3932(98)00007-4, PMID 9751437.
- Beach TG, Monsell SE, Phillips LE, Kukull W. Accuracy of the clinical diagnosis of Alzheimer disease at National Institute on Aging Alzheimer disease centers, 2005-2010. J Neuropathol Exp Neurol. 2012 Apr 1;71(4):266-73. doi: 10.1097/NEN.0b013e31824b211b, PMID 22437338.
- Camicioli R. Diagnosis and differential diagnosis of dementia. Dementia. 2013:1-13. doi: 10.1002/9781118656082.ch1.
- Knopman DS, DeKosky ST, Cummings JL, Chui H, Corey-Bloom J, Relkin N, et al. Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2001 May 8;56(9):1143-53. doi: 10.1212/wnl.56.9.1143, PMID 11342678.
- Nordberg A. PET studies and cholinergic therapy in Alzheimer’s disease. Rev Neurol (Paris). 1999;155;Suppl 4:S53-63. PMID 10637939.
- Khachaturian ZS, Radebaugh TS. J Alzheimers Dis. 2019.
- Gosche KM, Mortimer JA, Smith CD, Markesbery WR, Snowdon DA. Hippocampal volume as an index of Alzheimer neuropathology: findings from the Nun Study. Neurology. 2002;58(10):1476-82. doi: 10.1212/wnl.58.10.1476, PMID 12034782.
- Mellon EA, Pilkinton DT, Clark CM, Elliott MA, Witschey WRT, Borthakur A, et al. Sodium MR imaging detection of mild Alzheimer disease: preliminary study [preliminary study]. AJNR Am J Neuroradiol. 2009;30(5):978-84. doi: 10.3174/ajnr.A1495, PMID 19213826.
- Pais M, Martinez L, Ribeiro O, Loureiro J, Fernandez R, Valiengo L, et al. Early diagnosis and treatment of Alzheimer’s disease: new definitions and challenges. Braz J Psychiatry. 2020;42(4):431-41. doi: 10.1590/1516-4446-2019-0735, PMID 31994640.
- Bondi MW, Edmonds EC, Salmon DP. Alzheimer’s disease: past, present, and future. J Int Neuropsychol Soc. 2017/12/04;23(9-10):818-31. doi: 10.1017/S135561771700100X, PMID 29198280.
- Hampel H, Frank R, Broich K, Teipel SJ, Katz RG, Hardy J, et al. Biomarkers for Alzheimer’s disease: academic, industry and regulatory perspectives. Nat Rev Drug Discov. 2010;9(7):560-74. doi: 10.1038/nrd3115, PMID 20592748.
- Jack CR, Bennett DA, Blennow K, Carrillo MC, Feldman HH, Frisoni GB et al.A/T/N: an unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology. 2016 Aug 2;87(5):539-47. doi: 10.1212/WNL.0000000000002923, PMID 27371494.
- Diniz BSO, Pinto Júnior JA, Forlenza OV. Do CSF total tau, phosphorylated tau, and β-amyloid 42 help to predict progression of mild cognitive impairment to Alzheimer’s disease? A systematic review and meta-analysis of the literature. World J Biol Psychiatry. 2008 Jan 1;9(3):172-82. doi: 10.1080/15622970701535502, PMID 17886169.
- Hansson O, Buchhave P, Zetterberg H, Blennow K, Minthon L, Warkentin S et al. Combined rCBF and CSF biomarkers predict progression from mild cognitive impairment to Alzheimer’s disease. Neurobiol Aging. 2007 Aug 1;30:165–73:165-73.
- Forlenza OV, Diniz BS, Radanovic M, Santos FS, Talib LL, Gattaz WF. Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial. Br J Psychiatry. 2011;198(5):351-6. doi: 10.1192/bjp.bp.110.080044, PMID 21525519.
- Fish PV, Steadman D, Bayle ED, Whiting P. New approaches for the treatment of Alzheimer’s disease. Bioorg Med Chem Lett. 2019;29(2):125-33. doi: 10.1016/j.bmcl.2018.11.034, PMID 30501965.
- Bateman RJ, Blennow K, Doody R, Hendrix S, Lovestone S, Salloway S, et al. Plasma biomarkers of AD emerging as essential tools for drug development: an EU/US CTAD task force report. J Prev Alzheimers Dis. 2019;6(3):169-73. doi: 10.14283/jpad.2019.21, PMID 31062827.
- Jack Jr. CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA Research Framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 2018;14(4):535-62. doi: 10.1016/j.jalz.2018.02.018, PMID 29653606.
- Bateman RJ, Xiong C, Benzinger TLS, Fagan AM, Goate A, Fox NC, et al. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med. 2012 Jul 11;367(9):795-804. doi: 10.1056/NEJMoa1202753, PMID 22784036.
- Counts SE, Ikonomovic MD, Mercado N, Vega IE, Mufson EJ. Biomarkers for the early detection and progression of Alzheimer’s disease. Neurotherapeutics. 2017;14(1):35-53. doi: 10.1007/s13311-016-0481-z, PMID 27738903.
- Blennow K. A review of fluid biomarkers for Alzheimer’s disease: moving from CSF to blood. Neurol Ther. 2017;6(1);Suppl 1:15-24. doi: 10.1007/s40120-017-0073-9, PMID 28733960.
- Matsuda H, Shigemoto Y, Sato N. Neuroimaging of Alzheimer’s disease: focus on amyloid and tau PET. Jpn J Radiol. 2019;37(11):735-49. doi: 10.1007/s11604-019-00867-7, PMID 31493197.
- Wang L, Benzinger TL, Su Y, Christensen J, Friedrichsen K, Aldea P, et al. Evaluation of tau imaging in staging Alzheimer disease and revealing interactions between β-amyloid and tauopathy. JAMA Neurol. 2016 Sep 1;73(9):1070-7. doi: 10.1001/jamaneurol.2016.2078, PMID 27454922.
- Cho H, Choi JY, Hwang MS, Kim YJ, Lee HM, Lee HS, et al. In vivo cortical spreading pattern of tau and amyloid in the Alzheimer disease spectrum. Ann Neurol. 2016 Aug 1;80(2):247-58. doi: 10.1002/ana.24711, PMID 27323247.
- Marquié M, Normandin MD, Meltzer AC, Siao Tick Chong M, Andrea NV, Antón-Fernández A, et al. Pathological correlations of [F-18]-AV-1451 imaging in non-alzheimer tauopathies. Ann Neurol. 2017;81(1):117-28. doi: 10.1002/ana.24844, PMID 27997036.
- Márquez F, Yassa MA. Neuroimaging biomarkers for Alzheimer’s disease. Mol Neurodegener. 2019;14(1):21. doi: 10.1186/s13024-019-0325-5, PMID 31174557.
- Thies W, Bleiler L. Alzheimer’s disease facts and figures Alzheimer’s Association *. Alzheimers Dem. 2012;8(2):131-68. doi: 10.1016/j.jalz.2012.02.001.
- Birks JS. Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev. 2006;2006(1):CD005593. doi: 10.1002/14651858.CD005593, PMID 16437532.
- Courtney C, Farrell DC, Gray R, Hills RK, Lynch L, Sellwood E, et al. Long-term donepezil treatment in 565 patients with Alzheimer’s disease (AD2000): randomised double-blind trial. Lancet. 2004;363(9427):2105-15. doi: 10.1016/S0140-6736(04)16499-4, PMID 15220031.
- Maidment ID, Fox CG, Boustani M, Rodriguez J, Brown RC, Katona CL. Efficacy of memantine on behavioral and psychological symptoms related to dementia: A systematic meta-analysis. Ann Pharmacother. 2008 Jan 1;42(1):32-8. doi: 10.1345/aph.1K372, PMID 18056833.
- Zec RF, Burkett NR. Non-pharmacological and pharmacological treatment of the cognitive and behavioral symptoms of Alzheimer disease. NeuroRehabilitation. 2008;23(5):425-38. doi: 10.3233/NRE-2008-23506, PMID 18957729.
- Vigen CLP, Mack WJ, Keefe RSE, Sano M, Sultzer DL, Stroup TS, et al. Cognitive effects of atypical antipsychotic medications in patients with Alzheimer’s disease: outcomes from CATIE-AD. Am J Psychiatry. 2011 Aug 1;168(8):831-9. doi: 10.1176/appi.ajp.2011.08121844, PMID 21572163.
- Corbett A, Williams G, Ballard C. Drug repositioning: an opportunity to develop novel treatments for Alzheimer’s disease. Pharmaceuticals (Basel). 2013;6(10):1304-21. doi: 10.3390/ph6101304, PMID 24275851.
- Van Marum RJ. Current and future therapy in Alzheimer’s disease. Fundam Clin Pharmacol. 2008 Jun 1;22(3):265-74. doi: 10.1111/j.1472-8206.2008.00578.x, PMID 18485144.
