Characterizing White Matter Tract Degeneration in Syndromic Variants of Alzheimer’s Disease: A Diffusion Tensor Imaging Study

Article type: Research Article

Authors: Madhavan, Ajay^a | Schwarz, Christopher G.^a | Duffy, Joseph R.^b | Strand, Edythe A.^b | Machulda, Mary M.^c | Drubach, Daniel A.^d | Kantarci, Kejal^a | Przybelski, Scott A.^e | Reid, Robert I.^f | Senjem, Matthew L.^{a; f} | Gunter, Jeffrey L.^{a; f} | Apostolova, Liana G.^g | Lowe, Val J.^a | Petersen, Ronald C.^d | Jack Jr., Clifford R.^a | Josephs, Keith A.^d | Whitwell, Jennifer L.^{a; *}

Affiliations: [a] Department of Radiology, Mayo Clinic, Rochester, MN, USA | [b] Department of Neurology (Speech Pathology), Mayo Clinic, Rochester, MN, USA | [c] Department of Psychiatry and Psychology (Neuropsychology), Mayo Clinic, Rochester, MN, USA | [d] Department of Neurology (Behavioral Neurology), Mayo Clinic, Rochester, MN, USA | [e] Department of Health Sciences Research (Biostatistics), Mayo Clinic, Rochester, MN, USA | [f] Department of Information Technology, Mayo Clinic, Rochester, MN, USA | [g] Department of Neurology, University of California Los Angeles, Los Angeles, CA, USA

Correspondence: [*] Correspondence to: Jennifer L. Whitwell, PhD, Associate Professor of Radiology, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA. Tel.: +1 507 284 5576; Fax: +1 507 284 9778; E-mail: whitwell.jennifer@mayo.edu

Abstract: Background:Different clinical syndromes can arise from Alzheimer’s disease (AD) neuropathology, including dementia of the Alzheimer’s type (DAT), logopenic primary progressive aphasia (lvPPA), and posterior cortical atrophy (PCA). Objective:To assess similarities and differences in patterns of white matter tract degeneration across these syndromic variants of AD. Methods:Sixty-four subjects (22 DAT, 24 lvPPA, and 18 PCA) that had diffusion tensor imaging and showed amyloid-β deposition on PET were assessed in this case-control study. A whole-brain voxel-based analysis was performed to assess differences in fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity across groups. Results:All three groups showed overlapping diffusion abnormalities in a network of tracts, including fornix, corpus callosum, posterior thalamic radiations, superior longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and uncinate fasciculus. Subtle regional differences were also observed across groups, with DAT particularly associated with degeneration of fornix and cingulum, lvPPA with left inferior fronto-occipital fasciculus and uncinate fasciculus, and PCA with posterior thalamic radiations, superior longitudinal fasciculus, posterior cingulate, and splenium of the corpus callosum. Conclusion:These findings show that while each AD phenotype is associated with degeneration of a specific structural network of white matter tracts, striking spatial overlap exists among the three network patterns that may be related to AD pathology.

Keywords: Alzheimer’s disease, diffusion tensor imaging, logopenic, posterior cortical atrophy, white matter

DOI: 10.3233/JAD-150502

Journal: Journal of Alzheimer's Disease, vol. 49, no. 3, pp. 633-643, 2016