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Predicting Alzheimer disease with β‐amyloid imaging: Results from the Australian imaging, biomarkers, and lifestyle study of ageing
Open accessAbstract
Objective: Biomarkers for Alzheimer disease (AD) can detect the disease pathology in asymptomatic subjects and individuals with mild cognitive impairment (MCI), but their cognitive prognosis remains uncertain. We aimed to determine the prognostic value of β‐amyloid imaging, alone and in combination with memory performance, hippocampal atrophy, and apolipoprotein E ε4 status in nondemented, older individuals. Methods: A total of 183 healthy individuals (age = 72.0 ± 7.26 years) and 87 participants with MCI (age = 73.7 ± 8.27) in the Australian Imaging, Biomarkers, and Lifestyle study of ageing were studied. Clinical reclassification was performed after 3 years, blind to biomarker findings. β‐Amyloid imaging was considered positive if the 11 C‐Pittsburgh compound B cortical to reference ratio was ≥1.5. Results: Thirteen percent of healthy persons progressed (15 to MCI, 8 to dementia), and 59% of the MCI cohort progressed to probable AD. Multivariate analysis showed β‐amyloid imaging as the single variable most strongly associated with progression. Of combinations, subtle memory impairment ( Z score = −0.5 to −1.5) with a positive amyloid scan was most strongly associated with progression in healthy individuals (odds ratio [OR] = 16, 95% confidence interval [CI] = 3.7–68; positive predictive value [PPV] = 50%, 95% CI = 19–81; negative predictive value [NPV] = 94%, 95% CI = 88–98). Almost all amnestic MCI subjects ( Z score ≤ −1.5) with a positive amyloid scan developed AD (OR = ∞; PPV = 86%, 95% CI = 72–95; NPV = 100%, 95% CI = 80–100). Hippocampal atrophy and ε4 status did not add further predictive value. Interpretation: Subtle memory impairment with a positive β‐amyloid scan identifies healthy individuals at high risk for MCI or AD. Clearly amnestic patients with a positive amyloid scan have prodromal AD and a poor prognosis for dementia within 3 years. Ann Neurol 2013;74:905–913
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“Numerous studies have shown that CU individuals with abnormal amyloid biomarkers have more rapid progression of atrophy, hypometabolism, and clinical/cognitive decline than individuals without biomarker evidence of Aβ deposition [13,33,80,93–99]”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [93]
In the citing paper
“Older studies of 11C-Pittsburgh compound B imaging suggested that only 13% of cognitively normal individuals that are positive for Aβ will transition to mild cognitive impairment (MCI) or AD (Rowe et al., 2013), whereas recent positron emission tomography (PET) imaging of tau indicates a stronger correlation of tau changes with cognitive impairment and transition to MCI (Hanseeuw et al., 2019).”
From Dendritic Spine Remodeling and Synaptic Tau Levels in PS19 Tauopathy Mice (2021) · cites this paper as Rowe et al., 2013
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Metadata
- Authors
- Rowe, C. C., Bourgeat, P., Ellis, K. A., Brown, B., Lim, Y. Y., Mulligan, R., Jones, G., Maruff, P., Woodward, M., Price, R., Robins, P., Tochon‐Danguy, H., O'Keefe, G., Pike, K. E., Yates, P., Szoeke, C., Salvado, O., Macaulay, S. L., O'Meara, T., Head, R., Cobiac, L., Savage, G., Martins, R., Masters, C. L., Ames, D., & Villemagne, V. L.
- Affiliations
- Austin Health (AU)
- Australian e-Health Research Centre (AU)
- The University of Melbourne (AU)
- Edith Cowan University (AU)
- Sir Charles Gairdner Hospital (AU)
- La Trobe University (AU)
- National Ageing Research Institute (AU)
- Commonwealth Scientific and Industrial Research Organisation (AU)
- Australian Research Council (AU)
- Corresponding author
- Rowe, Christopher C.
- ORCID
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2013-12
- Volume
- 74
- Issue
- 6
- Pages
- 905-913
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2003569140
- Cited by
- 222
- References
- 39
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 9 · 2023: 15 · 2022: 19 · 2021: 22 · 2020: 18 · 2019: 24 · 2018: 34 · 2017: 13 · 2016: 19 · 2015: 19 · 2014: 17 · 2013: 1
- FWCI
- 13.27
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Annals of Neurology (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Research Bank (Australian Catholic University) (submittedVersion)
- Murdoch University Research Portal (submittedVersion)
- Australasian Journal of Paramedicine (submittedVersion, cc-by-nc)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion, other-oa)
- Griffith Research Online (submittedVersion, cc-by-nc)
- Funders
- Commonwealth Scientific Industrial Research Organization (CSIRO)
- Science Industry Endowment Fund
- National Health and Medical Research Council of Australia (1011689)
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Oncology › Cancer-related cognitive impairment studies
- Keywords
- Alzheimer's disease, amyloid-beta imaging, Pittsburgh compound B, mild cognitive impairment, amnestic MCI, dementia progression, prodromal Alzheimer's disease, memory impairment, hippocampal atrophy, APOE ε4, predictive value, non-demented elderly
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Apolipoproteins E, Atrophy, Australia, Female, Hippocampus, Humans, Life Style, Male, Memory Disorders, Middle Aged, Predictive Value of Tests, Biomarkers, Single-Blind Method, Amyloid beta-Peptides, Cognitive Dysfunction
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