- Weksler ME. The immunotherapy of Alzheimer’s disease. Immun Ageing. 2004;1(1):2. doi: 10.1186/1742-4933-1-2, PMID 15679923.
- Mann DMA, Hardy J. Amyloid or tau: the chicken or the egg? Acta Neuropathol. 2013;126(4):609-13. doi: 10.1007/s00401-013-1162-1, PMID 23925566.
- Weller J, Budson A. Current understanding of Alzheimer?s disease diagnosis and treatment [version 1; peer review: 2 approved] . F1000Res. F1000Res. 2018;7(1161). doi: 10.12688/f1000research.14506.1, PMID 30135715.
- Braak H, Del Tredici K [reply]. Reply: the early pathological process in sporadic Alzheimer’s disease. Acta Neuropathol. 2013;126(4):615-8. doi: 10.1007/s00401-013-1170-1, PMID 23982593.
- Kosik KS. Diseases: study neuron networks to tackle Alzheimer’s. Nature. 2013;503(7474):31-2. doi: 10.1038/503031a, PMID 24218661.
- Aisen P, Touchon J, Amariglio R, Andrieu S, Bateman R, Breitner J, et al. EU/US/CTAD Task Force: Lessons learned from recent and current Alzheimer’s prevention trials. J Prev Alzheimers Dis. 2017;4(2):116-24. doi: 10.14283/jpad.2017.13, PMID 29186281.
- Pooler AM, Polydoro M, Wegmann S, Nicholls SB, Spires-Jones TL, Hyman BT. Propagation of tau pathology in Alzheimer’s disease: identification of novel therapeutic targets. Alzheimers Res Ther. 2013;5(5):49. doi: 10.1186/alzrt214, PMID 24152385.
- Doody RS, Thomas RG, Farlow M, Iwatsubo T, Vellas B, Joffe S, et al. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer’s disease. N Engl J Med. 2014 Jan 23;370(4):311-21. doi: 10.1056/NEJMoa1312889, PMID 24450890.
- Salloway S, Sperling R, Fox NC, Blennow K, Klunk W, Raskind M, et al. Two Phase 3 trials of Bapineuzumab in mild-to-moderate Alzheimer’s disease. N Engl J Med. 2014 Jan 23;370(4):322-33. doi: 10.1056/NEJMoa1304839, PMID 24450891.
- Honig LS, Vellas B, Woodward M, Boada M, Bullock R, Borrie M, et al. Trial of solanezumab for mild dementia due to Alzheimer’s disease. N Engl J Med. 2018 Jan 24;378(4):321-30. doi: 10.1056/NEJMoa1705971, PMID 29365294.
- Vassar R. BACE1 inhibitor drugs in clinical trials for Alzheimer’s disease. Alzheimers Res Ther. 2014;6(9):89. doi: 10.1186/s13195-014-0089-7, PMID 25621019.
- Kennedy ME, Stamford AW, Chen X, Cox K, Cumming JN, Dockendorf MF, et al. The BACE1 inhibitor verubecestat (MK-8931) reduces CNS β-amyloid in animal models and in Alzheimer’s disease patients. Sci Transl Med. 2016;8(363):363ra150-. doi: 10.1126/scitranslmed.aad9704, PMID 27807285.
- Jacobsen H, Ozmen L, Caruso A, Narquizian R, Hilpert H, Jacobsen B, et al. Combined treatment with a BACE inhibitor and anti-Aβ antibody gantenerumab enhances amyloid reduction in APPLondon mice. J Neurosci. 2014 Aug 27;34(35):11621-30. doi: 10.1523/JNEUROSCI.1405-14.2014, PMID 25164658.
- Perry D, Sperling R, Katz R, Berry D, Dilts D, Hanna D, et al. Building a roadmap for developing combination therapies for Alzheimer’s disease. Expert Rev Neurother. 2015 Mar 1;15(3):327-33. doi: 10.1586/14737175.2015.996551, PMID 25708309.
- Pedersen JT, Sigurdsson EM. Tau immunotherapy for Alzheimer’s disease. Trends Mol Med. 2015 Jun 1;21(6):394-402. doi: 10.1016/j.molmed.2015.03.003, PMID 25846560.
- Rosenmann H. Immunotherapy for targeting tau pathology in Alzheimer’s disease and tauopathies. Curr Alzheimer Res. 2013;10(3):217-28. doi: 10.2174/1567205011310030001, PMID 23534533.
