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| 001 | 282289 | ||
| 005 | 20251114124626.0 | ||
| 024 | 7 | _ | |a 10.1038/s41380-025-03280-x |2 doi |
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| 037 | _ | _ | |a DZNE-2025-01260 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Rodriguez-Vieitez, Elena |0 0000-0002-6639-8141 |b 0 |
| 245 | _ | _ | |a Cortical microstructure is associated with disease severity and clinical progression in genetic frontotemporal dementia: a GENFI study. |
| 260 | _ | _ | |a [London] |c 2025 |b Springer Nature |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1763120644_8296 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
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| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a The study of genetic frontotemporal dementia (FTD) allows investigating its earliest presymptomatic stages. Using cross-sectional T1-weighted and diffusion-weighted MRI, we test the hypothesis that cortical microstructural alterations, quantified as cortical mean diffusivity (cMD), are detectable earlier and are more strongly associated with clinical progression than cortical thickness (CTh). The sample comprised n = 710 individuals (47.8 ± 13.5 years, 56.6% female, 14.1 ± 3.3 years of education), including 118 symptomatic carriers and 305 presymptomatic carriers with mutations in C9orf72, GRN or MAPT genes, and 287 non-carriers, collected from 24 GENFI sites. A subset of n = 453 individuals (289 carriers, 164 non-carriers) were investigated across Clinical Dementia Rating (CDR) = 0, 0.5 and ≥1 stages. Two subsets had longitudinal clinical outcome measures, including n = 403 individuals (239 carriers, 164 non-carriers) with Cambridge Behavioural Inventory-Revised scores during 2.8 ± 1.6 years, and n = 261 individuals (164 carriers, 97 non-carriers) with CDR Sum-of-Boxes scores during 2.0 ± 0.8 years. Regional cMD and CTh were entered into linear mixed-effects models incorporating age, sex and education as covariates; site, and individual nested within site were random intercepts. The results demonstrated that cMD is more sensitive than CTh to track early cortical injury, with elevated cMD first observed at CDR = 0 in C9orf72 carriers, followed by MAPT carriers (from CDR = 0.5 stage), and by GRN carriers (beginning at CDR ≥ 1). At all stages, cortical microstructural injury had stronger effect size and was more widespread than cortical thinning. In all mutation carrier types, cMD was more strongly associated than CTh with subsequent clinical progression. Cortical microstructure is a promising biomarker to identify at-risk individuals before atrophy and clinical progression, with utility in therapeutic trials. |
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| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de |
| 650 | _ | 7 | |a tau Proteins |2 NLM Chemicals |
| 650 | _ | 7 | |a C9orf72 Protein |2 NLM Chemicals |
| 650 | _ | 7 | |a Progranulins |2 NLM Chemicals |
| 650 | _ | 7 | |a MAPT protein, human |2 NLM Chemicals |
| 650 | _ | 7 | |a GRN protein, human |2 NLM Chemicals |
| 650 | _ | 7 | |a C9orf72 protein, human |2 NLM Chemicals |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a Female |2 MeSH |
| 650 | _ | 2 | |a Male |2 MeSH |
| 650 | _ | 2 | |a Frontotemporal Dementia: genetics |2 MeSH |
