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Comparison of Group-Level and Individualized Brain Regions for Measuring Change in Longitudinal Tau Positron Emission Tomography in Alzheimer Disease
IMPORTANCE: Longitudinal tau positron emission tomography (PET) is a relevant outcome in clinical trials evaluating disease-modifying therapies in Alzheimer disease (AD). A key unanswered question is whether the use of participant-specific (individualized) regions of interest (ROIs) is superior to c...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Medical Association
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10167602/ https://www.ncbi.nlm.nih.gov/pubmed/37155176 http://dx.doi.org/10.1001/jamaneurol.2023.1067 |
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author | Leuzy, Antoine Binette, Alexa Pichet Vogel, Jacob W. Klein, Gregory Borroni, Edilio Tonietto, Matteo Strandberg, Olof Mattsson-Carlgren, Niklas Palmqvist, Sebastian Pontecorvo, Michael J. Iaccarino, Leonardo Stomrud, Erik Ossenkoppele, Rik Smith, Ruben Hansson, Oskar |
author_facet | Leuzy, Antoine Binette, Alexa Pichet Vogel, Jacob W. Klein, Gregory Borroni, Edilio Tonietto, Matteo Strandberg, Olof Mattsson-Carlgren, Niklas Palmqvist, Sebastian Pontecorvo, Michael J. Iaccarino, Leonardo Stomrud, Erik Ossenkoppele, Rik Smith, Ruben Hansson, Oskar |
author_sort | Leuzy, Antoine |
collection | PubMed |
description | IMPORTANCE: Longitudinal tau positron emission tomography (PET) is a relevant outcome in clinical trials evaluating disease-modifying therapies in Alzheimer disease (AD). A key unanswered question is whether the use of participant-specific (individualized) regions of interest (ROIs) is superior to conventional approaches where the same ROI (group-level) is used for each participant. OBJECTIVE: To compare group- and participant-level ROIs in participants at different stages of the AD clinical continuum in terms of annual percentage change in tau-PET standardized uptake value ratio (SUVR) and sample size requirements. DESIGN, SETTING, AND PARTICIPANTS: This was a longitudinal cohort study with consecutive participant enrollment between September 18, 2017, and November 15, 2021. Included in the analysis were participants with mild cognitive impairment and AD dementia from the prospective and longitudinal Swedish Biomarkers For Identifying Neurodegenerative Disorders Early and Reliably 2 (BioFINDER-2) study; in addition, a validation sample (the AVID 05e, Expedition-3, Alzheimer’s Disease Neuroimaging Initiative [ADNI], and BioFINDER-1 study cohorts) was also included. EXPOSURES: Tau PET (BioFINDER-2, [(18)F]RO948; validation sample, [(18)F]flortaucipir), 7 group-level (5 data-driven stages, meta-temporal, whole brain), and 5 individualized ROIs. MAIN OUTCOMES AND MEASURES: Annual percentage change in tau-PET SUVR across ROIs. Sample size requirements in simulated clinical trials using tau PET as an outcome were also calculated. RESULTS: A total of 215 participants (mean [SD] age, 71.4 (7.5) years; 111 male [51.6%]) from the BioFINDER-2 study were included in this analysis: 97 amyloid-β (Aβ)–positive cognitively unimpaired (CU) individuals, 77 with Aβ-positive mild cognitive impairment (MCI), and 41 with AD dementia. In the validation sample were 137 Aβ-positive CU participants, 144 with Aβ-positive MCI, and 125 with AD dementia. Mean (SD) follow-up time was 1.8 (0.3) years. Using group-level ROIs, the largest annual percentage increase in tau-PET SUVR in Aβ-positive CU individuals was seen in a composite ROI combining the entorhinal cortex, hippocampus, and amygdala (4.29%; 95% CI, 3.42%-5.16%). In individuals with Aβ-positive MCI, the greatest change was seen in the temporal cortical regions (5.82%; 95% CI, 4.67%-6.97%), whereas in those with AD dementia, the greatest change was seen in the parietal regions (5.22%; 95% CI, 3.95%-6.49%). Significantly higher estimates of annual percentage change were found using several of the participant-specific ROIs. Importantly, the simplest participant-specific approach, where change in tau PET was calculated in an ROI that best matched the participant’s data-driven disease stage, performed best in all 3 subgroups. For the power analysis, sample size reductions for the participant-specific ROIs ranged from 15.94% (95% CI, 8.14%-23.74%) to 72.10% (95% CI, 67.10%-77.20%) compared with the best-performing group-level ROIs. Findings were replicated using [(18)F]flortaucipir. CONCLUSIONS AND RELEVANCE: Finding suggest that certain individualized ROIs carry an advantage over group-level ROIs for assessing longitudinal tau changes and increase the power to detect treatment effects in AD clinical trials using longitudinal tau PET as an outcome. |
format | Online Article Text |
