A phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer disease
Open accessAbstract
OBJECTIVE: This randomized, double-blind, placebo-controlled, dose-ranging phase 2 study explored safety, efficacy, and biomarker effects of ELND005 (an oral amyloid anti-aggregation agent) in mild to moderate Alzheimer disease (AD). METHODS: A total of 353 patients were randomized to ELND005 (250, 1,000, or 2,000 mg) or placebo twice daily for 78 weeks. Coprimary endpoints were the Neuropsychological Test Battery (NTB) and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale. The primary analysis compared 250 mg (n =84) to placebo (n =82) after an imbalance of infections and deaths led to early discontinuation of the 2 higher dose groups. RESULTS: The 250 mg dose demonstrated acceptable safety. The primary efficacy analysis at 78 weeks revealed no significant differences between the treatment groups on the NTB or ADCS-ADL. Brain ventricular volume showed a small but significant increase in the overall 250 mg group (p =0.049). At the 250 mg dose, scyllo-inositol concentrations increased in CSF and brain and CSF Aβx-42 was decreased significantly compared to placebo (p =0.009). CONCLUSIONS: Primary clinical efficacy outcomes were not significant. The safety and CSF biomarker results will guide selection of the optimal dose for future studies, which will target earlier stages of AD. CLASSIFICATION OF EVIDENCE: Due to the small sample sizes, this Class II trial provides insufficient evidence to support or refute a benefit of ELND005.
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?
Scyllo-inositol is an Aβ42 aggregation inhibitor that was studied in Alzheimer's disease subjects (ELND005); a phase 2 clinical study found no confirmation of ELND005's clinical benefit and the study was stopped due to severe toxicity concerns.
“The oral drug, scyllo-inositol is a Aβ42 aggregation inhibitor that was studied in AD subjects (ELND005). A clinical study (phase 2) in patients with AD found no confirmation of ELND005′s clinical benefit, and the study was stopped due to severe toxicity concerns (Salloway et al., 2011).”
From An update on the novel and approved drugs for Alzheimer disease (2022) · cites this paper as Salloway et al., 2011
Further development of ELND005 at a lower dose has not progressed in the last 8 years.
“Further development of the agent at a lower dose has not progressed in the last 8 years.50”
From Current and Future Treatments in Alzheimer Disease: An Update (2020) · cites this paper as [50]
A phase 2 clinical trial in patients with Alzheimer disease did not provide evidence to support a clinical benefit of ELND005, while severe toxicity issues (infections) forced cessation of the study.
“A phase 2 clinical trial in patients with AD did not provide evidence to support a clinical benefit of ELND005 while severe toxicity issues (infections) forced the cessation of the study.”
From Current and Future Treatments in Alzheimer Disease: An Update (2020) · cites this paper as [50]
The last Aβ42 aggregation inhibitor tested in humans was the oral agent scyllo-inositol (ELND005).
“The last Aβ42 aggregation inhibitor which was tested in humans was the oral agent scyllo-inositol (ELND005).”
From Current and Future Treatments in Alzheimer Disease: An Update (2020) · cites this paper as [50]
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
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975) · Journal of Psychiatric Research · doi:10.1016/0022-3956(75)90026-6 · Cited by 88,282 · see citing works
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915 · see citing works
The Clinical Dementia Rating (CDR): Current version and scoring rules
Morris, J. C. (1993) · Neurology · doi:10.1212/wnl.43.11.2412-a · Cited by 9,882 · see citing works
The Neuropsychiatric Inventory: Comprehensive assessment of psychopathology in dementia
Cummings, J. L., Mega, M., Gray, K., Rosenberg-Thompson, S., Carusi, D. A., & Gornbein, J. (1994) · Neurology · doi:10.1212/wnl.44.12.2308 · Cited by 7,568 · see citing works
A New Clinical Scale for the Staging of Dementia
Hughes, C. P., Berg, L., Danziger, W., Coben, L. A., & Martin, R. L. (1982) · British Journal of Psychiatry · doi:10.1192/bjp.140.6.566 · Cited by 7,056 · see citing works
Querfurth, H. W., & LaFerla, F. M. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0909142 · Cited by 4,569 · see citing works
A new rating scale for Alzheimer's disease
(1984) · American Journal of Psychiatry · doi:10.1176/ajp.141.11.1356 · Cited by 4,175 · see citing works
Alzheimer's Disease Neuroimaging Initiative (ADNI)
Petersen, R. C., Aisen, P. S., Beckett, L. A., Donohue, M. C., Gamst, A. C., Harvey, D. J., Jack, C. R., Jagust, W. J., Shaw, L. M., Toga, A. W., et al. (2010) · Neurology · doi:10.1212/wnl.0b013e3181cb3e25 · Cited by 2,572 · see citing works
Accurate, Robust, and Automated Longitudinal and Cross-Sectional Brain Change Analysis
Smith, S. M., Zhang, Y., Jenkinson, M., Chen, J. M., Matthews, P. M., Federico, A., & Stefano, N. D. (2002) · NeuroImage · doi:10.1006/nimg.2002.1040 · Cited by 2,013 · see citing works
Shankar, G. M., Bloodgood, B. L., Townsend, M., Walsh, D. M., Selkoe, D. J., & Sabatini, B. L. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.4970-06.2007 · Cited by 1,592 · see citing works
Clinical effects of Aβ immunization (AN1792) in patients with AD in an interrupted trial
Gilman, S., Koller, M., Black, R. S., Jenkins, L., Griffith, S. G., Fox, N. C., Eisner, L., Kirby, L., Rovira, M. B., Forette, F., et al. (2005) · Neurology · doi:10.1212/01.wnl.0000159740.16984.3c · Cited by 1,329 · see citing works
