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CC BY-NC-ND 4.0 · Arq Neuropsiquiatr 2022; 80(S 05): 15-23
DOI: 10.1590/0004-282X-ANP-2022-S117
DOI: 10.1590/0004-282X-ANP-2022-S117
NEUROLOGY OF COGNITIVE AND BEHAVIORAL DISORDERS
Are we ready to use anti-amyloid therapy in Alzheimer's disease?
Estamos prontos para o uso de terapia anti-amiloide na doença de Alzheimer?
ABSTRACT
Alzheimer’s disease (AD) is the most common neurodegenerative disease. Biomarkers have demonstrated that AD pathology exists over the disease continuum from a stage preceding symptoms over 15-25 years to the progressively more impaired symptomatic states, mild cognitive impairment (MCI), and dementia. Biomarkers include: amyloid (Aß), phosphorylated tau, and neurodegeneration. The plasma assays for Aß and tau show great promise for clinical and research use. This review has aimed not only to present the ATN diagnostic classification and the preclinical AD concepts in addressing some possibilities of cognitive assessment instruments, but also to briefly summarize the main anti-amyloid monoclonal antibodies studied in clinical trials. In addition, this paper presents a critical analysis by experts in cognitive neurology while addressing the question as to whether we are prepared for the anti-amyloid therapy era or not.
RESUMO
A doença de Alzheimer (DA) é a doença neurodegenerativa mais comum. Os biomarcadores demonstraram que a patologia da DA existe ao longo do continuum da doença, desde um estágio anterior à sintomatologia, ao longo de 15 a 25 anos, até os estados sintomáticos progressivamente mais prejudicados, comprometimento cognitivo leve (CCL) e demência. Eles subdividem-se em três categorias: amiloide (Aß), tau fosforilada e neurodegeneração. A dosagem de Aß e tau plasmáticos mostra uma grande promessa para uso clínico e de pesquisa. Esta revisão teve como objetivo apresentar a classificação diagnóstica da ATN, os conceitos pré-clínicos da DA e abordar algumas possibilidades de instrumentos de avaliação cognitiva, mas principalmente resumir brevemente os principais anticorpos monoclonais anti-amiloide estudados em ensaios clínicos. Além disso, este artigo apresenta uma análise crítica de especialistas em neurologia cognitiva: estamos ou não preparados para a era da terapia anti-amiloide?
Authors’ contributions:
SMDB: conceptualization, writing, revision; JS: writing, conceptualization; KGCF, RS, CRB: writing.
Publication History
Received: 15 March 2022
Accepted: 29 April 2022
Article published online:
06 February 2023
© 2022. Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
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References
- 1 Scheltens P, De Strooper B, Kivipelto M, Holstege H, Chételat G, Teunissen CE. et al. Alzheimer’s disease. Lancet 2021; 397 10284 1577-1590 https://doi.org/10.1016/s0140-6736(20)32205-4
- 2 Jack Jr CR, Albert MS, Knopman DS, McKhann GM, Sperling RA, Carrillo MC. et al. Introduction to revised criteria for the diagnosis of Alzheimer’s disease: National Institute on Aging and the Alzheimer Association Workgroups. Alzheimers Dement 2011; 7 (03) 257-262 https://doi.org/10.1016/j.jalz.2011.03.004
- 3 Hyman BT, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Carrillo MC. et al. National Institute on Aging-Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease. Alzheimers Dement 2012; 8 (01) 1-13 https://doi.org/10.1016/j.jalz.2011.10.007
- 4 Hardy JA, Higgins GA. Alzheimer’s Disease: The Amyloid Alzheimer’s disease. Science 1992; 256 5054 184-185
