Dataset Information

Positron emission tomography and magnetic resonance imaging methods and datasets within the Dominantly Inherited Alzheimer Network (DIAN).

ABSTRACT: The Dominantly Inherited Alzheimer Network (DIAN) is an international collaboration studying autosomal dominant Alzheimer disease (ADAD). ADAD arises from mutations occurring in three genes. Offspring from ADAD families have a 50% chance of inheriting their familial mutation, so non-carrier siblings can be recruited for comparisons in case-control studies. The age of onset in ADAD is highly predictable within families, allowing researchers to estimate an individual's point in the disease trajectory. These characteristics allow candidate AD biomarker measurements to be reliably mapped during the preclinical phase. Although ADAD represents a small proportion of AD cases, understanding neuroimaging-based changes that occur during the preclinical period may provide insight into early disease stages of 'sporadic' AD also. Additionally, this study provides rich data for research in healthy aging through inclusion of the non-carrier controls. Here we introduce the neuroimaging dataset collected and describe how this resource can be used by a range of researchers.

SUBMITTER: McKay NS

PROVIDER: S-EPMC10400428 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Positron emission tomography and magnetic resonance imaging methods and datasets within the Dominantly Inherited Alzheimer Network (DIAN).

McKay Nicole S NS Gordon Brian A BA Hornbeck Russ C RC Dincer Aylin A Flores Shaney S Keefe Sarah J SJ Joseph-Mathurin Nelly N Jack Clifford R CR Koeppe Robert R Millar Peter R PR Ances Beau M BM Chen Charles D CD Daniels Alisha A Hobbs Diana A DA Jackson Kelley K Koudelis Deborah D Massoumzadeh Parinaz P McCullough Austin A Nickels Michael L ML Rahmani Farzaneh F Swisher Laura L Wang Qing Q Allegri Ricardo F RF Berman Sarah B SB Brickman Adam M AM Brooks William S WS Cash David M DM Chhatwal Jasmeer P JP Day Gregory S GS Farlow Martin R MR la Fougère Christian C Fox Nick C NC Fulham Michael M Ghetti Bernardino B Graff-Radford Neill N Ikeuchi Takeshi T Klunk William W Lee Jae-Hong JH Levin Johannes J Martins Ralph R Masters Colin L CL McConathy Jonathan J Mori Hiroshi H Noble James M JM Reischl Gerald G Rowe Christopher C Salloway Stephen S Sanchez-Valle Raquel R Schofield Peter R PR Shimada Hiroyuki H Shoji Mikio M Su Yi Y Suzuki Kazushi K Vöglein Jonathan J Yakushev Igor I Cruchaga Carlos C Hassenstab Jason J Karch Celeste C McDade Eric E Perrin Richard J RJ Xiong Chengjie C Morris John C JC Bateman Randall J RJ Benzinger Tammie L S TLS

Nature neuroscience 20230710 8

The Dominantly Inherited Alzheimer Network (DIAN) is an international collaboration studying autosomal dominant Alzheimer disease (ADAD). ADAD arises from mutations occurring in three genes. Offspring from ADAD families have a 50% chance of inheriting their familial mutation, so non-carrier siblings can be recruited for comparisons in case-control studies. The age of onset in ADAD is highly predictable within families, allowing researchers to estimate an individual's point in the disease traject ...[more]