Self-citationPathological verification of ischemic score in differentiation of dementias
Rosen, W. G., Terry, R. D., Fuld, P. A., Katzman, R., & Peck, A. (1980) · Annals of Neurology · doi:10.1002/ana.410070516 · Cited by 1,273 · see citing works
An Inventory to Assess Activities of Daily Living for Clinical Trials in Alzheimerʼs Disease
Galasko, D., Bennett, D. A., Sano, M., Ernesto, C., Thomas, R., Grundman, M., & Ferris, S. H. (1997) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-199700112-00005 · Cited by 1,198 · see citing works
Galasko, D. R., Bennett, D., Sano, M., Ernesto, C., Thomas, R., Grundman, M., & Ferris, S. H. (1997) · PubMed · Cited by 767 · 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
Self-citationLannfelt, L., Blennow, K., Zetterberg, H., Batsman, S., Ames, D., Harrison, J., Masters, C. L., Targum, S., Bush, A. I., Murdoch, R., et al. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70167-4 · Cited by 725 · see citing works
Rinne, J. O., Brooks, D. J., Rossor, M. N., Fox, N. C., Bullock, R., Klunk, W. E., Mathis, C. A., Blennow, K., Barakos, J., Okello, A. A., et al. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70043-0 · Cited by 701 · see citing works
Effects of Aβ immunization (AN1792) on MRI measures of cerebral volume in Alzheimer disease
Fox, N. C., Black, R. S., Gilman, S., Rossor, M. N., Griffith, S. G., Jenkins, L., & Koller, M. (2005) · Neurology · doi:10.1212/01.wnl.0000159743.08996.99 · Cited by 550 · see citing works
Self-citationGalasko, D., Chang, L., Motter, R., Clark, C. M., Kaye, J., Knopman, D., Thomas, R., Kholodenko, D., Schenk, D., Lieberburg, I., et al. (1998) · Archives of Neurology · doi:10.1001/archneur.55.7.937 · Cited by 442 · see citing works
Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe
Feldman, H. H., Doody, R. S., Kivipelto, M., Sparks, D. L., Waters, D. D., Jones, R. W., Schwam, E., Schindler, R., Hey-Hadavi, J., DeMicco, D. A., et al. (2010) · Neurology · doi:10.1212/wnl.0b013e3181d6476a · Cited by 438 · see citing works
The role of cerebral amyloid accumulation in common forms of Alzheimer disease
Gandy, S. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25100 · Cited by 394 · see citing works
McLaurin, J., Kierstead, M. E., Brown, M. E., Hawkes, C. A., Lambermon, M. H. L., Phinney, A. L., Darabie, A. A., Cousins, J. E., French, J. E., Lan, M. F., et al. (2006) · Nature Medicine · doi:10.1038/nm1423 · Cited by 366 · see citing works
Fox, N. C., Cousens, S., Scahill, R. I., Harvey, R. J., & Rossor, M. N. (2000) · Archives of Neurology · doi:10.1001/archneur.57.3.339 · Cited by 354 · see citing works
Genetic dissection of Alzheimer's disease and related dementias: amyloid and its relationship to tau
Hardy, J., Duff, K., Hardy, K. G., Pérez‐Tur, J., & Hutton, M. (1998) · Nature Neuroscience · doi:10.1038/1565 · Cited by 345 · see citing works
Alzheimer Disease and Mortality: A 15-Year Epidemiological Study
Ganguli, M., Dodge, H. H., Shen, C., Pandav, R. S., & DeKosky, S. T. (2005) · Archives of Neurology · doi:10.1001/archneur.62.5.779 · Cited by 297 · see citing works
McLaurin, J., Golomb, R., Jurewicz, A., Antel, J. P., & Fraser, P. E. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m906994199 · Cited by 265 · see citing works
Cause of death in patients with dementia disorders
Brunnström, H. R., & Englund, E. M. (2009) · European Journal of Neurology · doi:10.1111/j.1468-1331.2008.02503.x · Cited by 246 · see citing works
A Neuropsychological Test Battery for Use in Alzheimer Disease Clinical Trials
Harrison, J., Minassian, S. L., Jenkins, L., Black, R. S., Koller, M., & Grundman, M. (2007) · Archives of Neurology · doi:10.1001/archneur.64.9.1323 · Cited by 225 · see citing works
Collins, D. L., & Pruessner, J. C. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.04.193 · Cited by 218 · see citing works
Relating neocortical pathology to disability progression in multiple sclerosis using MRI
Chen, J.-T., Narayanan, S., Collins, D., Smith, S. M., Matthews, P., & Arnold, D. (2004) · NeuroImage · doi:10.1016/j.neuroimage.2004.07.046 · Cited by 169 · see citing works
Orally available compound prevents deficits in memory caused by the Alzheimer amyloid‐β oligomers
Townsend, M., Cleary, J. P., Mehta, T., Hofmeister, J. J., Lesné, S., O‘Hare, E., Walsh, D. M., & Selkoe, D. J. (2006) · Annals of Neurology · doi:10.1002/ana.21051 · Cited by 166 · see citing works
Gauthier, S. G., Aisen, P. S. S., Ferris, S. H., Saumier, D., Duong, A., Haine, D., Garceau, D., Suhy, J., Oh, J., Lau, W. C., et al. (2009) · The journal of nutrition health & aging · doi:10.1007/s12603-009-0106-x · Cited by 136 · see citing works
Properties of scyllo–inositol as a therapeutic treatment of AD-like pathology
Fenili, D., Brown, M., Rappaport, R. V., & McLaurin, J. (2007) · Journal of Molecular Medicine · doi:10.1007/s00109-007-0156-7 · Cited by 133 · see citing works
Smith, S. M., Rao, A. W., Stefano, N. D., Jenkinson, M., Schott, J. M., Matthews, P. M., & Fox, N. C. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2007.04.035 · Cited by 110 · see citing works
Towards Disease-Modifying Treatment of Alzheimers Disease: Drugs Targeting β -Amyloid
Frisardi, V., Solfrizzi, V., Imbimbo, B. P., Capurso, C. A., D’Introno, A., Colacicco, A. M., Vendemiale, G., Seripa, D., Pilotto, A., Capurso, C. A., et al. (2010) · Current Alzheimer Research · doi:10.2174/156720510790274400 · Cited by 107 · see citing works
Doraiswamy, P. M., Kaiser, L., Bieber, F., & Garman, R. L. (2001) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-200110000-00003 · Cited by 104 · see citing works
CDP-diglyceride:inositol transferase from rat liver. Purification and properties.
