The Structural Changes of Frontal Subregions and Their Correlations with Cognitive Impairment in Patients with Alzheimer's Disease

The frontal lobe is affected by Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, we still lack sufficient understanding of subregion atrophy in the frontal cortex, and the relationship between subregions volume and cognitive decline in AD or MCI remains unclear.This study enrolled 434 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI), including 150 cognitively normals (CN), 187 subjects with MCI, and 97 patients with AD. The gray matter of frontal regions and subregions was divided based on the BNA-246 atlas and its volume was measured by voxel-based morphometry (VBM). Analysis of covariance was performed to compare the differences in frontal regions and subregions volume. Then, receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to analyze the discriminative ability of subregion volume to distinguish the three groups. In addition, we investigated the association of subregion volume with Mini-Mental State Examination (MMSE) score and Alzheimer's Disease Assessment Scale-Cognitive Behavior section (ADAS-cog) scores with age, gender, education, and the estimated total intracranial volume (eTIV) as covariates.In addition to the regions of frontal lobe atrophy found in previous studies, atrophy of the precentral gyrus (PrG) and some of its subregions were found in MCI. The volume of the right dorsal area 9/46 (MFG_7_1) was the best index to differentiate AD from CN, with an AUC value of 0.7. Moreover, we found that some subregions are associated with cognition in patients with MCI and AD.Frontal lobe atrophy in MCI is more extensive than we assumed. In addition, the volume of right MFG_7_1 has the potential to distinguish AD from CN.