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Injury markers predict time to dementia in subjects with MCI and amyloid pathology.
Neurology 2012; 79(17):1809-16Neur

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 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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23019259

Citation

van Rossum, Ineke A., et al. "Injury Markers Predict Time to Dementia in Subjects With MCI and Amyloid Pathology." Neurology, vol. 79, no. 17, 2012, pp. 1809-16.
van Rossum IA, Vos SJ, Burns L, et al. Injury markers predict time to dementia in subjects with MCI and amyloid pathology. Neurology. 2012;79(17):1809-16.
van Rossum, I. A., Vos, S. J., Burns, L., Knol, D. L., Scheltens, P., Soininen, H., ... Visser, P. J. (2012). Injury markers predict time to dementia in subjects with MCI and amyloid pathology. Neurology, 79(17), pp. 1809-16. doi:10.1212/WNL.0b013e3182704056.
van Rossum IA, et al. Injury Markers Predict Time to Dementia in Subjects With MCI and Amyloid Pathology. Neurology. 2012 Oct 23;79(17):1809-16. PubMed PMID: 23019259.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Injury markers predict time to dementia in subjects with MCI and amyloid pathology. AU - van Rossum,Ineke A, AU - Vos,Stephanie J B, AU - Burns,Leah, AU - Knol,Dirk L, AU - Scheltens,Philip, AU - Soininen,Hilkka, AU - Wahlund,Lars-Olof, AU - Hampel,Harald, AU - Tsolaki,Magda, AU - Minthon,Lennart, AU - L'italien,Gilbert, AU - van der Flier,Wiesje M, AU - Teunissen,Charlotte E, AU - Blennow,Kaj, AU - Barkhof,Frederik, AU - Rueckert,Daniel, AU - Wolz,Robin, AU - Verhey,Frans, AU - Visser,Pieter Jelle, Y1 - 2012/09/26/ PY - 2012/9/29/entrez PY - 2012/9/29/pubmed PY - 2013/1/16/medline SP - 1809 EP - 16 JF - Neurology JO - Neurology VL - 79 IS - 17 N2 - 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. SN - 1526-632X UR - https://www.unboundmedicine.com/medline/citation/23019259/Injury_markers_predict_time_to_dementia_in_subjects_with_MCI_and_amyloid_pathology_ L2 - http://www.neurology.org/cgi/pmidlookup?view=long&pmid=23019259 DB - PRIME DP - Unbound Medicine ER -