Takenawa, T., & Egawa, K. (1977) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)63366-1 · Cited by 99 · see citing works
How Well Do the ADAS-cog and its Subscales Measure Cognitive Dysfunction in Alzheimer’s Disease?
Benge, J., Balsis, S., Geraci, L., Massman, P., & Doody, R. (2009) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000230709 · Cited by 77 · see citing works
Alzheimer's disease therapeutic research: the path forward
Aisen, P. S. S. (2009) · Alzheimer s Research & Therapy · doi:10.1186/alzrt2 · Cited by 57 · see citing works
Scyllo‐inositol in normal aging human brain: 1H magnetic resonance spectroscopy study at 4 Tesla
Kaiser, L. G., Schuff, N. W., Cashdollar, N. M., & Weiner, M. W. (2004) · NMR in Biomedicine · doi:10.1002/nbm.927 · Cited by 48 · see citing works
Garzone, P. D., Koller, M., Pastrak, A., Jhee, S. S., Ereshefsky, L., Moran, S., Cedarbaum, J. M., Xu, V., & Ross, B. D. (2009) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2009.04.526 · Cited by 10 · see citing works
Flagged first, then by citations
1 of the 42 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Brunnstrom HR, Englund EM. Causes of death in pa- tients with dementia disorders. Eur J Neurol 2009;16: 488 -492.
Cited by
Sorted by citations
Scheltens, P., Blennow, K., Breteler, M. M. B., de Strooper, B., Frisoni, G. B., Salloway, S., & Van der Flier, W. M. (2016) · The Lancet · doi:10.1016/s0140-6736(15)01124-1 · Cited by 3,125 · see citing works
Alzheimer Mechanisms and Therapeutic Strategies
Huang, Y., & Mucke, L. (2012) · Cell · doi:10.1016/j.cell.2012.02.040 · Cited by 1,758 · see citing works
Phase 3 Trials of Solanezumab for Mild-to-Moderate Alzheimer's Disease
Doody, R. S., Thomas, R. G., Farlow, M., Iwatsubo, T., Vellas, B., Joffe, S., Kieburtz, K., Raman, R., Sun, X., Aisen, P. S., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1312889 · Cited by 1,668 · see citing works
Current and Future Treatments in Alzheimer Disease: An Update
Yiannopoulou, K. G., & Papageorgiou, S. G. (2020) · Journal of Central Nervous System Disease · doi:10.1177/1179573520907397 · Cited by 966 · see citing works
A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease
Panza, F., Lozupone, M., Logroscino, G., & Imbimbo, B. P. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-018-0116-6 · Cited by 965 · see citing works
Current and future treatments for Alzheimer's disease
Yiannopoulou, K. G., & Papageorgiou, S. G. (2013) · Therapeutic Advances in Neurological Disorders · doi:10.1177/1756285612461679 · Cited by 677 · see citing works
“The safety and cerebrospinal fluid (CSF) biomarker results will guide selection of the optimal dose for future studies, which will target earlier stages of AD [Salloway et al. 2011].”
BackgroundSchneider, L. S., Mangialasche, F., Andreasen, N., Feldman, H., Giacobini, E., Jones, R., Mantua, V., Mecocci, P., Pani, L., Winblad, B., et al. (2014) · Journal of Internal Medicine · doi:10.1111/joim.12191 · Cited by 651 · see citing works
Alzheimer’s disease hypothesis and related therapies
Du, X., Wang, X., & Geng, M. (2018) · Translational Neurodegeneration · doi:10.1186/s40035-018-0107-y · Cited by 604 · see citing works
“Likewise, the small molecule Aβ binder scyllo-inositol [23] and tramiprosate [24–26] also failed in clinical trials.”
BackgroundAlzheimer’s disease: Recent treatment strategies
Vaz, M., & Silvestre, S. (2020) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2020.173554 · Cited by 547 · see citing works
Weiner, M. W., Veitch, D. P., Aisen, P. S. S., Beckett, L. A., Cairns, N. J., Green, R. C., Harvey, D. J., Jack, C. R., Jagust, W. J., Morris, J. C., et al. (2016) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2016.10.006 · Cited by 499 · see citing works
Alzheimer disease therapy—moving from amyloid-β to tau
Giacobini, E., & Gold, G. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2013.223 · Cited by 483 · see citing works
The amyloid cascade-inflammatory hypothesis of Alzheimer disease: implications for therapy
McGeer, P. L., & McGeer, E. G. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1177-7 · Cited by 467 · see citing works
Mummery, C. J., Börjesson-Hanson, A., Blackburn, D. J., Vijverberg, E. G. B., De Deyn, P. P., Ducharme, S., Jonsson, M., Schneider, A., Rinne, J. O., Ludolph, A. C., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02326-3 · Cited by 347 · see citing works
“Quantitative increases in VV have been observed in treatment groups relative to placebo in clinical studies of patients with AD 38–41 while other clinical studies of AD have not reported treatment related-increases 42–45 .”
