TY - JOUR
T1 - Differential default mode network trajectories in asymptomatic individuals at risk for Alzheimer's disease
AU - INSIGHT-preAD Study Group
AU - Alzheimer Precision Medicine Initiative (APMI)
AU - Chiesa, Patrizia A.
AU - Cavedo, Enrica
AU - Vergallo, Andrea
AU - Lista, Simone
AU - Potier, Marie Claude
AU - Habert, Marie Odile
AU - Dubois, Bruno
AU - Thiebaut de Schotten, Michel
AU - Hampel, Harald
AU - Bakardjian, Hovagim
AU - Benali, Habib
AU - Bertin, Hugo
AU - Bonheur, Joel
AU - Boukadida, Laurie
AU - Boukerrou, Nadia
AU - Chiesa, Patrizia
AU - Colliot, Olivier
AU - Dubois, Marion
AU - Epelbaum, Stéphane
AU - Gagliardi, Geoffroy
AU - Genthon, Remy
AU - Houot, Marion
AU - Kas, Aurélie
AU - Lamari, Foudil
AU - Levy, Marcel
AU - Metzinger, Christiane
AU - Mochel, Fanny
AU - Nyasse, Francis
AU - Poisson, Catherine
AU - Revillon, Marie
AU - Santos, Antonio
AU - Andrade, Katia Santos
AU - Sole, Marine
AU - Surtee, Mohmed
AU - de Schotten, Michel Thiebaud
AU - Younsi, Nadjia
AU - Afshar, Mohammad
AU - Aguilar, Lisi Flores
AU - Akman-Anderson, Leyla
AU - Arenas, Joaquín
AU - Avila, Jesus
AU - Babiloni, Claudio
AU - Baldacci, Filippo
AU - Batrla, Richard
AU - Benda, Norbert
AU - Black, Keith L.
AU - Bokde, Arun L.W.
AU - Bonuccelli, Ubaldo
AU - Broich, Karl
AU - O'Bryant, Sid E.
PY - 2019/7
Y1 - 2019/7
N2 - Introduction: The longitudinal trajectories of functional brain dynamics and the impact of genetic risk factors in individuals at risk for Alzheimer's disease are poorly understood. Methods: In a large-scale monocentric cohort of 224 amyloid stratified individuals at risk for Alzheimer's disease, default mode network (DMN) resting state functional connectivity (FC) was investigated between two serial time points across 2 years. Results: Widespread DMN FC changes were shown in frontal and posterior areas, as well as in the right hippocampus. There were no cross-sectional differences, however, apolipoprotein E ε4 (APOE ε4) carriers demonstrated slower increase in FC in frontal lobes. There was no impact of individual brain amyloid load status. Discussion: For the first time, we demonstrated that the pleiotropic biological effect of the APOE ε4 allele impacts the dynamic trajectory of the DMN during aging. Dynamic functional biomarkers may become useful surrogate outcomes for the development of preclinical targeted therapeutic interventions.
AB - Introduction: The longitudinal trajectories of functional brain dynamics and the impact of genetic risk factors in individuals at risk for Alzheimer's disease are poorly understood. Methods: In a large-scale monocentric cohort of 224 amyloid stratified individuals at risk for Alzheimer's disease, default mode network (DMN) resting state functional connectivity (FC) was investigated between two serial time points across 2 years. Results: Widespread DMN FC changes were shown in frontal and posterior areas, as well as in the right hippocampus. There were no cross-sectional differences, however, apolipoprotein E ε4 (APOE ε4) carriers demonstrated slower increase in FC in frontal lobes. There was no impact of individual brain amyloid load status. Discussion: For the first time, we demonstrated that the pleiotropic biological effect of the APOE ε4 allele impacts the dynamic trajectory of the DMN during aging. Dynamic functional biomarkers may become useful surrogate outcomes for the development of preclinical targeted therapeutic interventions.
KW - Alzheimer's disease
KW - Brain functional dynamics
KW - Precision medicine
KW - Subjective memory complaints
KW - fMRI
UR - http://www.scopus.com/inward/record.url?scp=85065804629&partnerID=8YFLogxK
U2 - 10.1016/j.jalz.2019.03.006
DO - 10.1016/j.jalz.2019.03.006
M3 - Article
C2 - 31113760
AN - SCOPUS:85065804629
VL - 15
SP - 940
EP - 950
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
SN - 1552-5260
IS - 7
ER -