title: Differences in structural covariance brain networks between behavioral variant frontotemporal dementia and Alzheimer's disease.
abstract: Disease-specific patterns of gray matter atrophy in Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) overlap with distinct structural covariance networks (SCNs) in cognitively healthy controls. This suggests that both types of dementia target specific structural networks. Here, we study SCNs in AD and bvFTD. We used structural magnetic resonance imaging data of 31 AD patients, 24 bvFTD patients, and 30 controls from two centers specialized in dementia. Ten SCNs were defined based on structural covariance of gray matter density using independent component analysis. We studied group differences in SCNs using F-tests, with Bonferroni corrected t-tests, adjusted for age, gender, and study center. Associations with cognitive performance were studied using linear regression analyses. Cross-sectional group differences were found in three SCNs (all P < 0.0025). In bvFTD, we observed decreased anterior cingulate network integrity compared with AD and controls. Patients with AD showed decreased precuneal network integrity compared with bvFTD and controls, and decreased hippocampal network and anterior cingulate network integrity compared with controls. In AD, we found an association between precuneal network integrity and global cognitive performance (P = 0.0043). Our findings show that AD and bvFTD target different SCNs. The comparison of both types of dementia showed decreased precuneal (i.e., default mode) network integrity in AD and decreased anterior cingulate (i.e., salience) network integrity in bvFTD. This confirms the hypothesis that AD and bvFTD have distinct anatomical networks of degeneration and shows that structural covariance gives valuable insights in the understanding of network pathology in dementia.
authors.affiliation: Department of Methodology and Statistics, Institute of Psychology, Leiden University, 2300 RB, Leiden, the Netherlands.|Department of Radiology, Leiden University Medical Center, Postzone C2-S, 2300 RC, Leiden, the Netherlands.|Leiden Institute for Brain and Cognition, Leiden University, 2300 RC, Leiden, the Netherlands.
authors.forename: Anne
authors.initials: A
authors.lastname: Hafkemeijer
authors.affiliation: Alzheimer Center & Department of Neurology, VU University Medical Center, 1007 MB, Amsterdam, the Netherlands.
authors.forename: Christiane
authors.initials: C
authors.lastname: Möller
authors.affiliation: Department of Radiology, Leiden University Medical Center, Postzone C2-S, 2300 RC, Leiden, the Netherlands.|Alzheimer Center & Department of Neurology, VU University Medical Center, 1007 MB, Amsterdam, the Netherlands.|Alzheimer Center & Department of Neurology, Erasmus Medical Center, 3000 CA, Rotterdam, the Netherlands.
authors.forename: Elise G P
authors.initials: EG
authors.lastname: Dopper
authors.affiliation: Department of Radiology, Leiden University Medical Center, Postzone C2-S, 2300 RC, Leiden, the Netherlands.|Alzheimer Center & Department of Neurology, Erasmus Medical Center, 3000 CA, Rotterdam, the Netherlands.|Department of Neuropsychology, Erasmus Medical Center, 3000 CA, Rotterdam, the Netherlands.
authors.forename: Lize C
authors.initials: LC
authors.lastname: Jiskoot
authors.affiliation: Department of Radiology, Leiden University Medical Center, Postzone C2-S, 2300 RC, Leiden, the Netherlands.
authors.forename: Annette A
authors.initials: AA
authors.lastname: van den Berg-Huysmans
authors.affiliation: Alzheimer Center & Department of Neurology, Erasmus Medical Center, 3000 CA, Rotterdam, the Netherlands.|Department of Clinical Genetics, VU University Medical Center, 1007 MB, Amsterdam, the Netherlands.
authors.forename: John C
authors.initials: JC
authors.lastname: van Swieten
authors.affiliation: Alzheimer Center & Department of Neurology, VU University Medical Center, 1007 MB, Amsterdam, the Netherlands.|Department of Epidemiology and Biostatistics, VU University Medical Center, 1007 MB, Amsterdam, the Netherlands.
authors.forename: Wiesje M
authors.initials: WM
authors.lastname: van der Flier
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, 1007 MB, Amsterdam, the Netherlands.|Department of Physics and Medical Technology, VU University Medical Center, 1007 MB, Amsterdam, the Netherlands.
authors.forename: Hugo
authors.initials: H
authors.lastname: Vrenken
authors.affiliation: Alzheimer Center & Department of Neurology, VU University Medical Center, 1007 MB, Amsterdam, the Netherlands.
authors.forename: Yolande A L
authors.initials: YA
authors.lastname: Pijnenburg
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, 1007 MB, Amsterdam, the Netherlands.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: Alzheimer Center & Department of Neurology, VU University Medical Center, 1007 MB, Amsterdam, the Netherlands.
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.affiliation: Department of Radiology, Leiden University Medical Center, Postzone C2-S, 2300 RC, Leiden, the Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: van der Grond
authors.affiliation: Department of Methodology and Statistics, Institute of Psychology, Leiden University, 2300 RB, Leiden, the Netherlands.|Department of Radiology, Leiden University Medical Center, Postzone C2-S, 2300 RC, Leiden, the Netherlands.|Leiden Institute for Brain and Cognition, Leiden University, 2300 RC, Leiden, the Netherlands.
authors.forename: Serge A R B
authors.initials: SA
authors.lastname: Rombouts
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology* / Q000523:psychology; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D003071:Cognition; D003430:Cross-Sectional Studies; D005260:Female; D057180:Frontotemporal Dementia / Q000473:pathology* / Q000523:psychology; D066128:Gray Matter / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000473:pathology; D009929:Organ Size
keywords: AD; SCN; T1 weighted; frontotemporal lobar degeneration; gray matter; independent component analysis; magnetic resonance imaging