Serial MRI and CSF Biomarkers in Normal Aging, MCI, and AD

Objective: To compare the annual change in MRI and CSF biomarkers in cognitively normal (CN), amnestic mild cognitive impairment (aMCI), and Alzheimer disease (AD). Comparisons were based on intergroup discrimination, correlation with concurrent cognitive/functional changes, relationships to APOE genotype, and sample sizes for clinical trials.

Methods: We used data from the Alzheimer's Disease Neuroimaging Initiative study consisting of CN, aMCI, and AD cohorts with both baseline and 12-month follow-up CSF and MRI. The annual change in CSF (total-tau [t-tau], Abeta(1-42)) and MRI (change in ventricular volume) was obtained in 312 subjects (92 CN, 149 aMCI, 71 AD).

Results: There was no significant average annual change in either CSF biomarker in any clinical group except t-tau in CN; moreover, the annual change did not differ by clinical group in pairwise comparisons. In contrast, annual increase in ventricular volume increased in the following order, AD > aMCI > CN, and differences were significant between all clinical groups in pairwise comparisons. Ventricular volume increase correlated with concurrent worsening on cognitive/functional indices in aMCI and AD whereas evidence of a similar correlation with change in CSF measures was unclear. The annual changes in MRI differed by APOE epsilon4 status overall and among aMCI while annual changes in CSF biomarkers did not. Estimated sample sizes for clinical trials are notably less for MRI than the CSF or clinical measures.

Conclusions: Unlike the CSF biomarkers evaluated, changes in serial structural MRI are correlated with concurrent change on general cognitive and functional indices in impaired subjects, track with clinical disease stage, and are influenced by APOE genotype.