ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2014
An empirically derived composite cognitive test score with improved power to track and evaluate treatments for preclinical Alzheimer's disease.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 2 of them syntheses that pooled it.
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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
79 citing papers in PubMed, 2 syntheses or guidelines pooled it, 126 citations in OpenAlex.
- Prevalence and risk of progression of preclinical Alzheimer's disease stages: a systematic review and meta-analysis.Alzheimer's research & therapy · 2019Pooled it
- Detectable Neuropsychological Differences in Early Preclinical Alzheimer's Disease: A Meta-Analysis.Neuropsychology review · 2017Pooled it
- Measuring and increasing the brain health span across adulthood: a public health imperative.Scientific reports · 2026Trial
- Efficacy and Safety of MMFS-01, a Synapse Density Enhancer, for Treating Cognitive Impairment in Older Adults: A Randomized, Double-Blind, Placebo-Controlled Trial.Journal of Alzheimer's disease : JAD · 2016Trial
- Data‑driven cognitive composites predict Aβ‑related decline and progression to MCI: the ADOPIC study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Metabolic pathways associated with cardiometabolic risk effects on cognition in middle-aged adults: the CARDIA study.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Concordance Between Subtest-Based and Domain Score-Based Determinations of Cognitive Impairment on the SNSB-II.Dementia and neurocognitive disorders · 2026Article
- Sarcopenic Obesity and Longitudinal Trajectories on Cognitive Performance and Subtle Cognitive Impairment Over 6 Years in Older Adults.Journal of cachexia, sarcopenia and muscle · 2025Article
- The impact of recent approvals on future alzheimer's disease clinical development: Statistical considerations for combination trials.The journal of prevention of Alzheimer's disease · 2025Article
- Preliminary Effects of American Elderberry Juice on Cognitive Functioning in Mild Cognitive Impairment Patients: A Secondary Analysis of Cognitive Composite Scores in a Randomized Clinical Trial.Antioxidants (Basel, Switzerland) · 2025Article
- Fast Declining Prediction in Alzheimer's Disease from Early Clinical Assessment.Current neuropharmacology · 2025Observational
- Cerebral microvascular changes in healthy carriers of the APOE-ɛ4 Alzheimer's disease risk gene.PNAS nexus · 2024Article
- Longitudinal changes in qualitative aspects of semantic fluency in presymptomatic and prodromal genetic frontotemporal dementia.Journal of neurology · 2023Article
- Unsupervised high-frequency smartphone-based cognitive assessments are reliable, valid, and feasible in older adults at risk for Alzheimer's disease.Journal of the International Neuropsychological Society : JINS · 2023Article
- A public resource of baseline data from the Alzheimer's Prevention Initiative Autosomal-Dominant Alzheimer's Disease Trial.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- Traceability and comparability through crosswalks with the NeuroMET Memory Metric.Scientific reports · 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
- Original research: initial development of a pragmatic tool to estimate cognitive decline risk focusing on potentially modifiable factors in Parkinson's disease.Frontiers in neuroscience · 2023Article
- Original research: longitudinal evaluation of cognitively demanding daily function using performance-based functional assessment highlights heterogeneous trajectories in cognitive and functional abilities in people with Parkinson's disease.Frontiers in neuroscience · 2023Article
- Combining tau-PET and fMRI meta-analyses for patient-centered prediction of cognitive decline in Alzheimer's disease.Alzheimer's research & therapy · 2022Article
19 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
10 authors at 7 institutions in 1 country.
Funding
Abstract
backgroundThere is growing interest in the evaluation of preclinical Alzheimer's disease (AD) treatments. As a result, there is a need to identify a cognitive composite that is sensitive to track preclinical AD decline to be used as a primary endpoint in treatment trials.
methodsLongitudinal data from initially cognitively normal, 70- to 85-year-old participants in three cohort studies of aging and dementia from the Rush Alzheimer's Disease Center were examined to empirically define a composite cognitive endpoint that is sensitive to detect and track cognitive decline before the onset of cognitive impairment. The mean-to-standard deviation ratios (MSDRs) of change over time were calculated in a search for the optimal combination of cognitive tests/subtests drawn from the neuropsychological battery in cognitively normal participants who subsequently progressed to clinical stages of AD during 2- and 5-year periods, using data from those who remained unimpaired during the same period to correct for aging and practice effects. Combinations that performed well were then evaluated for representation of relevant cognitive domains, robustness across individual years before diagnosis, and occurrence of selected items within top performing combinations.
resultsThe optimal composite cognitive test score comprised seven cognitive tests/subtests with an MSDR = 0.964. By comparison, the most sensitive individual test score was Logical Memory Delayed Recall with an MSDR = 0.64.
conclusionsWe have identified a composite cognitive test score representing multiple cognitive domains that has improved power compared with the most sensitive single test item to track preclinical AD decline and evaluate preclinical AD treatments. We are confirming the power of the composite in independent cohorts and with other analytical approaches, which may result in refinements, have designated it as the primary endpoint in the Alzheimer's Prevention Initiative's preclinical treatment trials for individuals at high imminent risk for developing symptoms due to late-onset AD.
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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.