ArticleAlzheimer's & dementia (New York, N. Y.)2017
Cross-validation of optimized composites for preclinical Alzheimer's disease.
Article in Alzheimer's & dementia (New York, N. Y.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Hypertension acts together with Aβ pathology in late-life to promote memory loss.The journal of prevention of Alzheimer's disease · 2026Article
- Enhanced sensitivity to plasma p-tau217 with proper names recall in the preclinical Alzheimer's cognitive composite.Brain communications · 2026Article
- Development of language composites for enhanced sensitivity to multiple plasma biomarkers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Mid-to-Late Life Healthy Lifestyle Modifies Genetic Risk for Longitudinal Cognitive Aging among Asymptomatic Individuals.medRxiv : the preprint server for health sciences · 2024Article
- Longitudinal normative standards for cognitive tests and composites using harmonized data from two Wisconsin AD-risk-enriched cohorts.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Apolipoprotein E moderates the association between non-APOE polygenic risk score for Alzheimer's disease and aging on preclinical cognitive function.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Apolipoprotein E moderates the association between Non-medRxiv : the preprint server for health sciences · 2023Article
- Mayo-PACC: A parsimonious preclinical Alzheimer's disease cognitive composite comprised of public-domain measures to facilitate clinical translation.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- Why a clinical trial is as good as its outcome measure: A framework for the selection and use of cognitive outcome measures for clinical trials of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- Effect of Pathway-specific Polygenic Risk Scores for Alzheimer's Disease (AD) on Rate of Change in Cognitive Function and AD-related Biomarkers among Asymptomatic Individuals.medRxiv : the preprint server for health sciences · 2023Article
- Impact of asthma on the brain: evidence from diffusion MRI, CSF biomarkers and cognitive decline.Brain communications · 2023Article
- Effect of Pathway-Specific Polygenic Risk Scores for Alzheimer's Disease (AD) on Rate of Change in Cognitive Function and AD-Related Biomarkers Among Asymptomatic Individuals.Journal of Alzheimer's disease : JAD · 2023Article
- Asthma amplifies dementia risk: Evidence from CSF biomarkers and cognitive decline.Alzheimer's & dementia (New York, N. Y.) · 2022Article
- NIA-AA Alzheimer's Disease Framework: Clinical Characterization of Stages.Annals of neurology · 2021Article
- Identifying Sensitive Measures of Cognitive Decline at Different Clinical Stages of Alzheimer's Disease.Journal of the International Neuropsychological Society : JINS · 2021Article
- Cognition at age 70: Life course predictors and associations with brain pathologies.Neurology · 2019Article
- Measuring longitudinal cognition: Individual tests versus composites.Alzheimer's & dementia (Amsterdam, Netherlands) · 2019Article
- Design and sample size considerations for Alzheimer's disease prevention trials using multistate models.Clinical trials (London, England) · 2019Article
- Optimizing the preclinical Alzheimer's cognitive composite with semantic processing: The PACC5.Alzheimer's & dementia (New York, N. Y.) · 2017Article
- Power analysis to detect treatment effects in longitudinal clinical trials for Alzheimer's disease.Alzheimer's & dementia (New York, N. Y.) · 2017Article
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Authors and funding
8 authors.
Funding
Abstract
introductionWe discuss optimization and validation of composite endpoints for pre-symptomatic Alzheimer's clinical trials. Optimized composites offer hope of substantial gains in statistical power or reduction in sample size. But there is tradeoff between optimization and face validity such that optimization should only be considered if there is a convincing rationale. As with statistically derived regions of interest in neuroimaging, validation on independent datasets is essential.
methodsUsing four datasets, we consider the optimized weighting of four components of a cognitive composite which includes measures of (1) global cognition, (2) semantic memory, (3) episodic memory, and (4) executive function. Weights are optimized to either discriminate amyloid positivity or maximize power to detect a treatment effect in an amyloid positive population. We apply repeated 5×3-fold cross-validation to quantify the out-of-sample performance of optimized composite endpoints.
resultsWe found the optimized weights varied greatly across the folds of the cross validation with either optimization method. Both optimization methods tend to down-weight the measures of global cognition and executive function. However when these optimized composites were applied to the validation sets, they did not provide consistent improvements in power. In fact, overall, the optimized composites performed worse than those without optimization. DISCUSSION: We find that component weight optimization does not yield valid improvements in sensitivity of this composite to detect treatment effects.
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