id | pubmed-10167602 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Medical Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-101676022023-05-10 Comparison of Group-Level and Individualized Brain Regions for Measuring Change in Longitudinal Tau Positron Emission Tomography in Alzheimer Disease Leuzy, Antoine Binette, Alexa Pichet Vogel, Jacob W. Klein, Gregory Borroni, Edilio Tonietto, Matteo Strandberg, Olof Mattsson-Carlgren, Niklas Palmqvist, Sebastian Pontecorvo, Michael J. Iaccarino, Leonardo Stomrud, Erik Ossenkoppele, Rik Smith, Ruben Hansson, Oskar JAMA Neurol Original Investigation IMPORTANCE: Longitudinal tau positron emission tomography (PET) is a relevant outcome in clinical trials evaluating disease-modifying therapies in Alzheimer disease (AD). A key unanswered question is whether the use of participant-specific (individualized) regions of interest (ROIs) is superior to conventional approaches where the same ROI (group-level) is used for each participant. OBJECTIVE: To compare group- and participant-level ROIs in participants at different stages of the AD clinical continuum in terms of annual percentage change in tau-PET standardized uptake value ratio (SUVR) and sample size requirements. DESIGN, SETTING, AND PARTICIPANTS: This was a longitudinal cohort study with consecutive participant enrollment between September 18, 2017, and November 15, 2021. Included in the analysis were participants with mild cognitive impairment and AD dementia from the prospective and longitudinal Swedish Biomarkers For Identifying Neurodegenerative Disorders Early and Reliably 2 (BioFINDER-2) study; in addition, a validation sample (the AVID 05e, Expedition-3, Alzheimer’s Disease Neuroimaging Initiative [ADNI], and BioFINDER-1 study cohorts) was also included. EXPOSURES: Tau PET (BioFINDER-2, [(18)F]RO948; validation sample, [(18)F]flortaucipir), 7 group-level (5 data-driven stages, meta-temporal, whole brain), and 5 individualized ROIs. MAIN OUTCOMES AND MEASURES: Annual percentage change in tau-PET SUVR across ROIs. Sample size requirements in simulated clinical trials using tau PET as an outcome were also calculated. RESULTS: A total of 215 participants (mean [SD] age, 71.4 (7.5) years; 111 male [51.6%]) from the BioFINDER-2 study were included in this analysis: 97 amyloid-β (Aβ)–positive cognitively unimpaired (CU) individuals, 77 with Aβ-positive mild cognitive impairment (MCI), and 41 with AD dementia. In the validation sample were 137 Aβ-positive CU participants, 144 with Aβ-positive MCI, and 125 with AD dementia. Mean (SD) follow-up time was 1.8 (0.3) years. Using group-level ROIs, the largest annual percentage increase in tau-PET SUVR in Aβ-positive CU individuals was seen in a composite ROI combining the entorhinal cortex, hippocampus, and amygdala (4.29%; 95% CI, 3.42%-5.16%). In individuals with Aβ-positive MCI, the greatest change was seen in the temporal cortical regions (5.82%; 95% CI, 4.67%-6.97%), whereas in those with AD dementia, the greatest change was seen in the parietal regions (5.22%; 95% CI, 3.95%-6.49%). Significantly higher estimates of annual percentage change were found using several of the participant-specific ROIs. Importantly, the simplest participant-specific approach, where change in tau PET was calculated in an ROI that best matched the participant’s data-driven disease stage, performed best in all 3 subgroups. For the power analysis, sample size reductions for the participant-specific ROIs ranged from 15.94% (95% CI, 8.14%-23.74%) to 72.10% (95% CI, 67.10%-77.20%) compared with the best-performing group-level ROIs. Findings were replicated using [(18)F]flortaucipir. CONCLUSIONS AND RELEVANCE: Finding suggest that certain individualized ROIs carry an advantage over group-level ROIs for assessing longitudinal tau changes and increase the power to detect treatment effects in AD clinical trials using longitudinal tau PET as an outcome. American Medical Association 2023-05-08 2023-06 /pmc/articles/PMC10167602/ /pubmed/37155176 http://dx.doi.org/10.1001/jamaneurol.2023.1067 Text en Copyright 2023 Leuzy A et al. JAMA Neurology. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the CC-BY License. |
spellingShingle | Original Investigation Leuzy, Antoine Binette, Alexa Pichet Vogel, Jacob W. Klein, Gregory Borroni, Edilio Tonietto, Matteo Strandberg, Olof Mattsson-Carlgren, Niklas Palmqvist, Sebastian Pontecorvo, Michael J. Iaccarino, Leonardo Stomrud, Erik Ossenkoppele, Rik Smith, Ruben Hansson, Oskar Comparison of Group-Level and Individualized Brain Regions for Measuring Change in Longitudinal Tau Positron Emission Tomography in Alzheimer Disease |
title | Comparison of Group-Level and Individualized Brain Regions for Measuring Change in Longitudinal Tau Positron Emission Tomography in Alzheimer Disease |
title_full | Comparison of Group-Level and Individualized Brain Regions for Measuring Change in Longitudinal Tau Positron Emission Tomography in Alzheimer Disease |
title_fullStr | Comparison of Group-Level and Individualized Brain Regions for Measuring Change in Longitudinal Tau Positron Emission Tomography in Alzheimer Disease |
title_full_unstemmed | Comparison of Group-Level and Individualized Brain Regions for Measuring Change in Longitudinal Tau Positron Emission Tomography in Alzheimer Disease |
title_short | Comparison of Group-Level and Individualized Brain Regions for Measuring Change in Longitudinal Tau Positron Emission Tomography in Alzheimer Disease |
title_sort | comparison of group-level and individualized brain regions for measuring change in longitudinal tau positron emission tomography in alzheimer disease |
topic | Original Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10167602/ https://www.ncbi.nlm.nih.gov/pubmed/37155176 http://dx.doi.org/10.1001/jamaneurol.2023.1067 |
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