The DOI matches its Crossref record; 43 of the 44 references it cites were found in a registry or an index.
Effect of Tarenflurbil on Cognitive Decline and Activities of Daily Living in Patients With Mild Alzheimer Disease<subtitle>A Randomized Controlled Trial</subtitle>
Open accessAbstract
CONTEXT: Amyloid-beta peptide (Abeta(42)) has been implicated in the pathogenesis of Alzheimer disease (AD). Tarenflurbil, a selective Abeta(42)-lowering agent, demonstrated encouraging results on cognitive and functional outcomes among mildly affected patients in an earlier phase 2 trial. OBJECTIVE: To determine the efficacy, safety, and tolerability of tarenflurbil. DESIGN, SETTING, AND PATIENTS: A multicenter, randomized, double-blind, placebo-controlled trial enrolling patients with mild AD was conducted at 133 trial sites in the United States between February 21, 2005, and April 30, 2008. Concomitant treatment with cholinesterase inhibitors or memantine was permitted. INTERVENTION: Tarenflurbil, 800 mg, or placebo, administered twice a day. MAIN OUTCOME MEASURES: Co-primary efficacy end points were the change from baseline to month 18 in total score on the subscale of the Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog, 80-point version) and Alzheimer Disease Cooperative Studies-activities of daily living (ADCS-ADL) scale. Additional prespecified slope analyses explored the possibility of disease modification. RESULTS: Of the 1684 participants randomized, 1649 were included in the analysis, and 1046 completed the trial. Tarenflurbil had no beneficial effect on the co-primary outcomes (difference in change from baseline to month 18 vs placebo, based on least squares means: 0.1 for ADAS-Cog; 95% CI, -0.9 to 1.1; P = .86 and -0.5 for ADCS-ADL; 95% CI, -1.9 to 0.9; P = .48) using an intent-to-treat analysis. No significant differences occurred in the secondary outcomes. The ADAS-Cog score decreased by 7.1 points over 18 months. The tarenflurbil group had a small increase in frequency of dizziness, anemia, and infections. CONCLUSION: Tarenflurbil did not slow cognitive decline or the loss of activities of daily living in patients with mild AD. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00105547.
Overview
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
Verification
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?
In the citing paper
“Despite promising preclinical data, unfortunately a phase 3 clinical trial did not demonstrate any benefits on cognition or ADLs over the course of 18 months (Green et al., 2009).”
From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Green et al., 2009
In the citing paper
“A drug intended to modify γ secretase activity similarly failed [256].”
From The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives (2014) · cites this paper as [256]
In the citing paper
“Gintonin, a bioactive glycoprotein reduces the formation of A 𝛽, improves learning and memory capacity through the activation of phosphatidic acid receptors involved in hemolysis [26 , 27] .”
From Phytotherapy: A promising approach for the treatment of Alzheimer's disease (2022) · cites this paper as [26]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
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
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
Hirono, N., Mori, E., Ikejiri, Y., Imamura, T., Shimomura, T., Hashimoto, M., Yamashita, H., & Ikeda, M. (1997) · PubMed · Cited by 21,010
Kok, J. S., Berg, I. J., & Scherder, E. J. A. (2013) · Dementia and Geriatric Cognitive Disorders Extra · doi:10.1159/000353441 · Cited by 20,589
Older Adults' Reasons for Using Technology while Aging in Place
Peek, S. T. M., Luijkx, K. G., Rijnaard, M. D., Nieboer, M. E., van der Voort, C. S., Aarts, S., van Hoof, J., Vrijhoef, H. J., & Wouters, E. (2015) · Gerontology · doi:10.1159/000430949 · Cited by 19,851
Sensitivity and False Alarm Rate of a Fall Sensor in Long-Term Fall Detection in the Elderly
Kangas, M., Korpelainen, R., Vikman, I., Nyberg, L., & Jämsä, T. J. (2014) · Gerontology · doi:10.1159/000362720 · Cited by 19,006
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
Alzheimer's disease: the amyloid cascade hypothesis
Hardy, J. A., & Higgins, G. A. (1992) · Science · doi:10.1126/science.1566067 · Cited by 7,484
Alzheimer's Disease: Genes, Proteins, and Therapy
