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Atrophy Rates in Asymptomatic Amyloidosis: Implications for Alzheimer Prevention Trials
There is considerable interest in designing therapeutic studies of individuals at risk of Alzheimer disease (AD) to prevent the onset of symptoms. Cortical β-amyloid plaques, the first stage of AD pathology, can be detected in vivo using positron emission tomography (PET), and several studies have s...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3599038/ https://www.ncbi.nlm.nih.gov/pubmed/23554933 http://dx.doi.org/10.1371/journal.pone.0058816 |
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author | Andrews, K. Abigail Modat, Marc Macdonald, Kate E. Yeatman, Tom Cardoso, M. Jorge Leung, Kelvin K. Barnes, Josephine Villemagne, Victor L. Rowe, Christopher C. Fox, Nick C. Ourselin, Sebastien Schott, Jonathan M. |
author_facet | Andrews, K. Abigail Modat, Marc Macdonald, Kate E. Yeatman, Tom Cardoso, M. Jorge Leung, Kelvin K. Barnes, Josephine Villemagne, Victor L. Rowe, Christopher C. Fox, Nick C. Ourselin, Sebastien Schott, Jonathan M. |
author_sort | Andrews, K. Abigail |
collection | PubMed |
description | There is considerable interest in designing therapeutic studies of individuals at risk of Alzheimer disease (AD) to prevent the onset of symptoms. Cortical β-amyloid plaques, the first stage of AD pathology, can be detected in vivo using positron emission tomography (PET), and several studies have shown that ∼1/3 of healthy elderly have significant β-amyloid deposition. Here we assessed whether asymptomatic amyloid-PET-positive controls have increased rates of brain atrophy, which could be harnessed as an outcome measure for AD prevention trials. We assessed 66 control subjects (age = 73.5±7.3 yrs; MMSE = 29±1.3) from the Australian Imaging Biomarkers & Lifestyle study who had a baseline Pittsburgh Compound B (PiB) PET scan and two 3T MRI scans ∼18-months apart. We calculated PET standard uptake value ratios (SUVR), and classified individuals as amyloid-positive/negative. Baseline and 18-month MRI scans were registered, and brain, hippocampal, and ventricular volumes and annualized volume changes calculated. Increasing baseline PiB-PET measures of β-amyloid load correlated with hippocampal atrophy rate independent of age (p = 0.014). Twenty-two (1/3) were PiB-positive (SUVR>1.40), the remaining 44 PiB-negative (SUVR≤1.31). Compared to PiB-negatives, PiB-positive individuals were older (76.8±7.5 vs. 71.7±7.5, p<0.05) and more were APOE4 positive (63.6% vs. 19.2%, p<0.01) but there were no differences in baseline brain, ventricle or hippocampal volumes, either with or without correction for total intracranial volume, once age and gender were accounted for. The PiB-positive group had greater total hippocampal loss (0.06±0.08 vs. 0.02±0.05 ml/yr, p = 0.02), independent of age and gender, with non-significantly higher rates of whole brain (7.1±9.4 vs. 4.7±5.5 ml/yr) and ventricular (2.0±3.0 vs. 1.1±1.0 ml/yr) change. Based on the observed effect size, recruiting 384 (95%CI 195–1080) amyloid-positive subjects/arm will provide 80% power to detect 25% absolute slowing of hippocampal atrophy rate in an 18-month treatment trial. We conclude that hippocampal atrophy may be a feasible outcome measure for secondary prevention studies in asymptomatic amyloidosis. |
format | Online Article Text |
id | pubmed-3599038 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35990382013-04-02 Atrophy Rates in Asymptomatic Amyloidosis: Implications for Alzheimer Prevention Trials Andrews, K. Abigail Modat, Marc Macdonald, Kate E. Yeatman, Tom Cardoso, M. Jorge Leung, Kelvin K. Barnes, Josephine Villemagne, Victor L. Rowe, Christopher C. Fox, Nick C. Ourselin, Sebastien Schott, Jonathan M. PLoS One Research Article There is considerable interest in designing therapeutic studies of individuals at risk of Alzheimer disease (AD) to prevent the onset of symptoms. Cortical β-amyloid plaques, the first stage of AD pathology, can be detected in vivo using positron emission tomography (PET), and several studies have shown that ∼1/3 of healthy elderly have significant β-amyloid deposition. Here we assessed whether asymptomatic amyloid-PET-positive controls have increased rates of brain atrophy, which could be harnessed as an outcome measure for AD prevention trials. We assessed 66 control subjects (age = 73.5±7.3 yrs; MMSE = 29±1.3) from the Australian Imaging Biomarkers & Lifestyle study who had a baseline Pittsburgh Compound B (PiB) PET scan and two 3T MRI scans ∼18-months apart. We calculated PET standard uptake value ratios (SUVR), and classified individuals as amyloid-positive/negative. Baseline and 18-month MRI scans were registered, and brain, hippocampal, and ventricular volumes and annualized volume changes calculated. Increasing baseline PiB-PET measures of β-amyloid load correlated with hippocampal atrophy rate independent of age (p = 0.014). Twenty-two (1/3) were PiB-positive (SUVR>1.40), the remaining 44 PiB-negative (SUVR≤1.31). Compared to PiB-negatives, PiB-positive individuals were older (76.8±7.5 vs. 71.7±7.5, p<0.05) and more were APOE4 positive (63.6% vs. 19.2%, p<0.01) but there were no differences in baseline brain, ventricle or hippocampal volumes, either with or without correction for total intracranial volume, once age and gender were accounted for. The PiB-positive group had greater total hippocampal loss (0.06±0.08 vs. 0.02±0.05 ml/yr, p = 0.02), independent of age and gender, with non-significantly higher rates of whole brain (7.1±9.4 vs. 4.7±5.5 ml/yr) and ventricular (2.0±3.0 vs. 1.1±1.0 ml/yr) change. Based on the observed effect size, recruiting 384 (95%CI 195–1080) amyloid-positive subjects/arm will provide 80% power to detect 25% absolute slowing of hippocampal atrophy rate in an 18-month treatment trial. We conclude that hippocampal atrophy may be a feasible outcome measure for secondary prevention studies in asymptomatic amyloidosis. Public Library of Science 2013-03-15 /pmc/articles/PMC3599038/ /pubmed/23554933 http://dx.doi.org/10.1371/journal.pone.0058816 Text en © 2013 Andrews et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Andrews, K. Abigail Modat, Marc Macdonald, Kate E. Yeatman, Tom Cardoso, M. Jorge Leung, Kelvin K. Barnes, Josephine Villemagne, Victor L. Rowe, Christopher C. Fox, Nick C. Ourselin, Sebastien Schott, Jonathan M. Atrophy Rates in Asymptomatic Amyloidosis: Implications for Alzheimer Prevention Trials |
title | Atrophy Rates in Asymptomatic Amyloidosis: Implications for Alzheimer Prevention Trials |
title_full | Atrophy Rates in Asymptomatic Amyloidosis: Implications for Alzheimer Prevention Trials |
title_fullStr | Atrophy Rates in Asymptomatic Amyloidosis: Implications for Alzheimer Prevention Trials |
title_full_unstemmed | Atrophy Rates in Asymptomatic Amyloidosis: Implications for Alzheimer Prevention Trials |
title_short | Atrophy Rates in Asymptomatic Amyloidosis: Implications for Alzheimer Prevention Trials |
title_sort | atrophy rates in asymptomatic amyloidosis: implications for alzheimer prevention trials |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3599038/ https://www.ncbi.nlm.nih.gov/pubmed/23554933 http://dx.doi.org/10.1371/journal.pone.0058816 |
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