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Detailed comparison of amyloid PET and CSF biomarkers for identifying early Alzheimer disease

Palmqvist, Sebastian LU ; Zetterberg, H.; Mattsson, N.; Johansson, Per LU ; Minthon, Lennart LU ; Blennow, K.; Ohlsson, Mattias LU and Hansson, Oskar LU (2015) In Neurology 85(14). p.1240-1249
Abstract
Objective:To compare the diagnostic accuracy of CSF biomarkers and amyloid PET for diagnosing early-stage Alzheimer disease (AD).Methods:From the prospective, longitudinal BioFINDER study, we included 122 healthy elderly and 34 patients with mild cognitive impairment who developed AD dementia within 3 years (MCI-AD). -Amyloid (A) deposition in 9 brain regions was examined with [F-18]-flutemetamol PET. CSF was analyzed with INNOTEST and EUROIMMUN ELISAs. The results were replicated in 146 controls and 64 patients with MCI-AD from the Alzheimer's Disease Neuroimaging Initiative study.Results:The best CSF measures for identifying MCI-AD were A42/total tau (t-tau) and A42/hyperphosphorylated tau (p-tau) (area under the curve [AUC] 0.93-0.94).... (More)
Objective:To compare the diagnostic accuracy of CSF biomarkers and amyloid PET for diagnosing early-stage Alzheimer disease (AD).Methods:From the prospective, longitudinal BioFINDER study, we included 122 healthy elderly and 34 patients with mild cognitive impairment who developed AD dementia within 3 years (MCI-AD). -Amyloid (A) deposition in 9 brain regions was examined with [F-18]-flutemetamol PET. CSF was analyzed with INNOTEST and EUROIMMUN ELISAs. The results were replicated in 146 controls and 64 patients with MCI-AD from the Alzheimer's Disease Neuroimaging Initiative study.Results:The best CSF measures for identifying MCI-AD were A42/total tau (t-tau) and A42/hyperphosphorylated tau (p-tau) (area under the curve [AUC] 0.93-0.94). The best PET measures performed similarly (AUC 0.92-0.93; anterior cingulate, posterior cingulate/precuneus, and global neocortical uptake). CSF A42/t-tau and A42/p-tau performed better than CSF A42 and A42/40 (AUC difference 0.03-0.12, p < 0.05). Using nonoptimized cutoffs, CSF A42/t-tau had the highest accuracy of all CSF/PET biomarkers (sensitivity 97%, specificity 83%). The combination of CSF and PET was not better than using either biomarker separately.Conclusions:Amyloid PET and CSF biomarkers can identify early AD with high accuracy. There were no differences between the best CSF and PET measures and no improvement when combining them. Regional PET measures were not better than assessing the global A deposition. The results were replicated in an independent cohort using another CSF assay and PET tracer. The choice between CSF and amyloid PET biomarkers for identifying early AD can be based on availability, costs, and doctor/patient preferences since both have equally high diagnostic accuracy.Classification of evidence:This study provides Class III evidence that amyloid PET and CSF biomarkers identify early-stage AD equally accurately. (Less)
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published
subject
keywords
MILD COGNITIVE IMPAIRMENT, POSITRON-EMISSION-TOMOGRAPHY, CEREBROSPINAL-FLUID, ASSOCIATION WORKGROUPS, DIAGNOSTIC GUIDELINES, NATIONAL INSTITUTE, BETA, TAU, DEMENTIA, RECOMMENDATIONS
in
Neurology
volume
85
issue
14
pages
1240 - 1249
publisher
American Academy of Neurology
external identifiers
  • wos:000362203200003
  • scopus:84943227798
ISSN
1526-632X
DOI
10.1212/WNL.0000000000001991
language
English
LU publication?
yes
id
1a8076e5-53d3-48d4-a2eb-b67d898c9226 (old id 8221211)
date added to LUP
2016-02-15 11:10:56
date last changed
2017-11-19 04:02:22
@article{1a8076e5-53d3-48d4-a2eb-b67d898c9226,
  abstract     = {Objective:To compare the diagnostic accuracy of CSF biomarkers and amyloid PET for diagnosing early-stage Alzheimer disease (AD).Methods:From the prospective, longitudinal BioFINDER study, we included 122 healthy elderly and 34 patients with mild cognitive impairment who developed AD dementia within 3 years (MCI-AD). -Amyloid (A) deposition in 9 brain regions was examined with [F-18]-flutemetamol PET. CSF was analyzed with INNOTEST and EUROIMMUN ELISAs. The results were replicated in 146 controls and 64 patients with MCI-AD from the Alzheimer's Disease Neuroimaging Initiative study.Results:The best CSF measures for identifying MCI-AD were A42/total tau (t-tau) and A42/hyperphosphorylated tau (p-tau) (area under the curve [AUC] 0.93-0.94). The best PET measures performed similarly (AUC 0.92-0.93; anterior cingulate, posterior cingulate/precuneus, and global neocortical uptake). CSF A42/t-tau and A42/p-tau performed better than CSF A42 and A42/40 (AUC difference 0.03-0.12, p &lt; 0.05). Using nonoptimized cutoffs, CSF A42/t-tau had the highest accuracy of all CSF/PET biomarkers (sensitivity 97%, specificity 83%). The combination of CSF and PET was not better than using either biomarker separately.Conclusions:Amyloid PET and CSF biomarkers can identify early AD with high accuracy. There were no differences between the best CSF and PET measures and no improvement when combining them. Regional PET measures were not better than assessing the global A deposition. The results were replicated in an independent cohort using another CSF assay and PET tracer. The choice between CSF and amyloid PET biomarkers for identifying early AD can be based on availability, costs, and doctor/patient preferences since both have equally high diagnostic accuracy.Classification of evidence:This study provides Class III evidence that amyloid PET and CSF biomarkers identify early-stage AD equally accurately.},
  author       = {Palmqvist, Sebastian and Zetterberg, H. and Mattsson, N. and Johansson, Per and Minthon, Lennart and Blennow, K. and Ohlsson, Mattias and Hansson, Oskar},
  issn         = {1526-632X},
  keyword      = {MILD COGNITIVE IMPAIRMENT,POSITRON-EMISSION-TOMOGRAPHY,CEREBROSPINAL-FLUID,ASSOCIATION WORKGROUPS,DIAGNOSTIC GUIDELINES,NATIONAL INSTITUTE,BETA,TAU,DEMENTIA,RECOMMENDATIONS},
  language     = {eng},
  number       = {14},
  pages        = {1240--1249},
  publisher    = {American Academy of Neurology},
  series       = {Neurology},
  title        = {Detailed comparison of amyloid PET and CSF biomarkers for identifying early Alzheimer disease},
  url          = {http://dx.doi.org/10.1212/WNL.0000000000001991},
  volume       = {85},
  year         = {2015},
}