Alzheimer’s Disease: Key Insights from Two Decades of Clinical Trial Failures
Open accessAbstract
Given the acknowledged lack of success in Alzheimer's disease (AD) drug development over the past two decades, the objective of this review was to derive key insights from the myriad failures to inform future drug development. A systematic and exhaustive review was performed on all failed AD compounds for dementia (interventional phase II and III clinical trials from ClinicalTrials.gov) from 2004 to the present. Starting with the initial ∼2,700 AD clinical trials, ∼550 trials met our initial criteria, from which 98 unique phase II and III compounds with various mechanisms of action met our criteria of a failed compound. The two recent reported phase III successes of aducanumab and oligomannate are very encouraging; however, we are awaiting real-world validation of their effectiveness. These two successes against the 98 failures gives a 2.0% phase II and III success rate since 2003, when the previous novel compound was approved. Potential contributing methodological factors for the clinical trial failures were categorized into 1) insufficient evidence to initiate the pivotal trials, and 2) pivotal trial design shortcomings. Our evaluation found that rational drug development principles were not always followed for AD therapeutics development, and the question remains whether some of the failed compounds may have shown efficacy if the principles were better adhered to. Several recommendations are made for future AD therapeutic development. The whole database of the 98 failed compounds is presented in the Supplementary Material.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Aducanumab received accelerated approval by the FDA for the treatment of mild cognitive impairment due to AD and mild AD dementia on 7 June 2021.
“This led to the accelerated approval of Aducanumab by the FDA for the treatment of mild cognitive impairment due to AD and mild AD dementia on 7 June 2021.”
From Treatment of Alzheimer’s Disease: Beyond Symptomatic Therapies (2023) · cites this paper as [47]
The Introduction (page not provided) says the FDA approved aducanumab in 2021 based on the surrogate endpoint of reduced brain Aβ plaques, with a post-marketing trial required. It does not give 7 June as the approval date or specify mild cognitive impairment due to AD and mild AD dementia as the treatment population. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe approval of the first mAb against AD was given without a definitively proven clinical benefit based on its effects on AD biomarkers.
“The approval of the first mAb against AD was given without a definitively proven clinical benefit based on its effects on AD biomarkers [47,62,64,65].”
From Treatment of Alzheimer’s Disease: Beyond Symptomatic Therapies (2023) · cites this paper as [47]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Alzheimer's disease: the amyloid cascade hypothesis
Hardy, J. A., & Higgins, G. A. (1992) · Science · doi:10.1126/science.1566067 · Cited by 7,484 · see citing works
The amyloid hypothesis of Alzheimer's disease at 25 years
Selkoe, D. J., & Hardy, J. (2016) · EMBO Molecular Medicine · doi:10.15252/emmm.201606210 · Cited by 6,164 · see citing works
Innovation in the pharmaceutical industry: New estimates of R&D costs
DiMasi, J. A., Grabowski, H. G., & Hansen, R. W. (2016) · Journal of Health Economics · doi:10.1016/j.jhealeco.2016.01.012 · Cited by 3,359 · see citing works
2019 Alzheimer’s disease facts and figures.
Alzheimer's Association (2019) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2019.01.010 · Cited by 2,461 · see citing works
Inflammation as a central mechanism in Alzheimer's disease
Kinney, J. W., Bemiller, S. M., Murtishaw, A. S., Leisgang, A. M., Salazar, A. M., & Lamb, B. T. (2018) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2018.06.014 · Cited by 2,253 · see citing works
Two Phase 3 Trials of Bapineuzumab in Mild-to-Moderate Alzheimer's Disease
Salloway, S., Sperling, R., Fox, N. C., Blennow, K., Klunk, W., Raskind, M., Sabbagh, M., Honig, L. S., Porsteinsson, A. P., Ferris, S., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1304839 · Cited by 1,960 · see citing works
Masters, C. L., Bateman, R., Blennow, K., Rowe, C. C., Sperling, R. A., & Cummings, J. L. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.56 · Cited by 1,853 · see citing works
Oxidative Stress, Synaptic Dysfunction, and Alzheimer’s Disease
Tönnies, E., & Trushina, E. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-161088 · Cited by 1,750 · see citing works
Prevalence of Cerebral Amyloid Pathology in Persons Without Dementia: A Meta-analysis
Jansen, W. J., Ossenkoppele, R., Knol, D. L., Tijms, B. M., Scheltens, P., Verhey, F. R. J., Visser, P. J., Aalten, P., Aarsland, D., Alcolea, D., et al. (2015) · JAMA · doi:10.1001/jama.2015.4668 · Cited by 1,610 · see citing works
Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report
Nelson, P. T., Dickson, D. W., Trojanowski, J. Q., Jack, C. R., Boyle, P. A., Arfanakis, K., Rademakers, R., Alafuzoff, I., Attems, J., Brayne, C., et al. (2019) · Brain · doi:10.1093/brain/awz099 · Cited by 1,547 · see citing works
A Phase 3 Trial of Semagacestat for Treatment of Alzheimer's Disease
Doody, R. S., Raman, R., Farlow, M., Iwatsubo, T., Vellas, B., Joffe, S., Kieburtz, K., He, F., Sun, X., Thomas, R. G., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1210951 · Cited by 1,224 · see citing works
Trial of Solanezumab for Mild Dementia Due to Alzheimer’s Disease
Honig, L. S., Vellas, B., Woodward, M., Boada, M., Bullock, R., Borrie, M., Hager, K., Andreasen, N., Scarpini, E., Liu-Seifert, H., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1705971 · Cited by 1,049 · cited 3× · see citing works
“This is the norm even when prodromal or mild AD is targeted, as is the case with the failed amyloid targeting drugs elenbecestat [41], lanabecesat [44], crenezumab [47], solanezumab [39], and gantenerumab [40].”
