Frontoparietal network integrity supports cognitive function despite atrophy and hypoperfusion in pre-symptomatic frontotemporal dementia: multimodal analysis of brain function, structure and perfusion

INTRODUCTION Genetic mutation carriers of frontotemporal dementia can remain cognitively well despite neurodegeneration. A better understanding of brain structural, perfusion and functional patterns in pre-symptomatic stage could inform accurate staging and potential mechanisms. METHODS We included 207 pre-symptomatic genetic mutation carriers and 188 relatives without mutations. The grey matter volume, cerebral perfusion, and resting-state functional network maps were co-analyzed using linked independent component analysis (LICA). Multiple regression analysis was used to investigate the relationship of LICA components to genetic status and cognition. RESULTS Pre-symptomatic mutation carriers showed an age-related decrease in the left frontoparietal network integrity while non-carriers did not. Executive functions of mutation carriers became dependent on the left frontoparietal network integrity in older age. DISCUSSION The frontoparietal network integrity of pre-symptomatic mutation carriers showed a distinctive relationship to age and cognition compared to non-carriers, suggesting a contribution of the network integrity to brain resilience, despite atrophy and hypoperfusion.