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Cerebrospinal fluid biomarkers, education, brain volume, and future cognition.
Arch Neurol 2011; 68(9):1145-51AN

Abstract

BACKGROUND

Cross-sectional studies suggest that the cognitive impact of Alzheimer disease pathology varies depending on education and brain size.

OBJECTIVE

To evaluate the combination of cerebrospinal fluid biomarkers of β-amyloid(42) (Aβ(42)), tau, and phosphorylated tau (ptau(181)) with education and normalized whole-brain volume (nWBV) to predict incident cognitive impairment.

DESIGN

Longitudinal cohort study.

SETTING

Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University, St Louis, Missouri.

PARTICIPANTS

A convenience sample of 197 individuals 50 years and older with normal cognition (Clinical Dementia Rating of 0) at baseline observed for a mean of 3.3 years.

MAIN OUTCOME MEASURE

Time to Clinical Dementia Rating ≥ 0.5.

RESULTS

Three-factor interactions among the baseline biomarker values, education, and nWBV were found for Cox proportional hazards regression models testing tau (P = .02) and ptau (P = .008). In those with lower tau values, nWBV (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.31-0.91; P = .02), but not education, was related to time to cognitive impairment. For participants with higher tau values, education interacted with nWBV to predict incident impairment (P = .01). For individuals with lower ptau values, there was no effect of education or nWBV. Education interacted with nWBV to predict incident cognitive impairment in those with higher ptau values (P = .02).

CONCLUSION

In individuals with normal cognition and higher levels of cerebrospinal fluid tau and ptau at baseline, time to incident cognitive impairment is moderated by education and brain volume as predicted by the cognitive/brain reserve hypothesis.

Authors+Show Affiliations

Knight Alzheimer’s Disease Research Center, St Louis, MO, USA. cathyr@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)

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

Language

eng

PubMed ID

21911695

Citation

Roe, Catherine M., et al. "Cerebrospinal Fluid Biomarkers, Education, Brain Volume, and Future Cognition." Archives of Neurology, vol. 68, no. 9, 2011, pp. 1145-51.
Roe CM, Fagan AM, Grant EA, et al. Cerebrospinal fluid biomarkers, education, brain volume, and future cognition. Arch Neurol. 2011;68(9):1145-51.
Roe, C. M., Fagan, A. M., Grant, E. A., Marcus, D. S., Benzinger, T. L., Mintun, M. A., ... Morris, J. C. (2011). Cerebrospinal fluid biomarkers, education, brain volume, and future cognition. Archives of Neurology, 68(9), pp. 1145-51. doi:10.1001/archneurol.2011.192.
Roe CM, et al. Cerebrospinal Fluid Biomarkers, Education, Brain Volume, and Future Cognition. Arch Neurol. 2011;68(9):1145-51. PubMed PMID: 21911695.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cerebrospinal fluid biomarkers, education, brain volume, and future cognition. AU - Roe,Catherine M, AU - Fagan,Anne M, AU - Grant,Elizabeth A, AU - Marcus,Daniel S, AU - Benzinger,Tammie L S, AU - Mintun,Mark A, AU - Holtzman,David M, AU - Morris,John C, PY - 2011/9/14/entrez PY - 2011/9/14/pubmed PY - 2011/11/4/medline SP - 1145 EP - 51 JF - Archives of neurology JO - Arch. Neurol. VL - 68 IS - 9 N2 - BACKGROUND: Cross-sectional studies suggest that the cognitive impact of Alzheimer disease pathology varies depending on education and brain size. OBJECTIVE: To evaluate the combination of cerebrospinal fluid biomarkers of β-amyloid(42) (Aβ(42)), tau, and phosphorylated tau (ptau(181)) with education and normalized whole-brain volume (nWBV) to predict incident cognitive impairment. DESIGN: Longitudinal cohort study. SETTING: Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University, St Louis, Missouri. PARTICIPANTS: A convenience sample of 197 individuals 50 years and older with normal cognition (Clinical Dementia Rating of 0) at baseline observed for a mean of 3.3 years. MAIN OUTCOME MEASURE: Time to Clinical Dementia Rating ≥ 0.5. RESULTS: Three-factor interactions among the baseline biomarker values, education, and nWBV were found for Cox proportional hazards regression models testing tau (P = .02) and ptau (P = .008). In those with lower tau values, nWBV (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.31-0.91; P = .02), but not education, was related to time to cognitive impairment. For participants with higher tau values, education interacted with nWBV to predict incident impairment (P = .01). For individuals with lower ptau values, there was no effect of education or nWBV. Education interacted with nWBV to predict incident cognitive impairment in those with higher ptau values (P = .02). CONCLUSION: In individuals with normal cognition and higher levels of cerebrospinal fluid tau and ptau at baseline, time to incident cognitive impairment is moderated by education and brain volume as predicted by the cognitive/brain reserve hypothesis. SN - 1538-3687 UR - https://www.unboundmedicine.com/medline/citation/21911695/Cerebrospinal_fluid_biomarkers_education_brain_volume_and_future_cognition_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/archneurol.2011.192 DB - PRIME DP - Unbound Medicine ER -