Open AccessDiagnostic accuracy of CSF Ab42 and florbetapir PET for Alzheimer's disease
Author(s) -
Mattsson Niklas,
Insel Philip S.,
Landau Susan,
Jagust William,
Donohue Michael,
Shaw Leslie M.,
Trojanowski John Q.,
Zetterberg Henrik,
Blennow Kaj,
Weiner Michael
Publication year - 2014
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.81
Subject(s) - medicine , cerebrospinal fluid , dementia , positron emission tomography , confidence interval , neuroimaging , area under the curve , cognitive impairment , pathology , nuclear medicine , gastroenterology , disease , psychiatry
Background Reduced cerebrospinal fluid ( CSF ) β ‐amyloid42 (A β 42) and increased florbetapir positron emission tomography ( PET ) uptake reflects brain A β accumulation. These biomarkers are correlated with each other and altered in Alzheimer's disease ( AD ), but no study has directly compared their diagnostic performance. Methods We examined healthy controls (CN, N = 169) versus AD dementia patients ( N = 118), and stable ( sMCI ; no dementia, followed up for at least 2 years, N = 165) versus progressive MCI ( pMCI ; conversion to AD dementia, N = 59). All subjects had florbetapir PET (global and regional; temporal, frontal, parietal, and cingulate) and CSF A β 42 measurements at baseline. We compared area under the curve (AUC), sensitivity, and specificity (testing a priori and optimized cutoffs). Clinical diagnosis was the reference standard. Results CSF A β 42 and (global or regional) PET florbetapir did not differ in AUC ( CN vs. AD , CSF 84.4%; global PET 86.9%; difference [95% confidence interval] −6.7 to 1.5). CSF A β 42 and global PET florbetapir did not differ in sensitivity, but PET had greater specificity than CSF in most comparisons. Sixteen CN progressed to MCI and AD (six A β negative, seven A β positive, and three PET positive but CSF negative). Interpretation The overall diagnostic accuracies of CSF A β 42 and PET florbetapir were similar, but PET had greater specificity. This was because some CN and sMCI subjects appear pathological using CSF but not using PET, suggesting that low CSF A β 42 not always translates to cognitive decline or brain A β accumulation. Other factors, including costs and side effects, may also be considered when determining the optimal modality for different applications.