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.
Keywords: atrophy; cerebral blood flow; frontotemporal dementia; functional network; multimodal neuroimaging; pre‐symptomatic dementia.
© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.