ArticleNeuroImage. Clinical2013
Multilocus genetic profiling to empower drug trials and predict brain atrophy.
Article in NeuroImage. Clinical, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis 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.
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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.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- An Updated Analysis with 85,939 Samples Confirms the Association Between CR1 rs6656401 Polymorphism and Alzheimer's Disease.Molecular neurobiology · 2015Pooled it
- Proof-of-concept recall-by-genotype study of extremely low and high Alzheimer's polygenic risk reveals autobiographical deficits and cingulate cortex correlates.Alzheimer's research & therapy · 2023Article
- Modifiable cardiovascular risk factors and genetics for targeted prevention of dementia.European heart journal · 2023Article
- Gene expression and DNA methylation are extensively coordinated with MRI-based brain microstructural characteristics.Brain imaging and behavior · 2019Article
- A Longitudinal Imaging Genetics Study of Neuroanatomical Asymmetry in Alzheimer's Disease.Biological psychiatry · 2018Article
- GWAS-Linked Loci and Neuroimaging Measures in Alzheimer's Disease.Molecular neurobiology · 2017Article
- Evaluation of a Genetic Risk Score to Improve Risk Prediction for Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2016Article
- The genetic landscape of Alzheimer disease: clinical implications and perspectives.Genetics in medicine : official journal of the American College of Medical Genetics · 2016Review
- Neuroimaging genetic risk for Alzheimer's disease in preclinical individuals: From candidate genes to polygenic approaches.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2016Article
- The effect of the top 20 Alzheimer disease risk genes on gray-matter density and FDG PET brain metabolism.Alzheimer's & dementia (Amsterdam, Netherlands) · 2016Article
- The Role of PICALM in Alzheimer's Disease.Molecular neurobiology · 2015Review
- Magnetic resonance imaging in Alzheimer's Disease Neuroimaging Initiative 2.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2015Article
- Meta-analysis of association between the genetic polymorphisms on chromosome 11q and Alzheimer's disease susceptibility.International journal of clinical and experimental medicine · 2015Article
- Seemingly unrelated regression empowers detection of network failure in dementia.Neurobiology of aging · 2015Article
- The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data.Brain imaging and behavior · 2014Review
- Diagnostic effectiveness of quantitative [¹⁸F]flutemetamol PET imaging for detection of fibrillar amyloid β using cortical biopsy histopathology as the standard of truth in subjects with idiopathic normal pressure hydrocephalus.Acta neuropathologica communications · 2014Article
- Understanding cognitive deficits in Alzheimer's disease based on neuroimaging findings.Trends in cognitive sciences · 2013Review
- Article
- Optimizing Effect Sizes With Imaging Enrichment and Outcome Choices for Mild Alzheimer Disease Clinical Trials.Alzheimer disease and associated disordersArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Designers of clinical trials for Alzheimer's disease (AD) and mild cognitive impairment (MCI) are actively considering structural and functional neuroimaging, cerebrospinal fluid and genetic biomarkers to reduce the sample sizes needed to detect therapeutic effects. Genetic pre-selection, however, has been limited to Apolipoprotein E (ApoE). Recently discovered polymorphisms in the CLU, CR1 and PICALM genes are also moderate risk factors for AD; each affects lifetime AD risk by ~ 10-20%. Here, we tested the hypothesis that pre-selecting subjects based on these variants along with ApoE genotype would further boost clinical trial power, relative to considering ApoE alone, using an MRI-derived 2-year atrophy rate as our outcome measure. We ranked subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) based on their cumulative risk from these four genes. We obtained sample size estimates in cohorts enriched in subjects with greater aggregate genetic risk. Enriching for additional genetic biomarkers reduced the required sample sizes by up to 50%, for MCI trials. Thus, AD drug trial enrichment with multiple genotypes may have potential implications for the timeliness, cost, and power of trials.
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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.