Frontoparietal network integrity supports cognitive function 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 the 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 gray 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. Highlights A multimodal analysis of structure, perfusion, and functional networks. The frontoparietal network integrity decreases with age in pre‐symptomatic carriers only. Executive functions of pre‐symptomatic carriers dissociated from non‐carriers.