MRI Asymmetry Index of Hippocampal Subfields Increases Through the Continuum From the Mild Cognitive Impairment to the Alzheimer's Disease

Objective: It is well known that the hippocampus presents significant asymmetry in Alzheimer’s disease (AD) and that difference in volumes between left and right exists and varies with disease progression. However, few works investigated whether the asymmetry degree of subfields of hippocampus changes through the continuum from Mild Cognitive Impairment (MCI) to AD. Thus, aim of the present work was to evaluate the Asymmetry Index (AI) of hippocampal substructures as possible MRI biomarkers of Dementia. Moreover, we aimed to assess whether the subfields presented peculiar differences between left and right hemispheres. We also investigated the relationship between the asymmetry magnitude in hippocampal subfields and the decline of verbal memory as assessed by Rey’s auditory verbal learning test (RAVLT). Methods: Four-hundred subjects were selected from ADNI, equally divided into healthy controls (HC), AD, stable MCI (sMCI) and progressive MCI (pMCI). The structural baseline T1s were processed with FreeSurfer 6.0 and volumes of whole hippocampus (WH) and 12 subfields were extracted. The AI was calculated as: (|Left-Right|/(Left+Right))*100. ANCOVA was used for evaluating AI differences between diagnoses, while paired t-test was applied for assessing changes between left and right volumes, separately for each group. Partial correlation was performed for exploring relationship between RAVLT summary scores (Immediate, Learning, Forgetting, Percent Forgetting) and hippocampal substructures AI. The statistical threshold was Bonferroni corrected p<0.05/13=0.0038. Results: We found a general trend of increased degree of asymmetry with increasing severity of diagnosis. Indeed, AD presented the higher magnitude of asymmetry compared with HC, sMCI and pMCI, in the WH (AI mean 5.13±4.29 SD) and in each of its twelve subfields. Moreover, we found in AD a significant negative correlation (r =-0.33, p=0.00065) between the AI of parasubiculum (mean 12.70±9.59 SD) and the RAVLT Learning score (mean 1.70±1.62 SD). Conclusions: Our findings showed that hippocampal subfields AI varies differently among the four groups HC, sMCI, pMCI and AD. Moreover, we found - for the first time - that hippocampal substructures had different sub-patterns of lateralization compared with the whole hippocampus. Importantly, the severity in learning rate was correlated with pathological high degree of asymmetry in parasubiculum of AD patients.

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