Biomarkers for Alzheimer's disease: current status and prospects for the future
Blennow, K., & Zetterberg, H. (2018) · Journal of Internal Medicine · doi:10.1111/joim.12816 · Cited by 1,000 · see citing works
Alzheimer’s disease: risk factors and potentially protective measures
Silva, M. V. F., Loures, C. D. M. G., Alves, L. C. V., de Souza, L. C., Borges, K. B. G., & Ferriani, M. D. G. C. (2019) · Journal of Biomedical Science · doi:10.1186/s12929-019-0524-y · Cited by 962 · see citing works
Reconsideration of Amyloid Hypothesis and Tau Hypothesis in Alzheimer's Disease
Kametani, F., & Hasegawa, M. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00025 · Cited by 836 · see citing works
Alzheimer's disease drug development pipeline: 2019
Cummings, J., Lee, G., Ritter, A., Sabbagh, M., & Zhong, K. (2019) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2019.05.008 · Cited by 762 · see citing works
A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease
Salloway, S., Sperling, R., Gilman, S., Fox, N. C., Blennow, K., Raskind, M., Sabbagh, M., Honig, L. S., Doody, R., van Dyck, C. H., et al. (2009) · Neurology · doi:10.1212/wnl.0b013e3181c67808 · Cited by 753 · see citing works
Three dimensions of the amyloid hypothesis: time, space and 'wingmen'
Musiek, E. S., & Holtzman, D. M. (2015) · Nature Neuroscience · doi:10.1038/nn.4018 · Cited by 697 · see citing works
Randomized trial of verubecestat for mild-to-moderate Alzheimer's disease
Egan, M. F., Kost, J., Tariot, P. N., Aisen, P. S., Cummings, J. L., Vellas, B., Sur, C., Mukai, Y., Voss, T., Furtek, C., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1706441 · Cited by 685 · see citing works
Risk factors for Alzheimer’s disease
Armstrong, R. A. (2019) · Folia Neuropathologica · doi:10.5114/fn.2019.85929 · Cited by 617 · see citing works
Mehta, D. G., Jackson, R., Paul, G., Shi, J., & Sabbagh, M. N. (2017) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2017.1323868 · Cited by 608 · see citing works
A phase III randomized trial of gantenerumab in prodromal Alzheimer’s disease
for the SCarlet RoAD Investigators, Ostrowitzki, S., Lasser, R. A., Dorflinger, E., Scheltens, P., Barkhof, F., Nikolcheva, T., Ashford, E., Retout, S., Hofmann, C., et al. (2017) · Alzheimer's Research & Therapy · doi:10.1186/s13195-017-0318-y · Cited by 567 · see citing works
Randomized trial of verubecestat for prodromal Alzheimer's disease
Egan, M. F., Kost, J., Voss, T., Mukai, Y., Aisen, P. S., Cummings, J. L., Tariot, P. N., Vellas, B., van Dyck, C. H., Boada, M., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1812840 · Cited by 545 · see citing works
Qiu, S., Joshi, P. S., Miller, M. I., Xue, C., Zhou, X., Karjadi, C., Chang, G. H., Joshi, A. S., Dwyer, B., Zhu, S., et al. (2020) · Brain · doi:10.1093/brain/awaa137 · Cited by 472 · see citing works
Veitch, D. P., Weiner, M. W., Aisen, P. S., Beckett, L. A., Cairns, N. J., Green, R. C., Harvey, D., Jack, C. R., Jagust, W., Morris, J. C., et al. (2019) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.08.005 · Cited by 454 · see citing works
Kueper, J. K., Speechley, M. R., & Montero‐Odasso, M. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170991 · Cited by 434 · see citing works
Sex and the development of Alzheimer's disease
Pike, C. J. (2016) · Journal of Neuroscience Research · doi:10.1002/jnr.23827 · Cited by 405 · see citing works
Efficacy of PPAR-γ agonist pioglitazone in mild Alzheimer disease
Sato, T., Hanyu, H., Hirao, K., Kanetaka, H., Sakurai, H., & Iwamoto, T. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.10.009 · Cited by 387 · see citing works
The Amyloid Cascade Hypothesis in Alzheimer’s Disease: It’s Time to Change Our Mind
Ricciarelli, R., & Fedele, E. (2017) · Current Neuropharmacology · doi:10.2174/1570159x15666170116143743 · Cited by 380 · see citing works
A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease
Sano, M., Bell, K. L., Galasko, D., Galvin, J. E., Thomas, R. G., van Dyck, C. H., & Aisen, P. S. S. (2011) · Neurology · doi:10.1212/wnl.0b013e318228bf11 · Cited by 336 · see citing works
Fleisher, A., Raman, R., Siemers, E., Becerra, L. M., Clark, C. M., Dean, R. A., Farlow, M. R., Galvin, J. E., Peskind, E. R., Quinn, J. F., et al. (2008) · Archives of Neurology · doi:10.1001/archneur.65.8.1031 · Cited by 332 · see citing works
Early-onset Alzheimer Disease and Its Variants
Mendez, M. F. (2019) · Continuum · doi:10.1212/con.0000000000000687 · Cited by 307 · see citing works
Bapineuzumab for mild to moderate Alzheimer’s disease in two global, randomized, phase 3 trials
Vandenberghe, R., Rinne, J. O., Boada, M., Katayama, S., Scheltens, P., Vellas, B., Tuchman, M., Gass, A., Fiebach, J. B., Hill, D., et al. (2016) · Alzheimer's Research & Therapy · doi:10.1186/s13195-016-0189-7 · Cited by 304 · see citing works
Lessons Learned from Alzheimer Disease: Clinical Trials with Negative Outcomes
Cummings, J. (2018) · Clinical and Translational Science · doi:10.1111/cts.12491 · Cited by 298 · see citing works
Wilcock, G. K., Black, S. E., Hendrix, S. B., Zavitz, K. H., Swabb, E. A., & Laughlin, M. A. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70090-5 · Cited by 291 · see citing works
A Perspective on Multi-target Drugs for Alzheimer’s Disease
Benek, O., Korabecny, J., & Soukup, O. (2020) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2020.04.008 · Cited by 260 · see citing works
Mitochondria as Potential Targets in Alzheimer Disease Therapy: An Update
Cenini, G., & Voos, W. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00902 · Cited by 257 · see citing works
Ferreira, D., Verhagen, C., Hernandez-Cabrera, J. A., Cavallin, L., Guo, C., Ekman, U., Muehlboeck, J., Simmons, A., Barroso, J., Wahlund, L., et al. (2017) · Scientific Reports · doi:10.1038/srep46263 · Cited by 228 · see citing works
Geldmacher, D. S., Fritsch, T., McClendon, M. J., & Landreth, G. (2011) · Archives of Neurology · doi:10.1001/archneurol.2010.229 · Cited by 221 · see citing works
Pinton, S., Sampaio, T. B., Savall, A. S. P., & Gutierrez, M. Z. (2017) · Neural Regeneration Research · doi:10.4103/1673-5374.205084 · Cited by 219 · see citing works
