eprintid: 10139933 rev_number: 12 eprint_status: archive userid: 608 dir: disk0/10/13/99/33 datestamp: 2021-12-08 20:58:26 lastmod: 2021-12-08 20:58:26 status_changed: 2021-12-08 20:58:26 type: article metadata_visibility: show creators_name: Veale, T creators_name: Malone, IB creators_name: Poole, T creators_name: Parker, TD creators_name: Slattery, CF creators_name: Paterson, RW creators_name: Foulkes, AJM creators_name: Thomas, DL creators_name: Schott, JM creators_name: Zhang, H creators_name: Fox, NC creators_name: Cash, DM title: Loss and dispersion of superficial white matter in Alzheimer's disease: a diffusion MRI study ispublished: pub divisions: UCL divisions: B02 divisions: C07 divisions: D07 divisions: F82 divisions: F86 divisions: B04 divisions: C05 divisions: F48 keywords: U-fibres, diffusion MRI, superficial white matter, young-onset Alzheimer’s disease note: © The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. abstract: Pathological cerebral white matter changes in Alzheimer’s disease have been shown using diffusion tensor imaging. Superficial white matter changes are relatively understudied despite their importance in cortico-cortical connections. Measuring superficial white matter degeneration using diffusion tensor imaging is challenging due to its complex organizational structure and proximity to the cortex. To overcome this, we investigated diffusion MRI changes in young-onset Alzheimer’s disease using standard diffusion tensor imaging and Neurite Orientation Dispersion and Density Imaging to distinguish between disease-related changes that are degenerative (e.g. loss of myelinated fibres) and organizational (e.g. increased fibre dispersion). Twenty-nine young-onset Alzheimer’s disease patients and 22 healthy controls had both single-shell and multi-shell diffusion MRI. We calculated fractional anisotropy, mean diffusivity, neurite density index, orientation dispersion index and tissue fraction (1-free water fraction). Diffusion metrics were sampled in 15 a priori regions of interest at four points along the cortical profile: cortical grey matter, grey/white boundary, superficial white matter (1 mm below grey/white boundary) and superficial/deeper white matter (2 mm below grey/white boundary). To estimate cross-sectional group differences, we used average marginal effects from linear mixed effect models of participants’ diffusion metrics along the cortical profile. The superficial white matter of young-onset Alzheimer’s disease individuals had lower neurite density index compared to controls in five regions (superior and inferior parietal, precuneus, entorhinal and parahippocampus) (all P < 0.05), and higher orientation dispersion index in three regions (fusiform, entorhinal and parahippocampus) (all P < 0.05). Young-onset Alzheimer’s disease individuals had lower fractional anisotropy in the entorhinal and parahippocampus regions (both P < 0.05) and higher fractional anisotropy within the postcentral region (P < 0.05). Mean diffusivity was higher in the young-onset Alzheimer’s disease group in the parahippocampal region (P < 0.05) and lower in the postcentral, precentral and superior temporal regions (all P < 0.05). In the overlying grey matter, disease-related changes were largely consistent with superficial white matter findings when using neurite density index and fractional anisotropy, but appeared at odds with orientation dispersion and mean diffusivity. Tissue fraction was significantly lower across all grey matter regions in young-onset Alzheimer’s disease individuals (all P < 0.001) but group differences reduced in magnitude and coverage when moving towards the superficial white matter. These results show that microstructural changes occur within superficial white matter and along the cortical profile in individuals with young-onset Alzheimer’s disease. Lower neurite density and higher orientation dispersion suggests underlying fibres undergo neurodegeneration and organizational changes, two effects previously indiscernible using standard diffusion tensor metrics in superficial white matter. date: 2021-11-15 date_type: published official_url: https://doi.org/10.1093/braincomms/fcab272 oa_status: green full_text_type: pub pmcid: PMC8633427 language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1908018 doi: 10.1093/braincomms/fcab272 pii: fcab272 lyricists_name: Cash, David lyricists_name: Fox, Nicholas lyricists_name: Malone, Ian lyricists_name: Paterson, Ross lyricists_name: Schott, Jonathan lyricists_name: Thomas, David lyricists_name: Veale, Thomas lyricists_name: Zhang, Hui lyricists_id: DMCAS28 lyricists_id: NCIFO25 lyricists_id: IBMAL93 lyricists_id: RPATA12 lyricists_id: JMSCH12 lyricists_id: DTHOM65 lyricists_id: TDVEA36 lyricists_id: HZHAN50 actors_name: Barczynska, Patrycja actors_id: PBARC91 actors_role: owner full_text_status: public publication: Brain Communications volume: 3 number: 4 article_number: fcab272 event_location: England citation: Veale, T; Malone, IB; Poole, T; Parker, TD; Slattery, CF; Paterson, RW; Foulkes, AJM; ... Cash, DM; + view all <#> Veale, T; Malone, IB; Poole, T; Parker, TD; Slattery, CF; Paterson, RW; Foulkes, AJM; Thomas, DL; Schott, JM; Zhang, H; Fox, NC; Cash, DM; - view fewer <#> (2021) Loss and dispersion of superficial white matter in Alzheimer's disease: a diffusion MRI study. Brain Communications , 3 (4) , Article fcab272. 10.1093/braincomms/fcab272 <https://doi.org/10.1093/braincomms%2Ffcab272>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10139933/1/Cash_fcab272.pdf