ArticlePloS one2012
Enrichment and stratification for predementia Alzheimer disease clinical trials.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 3 of them syntheses that pooled it.
What it found
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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
42 citing papers in PubMed, 3 syntheses or guidelines pooled it, 68 citations in OpenAlex.
- Detectable Neuropsychological Differences in Early Preclinical Alzheimer's Disease: A Meta-Analysis.Neuropsychology review · 2017Pooled it
- Systematic review of strengths and limitations of randomized controlled trials for non-pharmacological interventions in mild cognitive impairment: focus on Alzheimer's disease.The journal of nutrition, health & aging · 2015Pooled it
- (11)C-PIB-PET for the early diagnosis of Alzheimer's disease dementia and other dementias in people with mild cognitive impairment (MCI).The Cochrane database of systematic reviews · 2014Pooled it
- Research diagnostic criteria for Alzheimer's disease: findings from the LipiDiDiet randomized controlled trial.Alzheimer's research & therapy · 2021Trial
- Real-World Multimodal Machine Learning for Risk Enrichment Across the Alzheimer's Disease Spectrum.Journal of clinical medicine · 2026Article
- Altered functional connectivity is associated with Repeatable Battery for the Assessment of Neuropsychological Status across the dementia spectrum.Journal of the International Neuropsychological Society : JINS · 2026Article
- A multimodal deep learning approach for the prediction of cognitive decline and its effectiveness in clinical trials for Alzheimer's disease.Translational psychiatry · 2024Article
- Does modulation of tau hyperphosphorylation represent a reasonable therapeutic strategy for Alzheimer's disease? From preclinical studies to the clinical trials.Molecular psychiatry · 2023Review
- Heterogeneity in Alzheimer's Disease Diagnosis and Progression Rates: Implications for Therapeutic Trials.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- DeepAtrophy: Teaching a neural network to detect progressive changes in longitudinal MRI of the hippocampal region in Alzheimer's disease.NeuroImage · 2021Article
- Longitudinal atrophy in early Braak regions in preclinical Alzheimer's disease.Human brain mapping · 2020Article
- Modifying the minimum criteria for diagnosing amnestic MCI to improve prediction of brain atrophy and progression to Alzheimer's disease.Brain imaging and behavior · 2020Article
- Bridging the Gap Between Fluid Biomarkers for Alzheimer's Disease, Model Systems, and Patients.Frontiers in aging neuroscience · 2020Review
- Neuroimaging Biomarkers for Alzheimer's Disease.Molecular neurodegeneration · 2019Review
- Predicting long-term clinical stability in amyloid-positive subjects by FDG-PET.Annals of clinical and translational neurology · 2019Article
- Review
- Amyloid and tau signatures of brain metabolic decline in preclinical Alzheimer's disease.European journal of nuclear medicine and molecular imaging · 2018Article
- Combining Polygenic Hazard Score With Volumetric MRI and Cognitive Measures Improves Prediction of Progression From Mild Cognitive Impairment to Alzheimer's Disease.Frontiers in neuroscience · 2018Article
- Article
- The effect of diagnostic criteria on outcome measures in preclinical and prodromal Alzheimer's disease: Implications for trial design.Alzheimer's & dementia (New York, N. Y.) · 2017Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The tau and amyloid pathobiological processes underlying Alzheimer disease (AD) progresses slowly over periods of decades before clinical manifestation as mild cognitive impairment (MCI), then more rapidly to dementia, and eventually to end-stage organ failure. The failure of clinical trials of candidate disease modifying therapies to slow disease progression in patients already diagnosed with early AD has led to increased interest in exploring the possibility of early intervention and prevention trials, targeting MCI and cognitively healthy (HC) populations. Here, we stratify MCI individuals based on cerebrospinal fluid (CSF) biomarkers and structural atrophy risk factors for the disease. We also stratify HC individuals into risk groups on the basis of CSF biomarkers for the two hallmark AD pathologies. Results show that the broad category of MCI can be decomposed into subsets of individuals with significantly different average regional atrophy rates. By thus selectively identifying individuals, combinations of these biomarkers and risk factors could enable significant reductions in sample size requirements for clinical trials of investigational AD-modifying therapies, and provide stratification mechanisms to more finely assess response to therapy. Power is sufficiently high that detecting efficacy in MCI cohorts should not be a limiting factor in AD therapeutics research. In contrast, we show that sample size estimates for clinical trials aimed at the preclinical stage of the disorder (HCs with evidence of AD pathology) are prohibitively large. Longer natural history studies are needed to inform design of trials aimed at the presymptomatic stage.
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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.