Efficacy and Safety of Lanabecestat for Treatment of Early and Mild Alzheimer Disease
Wessels, A. M., Tariot, P. N., Zimmer, J. A., Selzler, K. J., Bragg, S. M., Andersen, S. W., Landry, J., Krull, J. H., Downing, A. M., Willis, B. A., et al. (2019) · JAMA Neurology · doi:10.1001/jamaneurol.2019.3988 · Cited by 215 · see citing works
Nilvadipine in mild to moderate Alzheimer disease: A randomised controlled trial
Lawlor, B., Segurado, R., Kennelly, S., Olde Rikkert, M. G. M., Howard, R., Pasquier, F., Börjesson-Hanson, A., Tsolaki, M., Lucca, U., Molloy, D. W., et al. (2018) · PLOS Medicine · doi:10.1371/journal.pmed.1002660 · Cited by 193 · see citing works
ADCOMS: a composite clinical outcome for prodromal Alzheimer's disease trials
Wang, J., Logovinsky, V., Hendrix, S. B., Stanworth, S. H., Perdomo, C., Xu, L., Dhadda, S., Do, I., Rabe, M., Luthman, J., et al. (2016) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2015-312383 · Cited by 160 · see citing works
Less Alzheimer disease neuropathology in medicated hypertensive than nonhypertensive persons
Hoffman, L. B., Schmeidler, J., Lesser, G. T., Beeri, M. S., Purohit, D. P., Grossman, H. T., & Haroutunian, V. (2009) · Neurology · doi:10.1212/01.wnl.0000345881.82856.d5 · Cited by 159 · see citing works
Hanyu, H., Sato, T., Kiuchi, A., Sakurai, H., & Iwamoto, T. (2008) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2009.02067.x · Cited by 158 · see citing works
Imbalanced cholesterol metabolism in Alzheimer's disease
Xue-shan, Z., Peng, J., Wu, Q., Zhong, R., Li-hong, P., Tang, Z., Jiang, Z., Wang, G., & Liu, L. (2016) · Clinica Chimica Acta · doi:10.1016/j.cca.2016.02.024 · Cited by 155 · see citing works
Amyloid-β <sup>11</sup> C-PiB-PET imaging results from 2 randomized bapineuzumab phase 3 AD trials
Liu, E., Schmidt, M. E., Margolin, R., Sperling, R., Koeppe, R., Mason, N. S., Klunk, W. E., Mathis, C. A., Salloway, S., Fox, N. C., et al. (2015) · Neurology · doi:10.1212/wnl.0000000000001877 · Cited by 151 · see citing works
Tzioras, M., Davies, C., Newman, A., Jackson, R., & Spires‐Jones, T. (2019) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12529 · Cited by 147 · see citing works
Landmark Alzheimer’s drug approval confounds research community
Mullard, A. (2021) · Nature · doi:10.1038/d41586-021-01546-2 · Cited by 140 · see citing works
Neuroprotective therapeutics for Alzheimer's disease: progress and prospects
Palmer, A. M. (2011) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2010.12.007 · Cited by 133 · see citing works
Molloy, D. W., Standish, T., Zhou, Q. X., Guyatt, G. H., & The DARAD Study Group (2012) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.3846 · Cited by 129 · see citing works
Iturria‐Medina, Y., Carbonell, F., Sotero, R. C., Chouinard-Decorte, F., & Evans, A. C. (2017) · NeuroImage · doi:10.1016/j.neuroimage.2017.02.058 · Cited by 126 · see citing works
The amyloid cascade and Alzheimer's disease therapeutics: theory versus observation
Castellani, R. J., Plascencia‐Villa, G., & Perry, G. L. (2019) · Laboratory Investigation · doi:10.1038/s41374-019-0231-z · Cited by 124 · see citing works
PRECISION MEDICINE - THE GOLDEN GATE FOR DETECTION, TREATMENT AND PREVENTION OF ALZHEIMER’S DISEASE
Hampel, H. J., O’Bryant, S. E., Castrillo, J. I., Ritchie, C. W., Rojkova, K., Broich, K., Benda, N., Nisticò, R., Frank, R., Dubois, B., et al. (2016) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2016.112 · Cited by 116 · see citing works
RNA and Oxidative Stress in Alzheimer’s Disease: Focus on microRNAs
Nunomura, A., & Perry, G. L. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/2638130 · Cited by 110 · see citing works
Alzheimer’s Disease: Biomarkers in the Genome, Blood, and Cerebrospinal Fluid
Huynh, R. A., & Mohan, C. (2017) · Frontiers in Neurology · doi:10.3389/fneur.2017.00102 · Cited by 109 · see citing works
Data-driven FDG-PET subtypes of Alzheimer’s disease-related neurodegeneration
Levin, F., Ferreira, D., Lange, C., Dyrba, M., Westman, E., Buchert, R., Teipel, S. J., Grothe, M. J., & Initiative, F. T. A. D. N. (2021) · Alzheimer's Research & Therapy · doi:10.1186/s13195-021-00785-9 · Cited by 109 · see citing works
Defining the earliest pathological changes of Alzheimer's disease
Vickers, J. C., Mitew, S., Woodhouse, A., Fernández-Martos, C. M., Kirkcaldie, M. T., Canty, A. J., McCormack, G. H., & King, A. E. (2015) · Current Alzheimer Research · doi:10.2174/1567205013666151218150322 · Cited by 108 · see citing works
Alzheimer’s Disease and Diabetes: Insulin Signaling as the Bridge Linking Two Pathologies
Shieh, J. C.-C., Huang, P.-T., & Lin, Y. (2020) · Molecular Neurobiology · doi:10.1007/s12035-019-01858-5 · Cited by 104 · see citing works
Gabin, J. M., Tambs, K., Saltvedt, I. T., Sund, E. R., & Holmen, J. (2017) · Alzheimer s Research & Therapy · doi:10.1186/s13195-017-0262-x · Cited by 99 · see citing works
González, J. F., Alcántara, A. R., Doadrio, A. L., & Sánchez-Montero, J. M. (2019) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2019.1623201 · Cited by 98 · see citing works
Bradshaw‐Pierce, E. L., Spilker, M. E., Zang, R., Bansal, L., He, H., Jones, R. D. O., Le, K. N., Penney, M., Schuck, E. L., Topp, B. G., et al. (2019) · CPT Pharmacometrics & Systems Pharmacology · doi:10.1002/psp4.12463 · Cited by 93 · see citing works
Cebers, G., Alexander, R., Haeberlein, S. B., Han, D., Goldwater, R., Ereshefsky, L., Olsson, T., Ye, N., Rosen, L. B., Russell, M., et al. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160701 · Cited by 92 · see citing works
Economic analysis of opportunities to accelerate Alzheimer's disease research and development
Scott, T. J., O’Connor, A. C., Link, A. N., & Beaulieu, T. J. (2014) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12417 · Cited by 87 · see citing works
Hu, J., Geng, M., Li, J., Xin, X., Wang, J., Tang, M., Zhang, J., Zhang, X., & Ding, J. (2004) · Journal of Pharmacological Sciences · doi:10.1254/jphs.fpj04004x · Cited by 86 · see citing works
Ten Challenges of the Amyloid Hypothesis of Alzheimer’s Disease
Kepp, K. P. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160550 · Cited by 80 · see citing works
Is Alzheimer’s Disease a Neurogenesis Disorder?
Choi, S. H., & Tanzi, R. E. (2019) · Cell stem cell · doi:10.1016/j.stem.2019.06.001 · Cited by 78 · see citing works
Metabolic profiling distinguishes three subtypes of Alzheimer's disease
Bredesen, D. E. (2015) · Aging · doi:10.18632/aging.100801 · Cited by 76 · see citing works
Phase II clinical trials of anti–amyloid β antibodies: When is enough, enough?
Gold, M. (2017) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1016/j.trci.2017.04.005 · Cited by 75 · see citing works
Alterations in Glucose Metabolism in Alzheimer's Disease
Calsolaro, V., & Edison, P. (2016) · Recent Patents on Endocrine Metabolic & Immune Drug Discovery · doi:10.2174/1872214810666160615102809 · Cited by 67 · see citing works
Epidemiological Evidence of the Relationship Between Diabetes and Dementia
Ninomiya, T. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-3540-2_2 · Cited by 57 · see citing works
Wang, H., Sové, R. J., Jafarnejad, M., Rahmeh, S., Jaffee, E. M., Stearns, V., Torres, E. T. R., Connolly, R. M., & Popel, A. S. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.00141 · Cited by 51 · see citing works
Wang, C., Shou, Y., Pan, J., Du, Y. J., Liu, C., & Wang, H. (2018) · Nutritional Neuroscience · doi:10.1080/1028415x.2017.1416942 · Cited by 49 · see citing works
Status and future directions of clinical trials in Alzheimer's disease
Plascencia‐Villa, G., & Perry, G. L. (2020) · International review of neurobiology · doi:10.1016/bs.irn.2020.03.022 · Cited by 48 · see citing works
Diagnostic approaches to Alzheimer’s disease
Boss, M. A. (2000) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/s0925-4439(00)00044-2 · Cited by 43 · see citing works
Kennelly, S., Abdullah, L. I., Kenny, R. A., Mathura, V. S., Luis, C. A., Mouzon, B., Crawford, F., MULLAN, M. J., & LAWLOR, B. A. (2011) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.2735 · Cited by 41 · see citing works
Development Times and Approval Success Rates for Drugs to Treat Infectious Diseases
DiMasi, J. A., Florez, M. I., Stergiopoulos, S., Peña, Y., Smith, Z., Wilkinson, M., & Getz, K. A. (2019) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.1627 · Cited by 41 · see citing works
Meulenbroek, O., O'Dwyer, S., de Jong, D., van Spijker, G. J., Kennelly, S., Cregg, F., Rikkert, M. G. M. O., Abdullah, L. I., Wallin, A., Walsh, C., et al. (2016) · BMJ Open · doi:10.1136/bmjopen-2016-011584 · Cited by 27 · see citing works
Alzheimer's Disease: The Problem of Incorrect Clinical Diagnosis
McDaniel, L. D., Lukovits, T. G., & McDaniel, K. (1993) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/089198879300600409 · Cited by 25 · see citing works
Min, K. C., Dockendorf, M. F., Palcza, J. S., Tseng, J., Ma, L., Stone, J. A., Kleijn, H. J., Hodsman, P., Masuo, K., Tanen, M. R. L., et al. (2018) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.1258 · Cited by 24 · see citing works
Sarkar, J., Dwivedi, G., Chen, Q., Sheu, I. E., Paich, M., Chelini, C. M., D'Alessandro, P. M., & Burns, S. P. (2018) · PLoS ONE · doi:10.1371/journal.pone.0192472 · Cited by 20 · see citing works
Forman, M. S., Palcza, J. S., Tseng, J., Stone, J. A., Walker, B., Swearingen, D., Troyer, M. D., & Dockendorf, M. F. (2019) · Clinical and Translational Science · doi:10.1111/cts.12645 · Cited by 19 · see citing works
Disentangling Heterogeneity in Alzheimer’s Disease: Two Empirically-Derived Subtypes
Blanken, A. E., Dutt, S., Li, Y., Nation, D. A., & Initiative, A. D. N. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190230 · Cited by 16 · see citing works
The Relation of Diabetes to Memory Function
Arvanitakis, Z., Tatavarthy, M., & Bennett, D. A. (2020) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-020-01085-9 · Cited by 14 · see citing works
The Pulse of Drug Development for Alzheimers Disease
Rafii, M. S. (2010) · Reviews on Recent Clinical Trials · doi:10.2174/157488710790820490 · Cited by 5 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [14]Biogen (2021) Update on Regulatory Submission for Aducanumab in the European Union. https://investors.biogen.com/news-releases/news-release-details/update-regulatory-review-aducanumab-european-union, Accessed December, 2021.
- [15]Biogen (2021) Japan’s First Committee on New Drugs of The Pharmaceutical Affairs and Food Sanitation Council Seeks Additional Data; Aducanumab Remains under Review. https://investors.biogen.com/news-releases/news-release-details/japans-first-committee-new-drugs-pharmaceutical-affairs-and-food, Accessed December, 2021.