- 5 Greenberg SM, Bacskai BJ, Hernandez-Guillamon M, Pruzin J, Sperling R, Veluw SJV. Cerebral amyloid angiopathy and Alzheimer disease - one peptide, two pathways. Nat Rev Neurol 2020; 16 (01) 30-42 https://doi.org/10.1038/s41582-019-0281-2
- 6 Jack Jr CR, Hampel HJ, Universities S, Cu M, Petersen RC. A new classification system for AD, independent of cognition A / T / N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology 2016; 87 (05) 539-547
- 7 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 (04) 535-562 https://doi.org/10.1016/j.jalz.2018.02.018
- 8 Knopman DS, Haeberlein SB, Carrillo MC, Hendrix JA, Kerchner G, Margolin R. et al. The National Institute on Aging and the Alzheimer’s Association Research Framework for Alzheimer’s disease: Perspectives from the Research Roundtable. Alzheimers Dement 2018; 14 (04) 563-575 https://doi.org/10.1016/j.jalz.2018.03.002
- 9 Jessen F, Amariglio RE, Buckley RF, van der Flier WM, Han Y, Molinuevo JL. et al. The characterisation of subjective cognitive decline. Lancet Neurol 2020; 19 (03) 271-278 https://doi.org/10.1016/s1474-4422(19)30368-0
- 10 Rabin LA, Smart CM, Amariglio RE. Subjective cognitive decline in preclinical Alzheimer’s Disease. Annu Rev Clin Psychol 2017; 13: 369-366 https://doi.org/10.1146/annurev-clinpsy-032816-045136
- 11 Petersen RC, Aisen P, Boeve BF, Geda YE, Ivnik RJ, Knopman DS. et al. Mild cognitive impairment due to Alzheimer disease in the community. Ann Neurol. 2013; 74 (02) 199-208 https://doi.org/10.1002/ana.23931
- 12 Morris JC. Revised criteria for mild cognitive impairment may compromise the diagnosis of Alzheimer disease dementia. Arch Neurol 2012; 69 (06) 700-708 https://doi.org/10.1001/archneurol.2011.3152
- 13 Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12 (03) 189-198 https://doi.org/10.1016/0022-3956(75)90026-6
- 14 Brucki SMD, Nitrini R, Caramelli P, Bertolucci PHF, Okamoto IH. Sugestões para o uso do mini-exame do estado mental no Brasil. Arq Neuropsiquiatr 2003; 61(3B) 777-781 https://doi.org/10.1590/S0004-282X2003000500014
- 15 Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I. et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 2005; 53 (04) 695-699 https://doi.org/10.1111/j.1532-5415.2005.53221.x
- 16 Cesar KG, Yassuda MS, Porto FHG, Brucki SMD, Nitrini R. MoCA Test: normative and diagnostic accuracy data for seniors with heterogeneous educational levels in Brazil. Arq Neuropsiquiatr 2019; 77 (11) 775-781 https://doi.org/10.1590/0004-282x20190130
- 17 Nitrini R, Lefèvre BH, Mathias SC, Caramelli P, Carrilho PE, Sauaia N. et al. Neuropsychological tests of simple application for diagnosing dementia. Arq Neuropsiquiatr 1994; 52 (04) 457-465 https://doi.org/10.1590/s0004-282x1994000400001
- 18 Nitrini R, Brucki SMD, Yassuda MS, Fichman HC, Caramelli P. The Figure Memory Test: diagnosis of memory impairment in populations with heterogeneous educational background. Dement Neuropsychol 2021; 15 (02) 173-185 https://doi.org/10.1590/1980-57642021dn15-020004
- 19 Dubois B, Villain N, Frisoni GB, Rabinovici GD, Sabbagh M, Cappa S. et al. Clinical diagnosis of Alzheimer's disease: recommendations of the International Working Group. Lancet Neurol 2021; 20 (06) 484-496 https://doi.org/10.1016/S1474-4422(21)00066-1
- 20 Hansson O. Biomarkers for neurodegenerative diseases. Nat Med 2021; 27 (06) 954-963 https://doi.org/10.1038/s41591-021-01382-x
- 21 Teunissen CE, Verbek IMW, Thijssen EH, Vermunt L, Hansson O, Zetterberg H. et al. Blood-based biomarkers for Alzheimer's disease: towards clinical implementation. Lancet Neurol 2022; 21 (01) 66-77 https://doi.org/10.1016/S1474-4422(21)00361-6
