Testing the Right Target and Right Drug at the Right Stage
Open accessAbstract
Alzheimer's disease (AD) is the only leading cause of death for which no disease-modifying therapy is currently available. Recent disappointing trial results at the dementia stage of AD have raised multiple questions about our current approaches to the development of disease-modifying agents. Converging evidence suggests that the pathophysiological process of AD begins many years before the onset of dementia. So why do we keep testing drugs aimed at the initial stages of the disease process in patients at the end-stage of the illness?
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Starting anti-amyloid treatment only after dementia develops may be too late to alter the clinical course of the disease.
“Amyloid accumulation probably starts many years before the onset of symptoms,2,26,27 and initiation of anti-amyloid treatment only after dementia develops may be too late to affect the clinical course of the disease.28”
From Two Phase 3 Trials of Bapineuzumab in Mild-to-Moderate Alzheimer's Disease (2014) · cites this paper as [28]
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Sutphen, C. L., Fagan, A. M., & Holtzman, D. M. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.07.031 · Cited by 31 · see citing works
Schjønning Nielsen, M., Simonsen, A. H., Siersma, V., Engedal, K., Jelic, V., Andersen, B. B., Naik, M., Hasselbalch, S. G., & Høgh, P. (2018) · Dementia and Geriatric Cognitive Disorders Extra · doi:10.1159/000490788 · Cited by 15 · see citing works
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- Authors
- Sperling, R. A., Jack, C. R., & Aisen, P. S.
- Affiliations
- Brigham and Women's Hospital (US)
- Mayo Clinic (US)
- University of California San Diego (US)
- Corresponding author
- Sperling, Reisa A.
- Venue
- Science Translational Medicine
- Published
- 2011-11-30
- Volume
- 3
- Issue
- 111
- Pages
- 111cm33-111cm33
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- PMC
- PMC3752906
- OpenAlex
- W1964464904
- Cited by
- 550
- References
- 33
- Citations by year
- 2026: 14 · 2025: 18 · 2024: 36 · 2023: 36 · 2022: 36 · 2021: 43 · 2020: 55 · 2019: 38 · 2018: 32 · 2017: 32 · 2016: 46 · 2015: 43 · 2014: 43 · 2013: 42 · 2012: 35
- FWCI
- 4.15
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Science Translational Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (K24AG035007, P50AG005134, U19AG010483, P01AG036694)
- 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, disease-modifying therapy, drug development, preclinical disease, dementia, clinical trial endpoints, disease pathophysiology
- MeSH terms
- Alzheimer Disease, Clinical Trials as Topic, Humans, Molecular Targeted Therapy
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 ›
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