- Novak P, Schmidt R, Kontseková E, Zilka N, Kovacech B, Skrabana R et al. Safety and immunogenicity of the tau vaccine AADvac1 in patients with Alzheimer’s disease: a randomised, double-blind, placebo-controlled, phase 1 trial. Lancet Neurol. 2017;16(2):123-34. doi: 10.1016/S1474-4422(16)30331-3, PMID 27955995.
- Panza F, Frisardi V, Solfrizzi V, Imbimbo BP, Logroscino G, Santamato A, et al. Immunotherapy for Alzheimer’s disease: from anti-β-amyloid to tau-based immunization strategies. Immunotherapy. 2012 Feb 1;4(2):213-38. doi: 10.2217/imt.11.170, PMID 22339463.
References
Yiannopoulou KG, Papageorgiou SG. Current and future treatments in Alzheimer disease: an update. J Cent Nerv Syst Dis. 2020 Jan 1;12:1179573520907397. doi: 10.1177/1179573520907397, PMID 32165850.
Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP. The global prevalence of dementia: A systematic review and metaanalysis. Alzheimers Dement. 2013 Jan 1;9(1):63-75.e2. doi: 10.1016/j.jalz.2012.11.007, PMID 23305823.
Kingston A, Comas-Herrera A, Jagger C, MODEM project. Forecasting the care needs of the older population in England over the next 20 years: estimates from the Population Ageing and Care Simulation (PACSim) modelling study. Lancet Public Health. 2018 Sep 1;3(9):e447-55. doi: 10.1016/S2468-2667(18)30118-X, PMID 30174210.
Scheltens P, Blennow K, Breteler MMB, de Strooper B, Frisoni GB, Salloway S, et al. Alzheimer’s disease. Lancet. 2016 Jul 30;388(10043):505-17. doi: 10.1016/S0140-6736(15)01124-1.
Cummings J, Lee G, Ritter A, Sabbagh M, Zhong K. Alzheimer’s disease drug development pipeline: 2019. Alzheimers Dement (N Y). 2019 Jan 1;5(1):272-93. doi: 10.1016/j.trci.2019.05.008, PMID 31334330.
Magalingam KB, Radhakrishnan A, Ping NS, Haleagrahara N. Current concepts of neurodegenerative mechanisms in Alzheimer’s disease. BioMed Res Int. 2018;2018:3740461. doi: 10.1155/2018/3740461, PMID 29707568.
Dá Mesquita S, Ferreira AC, Sousa JC, Correia-Neves M, Sousa N, Marques F. Insights on the pathophysiology of Alzheimer’s disease: the crosstalk between amyloid pathology, neuroinflammation and the peripheral immune system. Neurosci Biobehav Rev. 2016;68:547-62. doi: 10.1016/j.neubiorev.2016.06.014, PMID 27328788.
Bhushan I, Kour M, Kour G, Gupta S, Sharma S, Yadav A. Alzheimer’s disease: causes & treatment – a review. Ann Biotechnol. 2018 Feb 19;1(1). doi: 10.33582/2637-4927/1002.
Povova J, Ambroz P, Bar M, Pavukova V, Serý O, Tomaskova H, et al. Epidemiological of and risk factors for Alzheimer’s disease: a review. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2012 Jun 1;156(2):108-14. doi: 10.5507/bp.2012.055, PMID 22837131.
Blennow K, de Leon MJ, Zetterberg H. Alzheimer’s disease. Lancet. 2006 Jul 29;368(9533):387-403. doi: 10.1016/S0140-6736(06)69113-7.
Burns A, Iliffe S. Alzheimer’s disease. BMJ. 2009 Feb 5;338:b158. doi: 10.1136/bmj.b158, PMID 19196745.
Burns A, Jacoby R, Levy R. Psychiatric phenomena in Alzheimer’s disease. I: Disorders of thought content. Br J Psychiatry. 2018/01/02;157(1):72–6. doi: 10.1192/bjp.157.1.72, PMID 2397365.
Snowdon DA, Greiner LH, Mortimer JA, Riley KP, Greiner PA, Markesbery WR. Brain infarction and the clinical expression of Alzheimer disease. The nun study. JAMA. 1997;277(10):813-7. doi: 10.1001/jama.277.10.813, PMID 9052711.
Association A. 2010 Alzheimer’s disease facts and figures. Alzheimers Dem. 2010;6(2):158-94. doi: 10.1016/j.jalz.2010.01.009.
Diagnostic and statistical manual of mental disorders: DSM-5TM. 5th ed. Diagnostic and statistical manual of mental disorders: DSM-5TM. 5th ed. Arlington, VA: American Psychiatric Publishing, Inc; 2013. 947, xliv. p. 947-xliv.
