Heterogeneous cortical atrophy patterns in MCI not captured by conventional diagnostic criteria.

OBJECTIVE: We investigated differences in regional cortical thickness between previously identified empirically derived mild cognitive impairment (MCI) subtypes (amnestic MCI, dysnomic MCI, dysexecutive/mixed MCI, and cluster-derived normal) in order to determine whether these cognitive subtypes would show different patterns of cortical atrophy.

METHODS: Participants were 485 individuals diagnosed with MCI and 178 cognitively normal individuals from the Alzheimer's Disease Neuroimaging Initiative. Cortical thickness estimates were computed for 32 regions of interest per hemisphere. Statistical group maps compared each MCI subtype to cognitively normal participants and to one another.

RESULTS: The pattern of cortical thinning observed in each MCI subtype corresponded to their cognitive profile. No differences in cortical thickness were found between the cluster-derived normal MCI subtype and the cognitively normal group. Direct comparison between MCI subtypes suggested that the cortical thickness patterns reflect increasing disease severity.

CONCLUSIONS: There is an ordered pattern of cortical atrophy among patients with MCI that coincides with their profiles of increasing cognitive dysfunction. This heterogeneity is not captured when patients are grouped by conventional diagnostic criteria. Results in the cluster-derived normal group further support the premise that the conventional MCI diagnostic criteria are highly susceptible to false-positive diagnostic errors. Findings suggest a need to (1) improve the diagnostic criteria by reducing reliance on conventional screening measures, rating scales, and a single memory measure in order to avoid false-positive errors; and (2) divide MCI samples into meaningful subgroups based on cognitive and biomarkers profiles-a method that may provide better staging of MCI and inform prognosis.