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Biomarker-Based Pre...
Biomarker-Based Prediction of Longitudinal Tau Positron Emission Tomography in Alzheimer Disease
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- Leuzy, Antoine (författare)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups
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- Smith, Ruben (författare)
- 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 Hospital
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- Cullen, Nicholas C. (författare)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups
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- Strandberg, Olof (författare)
- 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 Groups
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- Vogel, Jacob W. (författare)
- University of Pennsylvania
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- Binette, Alexa Pichet (författare)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups
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- Borroni, Edilio (författare)
- F. Hoffmann-La Roche AG
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- Janelidze, Shorena (författare)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups
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- Ohlsson, Tomas (författare)
- Skåne University Hospital
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- Jögi, Jonas (författare)
- 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 Hospital
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- Ossenkoppele, Rik (författare)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Amsterdam UMC - Vrije Universiteit Amsterdam
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- Palmqvist, Sebastian (författare)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital
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- Mattsson-Carlgren, Niklas (författare)
- 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 Hospital
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- Klein, Gregory (författare)
- F. Hoffmann-La Roche AG
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- Stomrud, Erik (författare)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Amsterdam UMC - Vrije Universiteit Amsterdam
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- Hansson, Oskar (författare)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital
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(creator_code:org_t)
- American Medical Association (AMA), 2022
- 2022
- Engelska 10 s.
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149. ; 79:2, s. 149-158
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http://dx.doi.org/10... (free)
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https://jamanetwork....
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- 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..
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
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Leuzy, Antoine
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Smith, Ruben
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Cullen, Nicholas ...
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Strandberg, Olof
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Vogel, Jacob W.
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Binette, Alexa P ...
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visa fler...
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Borroni, Edilio
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Janelidze, Shore ...
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Ohlsson, Tomas
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Jögi, Jonas
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Ossenkoppele, Ri ...
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Palmqvist, Sebas ...
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Mattsson-Carlgre ...
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Klein, Gregory
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Stomrud, Erik
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Hansson, Oskar
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