| 650 | _ | 2 | |a Frontotemporal Dementia: pathology |2 MeSH |
| 650 | _ | 2 | |a Frontotemporal Dementia: diagnostic imaging |2 MeSH |
| 650 | _ | 2 | |a Middle Aged |2 MeSH |
| 650 | _ | 2 | |a Disease Progression |2 MeSH |
| 650 | _ | 2 | |a tau Proteins: genetics |2 MeSH |
| 650 | _ | 2 | |a C9orf72 Protein: genetics |2 MeSH |
| 650 | _ | 2 | |a Progranulins: genetics |2 MeSH |
| 650 | _ | 2 | |a Adult |2 MeSH |
| 650 | _ | 2 | |a Cerebral Cortex: pathology |2 MeSH |
| 650 | _ | 2 | |a Cerebral Cortex: diagnostic imaging |2 MeSH |
| 650 | _ | 2 | |a Cross-Sectional Studies |2 MeSH |
| 650 | _ | 2 | |a Aged |2 MeSH |
| 650 | _ | 2 | |a Mutation: genetics |2 MeSH |
| 650 | _ | 2 | |a Magnetic Resonance Imaging: methods |2 MeSH |
| 650 | _ | 2 | |a Severity of Illness Index |2 MeSH |
| 650 | _ | 2 | |a Diffusion Magnetic Resonance Imaging: methods |2 MeSH |
| 700 | 1 | _ | |a Rydell, Melissa T |b 1 |
| 700 | 1 | _ | |a Ullgren, Abbe |b 2 |
| 700 | 1 | _ | |a Montal, Victor |b 3 |
| 700 | 1 | _ | |a Illán-Gala, Ignacio |b 4 |
| 700 | 1 | _ | |a Fortea, Juan |0 0000-0002-1340-638X |b 5 |
| 700 | 1 | _ | |a Jelic, Vesna |b 6 |
| 700 | 1 | _ | |a Bouzigues, Arabella |0 0000-0002-0267-8590 |b 7 |
| 700 | 1 | _ | |a Russell, Lucy L |b 8 |
| 700 | 1 | _ | |a Foster, Phoebe H |b 9 |
| 700 | 1 | _ | |a Ferry-Bolder, Eve |b 10 |
| 700 | 1 | _ | |a van Swieten, John C |b 11 |
| 700 | 1 | _ | |a Jiskoot, Lize C |b 12 |
| 700 | 1 | _ | |a Seelaar, Harro |0 0000-0003-1989-7527 |b 13 |
| 700 | 1 | _ | |a Sanchez-Valle, Raquel |b 14 |
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| 700 | 1 | _ | |a Vandenberghe, Rik |0 0000-0001-6237-2502 |b 17 |
| 700 | 1 | _ | |a de Mendonça, Alexandre |b 18 |
| 700 | 1 | _ | |a Tiraboschi, Pietro |b 19 |
| 700 | 1 | _ | |a Santana, Isabel |b 20 |
| 700 | 1 | _ | |a Gerhard, Alexander |b 21 |
| 700 | 1 | _ | |a Levin, Johannes |0 P:(DE-2719)2811659 |b 22 |u dzne |
| 700 | 1 | _ | |a Sorbi, Sandro |0 0000-0002-0380-6670 |b 23 |
| 700 | 1 | _ | |a Otto, Markus |0 0000-0003-4273-4267 |b 24 |
| 700 | 1 | _ | |a Pasquier, Florence |0 0000-0001-9880-9788 |b 25 |
| 700 | 1 | _ | |a Ducharme, Simon |0 0000-0002-7309-1113 |b 26 |
| 700 | 1 | _ | |a Butler, Chris R |0 0000-0002-7502-9284 |b 27 |
| 700 | 1 | _ | |a Le Ber, Isabelle |b 28 |
| 700 | 1 | _ | |a Finger, Elizabeth |b 29 |
| 700 | 1 | _ | |a Tartaglia, Maria Carmela |0 0000-0002-5944-8497 |b 30 |
| 700 | 1 | _ | |a Masellis, Mario |b 31 |
| 700 | 1 | _ | |a Rowe, James B |0 0000-0001-7216-8679 |b 32 |
| 700 | 1 | _ | |a Synofzik, Matthis |0 P:(DE-2719)2811275 |b 33 |
| 700 | 1 | _ | |a Moreno, Fermin |0 0000-0001-5200-3164 |b 34 |
| 700 | 1 | _ | |a Borroni, Barbara |b 35 |
| 700 | 1 | _ | |a Rohrer, Jonathan D |b 36 |
| 700 | 1 | _ | |a Westman, Eric |0 0000-0002-3115-2977 |b 37 |
| 700 | 1 | _ | |a Graff, Caroline |0 0000-0002-9949-2951 |b 38 |
| 700 | 1 | _ | |a Initiative, Genetic Frontotemporal Dementia |b 39 |e Collaboration Author |
| 700 | 1 | _ | |a van Swieten, John C |b 40 |e Contributor |
| 700 | 1 | _ | |a de Mendonça, Alexandre |b 41 |e Contributor |
| 700 | 1 | _ | |a Le Ber, Isabelle |b 42 |e Contributor |
| 773 | _ | _ | |a 10.1038/s41380-025-03280-x |g Vol. 30, no. 12, p. 5800 - 5812 |0 PERI:(DE-600)1502531-7 |n 12 |p 5800 - 5812 |t Molecular psychiatry |v 30 |y 2025 |x 1359-4184 |
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