Volumetric Analysis of Hippocampal Subregions and Subfields in Left and Right Predominant Semantic Dementia (P11-6.002)

Abstract

<h3>Objective:</h3> 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. <h3>Background:</h3> 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. <h3>Design/Methods:</h3> 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. <h3>Results:</h3> 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 <i>versus</i> 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 <i>versus</i> lpSMD. Absolute degree of asymmetry across regions was similar in both groups. <h3>Conclusions:</h3> 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. <b>Disclosure:</b> Arenn Faye Carlos, MD has nothing to disclose. Stephen Weigand has nothing to disclose. The institution of Rene Utianski has received research support from NIH. The institution of Joseph Duffy has received research support from NIH. Joseph Duffy has received publishing royalties from a publication relating to health care. Heather Clark has received personal compensation for serving as an employee of Mayo Clinic. The institution of Heather Clark has received research support from NIH. Heather Clark has received publishing royalties from a publication relating to health care. The institution of Dr. Machulda has received research support from NIH. Nha Trang Thu Pham has received personal compensation for serving as an employee of Mayo Clinic. Christopher Schwarz has received personal compensation for serving as an employee of Mayo Clinic. The institution of Christopher Schwarz has received research support from NIH. The institution of Dr. Jack has received research support from NIH. The institution of Dr. Jack has received research support from Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Clinic. Dr. Whitwell has nothing to disclose. Dr. Josephs has nothing to disclose.