Korolev I. Alzheimer’s disease: A clinical and basic science review. Med Student Res J. 2014 Jan 1;4:24-33.
Mann DMA. Pyramidal nerve cell loss in Alzheimer’s disease. Neurodegeneration. 1996;5(4):423-7. doi: 10.1006/neur.1996.0057, PMID 9117557.
Norfray JF, Provenzale JM. Alzheimer’s disease: neuropathologic findings and recent advances in imaging. AJR Am J Roentgenol. 2004;182(1):3-13. doi: 10.2214/ajr.182.1.1820003, PMID 14684506.
Selkoe DJ. Alzheimer’s disease is a synaptic failure. Science. 2002 [internet];298(5594):789-91. doi: 10.1126/science.1074069, PMID 12399581.
Petersen CR, Xu YC, Waring SC, O, O’Brien PC, Tangalos EG et al.';Brien PC, Tangalos EG, et alMedial temporal atrophy on MRI in normal aging and very mild Alzheimer’s disease. Neurology. 1997 Sep 1;49(3):786-94. doi: 10.1212/wnl.49.3.786, PMID 9305341.
Holtzman DM, Morris JC, Goate AM. Alzheimer’s disease: the challenge of the second century. Sci Transl Med. 2011;3(77):77sr1. doi: 10.1126/scitranslmed.3002369, PMID 21471435.
Bozoki AC, Korolev IO, Davis NC, Hoisington LA, Berger KL. Disruption of limbic white matter pathways in mild cognitive impairment and Alzheimer’s disease: a DTI/FDG‐PET Study. Hum Brain Mapp. 2012;33(8):1792-802. doi: 10.1002/hbm.21320, PMID 21674695.
Querfurth HW, LaFerla FM. Alzheimer’s disease. N Engl J Med. 2010 Jan 28;362(4):329-44. doi: 10.1056/NEJMra0909142, PMID 20107219.
Braak H, Thal DR, Ghebremedhin E, Del Tredici K. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J Neuropathol Exp Neurol. 2011 Nov 1;70(11):960-9. doi: 10.1097/NEN.0b013e318232a379, PMID 22002422.
Khan M, Ahsan F, Ahmad U, Akhtar J, Badruddeen MM. Alzheimer disease: a review. World J Pharm Pharm Sci. 2016 May 24;5:649-66.
Chandrashekar K, Meti V, Saritha MK. Recent advances in the management of Alzheimer’s disease. Int J Pharm Biol Sci. 2013 Jan 1;4:519-23.
Dickson DW, Crystal HA, Bevona C, Honer W, Vincent I, Davies P. Correlations of synaptic and pathological markers with cognition of the elderly. Neurobiol Aging. 1995;16(3):285-98; discussion 298. doi: 10.1016/0197-4580(95)00013-5, PMID 7566338.
Krishnan KRR. Organic bases of depression in the elderly. Annu Rev Med. 1991;42:261-6. doi: 10.1146/annurev.me.42.020191.001401, PMID 2035971.
Hu X, Crick SL, Bu G, Frieden C, Pappu RV, Lee JM. Amyloid seeds formed by cellular uptake, concentration, and aggregation of the amyloid-beta peptide. Proc Natl Acad Sci U S A. 2009;106(48):20324-9. doi: 10.1073/pnas.0911281106, PMID 19910533.
Schneck MK, Reisberg B, Ferris SH. An overview of current concepts of Alzheimer’s disease. Am J Psychiatry. 1982 Mar 1;139(2):165-73. doi: 10.1176/ajp.139.2.165, PMID 6119911.
Goldblum MC, Gomez CM, Dalla Barba GD, Boller F, Deweer B, Hahn V, et al. The influence of semantic and perceptual encoding on recognition memory in Alzheimer’s disease. Neuropsychologia. 1998;36(8):717-29. doi: 10.1016/s0028-3932(98)00007-4, PMID 9751437.
Beach TG, Monsell SE, Phillips LE, Kukull W. Accuracy of the clinical diagnosis of Alzheimer disease at National Institute on Aging Alzheimer disease centers, 2005-2010. J Neuropathol Exp Neurol. 2012 Apr 1;71(4):266-73. doi: 10.1097/NEN.0b013e31824b211b, PMID 22437338.
Camicioli R. Diagnosis and differential diagnosis of dementia. Dementia. 2013:1-13. doi: 10.1002/9781118656082.ch1.
Knopman DS, DeKosky ST, Cummings JL, Chui H, Corey-Bloom J, Relkin N, et al. Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2001 May 8;56(9):1143-53. doi: 10.1212/wnl.56.9.1143, PMID 11342678.
Nordberg A. PET studies and cholinergic therapy in Alzheimer’s disease. Rev Neurol (Paris). 1999;155;Suppl 4:S53-63. PMID 10637939.
Khachaturian ZS, Radebaugh TS. J Alzheimers Dis. 2019.
Gosche KM, Mortimer JA, Smith CD, Markesbery WR, Snowdon DA. Hippocampal volume as an index of Alzheimer neuropathology: findings from the Nun Study. Neurology. 2002;58(10):1476-82. doi: 10.1212/wnl.58.10.1476, PMID 12034782.
Mellon EA, Pilkinton DT, Clark CM, Elliott MA, Witschey WRT, Borthakur A, et al. Sodium MR imaging detection of mild Alzheimer disease: preliminary study [preliminary study]. AJNR Am J Neuroradiol. 2009;30(5):978-84. doi: 10.3174/ajnr.A1495, PMID 19213826.
Pais M, Martinez L, Ribeiro O, Loureiro J, Fernandez R, Valiengo L, et al. Early diagnosis and treatment of Alzheimer’s disease: new definitions and challenges. Braz J Psychiatry. 2020;42(4):431-41. doi: 10.1590/1516-4446-2019-0735, PMID 31994640.
Bondi MW, Edmonds EC, Salmon DP. Alzheimer’s disease: past, present, and future. J Int Neuropsychol Soc. 2017/12/04;23(9-10):818-31. doi: 10.1017/S135561771700100X, PMID 29198280.
Hampel H, Frank R, Broich K, Teipel SJ, Katz RG, Hardy J, et al. Biomarkers for Alzheimer’s disease: academic, industry and regulatory perspectives. Nat Rev Drug Discov. 2010;9(7):560-74. doi: 10.1038/nrd3115, PMID 20592748.
Jack CR, Bennett DA, Blennow K, Carrillo MC, Feldman HH, Frisoni GB et al.A/T/N: an unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology. 2016 Aug 2;87(5):539-47. doi: 10.1212/WNL.0000000000002923, PMID 27371494.
Diniz BSO, Pinto Júnior JA, Forlenza OV. Do CSF total tau, phosphorylated tau, and β-amyloid 42 help to predict progression of mild cognitive impairment to Alzheimer’s disease? A systematic review and meta-analysis of the literature. World J Biol Psychiatry. 2008 Jan 1;9(3):172-82. doi: 10.1080/15622970701535502, PMID 17886169.
Hansson O, Buchhave P, Zetterberg H, Blennow K, Minthon L, Warkentin S et al. Combined rCBF and CSF biomarkers predict progression from mild cognitive impairment to Alzheimer’s disease. Neurobiol Aging. 2007 Aug 1;30:165–73:165-73.
Forlenza OV, Diniz BS, Radanovic M, Santos FS, Talib LL, Gattaz WF. Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial. Br J Psychiatry. 2011;198(5):351-6. doi: 10.1192/bjp.bp.110.080044, PMID 21525519.
Fish PV, Steadman D, Bayle ED, Whiting P. New approaches for the treatment of Alzheimer’s disease. Bioorg Med Chem Lett. 2019;29(2):125-33. doi: 10.1016/j.bmcl.2018.11.034, PMID 30501965.
Bateman RJ, Blennow K, Doody R, Hendrix S, Lovestone S, Salloway S, et al. Plasma biomarkers of AD emerging as essential tools for drug development: an EU/US CTAD task force report. J Prev Alzheimers Dis. 2019;6(3):169-73. doi: 10.14283/jpad.2019.21, PMID 31062827.
Jack Jr. CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA Research Framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 2018;14(4):535-62. doi: 10.1016/j.jalz.2018.02.018, PMID 29653606.
Bateman RJ, Xiong C, Benzinger TLS, Fagan AM, Goate A, Fox NC, et al. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med. 2012 Jul 11;367(9):795-804. doi: 10.1056/NEJMoa1202753, PMID 22784036.
Counts SE, Ikonomovic MD, Mercado N, Vega IE, Mufson EJ. Biomarkers for the early detection and progression of Alzheimer’s disease. Neurotherapeutics. 2017;14(1):35-53. doi: 10.1007/s13311-016-0481-z, PMID 27738903.
Blennow K. A review of fluid biomarkers for Alzheimer’s disease: moving from CSF to blood. Neurol Ther. 2017;6(1);Suppl 1:15-24. doi: 10.1007/s40120-017-0073-9, PMID 28733960.
Matsuda H, Shigemoto Y, Sato N. Neuroimaging of Alzheimer’s disease: focus on amyloid and tau PET. Jpn J Radiol. 2019;37(11):735-49. doi: 10.1007/s11604-019-00867-7, PMID 31493197.
Wang L, Benzinger TL, Su Y, Christensen J, Friedrichsen K, Aldea P, et al. Evaluation of tau imaging in staging Alzheimer disease and revealing interactions between β-amyloid and tauopathy. JAMA Neurol. 2016 Sep 1;73(9):1070-7. doi: 10.1001/jamaneurol.2016.2078, PMID 27454922.
Cho H, Choi JY, Hwang MS, Kim YJ, Lee HM, Lee HS, et al. In vivo cortical spreading pattern of tau and amyloid in the Alzheimer disease spectrum. Ann Neurol. 2016 Aug 1;80(2):247-58. doi: 10.1002/ana.24711, PMID 27323247.
Marquié M, Normandin MD, Meltzer AC, Siao Tick Chong M, Andrea NV, Antón-Fernández A, et al. Pathological correlations of [F-18]-AV-1451 imaging in non-alzheimer tauopathies. Ann Neurol. 2017;81(1):117-28. doi: 10.1002/ana.24844, PMID 27997036.
Márquez F, Yassa MA. Neuroimaging biomarkers for Alzheimer’s disease. Mol Neurodegener. 2019;14(1):21. doi: 10.1186/s13024-019-0325-5, PMID 31174557.
Thies W, Bleiler L. Alzheimer’s disease facts and figures Alzheimer’s Association *. Alzheimers Dem. 2012;8(2):131-68. doi: 10.1016/j.jalz.2012.02.001.
Birks JS. Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev. 2006;2006(1):CD005593. doi: 10.1002/14651858.CD005593, PMID 16437532.
Courtney C, Farrell DC, Gray R, Hills RK, Lynch L, Sellwood E, et al. Long-term donepezil treatment in 565 patients with Alzheimer’s disease (AD2000): randomised double-blind trial. Lancet. 2004;363(9427):2105-15. doi: 10.1016/S0140-6736(04)16499-4, PMID 15220031.
Maidment ID, Fox CG, Boustani M, Rodriguez J, Brown RC, Katona CL. Efficacy of memantine on behavioral and psychological symptoms related to dementia: A systematic meta-analysis. Ann Pharmacother. 2008 Jan 1;42(1):32-8. doi: 10.1345/aph.1K372, PMID 18056833.
Zec RF, Burkett NR. Non-pharmacological and pharmacological treatment of the cognitive and behavioral symptoms of Alzheimer disease. NeuroRehabilitation. 2008;23(5):425-38. doi: 10.3233/NRE-2008-23506, PMID 18957729.
Vigen CLP, Mack WJ, Keefe RSE, Sano M, Sultzer DL, Stroup TS, et al. Cognitive effects of atypical antipsychotic medications in patients with Alzheimer’s disease: outcomes from CATIE-AD. Am J Psychiatry. 2011 Aug 1;168(8):831-9. doi: 10.1176/appi.ajp.2011.08121844, PMID 21572163.
Corbett A, Williams G, Ballard C. Drug repositioning: an opportunity to develop novel treatments for Alzheimer’s disease. Pharmaceuticals (Basel). 2013;6(10):1304-21. doi: 10.3390/ph6101304, PMID 24275851.
Van Marum RJ. Current and future therapy in Alzheimer’s disease. Fundam Clin Pharmacol. 2008 Jun 1;22(3):265-74. doi: 10.1111/j.1472-8206.2008.00578.x, PMID 18485144.
Weksler ME. The immunotherapy of Alzheimer’s disease. Immun Ageing. 2004;1(1):2. doi: 10.1186/1742-4933-1-2, PMID 15679923.
Mann DMA, Hardy J. Amyloid or tau: the chicken or the egg? Acta Neuropathol. 2013;126(4):609-13. doi: 10.1007/s00401-013-1162-1, PMID 23925566.
Weller J, Budson A. Current understanding of Alzheimer?s disease diagnosis and treatment [version 1; peer review: 2 approved] . F1000Res. F1000Res. 2018;7(1161). doi: 10.12688/f1000research.14506.1, PMID 30135715.
