TY - JOUR
T1 - Predicting Alzheimer disease with β-amyloid imaging
T2 - Results from the Australian imaging, biomarkers, and lifestyle study of ageing
AU - Rowe, Christopher C.
AU - Bourgeat, Pierrick
AU - Ellis, Kathryn A.
AU - Brown, Belinda
AU - Lim, Yen Ying
AU - Mulligan, Rachel
AU - Jones, Gareth
AU - Maruff, Paul
AU - Woodward, Michael
AU - Price, Roger
AU - Robins, Peter
AU - Tochon-Danguy, Henri
AU - O'Keefe, Graeme
AU - Pike, Kerryn E.
AU - Yates, Paul
AU - Szoeke, Cassandra
AU - Salvado, Olivier
AU - Macaulay, S. Lance
AU - O'Meara, Timothy
AU - Head, Richard
AU - Cobiac, Lynne
AU - Savage, Greg
AU - Martins, Ralph
AU - Masters, Colin L.
AU - Ames, David
AU - Villemagne, Victor L.
PY - 2013/12
Y1 - 2013/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84892913370&partnerID=8YFLogxK
U2 - 10.1002/ana.24040
DO - 10.1002/ana.24040
M3 - Article
C2 - 24448836
AN - SCOPUS:84892913370
SN - 0364-5134
VL - 74
SP - 905
EP - 913
JO - Annals of Neurology
JF - Annals of Neurology
IS - 6
ER -