Predicting Alzheimer disease with β-amyloid imaging

Results from the Australian imaging, biomarkers, and lifestyle study of ageing

Christopher C. Rowe*, Pierrick Bourgeat, Kathryn A. Ellis, Belinda Brown, Yen Ying Lim, Rachel Mulligan, Gareth Jones, Paul Maruff, Michael Woodward, Roger Price, Peter Robins, Henri Tochon-Danguy, Graeme O'Keefe, Kerryn E. Pike, Paul Yates, Cassandra Szoeke, Olivier Salvado, S. Lance Macaulay, Timothy O'Meara, Richard Head & 6 others Lynne Cobiac, Greg Savage, Ralph Martins, Colin L. Masters, David Ames, Victor L. Villemagne

*Corresponding author for this work

Research output: Contribution to journalArticle

129 Citations (Scopus)

Abstract

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 11C-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.

Original languageEnglish
Pages (from-to)905-913
Number of pages9
JournalAnnals of Neurology
Volume74
Issue number6
DOIs
Publication statusPublished - Dec 2013

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    Rowe, C. C., Bourgeat, P., Ellis, K. A., Brown, B., Lim, Y. Y., Mulligan, R., ... Villemagne, V. L. (2013). Predicting Alzheimer disease with β-amyloid imaging: Results from the Australian imaging, biomarkers, and lifestyle study of ageing. Annals of Neurology, 74(6), 905-913. https://doi.org/10.1002/ana.24040