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.
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 amnesticpatients with a positive amyloid scan have prodromal AD and a poor prognosis for dementia within 3 years.
Authors: Patricia A Boyle; Jingyun Yang; Lei Yu; Sue E Leurgans; Ana W Capuano; Julie A Schneider; Robert S Wilson; David A Bennett Journal: Brain Date: 2017-03-01 Impact factor: 13.501
Authors: David S Knopman; Samantha Budd Haeberlein; Maria C Carrillo; James A Hendrix; Geoff Kerchner; Richard Margolin; Paul Maruff; David S Miller; Gary Tong; Maria B Tome; Melissa E Murray; Peter T Nelson; Mary Sano; Niklas Mattsson; David L Sultzer; Thomas J Montine; Clifford R Jack; Hartmuth Kolb; Ronald C Petersen; Prashanthi Vemuri; Megan Zoschg Canniere; Julie A Schneider; Susan M Resnick; Gary Romano; Argonde Corien van Harten; David A Wolk; Lisa J Bain; Eric Siemers Journal: Alzheimers Dement Date: 2018-04 Impact factor: 21.566
Authors: David A Wolk; Carl Sadowsky; Beth Safirstein; Juha O Rinne; Ranjan Duara; Richard Perry; Marc Agronin; Jose Gamez; Jiong Shi; Adrian Ivanoiu; Lennart Minthon; Zuzana Walker; Steen Hasselbalch; Clive Holmes; Marwan Sabbagh; Marilyn Albert; Adam Fleisher; Paul Loughlin; Eric Triau; Kirk Frey; Peter Høgh; Andrea Bozoki; Roger Bullock; Eric Salmon; Gillian Farrar; Christopher J Buckley; Michelle Zanette; Paul F Sherwin; Andrea Cherubini; Fraser Inglis Journal: JAMA Neurol Date: 2018-09-01 Impact factor: 18.302
Authors: Johannes Brettschneider; Kelly Del Tredici; Virginia M-Y Lee; John Q Trojanowski Journal: Nat Rev Neurosci Date: 2015-01-15 Impact factor: 34.870
Authors: Yen Ying Lim; Jason Hassenstab; Carlos Cruchaga; Alison Goate; Anne M Fagan; Tammie L S Benzinger; Paul Maruff; Peter J Snyder; Colin L Masters; Ricardo Allegri; Jasmeer Chhatwal; Martin R Farlow; Neill R Graff-Radford; Christoph Laske; Johannes Levin; Eric McDade; John M Ringman; Martin Rossor; Stephen Salloway; Peter R Schofield; David M Holtzman; John C Morris; Randall J Bateman Journal: Brain Date: 2016-08-12 Impact factor: 13.501