Single-subject grey matter network trajectories over the disease course of autosomal dominant Alzheimer’s disease

• DOI: 10.1093/braincomms/fcaa102
• Publication Date: 2020-07-15T16:22:47Z
• Authors: Lisa Vermunt; Ellen Dicks; Guoqiao Wang; Aylin Dincer; Shaney Flores; Sarah J Keefe; Sarah B Berman; David M Cash; Jasmeer P Chhatwal; Carlos Cruchaga; Nick C Fox; Bernardino Ghetti; Neill R Graff-Rad...; Jason Hassenstab; Celeste M Karch; Christoph Laske; Johannes Levin; Colin L Masters; Eric McDade; Hiroshi Mori; John C Morris; James M Noble; Richard J Perrin; Peter R Schofield; Chengjie Xiong; Philip Scheltens; Pieter Jelle Visser; Randall J Bateman; Tammie L S Benzinger; Betty M Tijms; Brian A Gordon; ; Ricardo Allegri; Fatima Amtashar; Tammie Benzinger; Sarah Berman; Courtney Bodge; Susan Brandon; William Brooks; Jill Buck; Virginia Buckles; Sochenda Chea; Patricio Chrem; Helena Chui; Jake Cinco; Clifford Jack; Mirelle D’Mello; Tamara Donahue; Jane Douglas; Noelia Edigo; Nilufer Erekin-Taner; Anne Fagan; Marty Farlow; Angela Farrar; Howard Feldman; Gigi Flynn; Nick Fox; Erin Franklin; Hisako Fujii; Cortaiga Gant; Samantha Gardener; Bernardino Ghetti; Alison Goate; Jill Goldman; Brian Gordon; Julia Gray; Jenny Gurney; Jason Hassenstab; Mie Hirohara; David Holtzman; Russ Hornbeck; Siri Houeland DiBari; Takeshi Ikeuchi; Snezana Ikonomovic; Gina Jerome; Mathias Jucker; Kensaku Kasuga; Takeshi Kawarabay...; William Klunk; Robert Koeppe; Elke Kuder-Buletta; Christoph Laske; Johannes Levin; Daniel Marcus; Ralph Martins; Neal Scott Mason; Denise Maue-Dreyfus; Eric McDade; Lucy Montoya; Hiroshi Mori; Akem Nagamatsu; Katie Neimeyer; James Noble; Joanne Norton; Richard Perrin; Marc Raichle; John Ringman; Jee Hoon Roh; Peter Schofield; Hiroyuki Shimada; Tomoyo Shiroto; Mikio Shoji; Wendy Sigurdson; Hamid Sohrabi; Paige Sparks; Kazushi Suzuki; Laura Swisher; Kevin Taddei; Jen Wang; Peter Wang; Mike Weiner; Mary Wolfsberger; Chengjie Xiong; Xiong Xu
• Keywords: Grey matter; Early-onset Alzheimer's disease

Abstract Structural grey matter covariance networks provide an individual quantification of morphological patterns in the brain. The network integrity is disrupted sporadic Alzheimer’s disease, and properties show associations with level amyloid pathology cognitive decline. Therefore, these might be disease progression markers. However, it remains unclear when how changes progression. We investigated questions autosomal dominant mutation carriers, whose conserved age at dementia onset allows staging based upon their estimated years to symptom onset. From Dominantly Inherited Alzheimer Network observational cohort, we selected T1-weighted MRI scans from 269 carriers 170 non-carriers (mean 38 ± 15 years, mean −9 11), whom 237 had longitudinal a follow-up 3.0 years. Single-subject were extracted, calculated for each which describe topology, including size, clustering, path length small worldness. determined time point diverged global regional metrics, both cross-sectionally rate change over time. Based on cross-sectional data, earliest difference was observed normalized length, decreased precuneus area 13 12 before found between groups 6 onset, greater decline size carriers. further compared worldness established biomarkers (i.e. accumulation, cortical thickness, brain metabolism function). that accumulation baseline associated faster time, measures accompanied by metabolism, thinning In summary, alike prior These data suggest single-subject obtained structural form additional non-invasive tool understanding substrate measuring preclinical severe clinical stages disease.