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This cross-sectional clinicoradiologic study aimed to assess whole hippocampal, subregion, and\/or subfield volume loss in semantic dementia versus controls and across its variants. Thirty-five semantic dementia participants and 15 controls from the Neurodegenerative Research Group at Mayo Clinic who had completed 3.0-T volumetric magnetic resonance imaging and 18F-fluorodeoxyglucose-positron emission tomography were included. Classification as left-predominant (n = 25) or right-predominant (n = 10) variant was based on temporal lobe hypometabolism. Volumes of hippocampal subregions (head, body, and tail) and subfields (parasubiculum, presubiculum, subiculum, cornu ammonis 1, cornu ammonis 3, cornu ammonis 4, dentate gyrus, molecular layer, hippocampal\u2013amygdaloid transition area, and fimbria) were obtained using FreeSurfer 7. Subfield volumes were measured separately from head and body subregions. We fit linear mixed-effects models using log-transformed whole hippocampal\/subregion\/subfield volumes as dependent variables; age, sex, total intracranial volume, hemisphere and a group-by-hemisphere interaction as fixed effects; and subregion\/subfield nested within hemisphere as a random effect. Significant results (P &amp;lt; 0.05) are hereby reported. At the whole hippocampal level, the dominant (predominantly involved) hemisphere of both variants showed 23\u201327% smaller volumes than controls. The non-dominant (less involved) hemisphere of the right-predominant variant also showed volume loss versus controls and the left-predominant variant. At the subregional level, both variants showed 17\u201328% smaller dominant hemisphere head, body, and tail than controls, with the right-predominant variant also showing 8\u201312% smaller non-dominant hemisphere head than controls and left-predominant variant. At the subfield level, the left-predominant variant showed 12\u201336% smaller volumes across all dominant hemisphere subfields and 14\u201315% smaller non-dominant hemisphere parasubiculum, presubiculum (head and body), subiculum (head) and hippocampal\u2013amygdaloid transition area than controls. The right-predominant variant showed 16\u201349% smaller volumes across all dominant hemisphere subfields and 14\u201322% smaller parasubiculum, presubiculum, subiculum, cornu ammonis 3, hippocampal\u2013amygdaloid transition area (all from the head) and fimbria of non-dominant hemisphere versus controls. Comparison of dominant hemispheres showed 16\u201329% smaller volumes of the parasubiculum, presubiculum (head) and fimbria in the right-predominant than left-predominant variant; comparison of non-dominant hemispheres showed 12\u201315% smaller cornu ammonis 3, cornu ammonis 4, dentate gyrus, hippocampal\u2013amygdaloid transition area (all from the head) and cornu ammonis 1, cornu ammonis 3 and cornu ammonis 4 (all from the body) in the right-predominant variant. All hippocampal subregion\/subfield volumes are affected in semantic dementia, although some are more affected in both dominant and non-dominant hemispheres of the right-predominant than the left-predominant variant by the time of presentation. Involvement of hippocampal structures is apparently more subregion dependent than subfield dependent, indicating possible superiority of subregion volumes as disease biomarkers.<\/jats:p>","DOI":"10.1093\/braincomms\/fcae097","type":"journal-article","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T19:34:12Z","timestamp":1711049652000},"source":"Crossref","is-referenced-by-count":7,"title":["Volumetric analysis of hippocampal subregions and subfields in left and right semantic dementia"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2100-5033","authenticated-orcid":false,"given":"Arenn F","family":"Carlos","sequence":"first","affiliation":[{"name":"Department of Neurology, Mayo Clinic , Rochester, MN 55905 \u00a0 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen D","family":"Weigand","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Mayo Clinic , Rochester, MN 55905 \u00a0 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8206-3432","authenticated-orcid":false,"given":"Joseph R","family":"Duffy","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic , Rochester, MN 55905 \u00a0 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather M","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic , Rochester, MN 55905 \u00a0 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene L","family":"Utianski","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic , Rochester, MN 55905 \u00a0 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary M","family":"Machulda","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychology, Mayo Clinic , Rochester, MN 55905 \u00a0 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4390-685X","authenticated-orcid":false,"given":"Hugo","family":"Botha","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic , Rochester, MN 55905 \u00a0 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nha Trang","family":"Thu Pham","sequence":"additional","affiliation":[{"name":"Department of Radiology, Mayo Clinic , Rochester, MN 55905 \u00a0 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val J","family":"Lowe","sequence":"additional","affiliation":[{"name":"Department of Radiology, Mayo Clinic , Rochester, MN 55905 \u00a0 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1466-8357","authenticated-orcid":false,"given":"Christopher G","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Department of Radiology, Mayo Clinic , Rochester, MN 55905 \u00a0 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6914-1563","authenticated-orcid":false,"given":"Jennifer L","family":"Whitwell","sequence":"additional","affiliation":[{"name":"Department of Radiology, Mayo Clinic , Rochester, MN 55905 \u00a0 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2930-8634","authenticated-orcid":false,"given":"Keith A","family":"Josephs","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic , Rochester, MN 55905 \u00a0 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,3,25]]},"reference":[{"key":"2024043010205034900_fcae097-B1","volume-title":"Organization of memory","author":"Tulving","year":"1972"},{"key":"2024043010205034900_fcae097-B2","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1037\/0003-066X.40.4.385","article-title":"How many memory systems are there?","volume":"40","author":"Tulving","year":"1985","journal-title":"Am Psychol"},{"issue":"8","key":"2024043010205034900_fcae097-B3","doi-asserted-by":"crossref","first-page":"4030","DOI":"10.1007\/s00415-022-11073-3","article-title":"Frontotemporal lobar degeneration with TAR DNA-binding protein 43 (TDP-43): Its journey of more than 100 years","volume":"269","author":"Carlos","year":"2022","journal-title":"J Neurol"},{"issue":"7","key":"2024043010205034900_fcae097-B4","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1212\/WNL.25.7.627","article-title":"The syndrome of Gogi (word-meaning) aphasia. 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