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Search: WFRF:(Mattsson Tomas) > (2020-2024) > Biomarker-Based Pre...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00008895naa a2200481 4500
001oai:lup.lub.lu.se:349bc393-4748-41b4-b899-24312eb4b4f6
003SwePub
008220323s2022 | |||||||||||000 ||eng|
0247 a https://lup.lub.lu.se/record/349bc393-4748-41b4-b899-24312eb4b4f62 URI
0247 a https://doi.org/10.1001/jamaneurol.2021.46542 DOI
040 a (SwePub)lu
041 a engb eng
042 9 SwePub
072 7a art2 swepub-publicationtype
072 7a ref2 swepub-contenttype
1001 a Leuzy, Antoineu Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups4 aut0 (Swepub:lu)an3415le
2451 0a Biomarker-Based Prediction of Longitudinal Tau Positron Emission Tomography in Alzheimer Disease
264 1b American Medical Association (AMA),c 2022
300 a 10 s.
520 a Importance: There is currently no consensus as to which biomarkers best predict longitudinal tau accumulation at different clinical stages of Alzheimer disease (AD). Objective: To describe longitudinal [18F]RO948 tau positron emission tomography (PET) findings across the clinical continuum of AD and determine which biomarker combinations showed the strongest associations with longitudinal tau PET and best optimized clinical trial enrichment. Design, Setting, and Participants: This longitudinal cohort study consecutively enrolled amyloid-β (Aβ)-negative cognitively unimpaired (CU) participants, Aβ-positive CU individuals, Aβ-positive individuals with mild cognitive impairment (MCI), and individuals with AD dementia between September 2017 and November 2020 from the Swedish BioFINDER-2 (discovery cohort) and BioFINDER-1 (validation cohort) studies. Exposures: Baseline plasma and cerebrospinal fluid Aβ42/Aβ40, tau phosphorylated at threonine-217 (p-tau217), p-tau181 and neurofilament light, magnetic resonance imaging, amyloid PET ([18F]flutemetamol), and tau PET ([18F]RO948 in the BioFINDER-2 study; [18F]flortaucipir in the BioFINDER-1 study). Main Outcomes and Measures: Baseline tau PET standardized uptake value ratio (SUVR) and annual percent change in tau PET SUVR across regions of interest derived using a data-driven approach combining clustering and event-based modeling. Regression models were used to examine associations between individual biomarkers and longitudinal tau PET and to identify which combinations best predicted longitudinal tau PET. These combinations were then entered in a power analysis to examine how their use as an enrichment strategy would affect sample size in a simulated clinical trial. Results: Of 343 participants, the mean (SD) age was 72.56 (7.24) years, and 157 (51.1%) were female. The clustering/event-based modeling-based approach identified 5 regions of interest (stages). In Aβ-positive CU individuals, the largest annual increase in tau PET SUVR was seen in stage I (entorhinal cortex, hippocampus, and amygdala; 4.04% [95% CI, 2.67%-5.32%]). In Aβ-positive individuals with MCI and with AD dementia, the greatest increases were seen in stages II (temporal cortical regions; 4.45% [95% CI, 3.41%-5.49%]) and IV (certain frontal regions; 5.22% [95% CI, 3.95%-6.49%]), respectively. In Aβ-negative CU individuals and those with MCI, modest change was seen in stage I (1.38% [95% CI, 0.78%-1.99%] and 1.80% [95% CI, 0.76%-2.84%], respectively). When looking at individual predictors and longitudinal tau PET in the stages that showed most change, plasma p-tau217 (R2= 0.27, P <.005), tau PET (stage I baseline SUVR; R2= 0.13, P <.05) and amyloid PET (R2= 0.10, P <.05) were significantly associated with longitudinal tau PET in stage I in Aβ-positive CU individuals. In Aβ-positive individuals with MCI, plasma p-tau217 (R2= 0.24, P <.005) and tau PET (stage II baseline SUVR; R2= 0.44, P <.001) were significantly associated with longitudinal tau PET in stage II. Findings were replicated in BioFINDER-1 using longitudinal [18F]flortaucipir. For the power analysis component, plasma p-tau217 with tau PET resulted in sample size reductions of 43% (95% CI, 34%-46%; P <.005) in Aβ-positive CU individuals and of 68% (95% CI, 61%-73%; P <.001) in Aβ-positive individuals with MCI. Conclusions and Relevance: In trials using tau PET as the outcome, plasma p-tau217 with tau PET may prove optimal for enrichment in preclinical and prodromal AD. However, plasma p-tau217 was most important in preclinical AD, while tau PET was more important in prodromal AD..
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Neurologi0 (SwePub)302072 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Neurology0 (SwePub)302072 hsv//eng
7001 a Smith, Rubenu Lund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Regeneration in Movement Disorders,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital4 aut0 (Swepub:lu)mphy-rsm
7001 a Cullen, Nicholas C.u Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups4 aut0 (Swepub:lu)ni5875cu
7001 a Strandberg, Olofu Lund University,Lunds universitet,Medicinsk strålningsfysik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,MR Physics,Medical Radiation Physics, Lund,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Clinical Memory Research,Lund University Research Groups4 aut0 (Swepub:lu)teor-osn
7001 a Vogel, Jacob W.u University of Pennsylvania4 aut0 (Swepub:lu)ja8870vo
7001 a Binette, Alexa Pichetu Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups4 aut0 (Swepub:lu)al1314pi
7001 a Borroni, Ediliou F. Hoffmann-La Roche AG4 aut
7001 a Janelidze, Shorenau Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups4 aut0 (Swepub:lu)nkir-sje
7001 a Ohlsson, Tomasu Skåne University Hospital4 aut
7001 a Jögi, Jonasu Lund University,Lunds universitet,Klinisk fysiologi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Nuklearmedicin, Malmö,Forskargrupper vid Lunds universitet,Clinical Physiology (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Nuclear medicine, Malmö,Lund University Research Groups,Skåne University Hospital4 aut0 (Swepub:lu)klin-jjo
7001 a Ossenkoppele, Riku Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Amsterdam UMC - Vrije Universiteit Amsterdam4 aut0 (Swepub:lu)ri1513os
7001 a Palmqvist, Sebastianu Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital4 aut0 (Swepub:lu)med-spa
7001 a Mattsson-Carlgren, Niklasu Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,WCMM- Wallenberg center för molekylär medicinsk forskning,Medicinska fakulteten,Clinical Memory Research,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Faculty of Medicine,Skåne University Hospital4 aut0 (Swepub:lu)med-nmn
7001 a Klein, Gregoryu F. Hoffmann-La Roche AG4 aut
7001 a Stomrud, Eriku Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Amsterdam UMC - Vrije Universiteit Amsterdam4 aut0 (Swepub:lu)med-esr
7001 a Hansson, Oskaru Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital4 aut0 (Swepub:lu)mphy-ohn
7102 a Klinisk minnesforskningb Forskargrupper vid Lunds universitet4 org
7730 t JAMA Neurologyd : American Medical Association (AMA)g 79:2, s. 149-158q 79:2<149-158x 2168-6149
8564 u http://dx.doi.org/10.1001/jamaneurol.2021.4654x freey FULLTEXT
8564 u https://jamanetwork.com/journals/jamaneurology/articlepdf/2787209/jamaneurology_leuzy_2021_oi_210080_1639581502.57251.pdf
8564 8u https://lup.lub.lu.se/record/349bc393-4748-41b4-b899-24312eb4b4f6
8564 8u https://doi.org/10.1001/jamaneurol.2021.4654

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