ArticleAlzheimer's research & therapy2022
Cognitive composites for genetic frontotemporal dementia: GENFI-Cog.
Article in Alzheimer's research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 14 citations in OpenAlex.
- Progranulin AAV gene therapy for frontotemporal dementia: translational studies and phase 1/2 trial interim results.Nature medicine · 2024Trial
- Mapping the multiscale neuroanatomy of GRN-related frontotemporal dementia using mode-based morphometry.NeuroImage. Clinical · 2026Article
- Longitudinal behavioral and neuropsychiatric changes and their MRI correlates in predementiaJournal of Alzheimer's disease : JAD · 2025Article
- Executive Function Deficits in Genetic Frontotemporal Dementia: Results From the GENFI Study.Neurology. Genetics · 2025Article
- Structural and functional connectivity in tau mutation carriers: from presymptomatic to symptomatic frontotemporal dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Montreal Cognitive Assessment vs the Mini-Mental State Examination as a Screening Tool for Patients With Genetic Frontotemporal Dementia.Neurology · 2025Article
- Reliability and Validity of Smartphone Cognitive Testing for Frontotemporal Lobar Degeneration.JAMA network open · 2024Article
- Diagnostic accuracy of research criteria for prodromal frontotemporal dementia.Alzheimer's research & therapy · 2024Article
- Temporal order of clinical and biomarker changes in familial frontotemporal dementia.Nature medicine · 2022Article
- The utility of a composite endpoint for tracking disease progression in Lewy body dementia.Alzheimer's & dementia (New York, N. Y.)Article
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Authors and funding
38 authors at 20 institutions in 12 countries.
Funding
Abstract
backgroundClinical endpoints for upcoming therapeutic trials in frontotemporal dementia (FTD) are increasingly urgent. Cognitive composite scores are often used as endpoints but are lacking in genetic FTD. We aimed to create cognitive composite scores for genetic frontotemporal dementia (FTD) as well as recommendations for recruitment and duration in clinical trial design.
methodsA standardized neuropsychological test battery covering six cognitive domains was completed by 69 C9orf72, 41 GRN, and 28 MAPT mutation carriers with CDR® plus NACC-FTLD ≥ 0.5 and 275 controls. Logistic regression was used to identify the combination of tests that distinguished best between each mutation carrier group and controls. The composite scores were calculated from the weighted averages of test scores in the models based on the regression coefficients. Sample size estimates were calculated for individual cognitive tests and composites in a theoretical trial aimed at preventing progression from a prodromal stage (CDR® plus NACC-FTLD 0.5) to a fully symptomatic stage (CDR® plus NACC-FTLD ≥ 1). Time-to-event analysis was performed to determine how quickly mutation carriers progressed from CDR® plus NACC-FTLD = 0.5 to ≥ 1 (and therefore how long a trial would need to be).
resultsThe results from the logistic regression analyses resulted in different composite scores for each mutation carrier group (i.e. C9orf72, GRN, and MAPT). The estimated sample size to detect a treatment effect was lower for composite scores than for most individual tests. A Kaplan-Meier curve showed that after 3 years, ~ 50% of individuals had converted from CDR® plus NACC-FTLD 0.5 to ≥ 1, which means that the estimated effect size needs to be halved in sample size calculations as only half of the mutation carriers would be expected to progress from CDR® plus NACC FTLD 0.5 to ≥ 1 without treatment over that time period. DISCUSSION: We created gene-specific cognitive composite scores for C9orf72, GRN, and MAPT mutation carriers, which resulted in substantially lower estimated sample sizes to detect a treatment effect than the individual cognitive tests. The GENFI-Cog composites have potential as cognitive endpoints for upcoming clinical trials. The results from this study provide recommendations for estimating sample size and trial duration.
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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.