Neuropsychological Test Performance and MRI Markers of Dementia Risk Reducing Education Bias

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.