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Abstract
Objective: To investigate factors, including cognitive and brain reserve, which may independently predict prevalent and incident dementia of the Alzheimer type (DAT) and to determine whether inclusion of identified factors increases the predictive accuracy of the CSF biomarkers Aβ42, tau, ptau181, tau/Aβ42, and ptau181/Aβ42.
Methods: Logistic regression identified variables that predicted prevalent DAT when considered together with each CSF biomarker in a cross-sectional sample of 201 participants with normal cognition and 46 with DAT. The area under the receiver operating characteristic curve (AUC) from the resulting model was compared with the AUC generated using the biomarker alone. In a second sample with normal cognition at baseline and longitudinal data available (n = 213), Cox proportional hazards models identified variables that predicted incident DAT together with each biomarker, and the models' concordance probability estimate (CPE), which was compared to the CPE generated using the biomarker alone.
Results: APOE genotype including an ε4 allele, male gender, and smaller normalized whole brain volumes (nWBV) were cross-sectionally associated with DAT when considered together with every biomarker. In the longitudinal sample (mean follow-up = 3.2 years), 14 participants (6.6%) developed DAT. Older age predicted a faster time to DAT in every model, and greater education predicted a slower time in 4 of 5 models. Inclusion of ancillary variables resulted in better cross-sectional prediction of DAT for all biomarkers (p < 0.0021), and better longitudinal prediction for 4 of 5 biomarkers (p < 0.0022).
Conclusions: The predictive accuracy of CSF biomarkers is improved by including age, education, and nWBV in analyses.
Footnotes
Study funding: Supported by the NIH (NINDS P30 NS057105, NIA P50 AG005681, P01 AG003991, and P01 AG026276); the NCRR (KL2RR024994 and 1UL1RR024992); and the Charles F. and Joanne Knight Alzheimer's Research Initiative of the Washington University Alzheimer's Disease Research Center.
Editorial, page 496
Supplemental data at www.neurology.org
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- AD
- Alzheimer disease
- AUC
- area under the receiver operating characteristic curve
- CDR
- Clinical Dementia Rating
- CPE
- concordance probability estimate
- CS
- collateral source
- DAT
- dementia of the Alzheimer type
- GDS
- Geriatric Depression Scale
- LP
- lumbar puncture
- MMSE
- Mini Mental-State Examination
- nWBV
- normalized whole brain volume
- ROC
- receiver operating characteristic
- Received May 14, 2010.
- Accepted September 20, 2010.
- Copyright © 2011 by AAN Enterprises, Inc.
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