Cited by
Sorted by citations
The amyloid cascade hypothesis: an updated critical review
Kepp, K. P., Robakis, N. K. R. K., Høilund‐Carlsen, P. F., Sensi, S. L., & Vissel, B. (2023) · Brain · doi:10.1093/brain/awad159 · Cited by 294 · see citing works
Vrahatis, A. G., Skolariki, K., Krokidis, M. G., Lazaros, K., Exarchos, T. P., & Vlamos, P. (2023) · Sensors · doi:10.3390/s23094184 · Cited by 178 · see citing works
Yu, S. P., Jiang, M. Q., Shim, S. S., Pourkhodadad, S., & Wei, L. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00636-1 · Cited by 165 · see citing works
Yao, Q., Tang, F., Wang, Y., Yan, Y., Lin, D., Wang, T., Zhu, D., Tian, M., Lin, X., & Shi, J. (2022) · Brain stimulation · doi:10.1016/j.brs.2022.06.004 · Cited by 100 · see citing works
Treatment of Alzheimer’s Disease: Beyond Symptomatic Therapies
Buccellato, F. R., D’Anca, M., Tartaglia, G. M., Del Fabbro, M., Scarpini, E., & Galimberti, D. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241813900 · Cited by 94 · see citing works
“Consequently, the updated use recommendations of Aducanumab emphasize the importance of detecting past medical conditions that may predispose the patient to ARIA or may increase the likelihood of ARIA complications [47].”
BackgroundMethodAlzheimer's Disease Puzzle: Delving into Pathogenesis Hypotheses
(2024) · aging and disease · doi:10.14336/ad.2023.0608 · Cited by 183 · see citing works
Glial fibrillary acidic protein in Alzheimer’s disease: a narrative review
Leipp, F., Vialaret, J., Mohaupt, P., Coppens, S., Jaffuel, A., Niehoff, A., Lehmann, S., & Hirtz, C. (2024) · Brain Communications · doi:10.1093/braincomms/fcae396 · Cited by 83 · see citing works
The therapeutic landscape of tauopathies: challenges and prospects
Cummings, J. L., González, M. I., Pritchard, M. C., May, P. C., Toledo, L. M., & Harris, G. A. (2023) · Alzheimer s Research & Therapy · doi:10.1186/s13195-023-01321-7 · Cited by 80 · see citing works
Effects of choline containing phospholipids on the neurovascular unit: A review
Roy, P., Tomassoni, D., Nittari, G., Traini, E., & Amenta, F. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.988759 · Cited by 77 · see citing works
Cheng, F., Wang, F., Tang, J., Zhou, Y., Fu, Z., Zhang, P., Haines, J. L., Leverenz, J. B., Gan, L., Hu, J., et al. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2023.101379 · Cited by 63 · see citing works
Cell-type-directed network-correcting combination therapy for Alzheimer’s disease
Li, Y., Serras, C. P., Blumenfeld, J. R., Xie, M., Hao, Y., Deng, E., Chun, Y. Y., Holtzman, J., An, A., Yoon, S. Y., et al. (2025) · Cell · doi:10.1016/j.cell.2025.06.035 · Cited by 65 · see citing works
Lessons Learned from Approval of Aducanumab for Alzheimer's Disease
Heidebrink, J. L., & Paulson, H. L. (2024) · Annual Review of Medicine · doi:10.1146/annurev-med-051022-043645 · Cited by 58 · see citing works
Lizama, B. N., Kahle, J. S., Catalano, S. M., Caggiano, A. O., Grundman, M., & Hamby, M. E. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24076251 · Cited by 51 · see citing works
Yan, Y., Tian, M., Wang, T., Wang, X., Wang, Y., & Shi, J. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1209205 · Cited by 50 · see citing works
Chen, X., Huang, Y., Yang, S., Yang, S., Chen, L., Yu, X., Gan, N., & Huang, S. (2024) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2024.116738 · Cited by 47 · see citing works
Johnson, R. J., Tolan, D. R., Bredesen, D. E., Nagel, M. A., Sánchez‐Lozada, L. G., Fini, M. A., Burtis, S., Lanaspa, M. A., & Perlmutter, D. (2023) · American Journal of Clinical Nutrition · doi:10.1016/j.ajcnut.2023.01.002 · Cited by 44 · see citing works
Polis, B., & Samson, A. O. (2024) · Journal of Alzheimer's Disease · doi:10.3233/jad-240058 · Cited by 43 · see citing works
Mekala, A., & Qiu, H.-Y. (2025) · Biomolecules · doi:10.3390/biom15050712 · Cited by 41 · see citing works
Kazemeini, S., Nadeem-Tariq, A., Shih, R., Rafanan, J., Ghani, N., & Vida, T. A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252111720 · Cited by 41 · see citing works
Gut-brain axis: gut dysbiosis and psychiatric disorders in Alzheimer’s and Parkinson’s disease
Denman, C. R., Park, S. M., & Jo, J. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1268419 · Cited by 43 · see citing works
Tau‐targeting nanoparticles for treatment of Alzheimer's disease
Pawar, S., Rauf, M. A., Abdelhady, H. G., & Iyer, A. K. (2024) · Exploration · doi:10.1002/exp.20230137 · Cited by 36 · see citing works
Reas, E. T., Shadrin, A. A., Frei, O., Motazedi, E., McEvoy, L. K., Bahrami, S., van der Meer, D., Makowski, C., Loughnan, R. J., Wang, X., et al. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.13112 · Cited by 35 · see citing works
Rizzo, S. J. S., Homanics, G. E., Schaeffer, D. J., Schaeffer, L. K. H., Park, J. E., Oluoch, J., Zhang, T., Haber, A., Seyfried, N. T., Paten, B., et al. (2023) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.12417 · Cited by 35 · see citing works
Paolis, M. L. D., Paoletti, I., Zaccone, C., Capone, F., D’Amelio, M., & Krashia, P. (2024) · Translational Neurodegeneration · doi:10.1186/s40035-024-00423-y · Cited by 39 · see citing works
Tubulin Cytoskeleton in Neurodegenerative Diseases–not Only Primary Tubulinopathies
Cyske, Z., Gaffke, L., Pierzynowska, K., & Węgrzyn, G. (2022) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-022-01304-6 · Cited by 32 · see citing works
Bio–Nano Toolbox for Precision Alzheimer's Disease Gene Therapy
Liu, Y., Xia, X., Zheng, M., & Shi, B. (2024) · Advanced Materials · doi:10.1002/adma.202314354 · Cited by 30 · see citing works
Alzheimer’s Disease Treatment: The Search for a Breakthrough
Reiss, A. B., Muhieddine, D., Jacob, B., Mesbah, M., Pinkhasov, A., Gomolin, I. H., Stecker, M. M., Wısnıewskı, T., & Leon, J. D. (2023) · Medicina · doi:10.3390/medicina59061084 · Cited by 29 · see citing works
Moné, Y., Earl, J. P., Król, J. E., Ahmed, A., Sen, B., Ehrlich, G. D., & Lapides, J. R. (2023) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1123228 · Cited by 28 · see citing works
Microfluidic-based human prostate-cancer-on-chip
Jiang, L., Khawaja, H., Tahsin, S., Clarkson, T. A., Miranti, C. K., & Zohar, Y. (2024) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2024.1302223 · Cited by 26 · see citing works
The Therapeutic Potential of the Endocannabinoid System in Age-Related Diseases
Tudorancea, I. M., Ciorpac, M., Stanciu, G. D., Caratașu, C.-C., Săcărescu, A., Ignat, B. E., Burlui, A., Rezuş, E., Creangă-Murariu, I., Alexa‐Stratulat, T., et al. (2022) · Biomedicines · doi:10.3390/biomedicines10102492 · Cited by 26 · see citing works
Maggiore, A., Latina, V., D’Erme, M., Amadoro, G., & Coccurello, R. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102578 · Cited by 24 · see citing works
Ganesh, T. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c00655 · Cited by 23 · see citing works
Caballero, E., Hernando-Pérez, E., Tapias, V., Calvo-Rodríguez, M., Villalobos, C., & Núñez, L. (2022) · Biomedicines · doi:10.3390/biomedicines10051153 · Cited by 22 · see citing works
Nicola, L., Loo, S. J. Q., Lyon, G., Turknett, J., & Wood, T. R. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102356 · Cited by 21 · see citing works
Nelson, M. L., Pfeifer, J. A., Hickey, J. P., Collins, A. E., & Kalisch, B. E. (2023) · Biology · doi:10.3390/biology12071042 · Cited by 21 · see citing works
Deep learning-based patient stratification for prognostic enrichment of clinical dementia trials
Birkenbihl, C. J., de Jong, J., Yalchyk, I., & Fröhlich, H. (2024) · Brain Communications · doi:10.1093/braincomms/fcae445 · Cited by 20 · see citing works
Genomics of drug target prioritization for complex diseases
Chen, R. K., Duffy, Á., & Do, R. (2025) · Nature Reviews Genetics · doi:10.1038/s41576-025-00904-4 · Cited by 22 · see citing works
Dynamic clinical trial success rates for drugs in the 21st century
Zhou, Y., Zhang, Y., Xu, H., Chen, Z., Huang, S., Li, Y., Fu, J., Zhang, H., Zhao, D., Lian, X., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-64552-2 · Cited by 20 · see citing works
Du, Y., Bradshaw, W. J., Leisner, T. M., Annor‐Gyamfi, J. K., Qian, K., Bashore, F. M., Sikdar, A., Nwogbo, F. O., Ivanov, A. A., Frye, S. V., et al. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.105382 · Cited by 18 · see citing works
Chaudhuri, S., Cho, M., Stumpff, J., Bice, P. J., İş, Ö., Ertekin‐Taner, N., Saykin, A. J., & Nho, K. T. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00798-0 · Cited by 18 · see citing works
Tackling neurodegeneration in vitro with omics: a path towards new targets and drugs
Carraro, C., Montgomery, J. V., Klimmt, J., Paquet, D., Schultze, J. L., & Beyer, M. (2024) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2024.1414886 · Cited by 15 · see citing works
Restoring brain barriers: an innovative approach for treating neurological disorders
Lemarchant, S., Engelhardt, B., Cicchetti, F., Bix, G. J., Janus, A., Godfrin, Y., Blasco, H., Campbell, M., & Jacquet, A. D. R. (2025) · Fluids and Barriers of the CNS · doi:10.1186/s12987-025-00688-z · Cited by 16 · see citing works
Gehlot, P., Pathak, R., Kumar, S., Choudhary, N. K., & Vyas, V. K. (2024) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2024.117925 · Cited by 16 · see citing works
Spitz, S., Schobesberger, S., Brandauer, K., & Ertl, P. (2023) · Bioengineering & Translational Medicine · doi:10.1002/btm2.10604 · Cited by 15 · see citing works
The need for systems thinking to advance Alzheimer's disease research
Uleman, J. F., Quax, R., Melis, R. J. F., Hoekstra, A. G., & Rikkert, M. G. M. O. (2024) · Psychiatry Research · doi:10.1016/j.psychres.2024.115741 · Cited by 15 · see citing works
Forlenza, O. V., & Barbosa, B. J. A. P. (2025) · Dementia & Neuropsychologia · doi:10.1590/1980-5764-dn-2025-e001 · Cited by 14 · see citing works
Localized proteomic differences in the choroid plexus of Alzheimer's disease and epilepsy patients
Leitner, D., Kanshin, E., Faustin, A., Thierry, M., Friedman, D. J., Devore, S., Ueberheide, B. M., Devinsky, O., & Wısnıewskı, T. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1221775 · Cited by 15 · see citing works
Zhang, Q., Coury, R., & Tang, W. (2024) · Alzheimer s Research & Therapy · doi:10.1186/s13195-024-01421-y · Cited by 13 · see citing works
Miliotou, Α. N., Kotsoni, A., & Zacharia, L. C. (2025) · Biomolecules · doi:10.3390/biom15010128 · Cited by 13 · see citing works
Zhao, D., Wang, J., Zhu, Y., Zhang, H., Ni, C., Zhao, Z., Dai, J., He, R., Liu, G.-Z., Gan, C., et al. (2025) · Translational Neurodegeneration · doi:10.1186/s40035-025-00510-8 · Cited by 17 · see citing works
Akgüller, Ö., Balcı, M. A., & Cioca, G. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262010003 · Cited by 13 · see citing works
Ranganathan, R., Sapozhnikov, G., Wang, N., Li, S., & Song, Y. (2023) · Translational Medicine of Aging · doi:10.1016/j.tma.2023.06.004 · Cited by 13 · see citing works
Barbosa, B. J. A. P., Resende, E. D. P. F., Castilhos, R. M., Borelli, W. V., Frota, N. A. F., Balthazar, M. L. F., Filho, A. C. S. A., Smid, J., Barbosa, M. T., Coutinho, A. M., et al. (2024) · Dementia & Neuropsychologia · doi:10.1590/1980-5764-dn-2024-c002 · Cited by 16 · see citing works