β-amyloid Peptides and Amyloid Plaques in Alzheimer's Disease
Gouras, G. K., Olsson, T. T., & Hansson, O. (2014) · Neurotherapeutics · doi:10.1007/s13311-014-0313-y · Cited by 331 · see citing works
Salomone, S., Caraci, F., Leggio, G. M., Fedotova, J., & Drago, F. (2011) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2011.04134.x · Cited by 322 · see citing works
The Physiological Roles of Amyloid-β Peptide Hint at New Ways to Treat Alzheimer's Disease
Brothers, H. M., Gosztyla, M. L., & Robinson, S. R. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00118 · Cited by 314 · see citing works
“Increased infection rates, including orolabial herpes relapse, and upper respiratory infections, have been reported in clinical trials of ß- or γ-secretase inhibitors [Green et al., 2009; Doody et al., 2013; AlzForum (n.d.-d, h, m)] and the Aßbinding compound ELND005 (Salloway et al., 2011; Alonso et al., 2014).”
BackgroundLessons 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
Jeremic, D., Jiménez-Díaz, L., & Navarro-López, J. D. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101496 · Cited by 306 · see citing works
Efficacy of Souvenaid in Mild Alzheimer's Disease: Results from a Randomized, Controlled Trial
Scheltens, P., Twisk, J. W. R., Blesa, R., Scarpini, E. A., Arnim, C. A. F. V., Bongers, A., Harrison, J., Willemsen‐Swinkels, S. H. N., Stam, C. J., de Waal, H., et al. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-121189 · Cited by 306 · see citing works
Current and future treatments in Alzheimer’s disease
Atri, A. (2019) · Seminars in Neurology · doi:10.1055/s-0039-1678581 · Cited by 309 · see citing works
Current Research Therapeutic Strategies for Alzheimer’s Disease Treatment
Folch, J., Petrov, D., Ettcheto, M., Abad, S., Sánchez-López, E., García, M. L., Olloquequi, J., Beas-Zarate, C., Auladell, C., & Camins, A. (2016) · Neural Plasticity · doi:10.1155/2016/8501693 · Cited by 270 · see citing works
“This dose-finding, safety and efficacy trial did not meet its primary clinical efficiency outcomes [46].”
BackgroundTau-aggregation inhibitor therapy for Alzheimer's disease
Wischik, C. M., Harrington, C. R., & Storey, J. M. D. (2013) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.12.008 · Cited by 263 · see citing works
“Therapeutics 2 Failed (18mo, 353) Amyloid-lowering agent NCT00568776 [14]”
Alzheimer’s Amyloid-β is an Antimicrobial Peptide: A Review of the Evidence
Gosztyla, M. L., Brothers, H. M., & Robinson, S. R. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-171133 · Cited by 238 · see citing works
Therapeutic Approach to Alzheimer’s Disease: Current Treatments and New Perspectives
Pardo-Moreno, T., González-Acedo, A., Rivas-Domínguez, A., García-Morales, V., García-Cozar, F. J., Ramos-Rodríguez, J. J., & Melguizo-Rodríguez, L. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14061117 · Cited by 239 · see citing works
Combination Drug Therapy for the Management of Alzheimer’s Disease
Kabir, M. T., Uddin, M. S., Mamun, A. A., Jeandet, P., Aleya, L., Mansouri, R. A., Ashraf, G. M., Mathew, B., Bin-Jumah, M. N., & Abdel-Daim, M. M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093272 · Cited by 217 · see citing works
THOMAS, M. P., Mills, S. J., & Potter, B. V. L. (2015) · Angewandte Chemie International Edition · doi:10.1002/anie.201502227 · Cited by 190 · see citing works
Amyloid‐β immunotherapy for alzheimer disease: Is it now a long shot?
Panza, F., Lozupone, M., Seripa, D., & Imbimbo, B. P. (2019) · Annals of Neurology · doi:10.1002/ana.25410 · Cited by 178 · see citing works
Cerebrospinal fluid biomarkers in trials for Alzheimer and Parkinson diseases
Lleó, A., Cavedo, E., Parnetti, L., Vanderstichele, H., Herukka, S., Andreasen, N., Ghidoni, R., Lewczuk, P., Jeromin, A., Winblad, B. G., et al. (2014) · Nature Reviews Neurology · doi:10.1038/nrneurol.2014.232 · Cited by 159 · see citing works
Lannfelt, L., Möller, C., Basun, H., Osswald, G., Sehlin, D., Satlin, A., Logovinsky, V., & Gellerfors, P. (2014) · Alzheimer s Research & Therapy · doi:10.1186/alzrt246 · Cited by 152 · see citing works
Rajasekhar, K., & Govindaraju, T. (2018) · RSC Advances · doi:10.1039/c8ra03620a · Cited by 150 · see citing works
Therapeutic Strategies Targeting Amyloid-β in Alzheimer’s Disease
Pinheiro, L. M. V., & Faustino, C. M. C. (2019) · Current Alzheimer Research · doi:10.2174/1567205016666190321163438 · Cited by 142 · see citing works
Drug development for alzheimer’s disease: Microglia induced neuroinflammation as a target
Dong, Y., Li, X., Cheng, J., & Hou, L. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20030558 · Cited by 136 · see citing works
“Its phase II clinical trial demonstrated some beneficial effects in mild to moderate AD, however was insufficient for a robust benefit conclusion because of its small sample size [148,149].”
BackgroundInvestigational BACE inhibitors for the treatment of Alzheimer’s disease
Imbimbo, B. P., & Watling, M. (2019) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2019.1683160 · Cited by 132 · see citing works
Animal models of Alzheimer disease: historical pitfalls and a path forward
Cavanaugh, S. E. (2014) · ALTEX · doi:10.14573/altex.1310071 · Cited by 132 · see citing works
“…et al., 2011) Scyllo-inositol Aβ Reduced concentrations of soluble and aggregated Aβ, Not effective plaque burden, synaptic loss and local inflammatory responses, (Salloway et al. 2011) and improved cognitive function in mice (Fenili et al., 2007) AN-1792 Aβ immunization Production of…”
Alzheimer's disease failed clinical trials
Asher, S., & Priefer, R. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.120861 · Cited by 124 · see citing works
An update on the novel and approved drugs for Alzheimer disease
Alhazmi, H. A., & Albratty, M. (2022) · Saudi Pharmaceutical Journal · doi:10.1016/j.jsps.2022.10.004 · Cited by 122 · see citing works
“A clinical study (phase 2) in patients with AD found no confirmation of ELND0050s clinical benefit, and the study was stopped due to severe toxicity concerns (Salloway et al., 2011).”
Progress and Developments in Tau Aggregation Inhibitors for Alzheimer Disease
Bulic, B., Pickhardt, M., & Mandelkow�, E. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm3017317 · Cited by 116 · see citing works
The therapeutics of Alzheimer's disease: Where we stand and where we are heading
Selkoe, D. J. (2013) · Annals of Neurology · doi:10.1002/ana.24001 · Cited by 112 · see citing works
“The primary endpoints on a cognitive battery and an activities of daily living scale were not met, but CSF Ab42 levels were significantly lowered, and post hoc analyses suggested a trend toward some cognitive benefits and lower CSF phospho-tau levels in the mild patients.(42) This agent is now being tried against seco…”
BackgroundLópez-Gambero, A. J., Sanjuan, C., Serrano-Castro, P. J., Suárez, J., & de Fonseca, F. R. (2020) · Biomedicines · doi:10.3390/biomedicines8090295 · Cited by 110 · see citing works
Brain and cognition abnormalities in long-term anabolic-androgenic steroid users
Kaufman, M. J., Janes, A. C., Hudson, J. I., Brennan, B. P., Kanayama, G., Kerrigan, A. R., Jensen, J. E., & Pope, H. G. (2015) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2015.04.023 · Cited by 108 · see citing works
“If subsequent studies confirm that AAS use depletes scyllo-inositol, then scyllo-inositol supplementation, currently being studied as a treatment for Alzheimer’s disease (Salloway et al., 2011), could be tested in AAS users.”
BackgroundStem Cell Therapy for Alzheimer’s Disease: A Review of Recent Clinical Trials
Kang, J. M., Yeon, B. K., Cho, S., & Suh, Y. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160406 · Cited by 106 · see citing works
The binding of resveratrol to monomer and fibril amyloid beta
Ge, J., Qiao, J., Qi, C., Wang, C.-W., & Zhou, J. (2012) · Neurochemistry International · doi:10.1016/j.neuint.2012.08.012 · Cited by 105 · see citing works
“…Ab(1–40) or Ab(1–42), numerous agents have been tested for their potency in preventing the fibrillization of Ab in vitro or reducing plaque loads in transgenic mice, and some of these compounds have reached the human clinical trial stage (Jhee and Shiovitz et al., 2003; Salloway et al., 2011).”
Folch, J., Ettcheto, M., Petrov, D., Abad, S., Pedrós, I., Marin, M., Olloquequi, J., & Camins, A. (2017) · Neurología (English Edition) · doi:10.1016/j.nrleng.2015.03.019 · Cited by 105 · see citing works
Is the Amyloid Hypothesis of Alzheimer's disease therapeutically relevant?
Teich, A. F., & Arancio, O. (2012) · Biochemical Journal · doi:10.1042/bj20120653 · Cited by 102 · see citing works
Dunkel, P., Chai, C. L. L., Sperlágh, B., Huleatt, P. B., & Mátyus, P. (2012) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2012.703178 · Cited by 103 · see citing works
Further understanding the connection between Alzheimer's disease and Down syndrome
Snyder, H. M., Bain, L. J., Brickman, A. M., Carrillo, M. C., Esbensen, A. J., Espinosa, J. M., Fernandez, F., Fortea, J., Hartley, S. L., Head, E., et al. (2020) · Alzheimer's & Dementia · doi:10.1002/alz.12112 · Cited by 105 · see citing works
Folch, J., Ettcheto, M., Petrov, D., Abad, S., Pedrós, I., Marin, M., Olloquequi, J., & Camins, A. (2015) · Neurología · doi:10.1016/j.nrl.2015.03.012 · Cited by 102 · see citing works
Novel Disease-Modifying Therapies for Alzheimer's Disease
Jiang, T., Yu, J., & Tan, L. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-120640 · Cited by 93 · see citing works
Magnetic resonance imaging: A biomarker for cognitive impairment in Parkinson's disease?
Duncan, G. W., Firbank, M., O'Brien, J. T., & Burn, D. J. (2013) · Movement Disorders · doi:10.1002/mds.25352 · Cited by 88 · see citing works
“In early PD, in which it is believed that a-synuclein deposition is restricted to the brainstem and some limbic structures, significant cortical atrophy in cognitively intact patients is not observed with VBM,33,59,61,73,74 however, one study did report limited focal atrophy compared with age-matched controls.59 Corti…”
MethodInfluentialGuercio, B. J., Donovan, N. J., Munro, C. E., Aghjayan, S. L., Wigman, S. E., Locascio, J. J., Amariglio, R. E., Rentz, D. M., Johnson, K. A., Sperling, R. A., et al. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-150146 · Cited by 89 · see citing works
“Despite significant efforts to develop such therapies, few clinical trials have shown clinically significant benefit (3-5).”
Alzheimer’s disease: as it was in the beginning
Kozlov, S. O., Afonin, A. М., Evsyukov, I., & Бондаренко, А. Б. (2017) · Reviews in the Neurosciences · doi:10.1515/revneuro-2017-0006 · Cited by 84 · see citing works
A Systematic Review of Longitudinal Studies Which Measure Alzheimer’s Disease Biomarkers
Lawrence, E., Vegvari, C., Ower, A. K., Hadjichrysanthou, C., de Wolf, F., & Anderson, R. M. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170261 · Cited by 84 · see citing works
scyllo-Inositol, Preclinical, and Clinical Data for Alzheimer’s Disease
Ma, K., Thomason, L. A. M., & McLaurin, J. (2012) · Advances in pharmacology · doi:10.1016/b978-0-12-394816-8.00006-4 · Cited by 82 · see citing works
Two decades of new drug discovery and development for Alzheimer's disease
Liu, Z., Zhang, A., Sun, H. J., Han, Y., Kong, L. D., & Wang, X. (2017) · RSC Advances · doi:10.1039/c6ra26737h · Cited by 83 · see citing works
Jia, Q., Deng, Y., & Qing, H. (2014) · BioMed Research International · doi:10.1155/2014/837157 · Cited by 80 · see citing works
Cotinine: A Potential New Therapeutic Agent against Alzheimer's disease
Echeverrı́a, V., & Zeitlin, R. (2012) · CNS Neuroscience & Therapeutics · doi:10.1111/j.1755-5949.2012.00317.x · Cited by 81 · see citing works
“Therein, the anti-aggregation approach did not show significant clinical efficacy [103].”
BackgroundMalishev, R., Shaham‐Niv, S., Nandi, S., Kolusheva, S., Gazit, E., & Jelinek, R. (2017) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.6b00438 · Cited by 80 · see citing works
Neurotoxic β-amyloid oligomers cause mitochondrial dysfunction—the trigger for PANoptosis in neurons
Meng, X., Song, Q., Liu, Z., Liu, X., Wang, Y., & Liu, J. (2024) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2024.1400544 · Cited by 78 · see citing works
Ross, J., Sharma, S., Winston, J., Nunez, M., Bottini, G., Franceschi, M., Scarpini, E. A., Frigerio, E., Fiorentini, F., Fernández, M., et al. (2013) · Current Alzheimer Research · doi:10.2174/13892037113149990144 · Cited by 78 · see citing works
Moving beyond anti-amyloid therapy for the prevention and treatment of Alzheimer’s disease
Castello, M. A., Jeppson, J. D., & Soriano, S. (2014) · BMC Neurology · doi:10.1186/s12883-014-0169-0 · Cited by 77 · see citing works
Liu, T., & Bitan, G. (2012) · ChemMedChem · doi:10.1002/cmdc.201100585 · Cited by 75 · see citing works
Anti-amyloid-β protein agents for the treatment of Alzheimer’s disease: an update on emerging drugs
Lozupone, M., Solfrizzi, V., D’Urso, F., Di Gioia, I., Sardone, R., Dibello, V., Stallone, R., Liguori, A., Ciritella, C., Daniele, A., et al. (2020) · Expert Opinion on Emerging Drugs · doi:10.1080/14728214.2020.1808621 · Cited by 77 · see citing works
Webster, L., Groskreutz, D., Grinbergs‐Saull, A., Howard, R. J., O'Brien, J. T., Mountain, G. A., Banerjee, S., Woods, B. T., Perneczky, R., Lafortune, L., et al. (2017) · Health Technology Assessment · doi:10.3310/hta21260 · Cited by 73 · see citing works
Therapeutic potential of quinazoline derivatives for Alzheimer's disease: A comprehensive review
Haghighijoo, Z., Zamani, L., Moosavi, F., & Emami, S. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113949 · Cited by 75 · see citing works
Zheng, Y., Yu, B., Alexander, D. C., Steffen, L. M., & Boerwinkle, E. (2014) · American Journal of Epidemiology · doi:10.1093/aje/kwu073 · Cited by 74 · see citing works
Revisiting the role of brain and peripheral Aβ in the pathogenesis of Alzheimer's disease
Uddin, M. S., Kabir, M. T., Tewari, D., Mamun, A. A., Mathew, B., Aleya, L., Barreto, G. E., Bin-Jumah, M. N., Abdel‐Daim, M. M., & Ashraf, G. M. (2020) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2020.116974 · Cited by 68 · see citing works
Roles of Extracellular Chaperones in Amyloidosis
Wyatt, A. R., Yerbury, J. J., Dabbs, R. A., & Wilson, M. R. (2012) · Journal of Molecular Biology · doi:10.1016/j.jmb.2012.01.004 · Cited by 66 · see citing works
An update on the advancements in the treatment of agitation in Alzheimer’s disease
Porsteinsson, A. P., & Antonsdottir, I. M. (2017) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2017.1307340 · Cited by 67 · see citing works
“ELND005 has been shown to have amyloidand myoinositol-lowering effects [20] and beneficial trends on agitation and aggression as secondary symptoms of AD [21].”
BackgroundBöhm, C., Chen, F., Sévalle, J., Qamar, S., Dodd, R. B., Li, Y., Schmitt‐Ulms, G., Fraser, P. E., & George‐Hyslop, P. S. (2015) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2015.02.016 · Cited by 63 · see citing works
“had to be discontinued due to toxicity (Salloway et al., 2011).”