PMID: 37429916

Similar Datasets

Project description:BackgroundThe hybrid imaging positron emission tomography/magnetic resonance (PET/MR) is an important tool in the management of pediatric oncology patients, particularly in malignant musculoskeletal pathologies, because it combines the functional and metabolic information of tumor provided by PET with the high soft-tissue contrast and the functional information offered by magnetic resonance imaging (MRI).MethodsWe performed an observational retrospective study that included pediatric patients diagnosed with primary bone or soft-tissue sarcomas in the Pediatric Hematology and Oncology Unit at the HM Montepríncipe University Hospital, Boadilla del Monte, Madrid (Spain) who underwent whole-body 18F-fluorodeoxyglucose (18F-FDG) PET/MRI as a staging study and for follow-up evaluation for treatment response from September 2017 to January 2023. This study explores the protocols, the practical application of the PET/MRI technique and our clinical experience at our center in the diagnosis and follow-up of primary bone tumors and soft-tissue sarcomas in children.ResultsSeventy-one 18F-PET/MR studies were performed on 39 patients. Most of them (55%) were initial extension studies and (45%) were follow-up studies. Most of the patients studied were male (74.4%) with a median age of 15 years. Of the 39 cases, 51% were primary bone tumors while 18% were Langerhans cell histiocytosis and 21% soft tissue tumors. Of the 71 studies, five showed metastases at the initial diagnosis, three presented lymph node involvement, one with local infiltration, and one with pulmonary metastasis.ConclusionsPET/MR has represented a significant advancement in the evaluation of pediatric malignant neoplasms, with specific applications in musculoskeletal tumors showing clear benefits over PET/CT. The primary advantage is the reduction in ionizing radiation doses and the assessment of soft tissues, making it an excellent option for malignant musculoskeletal pathologies in pediatric patients who often require long-term follow-up. It is particularly useful for early tumor detection and functional therapy monitoring in oncology. The development of new protocols is making studies increasingly faster and better tolerated, even without the need for anesthesia. PET/MRI has shown to increase diagnostic accuracy in primary bone and soft tissue tumors, as it allows for the comprehensive evaluation of their morpho-metabolic characteristics, locoregional, and distant involvement in a single study. It is also useful in surgical planning and post-treatment follow-up.

Project description:ImportanceTau positron emission tomography (PET) tracers have proven useful for the differential diagnosis of dementia, but their utility for predicting cognitive change is unclear.ObjectiveTo examine the prognostic accuracy of baseline fluorine 18 (18F)-flortaucipir and [18F]RO948 (tau) PET in individuals across the Alzheimer disease (AD) clinical spectrum and to perform a head-to-head comparison against established magnetic resonance imaging (MRI) and amyloid PET markers.Design, setting, and participantsThis prognostic study collected data from 8 cohorts in South Korea, Sweden, and the US from June 1, 2014, to February 28, 2021, with a mean (SD) follow-up of 1.9 (0.8) years. A total of 1431 participants were recruited from memory clinics, clinical trials, or cohort studies; 673 were cognitively unimpaired (CU group; 253 [37.6%] positive for amyloid-β [Aβ]), 443 had mild cognitive impairment (MCI group; 271 [61.2%] positive for Aβ), and 315 had a clinical diagnosis of AD dementia (315 [100%] positive for Aβ).Exposures[18F]Flortaucipir PET in the discovery cohort (n = 1135) or [18F]RO948 PET in the replication cohort (n = 296), T1-weighted MRI (n = 1431), and amyloid PET (n = 1329) at baseline and repeated Mini-Mental State Examination (MMSE) evaluation.Main outcomes and measuresBaseline [18F]flortaucipir/[18F]RO948 PET retention within a temporal region of interest, MRI-based AD-signature cortical thickness, and amyloid PET Centiloids were used to predict changes in MMSE using linear mixed-effects models adjusted for age, sex, education, and cohort. Mediation/interaction analyses tested whether associations between baseline tau PET and cognitive change were mediated by baseline MRI measures and whether age, sex, and APOE genotype modified these associations.ResultsAmong 1431 participants, the mean (SD) age was 71.2 (8.8) years; 751 (52.5%) were male. Findings for [18F]flortaucipir PET predicted longitudinal changes in MMSE, and effect sizes were stronger than for AD-signature cortical thickness and amyloid PET across all participants (R2, 0.35 [tau PET] vs 0.24 [MRI] vs 0.17 [amyloid PET]; P < .001, bootstrapped for difference) in the Aβ-positive MCI group (R2, 0.25 [tau PET] vs 0.15 [MRI] vs 0.07 [amyloid PET]; P < .001, bootstrapped for difference) and in the Aβ-positive CU group (R2, 0.16 [tau PET] vs 0.08 [MRI] vs 0.08 [amyloid PET]; P < .001, bootstrapped for difference). These findings were replicated in the [18F]RO948 PET cohort. MRI mediated the association between [18F]flortaucipir PET and MMSE in the groups with AD dementia (33.4% [95% CI, 15.5%-60.0%] of the total effect) and Aβ-positive MCI (13.6% [95% CI, 0.0%-28.0%] of the total effect), but not the Aβ-positive CU group (3.7% [95% CI, -17.5% to 39.0%]; P = .71). Age (t = -2.28; P = .02), but not sex (t = 0.92; P = .36) or APOE genotype (t = 1.06; P = .29) modified the association between baseline [18F]flortaucipir PET and cognitive change, such that older individuals showed faster cognitive decline at similar tau PET levels.Conclusions and relevanceThe findings of this prognostic study suggest that tau PET is a promising tool for predicting cognitive change that is superior to amyloid PET and MRI and may support the prognostic process in preclinical and prodromal stages of AD.