MicroRNA-based recent research developments in Alzheimer's disease
Ramirez-Gomez, J., Dalal, S., Devara, D., Sharma, B., Rodarte, D., & Kumar, S. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877241313397 · Cited by 14 · see citing works
Samuels, J. D., Lukens, J. R., & Price, R. J. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15981 · Cited by 13 · see citing works
Understanding Barriers Along the Patient Journey in Alzheimer’s Disease Using Social Media Data
Monfared, A. A. T., Stern, Y., Doogan, S., Irizarry, M. C., & Zhang, Q. (2023) · Neurology and Therapy · doi:10.1007/s40120-023-00472-x · Cited by 12 · see citing works
Schreiner, T. G., Croitoru, C. G., Hodorog, D. N., & Cuciureanu, D. I. (2024) · Biomedicines · doi:10.3390/biomedicines12051096 · Cited by 12 · see citing works
The AROMHA brain health test is a remote olfactory assessment to screen for cognitive impairment
Jobin, B., Magdamo, C., Delphus, D., Runde, A., Reineke, S., Alejandro-Soto, A., Ergun, B., Mukhija, S., Albers, A. D., & Albers, M. W. (2025) · Scientific Reports · doi:10.1038/s41598-025-92826-8 · Cited by 15 · see citing works
Mạnh, N. V., Hoang, V.-H., Ngo, V. T. H., Kang, S., Jeong, J. J., Ha, H.-J., Kim, H., Kim, Y.-H., Ann, J., & Lee, J. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114837 · Cited by 12 · see citing works
Wickstead, E. S. (2023) · Biomedicines · doi:10.3390/biomedicines11082240 · Cited by 11 · see citing works
rTMS regulates homotopic functional connectivity in the SCD and MCI patients
Ge, H., Chen, S., Che, Z., Wu, H., Yang, X., Qiao, M., Chi, L., Fan, J., Zhong, Y., Zou, C., et al. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1301926 · Cited by 11 · see citing works
Owumi, S. E., Oluwawibe, B. J., Chimezie, J., Babalola, J. O., Ogunyemi, O. M., Gyebi, G. A., Otunla, M. T., Altayyar, A., Arunsi, U. O., Irozuru, C. E., et al. (2024) · BMC Pharmacology and Toxicology · doi:10.1186/s40360-024-00812-z · Cited by 11 · see citing works
Circulating Biomarkers for the Early Diagnosis of Alzheimer’s Disease
Nunkoo, V. S., Jurcău, A., Les, M., Cristian, A., Militaru, M., Marge, C., Iovanovici, D. C., & Jurcău, M. C. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26157268 · Cited by 12 · see citing works
Amylin and Secretases in the Pathology and Treatment of Alzheimer’s Disease
Singh, S. P., Yang, F., Sivils, A., Cegielski, V., & Chu, X. (2022) · Biomolecules · doi:10.3390/biom12070996 · Cited by 11 · see citing works
Antiepileptic Drugs as Potential Dementia Prophylactics Following Traumatic Brain Injury
Locskai, L. F., Alyenbaawi, H., & Allison, W. T. (2023) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-051921-013930 · Cited by 11 · see citing works
The Potential of a Stratified Approach to Drug Repurposing in Alzheimer’s Disease
Anderson, C., Bucholc, M., McClean, P. L., & Zhang, S. (2023) · Biomolecules · doi:10.3390/biom14010011 · Cited by 11 · see citing works
Auclair‐Ouellet, N., Kassem, O., Bronner, S., Oula, M.-L., & Binda, S. (2025) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1699884 · Cited by 11 · see citing works
Zheng, Y., Zhou, W., Chang, H., & Zheng, K. (2026) · Frontiers in Neuroscience · doi:10.3389/fnins.2026.1764964 · Cited by 12 · see citing works
Open science in precision medicine for neurodegenerative diseases
Leonard, H. L., Nalls, M. A., Day-Williams, A., Esmaeeli, S., Jarreau, P., Bandrés‐Ciga, S., Heutink, P., Sardi, S. P., & Singleton, A. (2024) · Nature Reviews Drug Discovery · doi:10.1038/d41573-024-00017-3 · Cited by 10 · see citing works
Tokuoka, S. M., Hamano, F., Kobayashi, A., Adachi, S., Andou, T., Natsume, T., & Oda, Y. (2024) · Scientific Reports · doi:10.1038/s41598-024-71097-9 · Cited by 10 · see citing works
Polygenic score integrating neurodegenerative and vascular risk informs dementia risk stratification
D’Aoust, T., Clocchiatti‐Tuozzo, S., Rivier, C. A., Mishra, A., Hachiya, T., Grenier‐Boley, B., Soumaré, A., Duperron, M., Grand, Q. L., Bouteloup, V., et al. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70014 · Cited by 10 · see citing works
Jing, Y., Zhao, G., Xu, Y., McGuire, T. F., Hou, G., Zhao, J. J., Chen, M., López, O. L., Xue, Y., & Xie, X. (2025) · The AAPS Journal · doi:10.1208/s12248-025-01059-0 · Cited by 10 · see citing works
Updates on Tau-Related Drug Targets and Potential Disease-Modifying Therapies for Alzheimer Disease
Djurovic-Topalovic, A., Horgan, N. G., & Fortin, J. S. (2025) · American Journal Of Pathology · doi:10.1016/j.ajpath.2025.05.020 · Cited by 10 · see citing works
Zhang, T., & Park, S. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26178545 · Cited by 13 · see citing works
Batten disease through different in vivo and in vitro models: A review
Nittari, G., Tomassoni, D., Roy, P., Martinelli, I., Tayebati, S. K., & Amenta, F. (2022) · Journal of Neuroscience Research · doi:10.1002/jnr.25147 · Cited by 10 · see citing works
Effects of Probiotics on Colitis-Induced Exacerbation of Alzheimer’s Disease in AppNL-G-F Mice
Sahu, B., Johnson, L. M., Sohrabi, M., Usatii, A. A., Craig, R. M. J., Kaelberer, J. B., Chandrasekaran, S. P., Kaur, H., Nookala, S., & Combs, C. K. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241411551 · Cited by 9 · see citing works
Biomarkers as Endpoints in Clinical Trials for Alzheimer’s Disease
Elghanam, Y., Purja, S., & Kim, E. Y. (2024) · Journal of Alzheimer s Disease · doi:10.3233/jad-240008 · Cited by 9 · see citing works
Fukumoto, H., Kao, T., Tai, C., Jang, M., & Miyamoto, M. (2024) · The FASEB Journal · doi:10.1096/fj.202401704r · Cited by 9 · see citing works
