مورد إلكتروني
Spatial patterns of neuroimaging biomarker change in individuals from families with autosomal dominant Alzheimer's disease: a longitudinal study
| العنوان: | Spatial patterns of neuroimaging biomarker change in individuals from families with autosomal dominant Alzheimer's disease: a longitudinal study |
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| المؤلفون: | Gordon, BA, Blazey, TM, Su, Y, Hari-Raj, A, Dincer, A, Flores, S, Christensen, J, McDade, E, Wang, G, Xiong, C, Cairns, NJ, Hassenstab, J, Marcus, DS, Fagan, AM, Jack, CR, Hornbeck, RC, Paumier, KL, Ances, BM, Berman, SB, Brickman, AM, Cash, DM, Chhatwal, JP, Correia, S, Förster, S, Fox, NC, Graff-Radford, NR, la Fougère, C, Levin, J, Masters, CL, Rossor, MN, Salloway, S, Saykin, AJ, Schofield, PR, Thompson, PM, Weiner, MM, Holtzman, DM, Raichle, ME, Morris, JC, Bateman, RJ, Benzinger, TLS |
| بيانات النشر: | 2018-03-01 |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Background: Models of Alzheimer's disease propose a sequence of amyloid β (Aβ) accumulation, hypometabolism, and structural decline that precedes the onset of clinical dementia. These pathological features evolve both temporally and spatially in the brain. In this study, we aimed to characterise where in the brain and when in the course of the disease neuroimaging biomarkers become abnormal. Methods: Between Jan 1, 2009, and Dec 31, 2015, we analysed data from mutation non-carriers, asymptomatic carriers, and symptomatic carriers from families carrying gene mutations in presenilin 1 (PSEN1), presenilin 2 (PSEN2), or amyloid precursor protein (APP) enrolled in the Dominantly Inherited Alzheimer's Network. We analysed 11C-Pittsburgh Compound B (11C-PiB) PET, 18F-Fluorodeoxyglucose (18F-FDG) PET, and structural MRI data using regions of interest to assess change throughout the brain. We estimated rates of biomarker change as a function of estimated years to symptom onset at baseline using linear mixed-effects models and determined the earliest point at which biomarker trajectories differed between mutation carriers and non-carriers. This study is registered at ClinicalTrials.gov (number NCT00869817) Findings: 11C-PiB PET was available for 346 individuals (162 with longitudinal imaging), 18F-FDG PET was available for 352 individuals (175 with longitudinal imaging), and MRI data were available for 377 individuals (201 with longitudinal imaging). We found a sequence to pathological changes, with rates of Aβ deposition in mutation carriers being significantly different from those in non-carriers first (across regions that showed a significant difference, at a mean of 18·9 years [SD 3·3] before expected onset), followed by hypometabolism (14·1 years [5·1] before expected onset), and lastly structural decline (4·7 years [4·2] before expected onset). This biomarker ordering was preserved in most, but not all, regions. The temporal emergence within a biomarker varied across th |
| مصطلحات الفهرس: | 1103 Clinical Sciences, 1109 Neurosciences, text, Journal Article |
| URL: | The Lancet Neurology, 17, 3, 241-250 |
| الإتاحة: | Open access content. Open access content https://creativecommons.org/licenses/by-nc-nd/4.0 free_to_read |
| أرقام أخرى: | LJ1 oai:unsworks.library.unsw.edu.au:1959.4/unsworks_56872 10.1016/S1474-4422(18)30028-0 urn:issn:1474-4422 urn:issn:1474-4465 1096324729 |
| المصدر المساهم: | UNIV OF NEW S WALES From OAIster®, provided by the OCLC Cooperative. |
| رقم الأكسشن: | edsoai.on1096324729 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |