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Updated: Jan 10, 2026
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Abbiategrasso Brain Bank Protocol for Collecting, Processing and Characterizing Aging Brains
Published on: June 3, 2020
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Cellular signatures underlying functional resilience in presymptomatic frontotemporal dementia
Kamen A Tsvetanov1,2, Maura Malpetti1,3, P Simon Jones1
1Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, University of Cambridge, Cambridge CB23 3EB, UK.
Brain : a Journal of Neurology
|November 24, 2025
Summary
Presymptomatic carriers of genetic frontotemporal dementia (FTD) maintain cognitive function due to preserved brain functional integration, offering hope for resilience-based therapies.
Area of Science:
- Neuroscience
- Genetics
- Cognitive Science
Background:
- Frontotemporal dementia (FTD) often exhibits autosomal dominant inheritance, allowing study of presymptomatic stages.
- Brain structural changes precede cognitive symptoms in FTD by over a decade, contrasting with post-symptom decline.
- Functional connectivity predicts cognitive function better than structural imaging in healthy aging.
Purpose of the Study:
- To test if brain-wide functional integration in presymptomatic FTD carriers confers resilience against progressive pathology.
- To investigate the relationship between functional integration, cognition, and atrophy in individuals at risk for FTD.
Main Methods:
- Assessed functional connectome integration using functional magnetic resonance imaging (fMRI) in 289 presymptomatic FTD carriers and 271 non-carriers.
- Employed canonical correlation and multiple linear regression models to analyze imaging, cognitive, and genetic data.
- Examined spatial overlap between functional integration maps and gene transcription profiles to explore cellular mechanisms of resilience.
Main Results:
- Presymptomatic carriers showed progressive atrophy but maintained normal cognitive function compared to non-carriers.
- Functional integration was preserved in presymptomatic carriers across age, while it declined in familial non-carriers, particularly in cognitive control networks.
- Behaviorally relevant changes in functional integration were independent of atrophy severity, suggesting a resilience mechanism.
Conclusions:
- Enhanced brain-wide functional integration appears to be a key resilience mechanism protecting against clinical FTD conversion.
- Findings suggest cellular resilience signatures involving glial cells, offering insights into mechanisms beyond standard neuroimaging.
- Results have implications for designing presymptomatic therapies targeting resilience in individuals at risk for dementia.
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