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Evaluation of CSF Biomarkers as Predictors of Alzheimer's Disease: A Clinical Follow-Up Study of 4.7 Years.

Hertze, Joakim LU ; Minthon, Lennart LU ; Zetterberg, Henrik; Vanmechelen, Eugeen; Blennow, Kaj and Hansson, Oskar (2010) In Journal of Alzheimer's Disease 21. p.1119-1128
Abstract
In this study, we determined the diagnostic accuracy of cerebrospinal fluid (CSF) biomarkers to predict development of Alzheimer's disease (AD) within five years in patients with mild cognitive impairment (MCI). To do so, the levels of tau, phosphorylated tau, Abeta42, Abeta40, Abeta38, sAbetaPPalpha, and sAbetaPPbeta were analyzed in 327 CSF samples obtained at baseline from patients with AD (n= 94), MCI (n= 166), depressive disorder (n= 29), and cognitively healthy controls (n= 38). In the cohort with MCI at baseline, 33% subsequently developed AD and 16% developed other types of dementia; however, 51% were still cognitively stable after a follow-up of 4.7 years (range 3.0-7.4). Optimal cut-offs for each biomarker or combinations of... (More)
In this study, we determined the diagnostic accuracy of cerebrospinal fluid (CSF) biomarkers to predict development of Alzheimer's disease (AD) within five years in patients with mild cognitive impairment (MCI). To do so, the levels of tau, phosphorylated tau, Abeta42, Abeta40, Abeta38, sAbetaPPalpha, and sAbetaPPbeta were analyzed in 327 CSF samples obtained at baseline from patients with AD (n= 94), MCI (n= 166), depressive disorder (n= 29), and cognitively healthy controls (n= 38). In the cohort with MCI at baseline, 33% subsequently developed AD and 16% developed other types of dementia; however, 51% were still cognitively stable after a follow-up of 4.7 years (range 3.0-7.4). Optimal cut-offs for each biomarker or combinations of biomarkers were defined in the AD, control, and depressive disorder groups. Several combinations resulted in sensitivity and specificity levels > 85% for differentiation of AD from controls and depressive disorder. Using the previously established cut-offs, a combination of Abeta42 and tau could predict future development of AD in MCI patients with a sensitivity of 88%, specificity 82%, positive predictive value 71%, and negative predictive value 94%. MCI patients with both low Abeta42 and high tau levels had a substantially increased risk of developing AD (OR 20; 95% CI 6-58), even after adjustment for confounding factors. Ultimately, CSF biomarkers can stratify MCI patients into those with very low or high risk for future development of AD. However, the specificities and positive predictive values are still too low to be able to diagnose AD before the patients fulfill the clinical criteria. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Alzheimer's Disease
volume
21
pages
1119 - 1128
publisher
IOS Press
external identifiers
  • wos:000283049700007
  • pmid:20693640
  • scopus:78650464378
ISSN
1387-2877
DOI
10.3233/JAD-2010-100207
language
English
LU publication?
yes
id
7f7d41f7-723e-4716-a2db-1320d7ec18b5 (old id 1665458)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20693640?dopt=Abstract
date added to LUP
2010-09-03 09:15:48
date last changed
2018-07-01 04:22:59
@article{7f7d41f7-723e-4716-a2db-1320d7ec18b5,
  abstract     = {In this study, we determined the diagnostic accuracy of cerebrospinal fluid (CSF) biomarkers to predict development of Alzheimer's disease (AD) within five years in patients with mild cognitive impairment (MCI). To do so, the levels of tau, phosphorylated tau, Abeta42, Abeta40, Abeta38, sAbetaPPalpha, and sAbetaPPbeta were analyzed in 327 CSF samples obtained at baseline from patients with AD (n= 94), MCI (n= 166), depressive disorder (n= 29), and cognitively healthy controls (n= 38). In the cohort with MCI at baseline, 33% subsequently developed AD and 16% developed other types of dementia; however, 51% were still cognitively stable after a follow-up of 4.7 years (range 3.0-7.4). Optimal cut-offs for each biomarker or combinations of biomarkers were defined in the AD, control, and depressive disorder groups. Several combinations resulted in sensitivity and specificity levels > 85% for differentiation of AD from controls and depressive disorder. Using the previously established cut-offs, a combination of Abeta42 and tau could predict future development of AD in MCI patients with a sensitivity of 88%, specificity 82%, positive predictive value 71%, and negative predictive value 94%. MCI patients with both low Abeta42 and high tau levels had a substantially increased risk of developing AD (OR 20; 95% CI 6-58), even after adjustment for confounding factors. Ultimately, CSF biomarkers can stratify MCI patients into those with very low or high risk for future development of AD. However, the specificities and positive predictive values are still too low to be able to diagnose AD before the patients fulfill the clinical criteria.},
  author       = {Hertze, Joakim and Minthon, Lennart and Zetterberg, Henrik and Vanmechelen, Eugeen and Blennow, Kaj and Hansson, Oskar},
  issn         = {1387-2877},
  language     = {eng},
  pages        = {1119--1128},
  publisher    = {IOS Press},
  series       = {Journal of Alzheimer's Disease},
  title        = {Evaluation of CSF Biomarkers as Predictors of Alzheimer's Disease: A Clinical Follow-Up Study of 4.7 Years.},
  url          = {http://dx.doi.org/10.3233/JAD-2010-100207},
  volume       = {21},
  year         = {2010},
}