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Cerebrospinal fluid biomarkers and rate of cognitive decline in very mild dementia of the Alzheimer type.
Arch Neurol 2009; 66(5):638-45AN

Abstract

BACKGROUND

Cerebrospinal fluid (CSF) levels of Abeta peptide 1-42 (Abeta 42), tau, and phosphorylated tau (ptau) are potential biomarkers of Alzheimer disease.

OBJECTIVE

To determine whether Abeta 42, tau, and ptau predict the rate of cognitive change in individuals with very mild dementia of the Alzheimer type (DAT).

DESIGN

Retrospective analysis of CSF biomarkers and clinical data.

SETTING

An academic Alzheimer disease research center.

PARTICIPANTS

Research volunteers in a longitudinal study of aging and cognition. Participants (n = 49) had a clinical diagnosis of very mild DAT with a Clinical Dementia Rating (CDR) of 0.5 at the time of lumbar puncture. All the participants had at least 1 follow-up assessment (mean [SD] follow-up, 3.5 [1.8] years).

MAIN OUTCOME MEASURES

Baseline CSF levels of Abeta 42, Abeta 40, tau, and ptau at threonine 181 (ptau181) and the rate of dementia progression as measured using the CDR sum of boxes (CDR-SB) score and psychometric performance.

RESULTS

The rate of dementia progression was significantly more rapid in individuals with lower baseline CSF Abeta 42 levels, higher tau or ptau181 levels, or high tau: Abeta 42 ratios. For example, the annual change in the CDR-SB score was 1.1 for the lowest 2 tertiles of Abeta 42 values and 0.3 for the highest tertile of Abeta 42 values.

CONCLUSIONS

In individuals with very mild DAT, lower CSF Abeta 42 levels, high tau or ptau181 levels, or high tau:Abeta 42 ratios quantitatively predict more rapid progression of cognitive deficits and dementia. Biomarkers of CSF may be useful prognostically and to identify individuals who are more likely to progress for participation in therapeutic clinical trials.

Authors+Show Affiliations

Department of Neurology, Washington University School of Medicine, Campus Box 8111, 660 S Euclid, St Louis, MO 63110, USA. sniderj@neuro.wustl.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19433664

Citation

Snider, Barbara J., et al. "Cerebrospinal Fluid Biomarkers and Rate of Cognitive Decline in Very Mild Dementia of the Alzheimer Type." Archives of Neurology, vol. 66, no. 5, 2009, pp. 638-45.
Snider BJ, Fagan AM, Roe C, et al. Cerebrospinal fluid biomarkers and rate of cognitive decline in very mild dementia of the Alzheimer type. Arch Neurol. 2009;66(5):638-45.
Snider, B. J., Fagan, A. M., Roe, C., Shah, A. R., Grant, E. A., Xiong, C., ... Holtzman, D. M. (2009). Cerebrospinal fluid biomarkers and rate of cognitive decline in very mild dementia of the Alzheimer type. Archives of Neurology, 66(5), pp. 638-45. doi:10.1001/archneurol.2009.55.
Snider BJ, et al. Cerebrospinal Fluid Biomarkers and Rate of Cognitive Decline in Very Mild Dementia of the Alzheimer Type. Arch Neurol. 2009;66(5):638-45. PubMed PMID: 19433664.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cerebrospinal fluid biomarkers and rate of cognitive decline in very mild dementia of the Alzheimer type. AU - Snider,Barbara J, AU - Fagan,Anne M, AU - Roe,Catherine, AU - Shah,Aarti R, AU - Grant,Elizabeth A, AU - Xiong,Chengjie, AU - Morris,John C, AU - Holtzman,David M, PY - 2009/5/13/entrez PY - 2009/5/13/pubmed PY - 2009/9/10/medline SP - 638 EP - 45 JF - Archives of neurology JO - Arch. Neurol. VL - 66 IS - 5 N2 - BACKGROUND: Cerebrospinal fluid (CSF) levels of Abeta peptide 1-42 (Abeta 42), tau, and phosphorylated tau (ptau) are potential biomarkers of Alzheimer disease. OBJECTIVE: To determine whether Abeta 42, tau, and ptau predict the rate of cognitive change in individuals with very mild dementia of the Alzheimer type (DAT). DESIGN: Retrospective analysis of CSF biomarkers and clinical data. SETTING: An academic Alzheimer disease research center. PARTICIPANTS: Research volunteers in a longitudinal study of aging and cognition. Participants (n = 49) had a clinical diagnosis of very mild DAT with a Clinical Dementia Rating (CDR) of 0.5 at the time of lumbar puncture. All the participants had at least 1 follow-up assessment (mean [SD] follow-up, 3.5 [1.8] years). MAIN OUTCOME MEASURES: Baseline CSF levels of Abeta 42, Abeta 40, tau, and ptau at threonine 181 (ptau181) and the rate of dementia progression as measured using the CDR sum of boxes (CDR-SB) score and psychometric performance. RESULTS: The rate of dementia progression was significantly more rapid in individuals with lower baseline CSF Abeta 42 levels, higher tau or ptau181 levels, or high tau: Abeta 42 ratios. For example, the annual change in the CDR-SB score was 1.1 for the lowest 2 tertiles of Abeta 42 values and 0.3 for the highest tertile of Abeta 42 values. CONCLUSIONS: In individuals with very mild DAT, lower CSF Abeta 42 levels, high tau or ptau181 levels, or high tau:Abeta 42 ratios quantitatively predict more rapid progression of cognitive deficits and dementia. Biomarkers of CSF may be useful prognostically and to identify individuals who are more likely to progress for participation in therapeutic clinical trials. SN - 1538-3687 UR - https://www.unboundmedicine.com/medline/citation/19433664/Cerebrospinal_fluid_biomarkers_and_rate_of_cognitive_decline_in_very_mild_dementia_of_the_Alzheimer_type_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/archneurol.2009.55 DB - PRIME DP - Unbound Medicine ER -