BackgroundSuccesses and Failures for Drugs in Late-Stage Development for Alzheimer’s Disease
Berk, C., & Sabbagh, M. N. (2013) · Drugs & Aging · doi:10.1007/s40266-013-0108-6 · Cited by 63 · see citing works
Imaging endpoints for clinical trials in Alzheimer’s disease
Cash, D. M., Rohrer, J. D., Ryan, N. S., Sebastien Ourselin, A., & Fox, N. C. (2014) · Alzheimer s Research & Therapy · doi:10.1186/s13195-014-0087-9 · Cited by 62 · see citing works
“Scyllo-inositol [31] 83 259 18 Whole brain (⇔), ventricles (⇑), hippocampi (⇔)”
BackgroundBeta-Amyloid and Tau-Protein: Structure, Interaction, and Prion-Like Properties
Tatarnikova, O. G., Орлов, М. А., & Bobkova, N. V. (2015) · Biochemistry (Moscow) · doi:10.1134/s000629791513012x · Cited by 59 · see citing works
Emerging drugs to reduce abnormal β-amyloid protein in Alzheimer’s disease patients
Panza, F., Seripa, D., Solfrizzi, V., Imbimbo, B. P., Lozupone, M., Leo, A., Sardone, R., Gagliardi, G., Lofano, L., Creanza, B. C., et al. (2016) · Expert Opinion on Emerging Drugs · doi:10.1080/14728214.2016.1241232 · Cited by 59 · see citing works
“Currently, disease-modifying therapeutic strategies for AD primarily focus on reducing Aβ production using BACE- or γ-secretase inhibitors [31,32], inhibiting Aβ deposition with antiaggregation compounds that inhibit Aβ oligomerization and block Aβ toxicity [33,34], facilitating Aβ clearance with active and passive im…”
BackgroundMoonga, I., Niccolini, F., Wilson, H., Pagano, G., Politis, M., & Initiative, T. A. D. N. (2017) · European Journal of Neurology · doi:10.1111/ene.13374 · Cited by 58 · see citing works
Proportion of Women and Reporting of Outcomes by Sex in Clinical Trials for Alzheimer Disease
Martínková, J., Quevenco, F., Karcher, H., Ferrari, A., Sandset, E. C., Szoeke, C. E. I., Hort, J., Schmidt, R., Chadha, A. S., & Ferretti, M. T. (2021) · JAMA Network Open · doi:10.1001/jamanetworkopen.2021.24124 · Cited by 60 · see citing works
Alzheimer’s disease and disseminated mycoses
Alonso, R., Pisa, D., Rábano, A., & Carrasco, L. (2014) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/s10096-013-2045-z · Cited by 68 · see citing works
Physiological Roles of Monomeric Amyloid-β and Implications for Alzheimer’s Disease Therapeutics
Jeong, H., Shin, H., Hong, S., & Kim, Y. S. (2022) · Experimental Neurobiology · doi:10.5607/en22004 · Cited by 56 · see citing works
Bennett, D. A., Yu, L., & Jager, P. L. D. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2014.01.037 · Cited by 53 · see citing works
“A number of disease modifying clinical trials have been conducted over the past decade, many focused on amyloid metabolism [34-45].”
BackgroundThe Use of Antimicrobial and Antiviral Drugs in Alzheimer’s Disease
Iqbal, U., Zeng, E., & Pasinetti, G. M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21144920 · Cited by 55 · see citing works
Drug delivery strategies with lipid-based nanoparticles for Alzheimer’s disease treatment
Jang, Y.-J., Kang, S.-J., Park, H. S., Lee, D., Kim, J. H., Kim, J.-E., Kim, D., Chung, C., Yoon, J., & Bhang, S. H. (2025) · Journal of Nanobiotechnology · doi:10.1186/s12951-025-03109-3 · Cited by 62 · see citing works
Hart, S. J., Visootsak, J., Tamburri, P., Phuong, P., Baumer, N., Hernandez, M., Skotko, B. G., Ochoa‐Lubinoff, C., Liogier D'Ardhuy, X., Kishnani, P. S., et al. (2017) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.38465 · Cited by 54 · see citing works
“A clinical trial of ELND005 in neurotypically developed adults with AD did not demonstrate significant effects on cognition or adaptive function (Salloway et al., 2011).”
BackgroundAndrade, S., Nunes, D., Dabur, M., Ramalho, M. J., Pereira, M. D. C., & Loureiro, J. A. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15010212 · Cited by 52 · see citing works
“Scyllo-inositol Mild to moderate AD 353 78 weeks II Acceptable safety; No therapeutic effects Completed 2007 [49]”
BackgroundMethodSupraphysiologic-dose anabolic–androgenic steroid use: A risk factor for dementia?
Kaufman, M. J., Kanayama, G., Hudson, J. I., & Pope, H. G. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.02.014 · Cited by 54 · see citing works
“These potentially beneficial effects have prompted development of sI and close sI analogs as potential treatments for AD/ADRD (Salloway et al., 2011; Morrone et al., 2016; Lee et al., 2017; Liu et al., 2018).”
Diagnosis and Treatment of Alzheimer’s Disease:
Bomasang-Layno, E., & Bronsther, R. (2021) · Delaware Journal of Public Health · doi:10.32481/djph.2021.09.009 · Cited by 52 · see citing works
Small-molecule drugs development for Alzheimer's disease
Yao, W., Yang, H., & Yang, J. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.1019412 · Cited by 50 · see citing works
Attar, A., & Bitan, G. (2014) · Current Pharmaceutical Design · doi:10.2174/13816128113199990496 · Cited by 48 · see citing works
“Phase-2 clinical trials for ELND-005 have been completed with mixed results, of which 9 deaths in the high-dose groups caused significant safety concerns and cognitive and functional co-primary endpoints did not achieve statistical significance [103].”
Overview of therapeutic targets in management of dementia
Malik, R., Kalra, S., Bhatia, S., Al‐Harrasi, A., Singh, G., Mohan, S., Makeen, H. A., Albratty, M., Meraya, A. M., Bahar, B., et al. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113168 · Cited by 48 · see citing works
What lessons can be learned from failed Alzheimer’s disease trials?
Toyn, J. H. (2015) · Expert Review of Clinical Pharmacology · doi:10.1586/17512433.2015.1034690 · Cited by 47 · see citing works
“Exploratory analysis, however, suggested a potential benefit in a prespecified mild AD subgroup [14].”
