title: Widespread disruption of functional brain organization in early-onset Alzheimer's disease.
abstract: Early-onset Alzheimer's disease (AD) patients present a different clinical profile than late-onset AD patients. This can be partially explained by cortical atrophy, although brain organization might provide more insight. The aim of this study was to examine functional connectivity in early-onset and late-onset AD patients. Resting-state fMRI scans of 20 early-onset (<65 years old), 28 late-onset (≥65 years old) AD patients and 15 "young" (<65 years old) and 31 "old" (≥65 years old) age-matched controls were available. Resting-state network-masks were used to create subject-specific maps. Group differences were examined using a non-parametric permutation test, accounting for gray-matter. Performance on five cognitive domains were used in a correlation analysis with functional connectivity in AD patients. Functional connectivity was not different in any of the RSNs when comparing the two control groups (young vs. old controls), which implies that there is no general effect of aging on functional connectivity. Functional connectivity in early-onset AD was lower in all networks compared to age-matched controls, where late-onset AD showed lower functional connectivity in the default-mode network. Functional connectivity was lower in early-onset compared to late-onset AD in auditory-, sensory-motor, dorsal-visual systems and the default mode network. Across patients, an association of functional connectivity of the default mode network was found with visuoconstruction. Functional connectivity of the right dorsal visual system was associated with attention across patients. In late-onset AD patients alone, higher functional connectivity of the sensory-motor system was associated with poorer memory performance. Functional brain organization was more widely disrupted in early-onset AD when compared to late-onset AD. This could possibly explain different clinical profiles, although more research into the relationship of functional connectivity and cognitive performance is needed.
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands; Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
authors: Sofie M
authors: SM
authors: Adriaanse
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands; Department of Neurology/Alzheimercenter Amsterdam, VU University Medical Center, Amsterdam, The Netherlands; Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
authors: Maja A A
authors: MA
authors: Binnewijzend
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands; Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
authors: Rik
authors: R
authors: Ossenkoppele
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands; Department of Neurology/Alzheimercenter Amsterdam, VU University Medical Center, Amsterdam, The Netherlands; Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
authors: Betty M
authors: BM
authors: Tijms
authors: Department of Neurology/Alzheimercenter Amsterdam, VU University Medical Center, Amsterdam, The Netherlands; Department of Epidemiology and biostatistics, VU University Medical Center, Amsterdam, The Netherlands; Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
authors: Wiesje M
authors: WM
authors: van der Flier
authors: Department of Medical Psychology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Teddy
authors: T
authors: Koene
authors: Department of Medical Psychology, VU University Medical Center, Amsterdam, The Netherlands; Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
authors: Lieke L
authors: LL
authors: Smits
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands; Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
authors: Alle Meije
authors: AM
authors: Wink
authors: Department of Neurology/Alzheimercenter Amsterdam, VU University Medical Center, Amsterdam, The Netherlands; Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
authors: Philip
authors: P
authors: Scheltens
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands; Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
authors: Bart N M
authors: BN
authors: van Berckel
authors: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands; Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
authors: Frederik
authors: F
authors: Barkhof
mesh_terms: D017668:Age of Onset; D000544:Alzheimer Disease / Q000503:physiopathology* / Q000523:psychology; D001921:Brain / Q000503:physiopathology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests