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Article type: Research Article
Authors: Singh, Neha Atulkumara | Graff-Radford, Jonathana | Machulda, Mary M.b | Pham, Nha Trang Thuc | Schwarz, Christopher G.c | Reid, Robert I.c; d | Lowe, Val J.c | Petersen, Ronald C.a | Jack Jr, Clifford R.c | Josephs, Keith A.a | Whitwell, Jennifer L.c; *
Affiliations: [a] Department of Neurology, Mayo Clinic, Rochester, MN, USA | [b] Department of Psychiatry & Psychology, Mayo Clinic, Rochester, MN, USA | [c] Department of Radiology, Mayo Clinic, Rochester, MN, USA | [d] Department of Information Technology, Mayo Clinic, Rochester, MN, USA
Correspondence: [*] Correspondence to: Jennifer L. Whitwell, PhD, Professor of Radiology, Mayo Clinic, 200 1st St SW, Rochester, MN 55905, USA. Tel.: +1 507 284 5576; Fax: +1 507 284 9778; E-mail: whitwell.jennifer@mayo.edu.
Abstract: Background:Posterior cortical atrophy (PCA) and logopenic progressive aphasia (LPA) are associated with characteristic patterns of structural network degeneration. Little is known about longitudinal patterns of white matter tract degeneration in these phenotypes. Objective:To assess longitudinal patterns of white matter degeneration and identify phenotype specific cross-sectional and longitudinal diffusion tensor imaging (DTI) biomarkers in PCA and LPA. Methods:Twenty-five PCA, 22 LPA and 25 cognitively unimpaired (CU) individuals were recruited and underwent structural MRI that included a DTI sequence with a follow-up one year later. Cross-sectional and longitudinal mixed effects models were fit to assess the effects of diagnosis on baseline and annualized change in regional DTI metrics. Discriminatory power was investigated using the area under the receiver operating characteristic curves (AUROC). Results:PCA and LPA showed overlapping white matter degeneration profiles predominantly in the left occipital and temporal lobes, the posterior thalamic radiation and sagittal stratum at baseline, as well as the parietal lobe longitudinally. PCA showed degeneration in the occipital and parietal white matter, cross-sectionally and longitudinally, compared to CU, while LPA showed greater degeneration in the temporal and inferior parietal white matter and the inferior fronto-occipital fasciculus cross-sectionally, and in parietal white matter longitudinally compared to CU. Cross-sectionally, integrity of the inferior occipital white matter was best able to differentiate PCA from LPA, with an AUROC of 0.82. Conclusion:These findings contribute to our understanding of white matter degeneration and support usage of DTI as a useful additional diagnostic biomarker for PCA and LPA.
Keywords: Atypical Alzheimer’s disease, diffusion tensor imaging, logopenic progressive aphasia, posterior cortical atrophy, white matter
DOI: 10.3233/JAD-221217
Journal: Journal of Alzheimer's Disease, vol. 94, no. 2, pp. 709-725, 2023
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