- 22 Vogel JW, Iturria-Medina Y, Strandberg OT, Smith R, Levitis E, Evans AC. et al. Spread of pathological tau proteins through communicating neurons in human Alzheimer's disease. Nat Commun 2020; 11 (01) 2612-2612 https://doi.org/10.1038/s41467-020-15701-2
- 23 Young PNE, Estarellas M, Coomans E, Srikrishna M, Beaumont H, Maass A. et al. Imaging biomarkers in neurodegeneration: Current and future practices. Alzheimers Res Ther 2020; 12 (01) 49-49 https://doi.org/10.1186/s13195-020-00612-7
- 24 World Health Organization. Globus Status Report on the Public Health Response to Dementia. Geneva: World Health Organization; 2021: 251-251
- 25 EM Reiman, Mattke S, Kordower JH, Khatchaturian ZS, Khachaturian AS. Developing a pathway to support the appropriate, affordable, and widespread use of effective Alzheimer’s prevention drugs. Alzheimers Dement 2022; 18 (01) 7-9 https://doi.org/10.1002/alz.12533
- 26 Lalli G, Schott JM, Hardy J, Strooper B. Aducanumab: a new phase in therapeutic development for Alzheimer’s disease?. EMBO Mol Med 2021; 13 (08) e14781 https://doi.org/10.15252/emmm.202114781
- 27 Two-Phase 3 Studies to Evaluate Aducanumab in Patients with early Alzheimer’s disease. https://investors.biogen.com 12 June 2021
- 28 Salloway S, Cummings J. Aducanumab, amyloid lowering, and slowing of Alzheimer Disease. Neurology 2021; 97 (11) 543-544 https://doi.org/10.1212/wnl.2022s1170000012451
- 29 Avgerinos KI, Ferrucci L, Kapogiannis D. Effects of monoclonal antibodies against amyloid-B on clinical and biomarker outcomes and adverse event risks: a systematic review and meta-analysis of phase III RCTs in Alzheimer’s disease. Ageing Res Rev 2021; 68: 101339-101339 https://doi.org/10.1016/j.arr.2021.101339
- 30 Cummings J, Aisen P, Apostolova LG, Atri A, Salloway S, Weiner M. Aducanumab: appropriate use recommendations. J Prev Alzheimers Dis 2021; 8 (04) 398-410 https://doi.org/10.14283/jpad.2021.41
- 31 Cummings J, Salloway S. Aducanumab: appropriate use recommendations. Alzheimer Dement 2022; 18 (03) 531-533 https://doi.org/10.1002/alz.12444
- 32 Canevelli M, Rossi PD, Astrone P, Consorti E, Vanacore N, Cesari M. “Real world” eligibility for aducanumab. J Am Geriatr Soc 2021; 69 (10) 2995-2998 https://doi.org/10.1111/jgs.17390
- 33 Anderson TS, Ayanian JZ, Souza J, Landon BE. Representativeness of participants eligible to be enrolled in clinical trials of aducanumab for Alzheimer Disease compared with Medicare beneficiaries with Alzheimer Disease and mild cognitive impairment. JAMA 2021; 326 (16) 1627-1629 https://doi.org/10.1001/jama.2021.15286
- 34 Lin GA, Whittington MD, Synnott PG, McKenna A, Campbell J, Pearson SD. et al. Aducanumab for Alzheimer’s disease: effectiveness and value; draft evidence report [Internet]. Institute for Clinical and Economic Review. 2021 2022 Mar 3 Available from: https://icer.org/wp-content/uploads/2020/10/ICER_ALZ_Draft_Evidence_Report_050521.pdf
- 35 Swanson CJ, Zhang Y, Dhadda S, Wang J, Kaplow J, Lai RYK. et al. A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer’s disease with lecanemab, an anti-AB protofibril antibody. Alzheimers Res Ther 2021; 13 (01) 80-80 https://doi.org/10.1186/s13195-021-00813-8
- 36 Pleen J, Townley R. Alzheimer’s disease clinical trial update 2019-2021. J Neurol 2022; 269 (02) 1038-1051 https://doi.org/10.1007/s00415-021-10790-5
