Cognitive composites for genetic frontotemporal dementia: GENFI-Cog
Jackie M Poos1,2, Katrina M Moore2, Jennifer Nicholas3
1Department of Neurology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Alzheimer'S Research & Therapy
|January 20, 2022
Summary
New cognitive composite scores for genetic frontotemporal dementia (FTD) trials, specifically for C9orf72, GRN, and MAPT mutations, reduce estimated sample sizes. These GENFI-Cog composites offer improved endpoints for clinical trial design and recruitment strategies.
Area of Science:
- Neuroscience
- Genetics
- Clinical Trials
Background:
- Clinical trial endpoints for frontotemporal dementia (FTD) are crucial.
- Existing cognitive composite scores are insufficient for genetic FTD subtypes.
- There is a need for gene-specific cognitive measures in FTD research.
Purpose of the Study:
- To develop gene-specific cognitive composite scores for C9orf72, GRN, and MAPT mutation carriers.
- To provide recommendations for sample size and trial duration in genetic FTD clinical trials.
- To establish reliable cognitive endpoints for therapeutic interventions in FTD.
Main Methods:
- Administered a standardized neuropsychological test battery to 69 C9orf72, 41 GRN, and 28 MAPT mutation carriers and 275 controls.
- Utilized logistic regression to identify optimal combinations of tests for distinguishing mutation carriers from controls.
- Calculated composite scores based on weighted regression coefficients and estimated sample sizes for hypothetical trials.
Main Results:
- Developed distinct composite scores for C9orf72, GRN, and MAPT mutation carriers.
- Composite scores significantly reduced the estimated sample size needed to detect treatment effects compared to individual tests.
- Time-to-event analysis indicated approximately 50% of carriers progress from prodromal to symptomatic stages within 3 years.
Conclusions:
- Gene-specific cognitive composite scores (GENFI-Cog) offer a more efficient endpoint for genetic FTD clinical trials.
- These composites can aid in optimizing sample size calculations and determining appropriate trial durations.
- The findings support the use of GENFI-Cog composites for future therapeutic trial design in genetic FTD.
Keywords:
AttentionCognitionComposite scoreExecutive functionFrontotemporal dementiaLanguageMemoryNeuropsychologySocial cognitionMore Related Videos
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