Braak H, Del Tredici K [reply]. Reply: the early pathological process in sporadic Alzheimer’s disease. Acta Neuropathol. 2013;126(4):615-8. doi: 10.1007/s00401-013-1170-1, PMID 23982593.
Kosik KS. Diseases: study neuron networks to tackle Alzheimer’s. Nature. 2013;503(7474):31-2. doi: 10.1038/503031a, PMID 24218661.
Aisen P, Touchon J, Amariglio R, Andrieu S, Bateman R, Breitner J, et al. EU/US/CTAD Task Force: Lessons learned from recent and current Alzheimer’s prevention trials. J Prev Alzheimers Dis. 2017;4(2):116-24. doi: 10.14283/jpad.2017.13, PMID 29186281.
Pooler AM, Polydoro M, Wegmann S, Nicholls SB, Spires-Jones TL, Hyman BT. Propagation of tau pathology in Alzheimer’s disease: identification of novel therapeutic targets. Alzheimers Res Ther. 2013;5(5):49. doi: 10.1186/alzrt214, PMID 24152385.
Doody RS, Thomas RG, Farlow M, Iwatsubo T, Vellas B, Joffe S, et al. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer’s disease. N Engl J Med. 2014 Jan 23;370(4):311-21. doi: 10.1056/NEJMoa1312889, PMID 24450890.
Salloway S, Sperling R, Fox NC, Blennow K, Klunk W, Raskind M, et al. Two Phase 3 trials of Bapineuzumab in mild-to-moderate Alzheimer’s disease. N Engl J Med. 2014 Jan 23;370(4):322-33. doi: 10.1056/NEJMoa1304839, PMID 24450891.
Honig LS, Vellas B, Woodward M, Boada M, Bullock R, Borrie M, et al. Trial of solanezumab for mild dementia due to Alzheimer’s disease. N Engl J Med. 2018 Jan 24;378(4):321-30. doi: 10.1056/NEJMoa1705971, PMID 29365294.
Vassar R. BACE1 inhibitor drugs in clinical trials for Alzheimer’s disease. Alzheimers Res Ther. 2014;6(9):89. doi: 10.1186/s13195-014-0089-7, PMID 25621019.
Kennedy ME, Stamford AW, Chen X, Cox K, Cumming JN, Dockendorf MF, et al. The BACE1 inhibitor verubecestat (MK-8931) reduces CNS β-amyloid in animal models and in Alzheimer’s disease patients. Sci Transl Med. 2016;8(363):363ra150-. doi: 10.1126/scitranslmed.aad9704, PMID 27807285.
Jacobsen H, Ozmen L, Caruso A, Narquizian R, Hilpert H, Jacobsen B, et al. Combined treatment with a BACE inhibitor and anti-Aβ antibody gantenerumab enhances amyloid reduction in APPLondon mice. J Neurosci. 2014 Aug 27;34(35):11621-30. doi: 10.1523/JNEUROSCI.1405-14.2014, PMID 25164658.
Perry D, Sperling R, Katz R, Berry D, Dilts D, Hanna D, et al. Building a roadmap for developing combination therapies for Alzheimer’s disease. Expert Rev Neurother. 2015 Mar 1;15(3):327-33. doi: 10.1586/14737175.2015.996551, PMID 25708309.
Pedersen JT, Sigurdsson EM. Tau immunotherapy for Alzheimer’s disease. Trends Mol Med. 2015 Jun 1;21(6):394-402. doi: 10.1016/j.molmed.2015.03.003, PMID 25846560.
Rosenmann H. Immunotherapy for targeting tau pathology in Alzheimer’s disease and tauopathies. Curr Alzheimer Res. 2013;10(3):217-28. doi: 10.2174/1567205011310030001, PMID 23534533.
Novak P, Schmidt R, Kontseková E, Zilka N, Kovacech B, Skrabana R et al. Safety and immunogenicity of the tau vaccine AADvac1 in patients with Alzheimer’s disease: a randomised, double-blind, placebo-controlled, phase 1 trial. Lancet Neurol. 2017;16(2):123-34. doi: 10.1016/S1474-4422(16)30331-3, PMID 27955995.
Panza F, Frisardi V, Solfrizzi V, Imbimbo BP, Logroscino G, Santamato A, et al. Immunotherapy for Alzheimer’s disease: from anti-β-amyloid to tau-based immunization strategies. Immunotherapy. 2012 Feb 1;4(2):213-38. doi: 10.2217/imt.11.170, PMID 22339463.