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This heterogeneity stems from the complex interplay of various clinical phenotypes, genetic mutations and underlying neuropathologies, such as TDP-43 and tau proteinopathies. Currently, there is no single confirmed biomarker that can reliably diagnose disease, specifically disease stage, disease subtype and underlying neuropathology. Recent research has indicated that neuroimaging techniques hold the most promise for the discovery of FTD biomarkers. We propose a protocol for a systematic review and meta-analysis to identify MRI and fluorodeoxyglucose positron emission tomography (FDG-PET) biomarkers associated with clinical, genetic and pathological subtypes of FTD. We aim to address the following research questions: can regional MRI volumetry and FDG-PET hypometabolism differentiate (1) FTD patients from healthy controls; (2) sporadic cases of FTD from healthy controls; (3) genetic cases of FTD (MAPT, GRN, and C9orf72 mutations); and (4) underlying neuropathology, specifically discriminating between tau- and TDP-43-based FTD?<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Literature searches will be performed across three databases: Ovid Medline, Ovid Embase and Web of Science. Publications that have fewer than five participants, are non-human-based, not written in the English language or contain unpublished data will be excluded. Two independent investigators will screen and subsequently evaluate which publications to include. Should any disagreements arise, a third investigator will settle the discrepancy. After the random-effects meta-analysis has been used to extract and pool the data, I\n                      <jats:sup>2<\/jats:sup>\n                      analysis will be used to quantify heterogeneity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Ethics approval will not be required for this research. On completion, the systematic review and meta-analysis will be published in a peer-reviewed journal.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PROSPERO registration number<\/jats:title>\n                    <jats:p>CRD42024545302.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-101729","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T18:35:29Z","timestamp":1765564529000},"page":"e101729","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Volumetric MRI and FDG-PET hypometabolism biomarkers of frontotemporal dementia: protocol for a systematic review and meta-analysis"],"prefix":"10.1136","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0420-5208","authenticated-orcid":false,"given":"Taylor J","family":"Solomon","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Monash University, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4275-7557","authenticated-orcid":false,"given":"Ana","family":"Antonic-Baker","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Monash University, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9884-5463","authenticated-orcid":false,"given":"Lorena","family":"Romero","sequence":"additional","affiliation":[{"name":"Ian Potter Library, Alfred Health, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Sinclair","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Monash University, Melbourne, Victoria, Australia"},{"name":"Department of Neurology, Alfred Health, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terence J","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Monash University, Melbourne, Victoria, Australia"},{"name":"Department of Neurology, Alfred Health, Melbourne, Victoria, Australia"},{"name":"Department of Neurology, Royal Melbourne Hospital, Melbourne, Victoria, Australia"},{"name":"Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1182-0907","authenticated-orcid":false,"given":"Lucy","family":"Vivash","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Monash University, Melbourne, Victoria, Australia"},{"name":"Department of Neurology, Alfred Health, Melbourne, Victoria, Australia"},{"name":"Department of Neurology, Royal Melbourne Hospital, Melbourne, Victoria, Australia"},{"name":"Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"key":"2026010703463925000_15.12.e101729.1","doi-asserted-by":"crossref","DOI":"10.3389\/fnins.2018.00473","article-title":"Pathogenesis of Frontotemporal Lobar Degeneration: Insights From Loss of Function Theory and Early Involvement of the Caudate Nucleus","volume":"12","author":"Sobue","year":"2018","journal-title":"Front Neurosci"},{"key":"2026010703463925000_15.12.e101729.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bionps.2023.100065"},{"key":"2026010703463925000_15.12.e101729.3","doi-asserted-by":"crossref","DOI":"10.3390\/ijms241411732","article-title":"Frontotemporal Dementia, Where Do We Stand? 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