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Cerebrospinal fluid tau/beta-amyloid(42) ratio as a prediction of cognitive decline in nondemented older adults.
Arch Neurol 2007; 64(3):343-9AN

Abstract

OBJECTIVES

To investigate the ability of cerebrospinal fluid (CSF) and plasma measures to discriminate early-stage Alzheimer disease (AD) (defined by clinical criteria and presence/absence of brain amyloid) from nondemented aging and to assess whether these biomarkers can predict future dementia in cognitively normal individuals.

DESIGN

Evaluation of CSF beta-amyloid(40) (Abeta(40)), Abeta(42), tau, phosphorylated tau(181), and plasma Abeta(40) and Abeta(42) and longitudinal clinical follow-up (from 1 to 8 years).

SETTING

Longitudinal studies of healthy aging and dementia through an AD research center.

PARTICIPANTS

Community-dwelling volunteers (n = 139) aged 60 to 91 years and clinically judged as cognitively normal (Clinical Dementia Rating [CDR], 0) or having very mild (CDR, 0.5) or mild (CDR, 1) AD dementia.

RESULTS

Individuals with very mild or mild AD have reduced mean levels of CSF Abeta(42) and increased levels of CSF tau and phosphorylated tau(181). Cerebrospinal fluid Abeta(42) level completely corresponds with the presence or absence of brain amyloid (imaged with Pittsburgh Compound B) in demented and nondemented individuals. The CSF tau/Abeta(42) ratio (adjusted hazard ratio, 5.21; 95% confidence interval, 1.58-17.22) and phosphorylated tau(181)/Abeta(42) ratio (adjusted hazard ratio, 4.39; 95% confidence interval, 1.62-11.86) predict conversion from a CDR of 0 to a CDR greater than 0.

CONCLUSIONS

The very mildest symptomatic stage of AD exhibits the same CSF biomarker phenotype as more advanced AD. In addition, levels of CSF Abeta(42), when combined with amyloid imaging, augment clinical methods for identifying in individuals with brain amyloid deposits whether dementia is present or not. Importantly, CSF tau/Abeta(42) ratios show strong promise as antecedent (preclinical) biomarkers that predict future dementia in cognitively normal older adults.

Authors+Show Affiliations

Department of Neurology, Washington University School of Medicine, 660 S Euclid Ave, Box 8111, St Louis, MO 63110, USA. fagana@neuro.wustl.eduNo 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

Language

eng

PubMed ID

17210801

Citation

Fagan, Anne M., et al. "Cerebrospinal Fluid Tau/beta-amyloid(42) Ratio as a Prediction of Cognitive Decline in Nondemented Older Adults." Archives of Neurology, vol. 64, no. 3, 2007, pp. 343-9.
Fagan AM, Roe CM, Xiong C, et al. Cerebrospinal fluid tau/beta-amyloid(42) ratio as a prediction of cognitive decline in nondemented older adults. Arch Neurol. 2007;64(3):343-9.
Fagan, A. M., Roe, C. M., Xiong, C., Mintun, M. A., Morris, J. C., & Holtzman, D. M. (2007). Cerebrospinal fluid tau/beta-amyloid(42) ratio as a prediction of cognitive decline in nondemented older adults. Archives of Neurology, 64(3), pp. 343-9.
Fagan AM, et al. Cerebrospinal Fluid Tau/beta-amyloid(42) Ratio as a Prediction of Cognitive Decline in Nondemented Older Adults. Arch Neurol. 2007;64(3):343-9. PubMed PMID: 17210801.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cerebrospinal fluid tau/beta-amyloid(42) ratio as a prediction of cognitive decline in nondemented older adults. AU - Fagan,Anne M, AU - Roe,Catherine M, AU - Xiong,Chengjie, AU - Mintun,Mark A, AU - Morris,John C, AU - Holtzman,David M, Y1 - 2007/01/08/ PY - 2007/1/11/pubmed PY - 2007/4/25/medline PY - 2007/1/11/entrez SP - 343 EP - 9 JF - Archives of neurology JO - Arch. Neurol. VL - 64 IS - 3 N2 - OBJECTIVES: To investigate the ability of cerebrospinal fluid (CSF) and plasma measures to discriminate early-stage Alzheimer disease (AD) (defined by clinical criteria and presence/absence of brain amyloid) from nondemented aging and to assess whether these biomarkers can predict future dementia in cognitively normal individuals. DESIGN: Evaluation of CSF beta-amyloid(40) (Abeta(40)), Abeta(42), tau, phosphorylated tau(181), and plasma Abeta(40) and Abeta(42) and longitudinal clinical follow-up (from 1 to 8 years). SETTING: Longitudinal studies of healthy aging and dementia through an AD research center. PARTICIPANTS: Community-dwelling volunteers (n = 139) aged 60 to 91 years and clinically judged as cognitively normal (Clinical Dementia Rating [CDR], 0) or having very mild (CDR, 0.5) or mild (CDR, 1) AD dementia. RESULTS: Individuals with very mild or mild AD have reduced mean levels of CSF Abeta(42) and increased levels of CSF tau and phosphorylated tau(181). Cerebrospinal fluid Abeta(42) level completely corresponds with the presence or absence of brain amyloid (imaged with Pittsburgh Compound B) in demented and nondemented individuals. The CSF tau/Abeta(42) ratio (adjusted hazard ratio, 5.21; 95% confidence interval, 1.58-17.22) and phosphorylated tau(181)/Abeta(42) ratio (adjusted hazard ratio, 4.39; 95% confidence interval, 1.62-11.86) predict conversion from a CDR of 0 to a CDR greater than 0. CONCLUSIONS: The very mildest symptomatic stage of AD exhibits the same CSF biomarker phenotype as more advanced AD. In addition, levels of CSF Abeta(42), when combined with amyloid imaging, augment clinical methods for identifying in individuals with brain amyloid deposits whether dementia is present or not. Importantly, CSF tau/Abeta(42) ratios show strong promise as antecedent (preclinical) biomarkers that predict future dementia in cognitively normal older adults. SN - 0003-9942 UR - https://www.unboundmedicine.com/medline/citation/17210801/Cerebrospinal_fluid_tau/beta_amyloid_42__ratio_as_a_prediction_of_cognitive_decline_in_nondemented_older_adults_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/archneur.64.3.noc60123 DB - PRIME DP - Unbound Medicine ER -