A Longitudinal Study on Resting State Functional Connectivity in Behavioral Variant Frontotemporal Dementia and Alzheimer's Disease.
Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are the most common types of early-onset dementia. We applied longitudinal resting state functional magnetic resonance imaging (fMRI) to delineate functional brain connections relevant for disease progression and diagnostic accuracy.



We used two-center resting state fMRI data of 20 AD patients (65.1±8.0 years), 12 bvFTD patients (64.7±5.4 years), and 22 control subjects (63.8±5.0 years) at baseline and 1.8-year follow-up. We used whole-network and voxel-based network-to-region analyses to study group differences in functional connectivity at baseline and follow-up, and longitudinal changes in connectivity within and between groups.



At baseline, connectivity between paracingulate gyrus and executive control network, between cuneal cortex and medial visual network, and between paracingulate gyrus and salience network was higher in AD compared with controls. These differences were also present after 1.8 years. At follow-up, connectivity between angular gyrus and right frontoparietal network, and between paracingulate gyrus and default mode network was lower in bvFTD compared with controls, and lower compared with AD between anterior cingulate gyrus and executive control network, and between lateral occipital cortex and medial visual network. Over time, connectivity decreased in AD between precuneus and right frontoparietal network and in bvFTD between inferior frontal gyrus and left frontoparietal network. Longitudinal changes in connectivity between supramarginal gyrus and right frontoparietal network differ between both patient groups and controls.



We found disease-specific brain regions with longitudinal connectivity changes. This suggests the potential of longitudinal resting state fMRI to delineate regions relevant for disease progression and for diagnostic accuracy, although no group differences in longitudinal changes in the direct comparison of AD and bvFTD were found.
Department of Methodology and Statistics, Institute of Psychology, Leiden University, Leiden, The Netherlands.|Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.|Leiden Institute for Brain and Cognition, Leiden University, Leiden, The Netherlands.
Anne
A
Hafkemeijer
Alzheimer Center & Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
Christiane
C
Möller
Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.|Alzheimer Center & Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.|Alzheimer Center & Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands.
Elise G P
EG
Dopper
Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.|Alzheimer Center & Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Neuropsychology, Erasmus Medical Center, Rotterdam, The Netherlands.
Lize C
LC
Jiskoot
Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
Annette A
AA
van den Berg-Huysmans
Alzheimer Center & Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
John C
JC
van Swieten
Alzheimer Center & Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.|Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
Wiesje M
WM
van der Flier
Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.|Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands.
Hugo
H
Vrenken
Alzheimer Center & Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
Yolande A L
YA
Pijnenburg
Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.|Institutes of Neurology and Healthcare Engineering, University College London, London, UK.
Frederik
F
Barkhof
Alzheimer Center & Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
Philip
P
Scheltens
Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
Jeroen
J
van der Grond
Department of Methodology and Statistics, Institute of Psychology, Leiden University, Leiden, The Netherlands.|Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.|Leiden Institute for Brain and Cognition, Leiden University, Leiden, The Netherlands.
Serge A R B
SA
Rombouts
D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001931:Brain Mapping; D005260:Female; D057180:Frontotemporal Dementia / Q000000981:diagnostic imaging / Q000503:physiopathology*; D066128:Gray Matter / Q000000981:diagnostic imaging; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000503:physiopathology*; D010100:Oxygen / Q000097:blood; D012146:Rest; D066127:White Matter / Q000000981:diagnostic imaging
D010100:Oxygen
Alzheimer’s disease; frontotemporal dementia; frontotemporal lobar degeneration; functional connectivity; longitudinal; resting state fMRI; resting state networks