Functional network resilience to pathology in presymptomatic genetic frontotemporal dementia

The presymptomatic phase of neurodegenerative diseases are characterized by structural brain changes without significant clinical features. We set out to investigate the contribution of functional network resilience to preserved cognition in presymptomatic genetic frontotemporal dementia. We studied...

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Published in:	Neurobiology of aging 2019-05, Vol.77, p.169-177
Main Authors:	Rittman, Timothy, Borchert, Robin, Jones, Simon, van Swieten, John, Galimberti, Daniela, Graff, Caroline, Frisoni, Giovanni B., Laforce, Robert, Finger, Elizabeth, Mendonça, Alexandre, Sorbi, Sandro, Rowe, James B., Afonso, Sónia, Almeida, Maria Rosario, Andersson, Christin, Antonell, Anna, Archetti, Silvana, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Benussi, Luisa, Bessi, Valentina, Binetti, Giuliano, Black, Sandra, Bocchetta, Martina, Borrego-Ecija, Sergi, Bras, Jose, Bruffaerts, Rose, Caroppo, Paola, Cash, David, Convery, Rhian, Cosseddu, Maura, de Arriba, María, Díaz, Zigor, Dick, Katrina M., Duro, Diana, Fenoglio, Chiara, Ferrari, Camilla, Ferreira, Catarina B., Flanagana, Toby, Freedman, Morris, Fumagalli, Giorgio, Gabilondo, Alazne, Gasparotti, Roberto, Gazzina, Stefano, Giaccone, Giorgio, Gorostidi, Ana, Greaves, Caroline, Guerreiro, Rita, Heller, Carolin, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Jiskoot, Lize, Karnath, Hans-Otto, Leitão, Maria João, Lladó, Albert, Lombardi, Gemma, Loosli, Sandra, Maruta, Carolina, Mead, Simon, Meeter, Lieke, Miltenberger, Gabriel, van Minkelen, Rick, Mitchell, Sara, Nacmias, Benedetta, Neason, Mollie, Olives, Jaume, Padovani, Alessandro, Panman, Jessica, Pievani, Michela, Premi, Enrico, Prioni, Sara, Prix, Catharina, Redaelli, Veronica, Rogaeva, Ekaterina, Rosa-Neto, Pedro, Rosser, Martin, Santiago, Beatriz, Scarpini, Elio, Schönecker, Sonja, Semler, Elisa, Shafei, Rachelle, Tábuas-Pereira, Miguel, Tainta, Mikel, Taipa, Ricardo, Tang-Wai, David, Timberlake, Carolyn, Tiraboschi, Pietro, Vandamme, Philip, Vandenbulcke, Mathieu, Veldsman, Michele, Verdelho, Ana, Villanua, Jorge, Warren, Jason, Wilke, Carlo, Woollacott, Ione, Wlasich, Elisabeth, Zulaica, Miren
Format:	Article
Language:	eng
Subjects:	Adult Aged Atrophy Brain - diagnostic imaging Brain - pathology Brain - physiopathology C9orf72 Protein - genetics Cognition Connectivity Female Frontotemporal dementia Frontotemporal Dementia - genetics Frontotemporal Dementia - pathology Frontotemporal Dementia - psychology Functional imaging Genetics Heterozygote Humans Magnetic Resonance Imaging Male Medicin och hälsovetenskap Middle Aged Nerve Net - diagnostic imaging Nerve Net - pathology Nerve Net - physiopathology Neuroimaging Organ Size tau Proteins - genetics
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Summary:	The presymptomatic phase of neurodegenerative diseases are characterized by structural brain changes without significant clinical features. We set out to investigate the contribution of functional network resilience to preserved cognition in presymptomatic genetic frontotemporal dementia. We studied 172 people from families carrying genetic abnormalities in C9orf72, MAPT, or PGRN. Networks were extracted from functional MRI data and assessed using graph theoretical analysis. We found that despite loss of both brain volume and functional connections, there is maintenance of an efficient topological organization of the brain's functional network in the years leading up to the estimated age of frontotemporal dementia symptom onset. After this point, functional network efficiency declines markedly. Reduction in connectedness was most marked in highly connected hub regions. Measures of topological efficiency of the brain's functional network and organization predicted cognitive dysfunction in domains related to symptomatic frontotemporal dementia and connectivity correlated with brain volume loss in frontotemporal dementia. We propose that maintaining the efficient organization of the brain's functional network supports cognitive health even as atrophy and connectivity decline presymptomatically. •Mechanisms of preserved function in presymptomatic dementia are not well understood.•We studied people with genetic frontotemporal dementia and their relatives.•Brain network efficiency was preserved prior to the onset of symptoms.•Highly connected hub regions were preferentially affected by neuropathology.•Interventions to support functional brain networks may delay the onset of dementia.
ISSN:	0197-4580 1558-1497 1558-1497