BackgroundCurrent Perspectives regarding Stem Cell-Based Therapy for Alzheimer’s Disease
Kwak, K.-A., Lee, S., Yang, J.-Y., & Park, Y. (2018) · Stem Cells International · doi:10.1155/2018/6392986 · Cited by 50 · see citing works
Fanton, S., Menezes, J., Krock, E., Sandström, A., Tour, J., Sandor, K., Jurczak, A., Hunt, M., Baharpoor, A., Kadetoff, D., et al. (2023) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2023.09.003 · Cited by 46 · see citing works
“, 2006), and drug trials aiming at increasing scyllo-inositol levels have been conducted in Alzheimer’s patients (Salloway et al., 2011).”
Rational heterodoxy: Cholesterol reformation of the amyloid doctrine
Castello, M. A., & Soriano, S. (2012) · Ageing Research Reviews · doi:10.1016/j.arr.2012.06.007 · Cited by 44 · see citing works
Watanabe, T., Shiino, A., & Akiguchi, I. (2012) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2012.01.006 · Cited by 45 · see citing works
C-Terminal Fragment, Aβ32–37, Analogues Protect Against Aβ Aggregation-Induced Toxicity
Bansal, S., Maurya, I. K., Yadav, N., Thota, C. K., Kumar, V., Tikoo, K., Chauhan, V. S., & Jain, R. (2016) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.6b00006 · Cited by 45 · see citing works
Lai, A. Y., & McLaurin, J. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2012.07.003 · Cited by 44 · see citing works
“Phase 2 clinical trials, in which SI was used to treat patients withmild ormoderate AD, have recently been published: in patients with mild AD, treatment with 250 mg SI bid has shown cognitive benefit [9].”
MethodJin, M., & Selkoe, D. J. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.05.020 · Cited by 44 · see citing works
Zhu, L., Li, R., Jiao, S., Wei, J., Yan, Y., Wang, Z. A., Li, J., & Du, Y. (2020) · Marine Drugs · doi:10.3390/md18100488 · Cited by 44 · see citing works
“Scyllo-inositol, a potent Aβ aggregation inhibitor [13], failed in a phase 2 randomized trial involving 353 Alzheimer patients due to the non-significantly clinical efficacy outcomes [14].”
BackgroundAlterations in Lipid and Inositol Metabolisms in Two Dopaminergic Disorders
Schulte, E. C., Altmaier, E., Berger, H. S., Do, K. T., Kastenmüller, G., Wahl, S., Adamski, J., Peters, A., Krumsiek, J., Suhre, K., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0147129 · Cited by 40 · see citing works
“Yet, scyllo- and chiro-inositols have been implicated as potential therapeutic agents in a number of neuropsychiatric diseases ranging from Alzheimer`s [39] to obsessive compulsive disorder [40].”
BackgroundThe TOMMORROW study: Design of an Alzheimer's disease delay‐of‐onset clinical trial
Burns, D. K., Chiang, C., Welsh-Bohmer, K. A., Brannan, S. K., Culp, M., O’Neil, J., Runyan, G., Harrigan, P., Plassman, B. L., Lutz, M. W., et al. (2019) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1016/j.trci.2019.09.010 · Cited by 42 · see citing works
Panza, F., Seripa, D., Lozupone, M., Solfrizzi, V., Imbimbo, B. P., Barulli, M. R., Tortelli, R., Capozzo, R., Bisceglia, P., Dimitri, A., et al. (2018) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2018.1389885 · Cited by 41 · see citing works
Do BACE inhibitor failures in Alzheimer patients challenge the amyloid hypothesis of the disease?
Panza, F., Lozupone, M., Watling, M. I. L., & Imbimbo, B. P. (2019) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2019.1621751 · Cited by 40 · see citing works
“Scyllo-inositol, an Aβ aggregation inhibitor, dose-dependently increased mortality in mild-to-moderate AD patients [22].”
Background
- Authors
- Salloway, S., Sperling, R., Keren, R., Porsteinsson, A. P., van Dyck, C. H., Tariot, P. N., Gilman, S., Arnold, D., Abushakra, S., Hernandez, C., Crans, G., Liang, E., Quinn, G., Bairu, M., Pastrak, A., Cedarbaum, J. M., & For the ELND005-AD201 Investigators
- Affiliations
- Brigham and Women's Hospital (US)
- From the Department of Neurology, Butler Hospital, and Department of Neurology, Alpert Medical School of Brown University (S.S.), Providence, RI; Center for Alzheimer Research and Treatment (R.S.), Brigham and Women's Hospital, Boston, MA; Ontario Shores Centre for Mental Health Sciences (R.K.), Whitby, Canada; Monroe Community Hospital (A.P.P.), University of Rochester Medical Center, Rochester, NY; Departments of Psychiatry and Neurobiology (C.H.v.D.), Yale University School of Medicine, New Haven...
- ORCID
- Venue
- Neurology
- Published
- 2011-09-27
- Volume
- 77
- Issue
- 13
- Pages
- 1253-1262
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC3179648
- OpenAlex
- W2119197968
- Cited by
- 258
- References
- 42
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 11 · 2023: 17 · 2022: 18 · 2021: 14 · 2020: 22 · 2019: 17 · 2018: 13 · 2017: 20 · 2016: 22 · 2015: 21 · 2014: 21 · 2013: 24 · 2012: 17
- FWCI
- 14.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Elan
- 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
- scyllo-inositol, Alzheimer's disease, amyloid-beta, cerebrospinal fluid biomarkers, activities of daily living, neuropsychological performance, dose-ranging, drug safety
- MeSH terms
- Administration, Oral, Aged, Aged, 80 and over, Alzheimer Disease, Dose-Response Relationship, Drug, Double-Blind Method, Female, Follow-Up Studies, Humans, Inositol, Magnetic Resonance Imaging, Male, Mental Status Schedule, Middle Aged, Peptide Fragments, Platelet Aggregation Inhibitors, Time Factors, Amyloid beta-Peptides, Treatment Outcome, Apolipoprotein E4
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
