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Neuropsychological Test Performance and MRI Markers of Dementia Risk

Reducing Education Bias

Walter, Stefan PhD*,†; Dufouil, Carole PhD; Gross, Alden L. PhD§; Jones, Richard N. ScD; Mungas, Dan PhD; Filshtein, Teresa J. PhD; Manly, Jennifer J. PhD#; Arpawong, Thalida E. PhD**; Glymour, M. Maria ScD

Alzheimer Disease & Associated Disorders: July–September 2019 - Volume 33 - Issue 3 - p 179–185
doi: 10.1097/WAD.0000000000000321
Original Articles

Background: To use neuropsychological assessments for studying the underlying disease processes contributing to dementia, it is crucial that they correspond to magnetic resonance imaging (MRI)-based measures of dementia, regardless of educational level.

Methods: French 3-City Dijon MRI study cohort members (n=1782) with assessments of white matter lesion volume (WMLV), hippocampal volume (HCV), and cerebrospinal fluid volume (CSFV), and 6 waves of neuropsychological assessments over 11 years, including Mini-Mental State Examination (MMSE), plus 5 other tests combined using a Z-score or item-response theory (IRT-cognition) comprised the study cohort. We evaluated, testing interactions, whether education modified associations of MRI markers with intercept or rate of change of MMSE, Z-score composite, or IRT-cognition.

Results: In linear models, education modified the associations of WMLV and CSFV with MMSE and CSFV and Z-score composite. In mixed models, education modified the associations of WMLV and CSFV with level of MMSE and the association of HCV with slope of MMSE. Education also modified the association with CSFV and slope of Z-score composite decline. There was no evidence that education modified associations between MRI measures and level or slope of IRT-cognition.

Conclusions: Longitudinal analysis of correctly scaled neuropsychological assessments may provide unbiased proxies for MRI-based measures of dementia risk.

*Foundation for Biomedical Research Getafe University Hospital, Getafe, Madrid

Department of Epidemiology and Biostatistics, University of California, San Francisco

Davis School of Medicine, University of California, Sacramento

**Davis School of Gerontology, University of Southern California, Los Angeles, CA

Inserm, Bordeaux Population Health Research Center, UMR 1219, University of Bordeaux, ISPED, Bordeaux, France

§Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD

Department of Psychiatry & Human Behavior, Department of Neurology, Warren Alpert Medical School, Brown University, Providence, RI

#Department of Neurology and the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, NY

Financial support was from the National Institute on Aging, including AG051170 (S.W., A.L.G., D.M., R.N.J., T.J.F., and M.M.G.) and AG056164 (J.J.M.).

The 3C Study is also supported by the Caisse Nationale Maladie des Travailleurs Salarie´s, Direction Générale de la Santé, MGEN, Institut de la Longévité, Conseils Regionaux of Aquitaine and Bourgogne, Fondation de France, and Ministry of Research–INSERM Program “Cohortes et collections de données biologiques.”

The authors declare no conflicts of interest.

Reprints: M. Maria Glymour, ScD, Department of Epidemiology and Biostatistics, 550 16th Street, University of California, San Francisco, CA 94158 (e-mail:

Received February 18, 2019

Accepted April 10, 2019

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