Project description:ImportanceMyocardial replacement fibrosis has been reported to occur in one-third of patients with mitral valve prolapse (MVP) and significant mitral regurgitation (MR). However, it remains unknown whether there are detectable changes in myocardial metabolism suggestive of inflammation or ischemia that accompany the development of fibrosis.ObjectivesTo characterize the burden and distribution of fluorine 18-labeled (18F) fluorodeoxyglucose (FDG) uptake and late gadolinium enhancement (LGE) in patients with degenerative MVP and ventricular ectopy.Design, setting, and participantsProspective observational study of 20 patients with MVP and significant primary degenerative MR who were referred for mitral valve repair and underwent hybrid positron emission tomography/magnetic resonance imaging (PET/MRI). Ventricular arrhythmias were categorized as either complex (n = 12) or minor (n = 8). Coregistered hybrid 18F FDG-PET and MRI LGE images were assessed and categorized. Recruitment occurred in the new patient clinic of a mitral valve repair reference center. This study was conducted from January 11, 2018, to June 26, 2019.ExposuresSimultaneous cardiac 18F FDG-PET and MRI with LGE imaging on a hybrid PET/MRI system and ambulatory rhythm monitoring.Main outcomes and measuresPatients were categorized by the presence and pattern of FDG uptake and LGE, the severity of ventricular arrhythmias, and the indication for mitral valve surgery.ResultsIn the cohort of 20 patients, the median age was 59.5 years (interquartile range, 52.5-63.2 years). Focal, or focal-on-diffuse uptake, of 18F-FDG (PET positive) was detected in 17 of 20 patients (85%). The FDG uptake coexisted with areas of LGE (PET/MRI positive) in 14 patients (70%). Of the 5 asymptomatic patients with normal ventricular indices and absence of any surgical indications, all were PET/MRI positive.Conclusions and relevanceIn this pilot study, we demonstrate a novel association between degenerative MVP and FDG uptake, a surrogate for myocardial inflammation and/or ischemia. Such evidence of myocardial injury, even in asymptomatic patients, suggests an ongoing subclinical disease process. These findings warrant further investigation into whether imaging for myocardial inflammation, ischemia, and scar has a role in arrhythmic risk stratification and whether it provides incremental prognostic value in patients with chronic severe mitral regurgitation undergoing active surveillance.

Dataset Information

Positron emission tomography and magnetic resonance imaging methods and datasets within the Dominantly Inherited Alzheimer Network (DIAN).

Publications

Positron emission tomography and magnetic resonance imaging methods and datasets within the Dominantly Inherited Alzheimer Network (DIAN).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets