Gray matter network disruptions and amyloid beta in cognitively normal adults

Betty M. Tijms*, Mara ten Kate, Alle Meije Wink, Pieter Jelle Visser, Mirian Ecay, Montserrat Clerigue, Ainara Estanga, Maite Garcia Sebastian, Andrea Izagirre, Jorge Villanua, Pablo Martinez Lage, Wiesje M. van der Flier, Philip Scheltens, Ernesto Sanz Arigita, Frederik Barkhof

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Gray matter networks are disrupted in Alzheimer's disease (AD). It is unclear when these disruptions start during the development of AD. Amyloid beta 1-42 (A beta(42)) is among the earliest changes in AD. We studied, in cognitively healthy adults, the relationship between A beta(42) levels in cerebrospinal fluid (CSF) and single-subject cortical gray matter network measures. Single-subject gray matter networks were extracted from structural magnetic resonance imaging scans in a sample of cognitively healthy adults (N = 185; age range 39-79, mini-mental state examination >25, N = 12 showed abnormal A beta(42) <550 pg/mL). Degree, clustering coefficient, and path length were computed at whole brain level and for 90 anatomical areas. Associations between continuous A beta(42) CSF levels and single-subject cortical gray matter network measures were tested. Smoothing splines were used to determine whether a linear or nonlinear relationship gave a better fit to the data. Lower A beta(42) CSF levels were linearly associated at whole brain level with lower connectivity density, and nonlinearly with lower clustering values and higher path length values, which is indicative of a less-efficient network organization. These relationships were specific to medial temporal areas, precuneus, and the middle frontal gyrus (all p <0.05). These results suggest that mostly within the normal spectrum of amyloid, lower A beta(42) levels can be related to gray matter networks disruptions.
Original languageEnglish
Pages (from-to)154-160
JournalNeurobiology of Aging
Publication statusPublished - Jan 2016


  • Alzheimer's disease
  • Cognitively normal adults
  • Amyloid beta
  • Single-subject
  • Gray matter
  • Graph theory
  • MRI


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