title: Gray matter network disruptions and amyloid beta in cognitively normal adults.
abstract: 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 (Aβ42) is among the earliest changes in AD. We studied, in cognitively healthy adults, the relationship between Aβ42 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 Aβ42 < 550 pg/mL). Degree, clustering coefficient, and path length were computed at whole brain level and for 90 anatomical areas. Associations between continuous Aβ42 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 Aβ42 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 Aβ42 levels can be related to gray matter networks disruptions.
authors.affiliation: Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands. Electronic address: b.tijms@vumc.nl.
authors.forename: Betty M
authors.initials: BM
authors.lastname: Tijms
authors.affiliation: Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands; Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Mara Ten
authors.initials: MT
authors.lastname: Kate
authors.affiliation: Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Alle Meije
authors.initials: AM
authors.lastname: Wink
authors.affiliation: Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.
authors.forename: Pieter Jelle
authors.initials: PJ
authors.lastname: Visser
authors.affiliation: Department of Neurology, CITA-Alzheimer Foundation, San Sebastian, Spain.
authors.forename: Mirian
authors.initials: M
authors.lastname: Ecay
authors.affiliation: Department of Neurology, CITA-Alzheimer Foundation, San Sebastian, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Clerigue
authors.affiliation: Department of Neurology, CITA-Alzheimer Foundation, San Sebastian, Spain.
authors.forename: Ainara
authors.initials: A
authors.lastname: Estanga
authors.affiliation: Department of Neurology, CITA-Alzheimer Foundation, San Sebastian, Spain.
authors.forename: Maite
authors.initials: M
authors.lastname: Garcia Sebastian
authors.affiliation: Department of Neurology, CITA-Alzheimer Foundation, San Sebastian, Spain.
authors.forename: Andrea
authors.initials: A
authors.lastname: Izagirre
authors.affiliation: Department of Neurology, CITA-Alzheimer Foundation, San Sebastian, Spain; Donostia Unit, Osatek SA, Donostia University Hospital, San Sebastian, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Villanua
authors.affiliation: Department of Neurology, CITA-Alzheimer Foundation, San Sebastian, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Martinez Lage
authors.affiliation: Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands; Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Wiesje M
authors.initials: WM
authors.lastname: van der Flier
authors.affiliation: Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.affiliation: Department of Neurology, CITA-Alzheimer Foundation, San Sebastian, Spain.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Sanz Arigita
authors.affiliation: Department of Radiology and Nuclear Medicine, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000134:cerebrospinal fluid / Q000473:pathology* / Q000523:psychology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D058245:Cognitive Reserve / Q000502:physiology*; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)
keywords: Alzheimer's disease; Amyloid beta; Cognitively normal adults; Graph theory; Gray matter; MRI; Single-subject