TY - JOUR
T1 - Functional network resilience to pathology in presymptomatic genetic frontotemporal dementia
AU - The Genetic Frontotemporal Dementia Initiative (GENFI)
AU - Rittman, Timothy
AU - Borchert, Robin
AU - Jones, Simon
AU - van Swieten, John
AU - Borroni, Barbara
AU - Galimberti, Daniela
AU - Masellis, Mario
AU - Tartaglia, Maria Carmela
AU - Graff, Caroline
AU - Tagliavini, Fabrizio
AU - Frisoni, Giovanni B.
AU - Laforce, Robert
AU - Finger, Elizabeth
AU - Mendonça, Alexandre
AU - Sorbi, Sandro
AU - Rohrer, Jonathan D.
AU - Rowe, James B.
AU - Afonso, Sónia
AU - Almeida, Maria Rosario
AU - Anderl-Straub, Sarah
AU - Andersson, Christin
AU - Antonell, Anna
AU - Archetti, Silvana
AU - Arighi, Andrea
AU - Balasa, Mircea
AU - Barandiaran, Myriam
AU - Bargalló, Nuria
AU - Bartha, Robart
AU - Bender, Benjamin
AU - Benussi, Luisa
AU - Bessi, Valentina
AU - Binetti, Giuliano
AU - Black, Sandra
AU - Bocchetta, Martina
AU - Borrego-Ecija, Sergi
AU - Bras, Jose
AU - Bruffaerts, Rose
AU - Caroppo, Paola
AU - Cash, David
AU - Castelo-Branco, Miguel
AU - Convery, Rhian
AU - Cope, Thomas
AU - Cosseddu, Maura
AU - de Arriba, María
AU - Di Fede, Giuseppe
AU - Díaz, Zigor
AU - Dick, Katrina M.
AU - Duro, Diana
AU - Fenoglio, Chiara
AU - Rademakers, Rosa
N1 - Publisher Copyright:
© 2019 The Authors
PY - 2019/5
Y1 - 2019/5
N2 - 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.
AB - 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.
KW - Cognition
KW - Connectivity
KW - Frontotemporal dementia
KW - Functional imaging
KW - Genetics
UR - http://www.scopus.com/inward/record.url?scp=85062232071&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85062232071&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2018.12.009
DO - 10.1016/j.neurobiolaging.2018.12.009
M3 - Article
C2 - 30831384
AN - SCOPUS:85062232071
SN - 0197-4580
VL - 77
SP - 169
EP - 177
JO - Neurobiology of aging
JF - Neurobiology of aging
ER -