- 37 Ostrowitzki S, Lasser RA, Dorflinger E, Scheltens P, Barkhof F, Nikolcheva T. et al. A phase III randomized trial of gantenerumab in prodromal Alzheimer’s disease. Alzheimers Res Ther 2017; 9 (01) 95-95 https://doi.org/10.1186/s13195-017-0318-y
- 38 Cummings JL, Cohen S, van Dyck CH, Brody M, Curtis C, Cho W. et al. ABBY - a phase 2 randomized trial of crenezumab in mild to moderate Alzheimer disease. Neurology 2018; 90 (21) e1889-e1897 https://doi.org/10.1212/wnl.2022s1172022s1175550
- 39 Salloway S, Honigberg LA, Cho W, Ward M, Friesenhahn M, Brunsteins F. et al. Amyloid positron emission tomography and cerebrospinal fluid results from a crenezumab anti-amyloid-beta antibody double-blind, placebo-controlled, randomized phase II study in mild to- moderate Alzheimer’s disease (BLAZE). Alzheimers Res Ther 2018; 10 (01) 96-96 https://doi.org/10.1186/s13195-018-0424-5
- 40 Roche. https://www.roche.com/investors/updates/inv-update-2019-01-3 12 March 2022
- 41 https://www.clinicaltrials.gov 12 March 2022
- 42 Doody RS, Thomas RG, Farlow M, Iwatsubo T, Vellas B, Kieburtz K. et al. Phase 3 trials of solanezumab for mild to-moderate Alzheimer’s disease. N Engl J Med 2014; 370 (04) 311-321 https://doi.org/10.1056/nejmoa1312889
- 43 Siemers ER, Sundell KL, Carlson C, Case M, Sethuraman G, Liu-Seifert H. et al. Phase 3 solanezumab trials: secondary outcomes in mild Alzheimer’s disease patients. Alzheimers Dement 2016; 12 (02) 110-120 https://doi.org/10.1016/j.jalz.2015.06.1893
- 44 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; 378 (04) 321-330 https://doi.org/10.1056/nejmoa1705971
- 45 Salloway S, Farlow M, McDade E, Clifford DB, Wang G, Llibre-Guerra JJ. et al. A trial of gantenerumab or solanezumab in dominantly inherited Alzheimer’s disease. Nat Med 2021; 27 (07) 1187-1196 https://doi.org/10.1038/s41591-021-01369-8
- 46 Fleisher AS, Lowe SL, Liu P, Shcherbinin S, Li L, Chua L. et al. Significant and sustained florbetapirF18 uptake reduction in patients with symptomatic Alzheimer’s disease with LY3002813, a β-amyloid plaque-specific antibody. Alzheimers Dement 2018; 14 (07) 239-240 https://doi.org/10.1016/j.jalz.2018.06.2378
- 47 Lowe SL, Willis BA, Hawdon A, Natanegara F, Chua L, Foster J. et al. Donanemab (LY3002813) dose-escalation study in Alzheimer’s disease. Alzheimers Dement (N Y) 2021; 7 (01) e12112 https://doi.org/10.1002/trc2.12112
- 48 Panza F, Lozupone M, Logroscino G, Imbimbo BP. A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease. Nat Rev Neurol 2019; 15 (02) 73-88 https://doi.org/10.1038/s41582-018-0116-6
- 49 Braak H, Del Tredici K. The pathological process underlying Alzheimer’s disease in individuals under thirty. Acta Neuropathol 2011; 121 (02) 171-181 https://doi.org/10.1007/s00401-010-0789-4
- 50 Knopman DS, Jack Jr CR, Wiste HJ, Weigand SD, Vemuri P, Lowe V. et al. Short- term clinical outcomes for stages of NIA- AA preclinical Alzheimer disease. Neurology 2012; 78 (20) 1576-1582 https://doi.org/10.1212/wnl.0b013e3182563bbe
- 51 Cubanski J, Neuman T. FDA’s Approval of Biogen’s New Alzheimer’s Drug Has Huge Cost Implications for Medicare and Beneficiaries [Internet]. Kaiser Family Foundation. 2021 2022 Mar 3 Available from: https://www.kff.org/medicare/issue-brief/fdas-approval-of-biogens-new-alzheimers-drug-has-huge-cost-implications-for-medicare-and-beneficiaries/
- 52 Chiong W, Tolchin BD, Bonnie RJ, Busl K, Cruz-Flores S, Epstein LG. et al. Decisions with Patients and Families Regarding Aducanumab in Alzheimer Disease, With Recommendations for Consent: AAN Position Statement. Neurology 2022; 98 (04) 154-159 https://doi.org/10.1212/WNL.2022s1170000013053