Frontoparietal network integrity supports cognitive function despite atrophy and hypoperfusion in pre-symptomatic frontotemporal dementia: multimodal analysis of brain function, structure and perfusion
Liu, X.; Jones, S.; Pasternak, M.; Masellis, M.; Bouzigues, A.; Russell, L. L.; Foster, P. H.; Ferry-Bolder, E.; van Swieten, J.; Jiskoot, L.; Seelaar, H.; Sanchez-Valle, R.; Laforce, R.; Graff, C.; Galimberti, D.; Vandenberghe, R.; de Mendonca, A.; Tiraboschi, P.; Santana, I.; Gerhard, A.; Levin, J.; Sorbi, S.; Otto, M.; Pasquier, F.; Ducharme, S.; Butler, C.; Le Ber, I.; Finger, E.; Tartaglia, M. C.; Synofzik, M.; Moreno, F.; Borroni, B.; Rohrer, J. D.; Tsvetanov, K. A.; Rowe, J. B.; The GENFI consortium,
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INTRODUCTIONGenetic 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. METHODSWe 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. RESULTSPre-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. DISCUSSIONThe 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.
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