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Injury markers predict time to dementia in subjects with MCI and amyloid pathology.

van Rossum, Ineke A; Vos, Stephanie J B; Burns, Leah; Knol, Dirk L; Scheltens, Philip; Soininen, Hilkka; Wahlund, Lars-Olof; Hampel, Harald; Tsolaki, Magda and Minthon, Lennart LU , et al. (2012) In Neurology
Abstract
OBJECTIVES:

Alzheimer disease (AD) can now be diagnosed in subjects with mild cognitive impairment (MCI) using biomarkers. However, little is known about the rate of decline in those subjects. In this cohort study, we aimed to assess the conversion rate to dementia and identify prognostic markers in subjects with MCI and evidence of amyloid pathology.



METHODS:

We pooled subjects from the VU University Medical Center Alzheimer Center and the Development of Screening Guidelines and Criteria for Predementia Alzheimer's Disease (DESCRIPA) study. We included subjects with MCI, an abnormal level of β-amyloid(1-42) (Aβ(1-42)) in the CSF, and at least one diagnostic follow-up visit. We assessed the effect of... (More)
OBJECTIVES:

Alzheimer disease (AD) can now be diagnosed in subjects with mild cognitive impairment (MCI) using biomarkers. However, little is known about the rate of decline in those subjects. In this cohort study, we aimed to assess the conversion rate to dementia and identify prognostic markers in subjects with MCI and evidence of amyloid pathology.



METHODS:

We pooled subjects from the VU University Medical Center Alzheimer Center and the Development of Screening Guidelines and Criteria for Predementia Alzheimer's Disease (DESCRIPA) study. We included subjects with MCI, an abnormal level of β-amyloid(1-42) (Aβ(1-42)) in the CSF, and at least one diagnostic follow-up visit. We assessed the effect of APOE genotype, CSF total tau (t-tau) and tau phosphorylated at threonine 181 (p-tau) and hippocampal volume on time to AD-type dementia using Cox proportional hazards models and on decline on the Mini-Mental State Examination (MMSE) using linear mixed models.



RESULTS:

We included 110 subjects with MCI with abnormal CSF Aβ(1-42) and a mean MMSE score of 26.3 ± 2.8. During a mean follow-up of 2.2 ± 1.0 (range 0.4-5.0) years, 63 subjects (57%) progressed to AD-type dementia. Abnormal CSF t-tau (hazard ratio [HR] 2.3, 95% confidence interval [CI] 1.1-4.6, p = 0.03) and CSF p-tau (HR 3.5, 95% CI 1.3-9.2, p = 0.01) concentration and hippocampal atrophy (HR 2.5, 95% CI 1.1-5.6, p = 0.02) predicted time to dementia. For subjects with both abnormal t-tau concentration and hippocampal atrophy, HR was 7.3 (95% CI 1.0-55.9, p = 0.06). Furthermore, abnormal CSF t-tau and p-tau concentrations and hippocampal atrophy predicted decline in MMSE score.



CONCLUSIONS:

In subjects with MCI and evidence of amyloid pathology, the injury markers CSF t-tau and p-tau and hippocampal atrophy can predict further cognitive decline. (Less)
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Neurology
publisher
American Academy of Neurology
external identifiers
  • WOS:000310430700016
  • PMID:23019259
  • Scopus:84865507195
ISSN
1526-632X
DOI
10.1212/WNL.0b013e3182704056
language
English
LU publication?
yes
id
46b49955-e2b6-4507-ac62-9dd5ad4b399b (old id 3123536)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23019259?dopt=Abstract
date added to LUP
2012-10-03 20:24:17
date last changed
2016-11-06 04:27:56
@misc{46b49955-e2b6-4507-ac62-9dd5ad4b399b,
  abstract     = {OBJECTIVES: <br/><br>
Alzheimer disease (AD) can now be diagnosed in subjects with mild cognitive impairment (MCI) using biomarkers. However, little is known about the rate of decline in those subjects. In this cohort study, we aimed to assess the conversion rate to dementia and identify prognostic markers in subjects with MCI and evidence of amyloid pathology. <br/><br>
<br/><br>
METHODS: <br/><br>
We pooled subjects from the VU University Medical Center Alzheimer Center and the Development of Screening Guidelines and Criteria for Predementia Alzheimer's Disease (DESCRIPA) study. We included subjects with MCI, an abnormal level of β-amyloid(1-42) (Aβ(1-42)) in the CSF, and at least one diagnostic follow-up visit. We assessed the effect of APOE genotype, CSF total tau (t-tau) and tau phosphorylated at threonine 181 (p-tau) and hippocampal volume on time to AD-type dementia using Cox proportional hazards models and on decline on the Mini-Mental State Examination (MMSE) using linear mixed models. <br/><br>
<br/><br>
RESULTS: <br/><br>
We included 110 subjects with MCI with abnormal CSF Aβ(1-42) and a mean MMSE score of 26.3 ± 2.8. During a mean follow-up of 2.2 ± 1.0 (range 0.4-5.0) years, 63 subjects (57%) progressed to AD-type dementia. Abnormal CSF t-tau (hazard ratio [HR] 2.3, 95% confidence interval [CI] 1.1-4.6, p = 0.03) and CSF p-tau (HR 3.5, 95% CI 1.3-9.2, p = 0.01) concentration and hippocampal atrophy (HR 2.5, 95% CI 1.1-5.6, p = 0.02) predicted time to dementia. For subjects with both abnormal t-tau concentration and hippocampal atrophy, HR was 7.3 (95% CI 1.0-55.9, p = 0.06). Furthermore, abnormal CSF t-tau and p-tau concentrations and hippocampal atrophy predicted decline in MMSE score. <br/><br>
<br/><br>
CONCLUSIONS:<br/><br>
In subjects with MCI and evidence of amyloid pathology, the injury markers CSF t-tau and p-tau and hippocampal atrophy can predict further cognitive decline.},
  author       = {van Rossum, Ineke A and Vos, Stephanie J B and Burns, Leah and Knol, Dirk L and Scheltens, Philip and Soininen, Hilkka and Wahlund, Lars-Olof and Hampel, Harald and Tsolaki, Magda and Minthon, Lennart and L'italien, Gilbert and van der Flier, Wiesje M and Teunissen, Charlotte E and Blennow, Kaj and Barkhof, Frederik and Rueckert, Daniel and Wolz, Robin and Verhey, Frans and Visser, Pieter Jelle},
  issn         = {1526-632X},
  language     = {eng},
  month        = {09},
  publisher    = {ARRAY(0x816e990)},
  series       = {Neurology},
  title        = {Injury markers predict time to dementia in subjects with MCI and amyloid pathology.},
  url          = {http://dx.doi.org/10.1212/WNL.0b013e3182704056},
  year         = {2012},
}