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Early white matter (WM) changes on MRI are associated with TAR DNA-binding protein 43 (TDP-43) pathology, often caused by progranulin (\n                      <jats:italic toggle=\"yes\">GRN<\/jats:italic>\n                      ) or chromosome 9 open reading frame 72 (\n                      <jats:italic toggle=\"yes\">C9orf72<\/jats:italic>\n                      ) mutations. Post-mortem studies suggest prominent myelin loss in\n                      <jats:italic toggle=\"yes\">GRN<\/jats:italic>\n                      carriers compared to\n                      <jats:italic toggle=\"yes\">C9orf72<\/jats:italic>\n                      carriers or controls. The T1-weighted\/T2-weighted (T1w\/T2w) ratio is an MRI marker sensitive to WM properties, including myelin lipid content.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      This study used the T1w\/T2w ratio to investigate WM integrity in familial FTD. We hypothesized that (1)\n                      <jats:italic toggle=\"yes\">GRN<\/jats:italic>\n                      mutation carriers would show reduced T1w\/T2w ratios compared to non-carrier controls; (2)\n                      <jats:italic toggle=\"yes\">C9orf72<\/jats:italic>\n                      mutation carriers would not differ significantly from non-carriers; and (3) lower T1w\/T2w ratios would associate with cognitive deficits.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Eighty participants (\n                      <jats:italic toggle=\"yes\">GRN<\/jats:italic>\n                      \u2009=\u200912,\n                      <jats:italic toggle=\"yes\">C9orf72<\/jats:italic>\n                      \u2009=\u200928, non-carrier controls\u2009=\u200940) completed neuropsychological testing across multiple cognitive domains and structural MRI. After generating standardized T1w\/T2w ratio maps, mean values were extracted from JHU Atlas-based WM lobe regions. General linear models evaluated group differences and MRI-cognition associations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">GRN<\/jats:italic>\n                      carriers exhibited significantly lower T1w\/T2w ratios in frontal and parietal lobe WM compared to non-carriers. Conversely,\n                      <jats:italic toggle=\"yes\">C9orf72<\/jats:italic>\n                      carriers did not differ from non-carriers. Across all participants, lower frontal T1w\/T2w ratios were associated with poorer working memory, language, and visuospatial function. Lower parietal ratios were associated with poorer visuospatial function.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study provides evidence for a reduction in the T1w\/T2w ratio in\n                      <jats:italic toggle=\"yes\">GRN<\/jats:italic>\n                      mutation carriers. This reduction associates with key cognitive impairments, highlighting a vulnerability of WM microstructural integrity in\n                      <jats:italic toggle=\"yes\">GRN<\/jats:italic>\n                      -related FTD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261493102","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:45:42Z","timestamp":1790682342000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association between white matter T1w\/T2w ratio and cognitive function in frontotemporal dementia mutation carriers"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8598-9123","authenticated-orcid":false,"given":"Hyunwoo","family":"Lee","sequence":"first","affiliation":[{"name":"University of British Columbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian R.A.","family":"Mackenzie","sequence":"additional","affiliation":[{"name":"University of British Columbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirza Faisal","family":"Beg","sequence":"additional","affiliation":[{"name":"Simon Fraser University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1729-3255","authenticated-orcid":false,"given":"Karteek","family":"Popuri","sequence":"additional","affiliation":[{"name":"Memorial University of Newfoundland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Wittenberg","sequence":"additional","affiliation":[{"name":"University of British Columbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winston","family":"Huang","sequence":"additional","affiliation":[{"name":"University of British Columbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ging-Yuek Robin","family":"Hsiung","sequence":"additional","affiliation":[{"name":"University of British Columbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00461-4"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13588"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1017\/cjn.2022.69"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1716-8"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-019-09363-4"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-51140-1_13"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2021.11.015"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05016"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05017"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15255"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.09.011"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.30194"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2018.12.018"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2020-322987"},{"key":"e_1_3_3_16_2","first-page":"1378","article-title":"Neuropsychological profiles in genetic frontotemporal dementia: a meta-analysis and systematic review","volume":"16","author":"Poos JM","year":"2024","unstructured":"Poos JM, van den Berg E, de Boer L, et al. 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