Selkoe, D. J. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.741 · Cited by 6,063
A new rating scale for Alzheimer's disease
(1984) · American Journal of Psychiatry · doi:10.1176/ajp.141.11.1356 · Cited by 4,175
The Neuropsychiatric Inventory
Cummings, J. L. (1997) · Neurology · doi:10.1212/wnl.48.5_suppl_6.10s · Cited by 2,055
The Clinical Diagnosis of Alzheimer's Disease
Wade, J. P. H., Mirsen, T. R., Hachinski, V. C., Fisman, M., Lau, C. S., & Merskey, H. (1987) · Archives of Neurology · doi:10.1001/archneur.1987.00520130016010 · Cited by 1,416
A subset of NSAIDs lower amyloidogenic Aβ42 independently of cyclooxygenase activity
Weggen, S., Eriksen, J. L., Das, P., Sagi, S. A., Wang, R., Pietrzik, C. U., Findlay, K. A., Smith, T. E., Murphy, M. P., Bulter, T., et al. (2001) · Nature · doi:10.1038/35102591 · Cited by 1,388
Pathological 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
Application of a multidimensional caregiver burden inventory
Novak, M., & Guest, C. (1989) · The Gerontologist · doi:10.1093/geront/29.6.798 · Cited by 1,205
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
Ibuprofen Suppresses Plaque Pathology and Inflammation in a Mouse Model for Alzheimer's Disease
Lim, G. P., Yang, F., Chu, T., Chen, P., Beech, W. K., Teter, B., Tran, T., Ubeda, O. J., Ashe, K. H., Frautschy, S. A., et al. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-15-05709.2000 · Cited by 876
Galasko, D. R., Bennett, D., Sano, M., Ernesto, C., Thomas, R., Grundman, M., & Ferris, S. H. (1997) · PubMed · Cited by 767
Clinical Dementia Rating (CDR)
Gauthier, S. G. (2001) · CRC Press eBooks · doi:10.3109/9780203213896-34 · Cited by 696
NSAIDs and enantiomers of flurbiprofen target γ-secretase and lower Aβ42 in vivo
Eriksen, J. L., Sagi, S. A., Smith, T. E., Weggen, S., Das, P., McLendon, D. C., Ozols, V. V., Jessing, K. W., Zavitz, K. H., Koo, E. H., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci18162 · Cited by 634
Aβ42 Is Essential for Parenchymal and Vascular Amyloid Deposition in Mice
McGowan, E., Pickford, F., Kim, J., Onstead, L., Eriksen, J., Yu, C., Skipper, L., Murphy, M. P., Beard, J., Das, P., et al. (2005) · Neuron · doi:10.1016/j.neuron.2005.06.030 · Cited by 565
High-Dose B Vitamin Supplementation and Cognitive Decline in Alzheimer Disease
Aisen, P. S. S. (2008) · JAMA · doi:10.1001/jama.300.15.1774 · Cited by 563
Amyloid-β as a positive endogenous regulator of release probability at hippocampal synapses
Abramov, E., Dolev, I., Fogel, H., Ciccotosto, G. D., Ruff, E., & Slutsky, I. (2009) · Nature Neuroscience · doi:10.1038/nn.2433 · Cited by 499
Yan, Q., Zhang, J., Liu, H., Babu-Khan, S., Vassar, R., Biere, A. L., Citron, M., & Landreth, G. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-20-07504.2003 · Cited by 469
Jantzen, P. T., Connor, K. E., DiCarlo, G., Wenk, G. L., Wallace, J. L., Rojiani, A. M., Coppola, D., Morgan, D., & Gordon, M. N. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-06-02246.2002 · Cited by 341
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
A γ‐secretase inhibitor decreases amyloid‐β production in the central nervous system
Bateman, R. J., Siemers, E. R., Mawuenyega, K. G., Wen, G., Browning, K. R., Sigurdson, W. C., Yarasheski, K. E., Friedrich, S. W., DeMattos, R. B., May, P. C., et al. (2009) · Annals of Neurology · doi:10.1002/ana.21623 · Cited by 322
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
Effects of a γ-secretase inhibitor in a randomized study of patients with Alzheimer disease
Siemers, E., Quinn, J. F., Kaye, J. A., Farlow, M. R., Porsteinsson, A. P., Tariot, P. N., Zoulnouni, P., Galvin, J. E., Holtzman, D. M., Knopman, D. S., et al. (2006) · Neurology · doi:10.1212/01.wnl.0000198762.41312.e1 · Cited by 291
Substrate-targeting γ-secretase modulators
Kukar, T. L., Ladd, T. B., Bann, M. A., Fraering, P. C., Narlawar, R., Maharvi, G. M., Healy, B., Chapman, R., Welzel, A. T., Price, R. W., et al. (2008) · Nature · doi:10.1038/nature07055 · Cited by 276
Martone, R., Zhou, H., Atchison, K., Comery, T., Xu, J. Z., Huang, X.-Y., Gong, X., Jin, M., Kreft, A., Harrison, B., et al. (2009) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.109.152975 · Cited by 163
Current Alzheimer's disease clinical trials: Methods and placebo outcomes
Schneider, L. S. S., & Sano, M. C. (2009) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2009.07.038 · Cited by 137
Kukar, T. L., Prescott, S., Eriksen, J. L., Holloway, V. M., Murphy, M. P., Koo, E. H., Golde, T. E., & Nicolle, M. M. (2007) · BMC Neuroscience · doi:10.1186/1471-2202-8-54 · Cited by 128
Zhu, C. W., Grossman, H. T., Neugroschl, J. A., Parker, S., Burden, A. R., Luo, X., & Sano, M. C. (2018) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1016/j.trci.2018.09.009 · Cited by 125
Farrer, L. A. (1997) · JAMA · doi:10.1001/jama.1997.03550160069041 · Cited by 124
Galasko, D. R., Graff‐Radford, N. R., May, S. J., Hendrix, S. B., Cottrell, B. A., Sagi, S. A., MATHER, G. G., Laughlin, M. A., Zavitz, K. H., Swabb, E. A., et al. (2007) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e31815d1048 · Cited by 122
Tracy, T. S., Rosenbluth, B. W., Wrighton, S. A., Gonzalez, F. J., & Korzekwa, K. R. (1995) · Biochemical Pharmacology · doi:10.1016/0006-2952(95)00048-5 · Cited by 99
Yao, Y., Chinnici, C. M., Tang, H., Trojanowski, J. Q., Lee, V. M. ‐., & Praticò, D. (2004) · Journal of Neuroinflammation · doi:10.1186/1742-2094-1-21 · Cited by 91
Pure Enantiomers of 2‐Arylpropionic Acids: Tools in Pain Research and Improved Drugs in Rheumatology
Brune, K., Geißlinger, G., & Menzel-Soglowek, S. (1992) · The Journal of Clinical Pharmacology · doi:10.1002/j.1552-4604.1992.tb04643.x · Cited by 84
Cummings, J. L., Mega, M., Gray, K., Rosenberg-Thompson, S., Carusi, D. A., & Gornbein, J. (1994) · PsycTESTS Dataset · doi:10.1037/t28621-000 · Cited by 35
Sano, M. C. (2008) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2008.05.562 · Cited by 23
Quality of life in Alzheimer's disease
Korczyn, A. D., & Davidson, M. (1999) · European Journal of Neurology · doi:10.1046/j.1468-1331.1999.640487.x · Cited by 19
High-Dose B Vitamin Supplementation and Cognitive Decline in Alzheimer Disease
Aisen, P. S. S., Schneider, L. S., Sano, M., Diaz-Arrastia, R. R., van Dyck, C. H., Weiner, M., Bottiglieri, T., Jin, S., Stokes, K. T., Thomas, R. G., et al. (2013) · Cited by 19
Cited by
Sorted by citations
Alzheimer Disease: An Update on Pathobiology and Treatment Strategies
Long, J. M., & Holtzman, D. M. (2019) · Cell · doi:10.1016/j.cell.2019.09.001 · Cited by 3,204
The projected effect of risk factor reduction on Alzheimer's disease prevalence
Barnes, D. E., & Yaffe, K. S. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(11)70072-2 · Cited by 2,815
Ballard, C., Gauthier, S., Corbett, A., Brayne, C., Aarsland, D., & Jones, E. (2011) · The Lancet · doi:10.1016/s0140-6736(10)61349-9 · Cited by 2,336
Alzheimer Mechanisms and Therapeutic Strategies
Huang, Y., & Mucke, L. (2012) · Cell · doi:10.1016/j.cell.2012.02.040 · Cited by 1,758
Alzheimer’s disease: Clinical trials and drug development
Mangialasche, F., Solomon, A., Winblad, B., Mecocci, P., & Kivipelto, M. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70119-8 · Cited by 1,217
Metadata
- Authors
- Green, R. C.
- Affiliations
- Boston University (US)
- Corresponding author
- Green, Robert C.
- ORCID
- Green, Robert C.
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2009-12-16
- Volume
- 302
- Issue
- 23
- Pages
- 2557
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC2902875
- OpenAlex
- W1982816514
- Cited by
- 643
- References
- 44
- Citations by year
- 2026: 11 · 2025: 25 · 2024: 39 · 2023: 22 · 2022: 28 · 2021: 32 · 2020: 43 · 2019: 32 · 2018: 26 · 2017: 40 · 2016: 40 · 2015: 31 · 2014: 44 · 2013: 52 · 2012: 63
- FWCI
- 38.79
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Pennsylvania
- National Institute for Health and Care Research
- National Institutes of Health (RR00533, HG02213, AG13846)
- National Institute on Aging (P30AG008051, K24AG027841, P50AG005142, P30AG013846, P30-AG13846))
- National Human Genome Research Institute (R01HG002213, R01 HG02213)
- National Center for Research Resources (M01-RR-00533, M01RR000533)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
- Keywords
- Alzheimer's disease, mild Alzheimer disease, cognitive decline, activities of daily living, disease modification, ADAS-Cog, drug safety and efficacy, dizziness, anemia, infection
- MeSH terms
- Activities of Daily Living, Aged, Aged, 80 and over, Alzheimer Disease, Cognition, Cognition Disorders, Double-Blind Method, Enzyme Inhibitors, Female, Flurbiprofen, Humans, Male, Middle Aged, Peptide Fragments, Amyloid beta-Peptides, Amyloid Precursor Protein Secretases
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
