A Longitudinal Study on Resting State Functional Connectivity in Behavioral Variant Frontotemporal Dementia and Alzheimer’s Disease

Article type: Research Article

Authors: Hafkemeijer, Anne^{a; b; c; *} | Möller, Christiane^d | Dopper, Elise G.P.^{b; d; e} | Jiskoot, Lize C.^{b; e; f} | van den Berg-Huysmans, Annette A.^b | van Swieten, John C.^{e; g} | van der Flier, Wiesje M.^{d; h} | Vrenken, Hugo^{i; j} | Pijnenburg, Yolande A.L.^d | Barkhof, Frederik^{i; k} | Scheltens, Philip^d | van der Grond, Jeroen^b | Rombouts, Serge A.R.B.^{a; b; c}

Affiliations: [a] Department of Methodology and Statistics, Institute of Psychology, Leiden University, Leiden, The Netherlands | [b] Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands | [c] Leiden Institute for Brain and Cognition, Leiden University, Leiden, The Netherlands | [d] Alzheimer Center & Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands | [e] Alzheimer Center & Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands | [f] Department of Neuropsychology, Erasmus Medical Center, Rotterdam, The Netherlands | [g] Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands | [h] Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands | [i] Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands | [j] Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands | [k] Institutes of Neurology and Healthcare Engineering, University College London, London, UK

Correspondence: [*] Correspondence to: Anne Hafkemeijer, Department of Radiology, Leiden University Medical Center, Postzone C2-S, PO Box 9600, 2300 RC Leiden, The Netherlands. Tel.: +31 71 526 3998; E-mail: A.Hafkemeijer@lumc.nl.

Abstract: Background/Objective: 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. Methods: 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. Results: 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. Conclusion: 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.

Keywords: Alzheimer’s disease, frontotemporal dementia, frontotemporal lobar degeneration, functional connectivity, longitudinal, resting state fMRI, resting state networks

DOI: 10.3233/JAD-150695

Journal: Journal of Alzheimer's Disease, vol. 55, no. 2, pp. 521-537, 2017