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Correlation of longitudinal cerebrospinal fluid biomarkers with cognitive decline in healthy older adults.

Stomrud, Erik LU ; Hansson, Oskar LU ; Zetterberg, Henrik; Blennow, Kaj; Minthon, Lennart LU and Londos, Elisabet LU (2010) In Archives of Neurology 67(2). p.217-223
Abstract
BACKGROUND: Abnormal cerebrospinal fluid (CSF) biomarker levels predict development of Alzheimer disease with good accuracy and are thought to precede cognitive deterioration. OBJECTIVE: To investigate whether changes in CSF biomarker levels over time in healthy older adults are associated with a concurrent decline in cognitive performance. DESIGN: Retrospective analysis of longitudinal CSF biomarker levels and clinical data. SETTING: A combined academic dementia disorder research center and dementia clinic. PARTICIPANTS: Thirty-seven cognitively healthy older volunteers (mean age, 73 years). MAIN OUTCOME MEASURES: Longitudinal CSF total tau protein, hyperphosphorylated tau protein 181, and beta-amyloid(1-42) protein levels and cognitive... (More)
BACKGROUND: Abnormal cerebrospinal fluid (CSF) biomarker levels predict development of Alzheimer disease with good accuracy and are thought to precede cognitive deterioration. OBJECTIVE: To investigate whether changes in CSF biomarker levels over time in healthy older adults are associated with a concurrent decline in cognitive performance. DESIGN: Retrospective analysis of longitudinal CSF biomarker levels and clinical data. SETTING: A combined academic dementia disorder research center and dementia clinic. PARTICIPANTS: Thirty-seven cognitively healthy older volunteers (mean age, 73 years). MAIN OUTCOME MEASURES: Longitudinal CSF total tau protein, hyperphosphorylated tau protein 181, and beta-amyloid(1-42) protein levels and cognitive assessments at baseline and at follow-up 4 years later. RESULTS: Low levels of CSF beta-amyloid(1-42) protein at follow-up were associated with decreased delayed word recall score on the Alzheimer Disease Assessment Scale-cognitive subscale (r(s) = -0.437, P < .01) and with slower results on A Quick Test of Cognitive Speed (r(s) = -0.540, P < .001). Individuals with a decrease during the 4-year study of 15% or more in CSF beta-amyloid(1-42) protein level performed worse on the Alzheimer Disease Assessment Scale-cognitive subscale delayed word recall (z = -2.18, P < .05) and A Quick Test of Cognitive Speed (z = -2.35, P < .05) at follow-up. An increase over time of 20% or more in CSF hyperphosphorylated tau protein 181 level correlated with slower results on A Quick Test of Cognitive Speed at follow-up (z = -2.13, P < .05). Furthermore, the presence of the APOE-epsilon4 (OMIM 107741) allele was associated with a greater longitudinal decrease in CSF beta-amyloid(1-42) protein level (chi(2) = 10.47, P < .05) and with a higher CSF total tau protein level at follow-up (chi(2) = 8.83, P < .05). No correlation existed between baseline CSF biomarker levels and baseline or follow-up cognitive scores. CONCLUSIONS: In this group of healthy older adults, changes in CSF biomarker levels previously associated with Alzheimer disease correlated with a decline in cognitive functions. Changes in CSF biomarker levels may identify early neurodegenerative processes of Alzheimer disease. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Archives of Neurology
volume
67
issue
2
pages
217 - 223
publisher
American Medical Association
external identifiers
  • wos:000274374600012
  • pmid:20142530
  • scopus:76149101242
ISSN
0003-9942
DOI
10.1001/archneurol.2009.316
language
English
LU publication?
yes
id
57cac646-717f-4a0f-ad70-cf3c72558fec (old id 1552786)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20142530?dopt=Abstract
date added to LUP
2010-03-02 21:29:16
date last changed
2018-06-17 04:56:28
@article{57cac646-717f-4a0f-ad70-cf3c72558fec,
  abstract     = {BACKGROUND: Abnormal cerebrospinal fluid (CSF) biomarker levels predict development of Alzheimer disease with good accuracy and are thought to precede cognitive deterioration. OBJECTIVE: To investigate whether changes in CSF biomarker levels over time in healthy older adults are associated with a concurrent decline in cognitive performance. DESIGN: Retrospective analysis of longitudinal CSF biomarker levels and clinical data. SETTING: A combined academic dementia disorder research center and dementia clinic. PARTICIPANTS: Thirty-seven cognitively healthy older volunteers (mean age, 73 years). MAIN OUTCOME MEASURES: Longitudinal CSF total tau protein, hyperphosphorylated tau protein 181, and beta-amyloid(1-42) protein levels and cognitive assessments at baseline and at follow-up 4 years later. RESULTS: Low levels of CSF beta-amyloid(1-42) protein at follow-up were associated with decreased delayed word recall score on the Alzheimer Disease Assessment Scale-cognitive subscale (r(s) = -0.437, P &lt; .01) and with slower results on A Quick Test of Cognitive Speed (r(s) = -0.540, P &lt; .001). Individuals with a decrease during the 4-year study of 15% or more in CSF beta-amyloid(1-42) protein level performed worse on the Alzheimer Disease Assessment Scale-cognitive subscale delayed word recall (z = -2.18, P &lt; .05) and A Quick Test of Cognitive Speed (z = -2.35, P &lt; .05) at follow-up. An increase over time of 20% or more in CSF hyperphosphorylated tau protein 181 level correlated with slower results on A Quick Test of Cognitive Speed at follow-up (z = -2.13, P &lt; .05). Furthermore, the presence of the APOE-epsilon4 (OMIM 107741) allele was associated with a greater longitudinal decrease in CSF beta-amyloid(1-42) protein level (chi(2) = 10.47, P &lt; .05) and with a higher CSF total tau protein level at follow-up (chi(2) = 8.83, P &lt; .05). No correlation existed between baseline CSF biomarker levels and baseline or follow-up cognitive scores. CONCLUSIONS: In this group of healthy older adults, changes in CSF biomarker levels previously associated with Alzheimer disease correlated with a decline in cognitive functions. Changes in CSF biomarker levels may identify early neurodegenerative processes of Alzheimer disease.},
  author       = {Stomrud, Erik and Hansson, Oskar and Zetterberg, Henrik and Blennow, Kaj and Minthon, Lennart and Londos, Elisabet},
  issn         = {0003-9942},
  language     = {eng},
  number       = {2},
  pages        = {217--223},
  publisher    = {American Medical Association},
  series       = {Archives of Neurology},
  title        = {Correlation of longitudinal cerebrospinal fluid biomarkers with cognitive decline in healthy older adults.},
  url          = {http://dx.doi.org/10.1001/archneurol.2009.316},
  volume       = {67},
  year         = {2010},
}