A Machine Learning Approach to Predict Cognitive Decline in Alzheimer Disease Clinical Trials
Nallapu, B. T., Petersen, K. K., Qian, T., Demirsoy, İ., Ghanbarian, E., Davatzikos, C. A., Lipton, R. B., Ezzati, A., Initiative, A. D. N., Weiner, M. W., et al. (2025) · Neurology · doi:10.1212/wnl.0000000000213490 · Cited by 9 · see citing works
Large language models for Alzheimer's disease drug discovery
Alkam, T., Tarshizi, E., & Benschoten, A. H. V. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877251346890 · Cited by 9 · see citing works
Murayama, M. A. (2023) · EXPERIMENTAL ANIMALS · doi:10.1538/expanim.22-0164 · Cited by 9 · see citing works
A Systematic Online Living Evidence Summary of experimental Alzheimer’s disease research
Hair, K., Wilson, E., Maksym, O., Macleod, M. R., & Sena, E. S. (2024) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2024.110209 · Cited by 9 · see citing works
Simmatis, L. E. R., Russo, E. E., Steininger, T., Riddell, H., Chen, E., Chiu, Q., Lin, M., Oh, D., Taheri, P., Harmsen, I. E., et al. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877251327754 · Cited by 8 · see citing works
Gopukumar, S. T., Dwivedi, D., Gowri, K., Karpakavalli, M., Nair, C., Singh, D., & Das, U. (2025) · Medicine in Drug Discovery · doi:10.1016/j.medidd.2025.100237 · Cited by 8 · see citing works
Current advancement in AI-integrated drug discovery: Methods and applications
Mathur, Y., Choudhury, A., Prabha, S., Saeed, M. U., Sulaimani, M. N., Mohammad, T., & Hassan, M. I. (2025) · Biotechnology Advances · doi:10.1016/j.biotechadv.2025.108642 · Cited by 8 · see citing works
Simakov, A., Chhor, S., Ismaïli, L., & Martin, H. (2025) · Molecules · doi:10.3390/molecules30092048 · Cited by 7 · see citing works
Barbosa, D. B., de Oliveira, L. M. G., Mendes, G. O., Costa, D. B., de Oliveira, T. A., da Silva, M. P., Damázio, L. C. M., Maia, E. H. B., Falkoski, D. L., Marra, I. F. D. S., et al. (2025) · ACS Omega · doi:10.1021/acsomega.5c07084 · Cited by 6 · see citing works
Cognitive adaptations for memory deficits in MCI and AD patients: A meta-analysis of EEG microstates
Piton, T., Smailović, U., Jelić, V., Koenig, T. W., Unschuld, P. G., & Bréchet, L. (2025) · NeuroImage Clinical · doi:10.1016/j.nicl.2025.103929 · Cited by 7 · see citing works
Advances in the drug treatment of Alzheimer’s disease: pathophysiology and mechanisms of action
Nowell, J., Crook, H., de Leon, M. J., & Edison, P. (2026) · BMJ · doi:10.1136/bmj-2023-078881 · Cited by 7 · see citing works
Alzheimer’s Disease Diagnosis and Management in the Age of Amyloid Monoclonal Antibodies
Hales, C. M. (2024) · Medical Clinics of North America · doi:10.1016/j.mcna.2024.10.003 · Cited by 7 · see citing works
Neuroglia in neurodegeneration: Alzheimer, Parkinson, and Huntington disease
Lim, D., Matute, C., Cavaliere, F., & Verkhratsky, A. (2025) · Handbook of clinical neurology · doi:10.1016/b978-0-443-19102-2.00012-0 · Cited by 7 · see citing works
Emerging concepts towards a translational framework in Alzheimer’s disease
Cozachenco, D., Zimmer, E. R., & Lourenco, M. V. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105246 · Cited by 7 · see citing works
Singh, A. S., Naqvi, A. R., & Chanu, M. T. (2026) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2026.01.050 · Cited by 7 · see citing works
Guizzaro, L., Bałkowiec-Iskra, E., Haberkamp, M., Mol, P. G. M., Moreau, A., Mueller-Berghaus, J., Philadelphy, D., Balabanov, P. P., Garcia, J., Thirstrup, S., et al. (2026) · The Lancet Regional Health - Europe · doi:10.1016/j.lanepe.2026.101644 · Cited by 6 · see citing works
Alım, Z., & Demir, Y. (2026) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-026-05347-0 · Cited by 6 · see citing works
Negrete-Diaz, F., Martinez-Rodriguez, S., Guedan-Duran, A., Romero-Lopez, A., & Panetsos, F. (2026) · Pharmacological Research · doi:10.1016/j.phrs.2026.108245 · Cited by 7 · see citing works
Retrospective Bayesian Evidence of Null Effect in Two Decades of Alzheimer’s Disease Clinical Trials
Costa, T., Manuello, J., Cauda, F., & Liloia, D. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-220942 · Cited by 6 · see citing works
Li, X., Yuan, M., Han, T., Han, Q., Yao, L., & Song, X. (2025) · Microchemical Journal · doi:10.1016/j.microc.2025.114974 · Cited by 5 · see citing works
Karur, P., Kaldas, M., Babu, Y. S. R., & Parmar, M. S. (2026) · Molecular Neurobiology · doi:10.1007/s12035-025-05647-1 · Cited by 5 · see citing works
de Munter, J., Chaprov, K., Lang, E., Sitdikova, K., Wolters, E. C., Svirin, E. P., Kassenova, A., Tsoy, A., Kramer, B. W. W., Askarova, S., et al. (2025) · Cells · doi:10.3390/cells14151168 · Cited by 5 · see citing works
- Authors
- Kim, C. K., Lee, Y. R., Ong, L., Gold, M., Kalali, A., & Sarkar, J.
- Affiliations
- Holmusk, New York, NY, USA
- AbbVie (United States) (US)
- Chairman, CNS Summit, San Diego, CA, USA
- Corresponding author
- Kim, C. Kwon
- Venue
- Journal of Alzheimer s Disease
- Publisher
- SAGE Publications
- Published
- 2022-05-03
- Volume
- 87
- Issue
- 1
- Pages
- 83-100
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- PMC
- PMC9198803
- OpenAlex
- W4220705385
- Cited by
- 241
- References
- 86
- Citations by year
- 2026: 60 · 2025: 71 · 2024: 57 · 2023: 43 · 2022: 10
- FWCI
- 6.29
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Alzheimer s Disease (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Cleveland Clinic
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- Alzheimer's disease, drug development failure
- MeSH terms
- Alzheimer Disease, Humans
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
