Brain functional network integrity sustains cognitive function despite atrophy in presymptomatic genetic...

Area of Science:

• Neuroscience
• Neurodegenerative Diseases
• Brain Imaging

Background:

• The presymptomatic phase of neurodegenerative diseases, like familial frontotemporal dementia (FTD), is characterized by prolonged periods of sustained cognitive function despite ongoing brain atrophy.
• Understanding the mechanisms that preserve cognition during this preclinical stage is crucial for early intervention strategies.

Purpose of the Study:

• To investigate the relationship between brain structure, function, and cognitive performance in presymptomatic carriers of familial frontotemporal dementia (FTD) mutations.
• To identify neural mechanisms underlying cognitive resilience in the face of preclinical neurodegeneration.

Main Methods:

• A cohort of 121 presymptomatic FTD mutation carriers and 134 non-carrier family members were studied.
• Multivariate data-driven approaches linked cognitive performance with structural and functional magnetic resonance imaging (MRI) data.
• Brain atrophy and network connectivity were compared between groups relative to the estimated time to symptom onset.

Main Results:

• Group differences in brain structure and function were observed, yet cognitive performance remained comparable between carriers and non-carriers.
• Behaviorally relevant structural and functional network differences were identified in presymptomatic carriers.
• While structure-function relationships were similar, functional connectivity-cognition coupling was stronger in carriers and increased with proximity to disease onset.

Conclusions:

• Enhanced functional network connectivity appears to be a key mechanism enabling presymptomatic FTD mutation carriers to maintain cognitive function.
• These findings highlight the brain's adaptive capacity in preclinical neurodegenerative conditions.
• The study underscores the importance of functional connectivity as a biomarker for cognitive reserve in FTD.