Regional Differences in White Matter Breakdown Between Frontotemporal Dementia and Early-Onset Alzheimer's Disease¹

Article type: Research Article

Authors: Lu, Po H.^{a; *} | Lee, Grace J.^b | Shapira, Jill^{a; c} | Jimenez, Elvira^{a; c} | Mather, Michelle J.^c | Thompson, Paul M.^{a; d} | Bartzokis, George^{d; e} | Mendez, Mario F.^{a; c}

Affiliations: [a] Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA | [b] Department of Psychology, School of Behavioral Health, Loma Linda University, Loma Linda, CA, USA | [c] Greater Los Angeles VA Healthcare System, West Los Angeles, CA, USA | [d] Laboratory of Neuroimaging, Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA | [e] Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

Correspondence: [*] Correspondence to: Po H. Lu, Psy.D., 710 Westwood Plaza, RNRC 2-258, Los Angeles, CA 90095-1769, USA. Tel.: +1 310 825 4996; Fax: +1 310 794 7491; E-mail: plu@mednet.ucla.edu.

Note: [1] This data was presented in part at the 8th annual meeting of the International Conference for Frontotemporal Dementia at Manchester, UK.

Abstract: Background:White matter abnormalities have been associated with both behavioral variant frontotemporal dementia (bvFTD) and Alzheimer’s disease (AD). Objective:Using MRI diffusion tensor imaging (DTI) measures, we compared white matter integrity between patients with bvFTD and those with early-onset AD and correlated these biomarkers with behavioral symptoms involving emotional blunting. Methods:We studied 8 bvFTD and 12 AD patients as well as 12 demographically-matched healthy controls (NCs). Using four DTI metrics (fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity), we assessed the frontal lobes (FWM) and genu of the corpus callosum (GWM), which are vulnerable late-myelinating regions, and a contrasting early-myelinating region (splenium of the corpus callosum). The Scale for Emotional Blunting Scale (SEB) was used to assess emotional functioning of the study participants. Results:Compared to AD patients and NCs, the bvFTD subjects exhibited significantly worse FWM and GWM integrity on all four DTI metrics sensitive to myelin and axonal integrity. In contrast, AD patients showed a numerical trend toward worse splenium of the corpus callosum integrity than bvFTD and NC groups. Significant associations between SEB ratings and GWM DTI measures were demonstrated in the combined bvFTD and AD sample. When examined separately, these relationships remained robust for the bvFTD group but not the AD group. Conclusions:The regional DTI alterations suggest that FTD and AD are each associated with a characteristic distribution of white matter degradation. White matter breakdown in late-myelinating regions was associated with symptoms of emotional blunting, particularly within the bvFTD group.

Keywords: Alzheimer's disease, behavioral variant, diffusion tensor imaging, early onset, frontotemporal dementia, magnetic resonance imaging, myelin, white matter

DOI: 10.3233/JAD-131481

Journal: Journal of Alzheimer's Disease, vol. 39, no. 2, pp. 261-269, 2014