Differential Hemispheric Predilection of Microstructural White Matter and Functional Connectivity Abnormalities between Respectively Semantic and Behavioral Variant Frontotemporal Dementia

Article type: Research Article

Authors: Meijboom, Rozanna^a | Steketee, Rebecca M.E.^a | Ham, Leontine S.^a | van der Lugt, Aad^a | van Swieten, John C.^b | Smits, Marion^{a; *}

Affiliations: [a] Department of Radiology and Nuclear Medicine, Erasmus MC – University Medical Centre Rotterdam, The Netherlands | [b] Department of Neurology, Erasmus MC – University Medical Centre Rotterdam, The Netherlands

Correspondence: [*] Correspondence to: Marion Smits, MD, PhD, Department of Radiology and Nuclear Medicine, Erasmus MC – University Medical Centre Rotterdam, PO Box 2040, 3000 CA Rotterdam,The Netherlands. Tel.: +31 10 7035372; Fax: +31 10 7034033; E-mail: [email protected].

Abstract: Semantic dementia (SD) and behavioral variant frontotemporal dementia (bvFTD), subtypes of frontotemporal dementia, are characterized by distinct clinical symptoms and neuroimaging features, with predominant left temporal grey matter (GM) atrophy in SD and bilateral or right frontal GM atrophy in bvFTD. Such differential hemispheric predilection may also be reflected by other neuroimaging features, such as brain connectivity. This study investigated white matter (WM) microstructure and functional connectivity differences between SD and bvFTD, focusing on the hemispheric predilection of these differences. Eight SD and 12 bvFTD patients, and 17 controls underwent diffusion tensor imaging and resting state functional MRI at 3T. Whole-brain WM microstructure was assessed to determine distinct WM tracts affected in SD and bvFTD. For these tracts, diffusivity measures and lateralization indices were calculated. Functional connectivity was established for GM regions affected in early stage SD or bvFTD. Results of a direct comparison between SD and bvFTD are reported. Whole-brain WM microstructure abnormalities were more pronounced in the left hemisphere in SD and bilaterally— with a slight predilection for the right— in bvFTD. Lateralization of tract-specific abnormalities was seen in SD only, toward the left hemisphere. Functional connectivity of disease-specific regions was mainly decreased bilaterally in SD and in the right hemisphere in bvFTD. SD and bvFTD show WM microstructure and functional connectivity abnormalities in different regions, that are respectively more pronounced in the left hemisphere in SD and in the right hemisphere in bvFTD. This indicates differential hemispheric predilection of brain connectivity abnormalities between SD and bvFTD.

Keywords: Behavioral variant frontotemporal dementia, diffusion tensor imaging, functional connectivity, lateralization, resting state functional MRI, semantic dementia, white matter microstructure

DOI: 10.3233/JAD-160564

Journal: Journal of Alzheimer's Disease, vol. 56, no. 2, pp. 789-804, 2017