To assess relative volume loss of hippocampal subregions/subfields in semantic dementia(SMD) compared to controls and determine whether subfield volumes differ between left-predominant(lpSMD) and right-predominant(rpSMD) SMD.

Semantic dementia is characterized by conceptual knowledge loss, with lpSMD associating more with impairment of verbal knowledge and rpSMD with behavioral changes and loss of non-verbal knowledge. The hippocampus participates in semantic memory preservation.

Thirty-four SMD and 15 controls from the Neurodegenerative Research Group that had completed 3T volumetric MRI and [¹⁸F]-fluorodeoxyglucose-PET scans were included. Participants were classified as lpSMD or rpSMD based on temporal lobe hypometabolism. Volumetric analysis of hippocampal subfields (CA1, CA3, CA4, dentate gyrus, molecular layer, fimbria, hippocampal-amgydaloid transition area [HATA], pre/parasubiculum and subiculum) were performed using FreeSurfer 7. Subfield volumes were measured separately from the head and body subregions. We fit a linear mixed effects model with log-transformed hippocampal subfield volume as the dependent variable; age, sex, total intracranial volume, hemisphere and a group-by-hemisphere interaction as fixed effects; and subfield nested within hemisphere as a random effect.

Twenty-seven participants (79%) were lpSMD, 7(21%) rpSMD. Compared to controls, lpSMD showed 21%-41% smaller volumes across all subregions/subfields of the dominant (predominantly involved) hemisphere and no differences in the non-dominant (spared) hemisphere. Contrarily, rpSMD showed 30%-50% volume reductions across all dominant hemisphere subregions/subfields versus controls, with the non-dominant hemisphere also showing 16-21% less volumes of the fimbria, HATA, parasubiculum, and presubiculum/subiculum of the head subregion. Comparison of dominant hemispheres showed 28% less volume of the parasubiculum in rpSMD; comparison of non-dominant hemispheres revealed 15% volume loss in entire CA3 and HATA in rpSMD versus lpSMD. Absolute degree of asymmetry across regions was similar in both groups.

All hippocampal subregional/subfield volumes are affected in SMD, with subregional/subfield volumes being more affected in some regions in both dominant and non-dominant hemispheres in rpSMD than in lpSMD.