Conversion of Mild Cognitive Impairment to Alzheimer Disease Predicted by Hippocampal Atrophy Maps

Abstract

Background While most patients with mild cognitive impairment (MCI) transition to Alzheimer disease (AD), others develop non-AD dementia, remain in the MCI state, or improve. Objective To test the following hypotheses: smaller hippocampal volumes predict conversion of MCI to AD, whereas larger hippocampal volumes predict cognitive stability and/or improvement; and patients with MCI who convert to AD have greater atrophy in the CA1 hippocampal subfield and subiculum. Design Prospective longitudinal cohort study. Setting University of California–Los Angeles Alzheimer’s Disease Research Center. Patients We followed up 20 MCI subjects clinically and neuropsychologically for 3 years. Main Outcome Measure Baseline regional hippocampal atrophy was analyzed with region-of-interest and 3-dimensional hippocampal mapping techniques. Results During the 3-year study, 6 patients developed AD (MCI-c), 7 remained stable (MCI-nc), and 7 improved (MCI-i). Patients with MCI-c had 9% smaller left and 13% smaller right mean hippocampal volumes compared with MCI-nc patients. Radial atrophy maps showed greater atrophy of the CA1 subregion in MCI-c. Patients with MCI-c had significantly smaller hippocampi than MCI-i patients (left, 24%; right, 27%). Volumetric analyses showed a trend for greater hippocampal atrophy in MCI-nc relative to MCI-i patients (eg, 16% volume loss). After permutation tests corrected for multiple comparison, the atrophy maps showed a significant difference on the right. Subicular differences were seen between MCI-c and MCI-i patients, and MCI-nc and MCI-i patients. Multiple linear regression analysis confirmed the group effect to be highly significant and independent of age, hemisphere, and Mini-Mental State Examination scores at baseline. Conclusions Smaller hippocampi and specifically CA1 and subicular involvement are associated with increased risk for conversion from MCI to AD. Patients with MCI-i tend to have larger hippocampal volumes and relative preservation of both the subiculum and CA1.