title: Joint assessment of white matter integrity, cortical and subcortical atrophy to distinguish AD from behavioral variant FTD: A two-center study.
abstract: We investigated the ability of cortical and subcortical gray matter (GM) atrophy in combination with white matter (WM) integrity to distinguish behavioral variant frontotemporal dementia (bvFTD) from Alzheimer's disease (AD) and from controls using voxel-based morphometry, subcortical structure segmentation, and tract-based spatial statistics. To determine which combination of MR markers differentiated the three groups with the highest accuracy, we conducted discriminant function analyses. Adjusted for age, sex and center, both types of dementia had more GM atrophy, lower fractional anisotropy (FA) and higher mean (MD), axial (L1) and radial diffusivity (L23) values than controls. BvFTD patients had more GM atrophy in orbitofrontal and inferior frontal areas than AD patients. In addition, caudate nucleus and nucleus accumbens were smaller in bvFTD than in AD. FA values were lower; MD, L1 and L23 values were higher, especially in frontal areas of the brain for bvFTD compared to AD patients. The combination of cortical GM, hippocampal volume and WM integrity measurements, classified 97-100% of controls, 81-100% of AD and 67-75% of bvFTD patients correctly. Our results suggest that WM integrity measures add complementary information to measures of GM atrophy, thereby improving the classification between AD and bvFTD.
authors.affiliation: Department of Neurology & Alzheimer Center, Neuroscience Campus, VU University Medical Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: Christiane
authors.initials: C
authors.lastname: Möller
authors.affiliation: Institute of Psychology, Leiden University, Leiden, The Netherlands ; Leiden Institute for Brain and Cognition, Leiden University, Leiden, The Netherlands.
authors.forename: Anne
authors.initials: A
authors.lastname: Hafkemeijer
authors.affiliation: Department of Neurology & Alzheimer Center, Neuroscience Campus, VU University Medical Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: Yolande A L
authors.initials: YA
authors.lastname: Pijnenburg
authors.affiliation: Institute of Psychology, Leiden University, Leiden, The Netherlands ; Leiden Institute for Brain and Cognition, Leiden University, Leiden, The Netherlands.
authors.forename: Serge A R B
authors.initials: SA
authors.lastname: Rombouts
authors.affiliation: Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: van der Grond
authors.affiliation: Department of Neurology & Alzheimer Center, Neuroscience Campus, VU University Medical Center Amsterdam, Amsterdam, The Netherlands ; Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands ; Department of Clinical Genetics, Neuroscience Campus, VU University Medical Center Amsterdam, Amsterdam, The Netherlands ; Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Elise
authors.initials: E
authors.lastname: Dopper
authors.affiliation: Department of Clinical Genetics, Neuroscience Campus, VU University Medical Center Amsterdam, Amsterdam, The Netherlands ; Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: John
authors.initials: J
authors.lastname: van Swieten
authors.affiliation: Department of Radiology & Nuclear Medicine, Neuroscience Campus, VU University Medical Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: Adriaan
authors.initials: A
authors.lastname: Versteeg
authors.affiliation: Department of Physics & Medical Technology, Neuroscience Campus, VU University Medical Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: Petra J W
authors.initials: PJ
authors.lastname: Pouwels
authors.affiliation: Department of Radiology & Nuclear Medicine, Neuroscience Campus, VU University Medical Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: Department of Neurology & Alzheimer Center, Neuroscience Campus, VU University Medical Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.affiliation: Department of Radiology & Nuclear Medicine, Neuroscience Campus, VU University Medical Center Amsterdam, Amsterdam, The Netherlands ; Department of Physics & Medical Technology, Neuroscience Campus, VU University Medical Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: Hugo
authors.initials: H
authors.lastname: Vrenken
authors.affiliation: Department of Neurology & Alzheimer Center, Neuroscience Campus, VU University Medical Center Amsterdam, Amsterdam, The Netherlands ; Department of Epidemiology & Biostatistics, Neuroscience Campus, VU University Medical Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: Wiesje M
authors.initials: WM
authors.lastname: van der Flier
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology*; D001284:Atrophy; D015415:Biomarkers; D002540:Cerebral Cortex / Q000473:pathology; D056324:Diffusion Tensor Imaging; D005260:Female; D057180:Frontotemporal Dementia / Q000473:pathology*; D066128:Gray Matter / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D066127:White Matter / Q000473:pathology*
chemical_list: D015415:Biomarkers
keywords: Alzheimer's disease; Diagnosis; Discriminant analyses; Frontotemporal dementia; Gray matter atrophy; White matter integrity