ReviewJournal of Alzheimer's disease : JAD2008
Why do so many drugs for Alzheimer's disease fail in development? Time for new methods and new practices?
Review in Journal of Alzheimer's disease : JAD, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
74 citing papers in PubMed, 1 synthesis or guideline pooled it, 139 citations in OpenAlex.
- Spectral-Domain OCT Measurements in Alzheimer's Disease: A Systematic Review and Meta-analysis.Ophthalmology · 2019Pooled it
- Accurate pain reporting training diminishes the placebo response: Results from a randomised, double-blind, crossover trial.PloS one · 2018Trial
- Phenserine efficacy in Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2010Trial
- Latent brain state dynamics predict early amyloid accumulation and cognitive impairment.bioRxiv : the preprint server for biology · 2026Article
- Article
- The Interplay of Inflammation and Gut-Microbiota Dysbiosis in Alzheimer's Disease: Mechanisms and Therapeutic Potential.International journal of molecular sciences · 2025Review
- Epoxide Hydrolase Inhibitors for the Treatment of Alzheimer's Disease and Other Neurological Disorders: A Comprehensive Review.Biomedicines · 2025Review
- Erqember Mitigates Neurotoxic Effects of Aluminum Chloride in Mice: Phytochemical Insights With Neurobehavioral and In Silico Approaches.Journal of toxicology · 2025Article
- Photodynamic and Photothermal Therapies using Nanotechnology Approach in Alzheimer's Disease.Current neuropharmacology · 2025Review
- Nanoscale flow cytometry-based quantification of blood-based extracellular vesicle biomarkers distinguishes MCI and Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Unveiling the potential of novel indol-3-yl-phenyl allylidene hydrazine carboximidamide derivatives as AChE/BACE 1 dual inhibitors: a combinedRSC advances · 2024Article
- A Chronic Increase in Blood-Brain Barrier Permeability Facilitates Intraneuronal Deposition of Exogenous Bloodborne Amyloid-Beta1-42 Peptide in the Brain and Leads to Alzheimer's Disease-Relevant Cognitive Changes in a Mouse Model.Journal of Alzheimer's disease : JAD · 2024Article
- Visualization of Amyloid Oligomers in the Brain of Patients with Alzheimer's Disease.Acta histochemica et cytochemica · 2023Review
- Creatine as a Therapeutic Target in Alzheimer's Disease.Current developments in nutrition · 2023Review
- Cholinergic Reinforcement Signaling Is Impaired by Amyloidosis Prior to Its Synaptic Loss.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Gamma neuromodulation improves episodic memory and its associated network in amnestic mild cognitive impairment: a pilot study.Neurobiology of aging · 2023Article
- Is blood-brain barrier a probable mediator of non-invasive brain stimulation effects on Alzheimer's disease?Communications biology · 2023Review
- Plasma NfL is associated with the APOE ε4 allele, brain imaging measurements of neurodegeneration, and lower recall memory scores in cognitively unimpaired late-middle-aged and older adults.Alzheimer's research & therapy · 2023Article
- A Review of the Recent Advances in Alzheimer's Disease Research and the Utilization of Network Biology Approaches for Prioritizing Diagnostics and Therapeutics.Diagnostics (Basel, Switzerland) · 2022Review
- New Drug Design Avenues Targeting Alzheimer's Disease by Pharmacoinformatics-Aided Tools.Pharmaceutics · 2022Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Alzheimer's disease (AD) drug developments and clinical trials (CT) remain vulnerable to problems that undermine research validity. Investigations of CT methods reveal how numerous factors decrease active drug-placebo group differences and increase variance, thereby reducing power to reach statistical significance for outcome measure differences in AD CTs. Such factors include, amongst many, inaccuracy, imprecision, bias, failures to follow or lack of operational protocols for applying CT methods, inter-site variance, and lack of homogeneous sampling using disorder criteria. After a review of the literature and survey of a sample of AD and Mild Cognitive Impairment (MCI) CTs, the authors question whether problems of human error preclude AD researchers from continuing their dependence on rated outcome measures for CTs. The authors propose that the realities of AD, especially a probable irreversible progression of neuropathology prior to onset of clinical symptoms or signs capable of differentiating persons at risk for AD from normal aged, require AD investigators and clinicians to privilege biomarkers and encourage their development as surrogate targets for preventive AD treatment developments, testing, and use in clinical practice.
Indexed as
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.