{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T09:27:59Z","timestamp":1775813279484,"version":"3.50.1"},"reference-count":24,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Objective: To investigate the integrated relationship between Cerebral Small Vessel Disease (CSVD) markers and quantitative facial soft-tissue measurements in Alzheimer\u2019s disease (AD) continuum, utilizing peripheral muscle health as a potential biomarker for systemic frailty and neurodegeneration. Methods: Retrospective analysis of 3T brain MRI data from 67 patients (AD, N = 45; Mild Cognitive Impairment [MCI], N = 22). CSVD markers were assessed using STRIVE and standardized scales (Fazekas, Potter). Facial soft-tissue metrics, including masseter and tongue volume, temporal muscle thickness (TMT), and fat infiltration (Mercuri Scale), were quantified via semi-automatic segmentation on T1-weighted sequences. Group comparisons (AD vs. MCI) used regression models adjusted for age and sex. The overall central\u2013peripheral relationship was explored via Canonical Correlation Analysis (CCA). Results: The AD group showed a highly significant cognitive decline (MMSE: 23.2 \u00b1 4.1 vs. 28.2 \u00b1 1.4, p &lt; 0.0001). Centrally, the presence of PVSs in the mesencephalic region was the most robust predictor for AD (p = 0.003). Peripherally, average masseter muscle volume was significantly lower in the AD group (p = 0.0273), and masseter fat infiltration was significantly higher (p = 0.025), supporting localized sarcopenia. The CCA demonstrated a statistically significant positive multivariate relationship (r = 0.51, Roy\u2019s Largest Root p = 0.015) between a higher combined CSVD burden and a worse soft tissue profile across the cohort. Conclusions: Quantitative indices of facial soft tissues, particularly masseter muscle volume and quality, reflect systemic frailty and cognitive deterioration along the AD continuum. The strong central\u2013peripheral correlation suggests that sarcopenia and CSVD are interconnected manifestations of a shared pathobiological process. These easily measurable facial markers could serve as valuable, non-invasive peripheral biomarkers, complementing traditional neuroimaging risk stratification in AD.<\/jats:p>","DOI":"10.3390\/brainsci16040403","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T13:09:31Z","timestamp":1775740171000},"page":"403","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Analysis of Cerebral Small Vessel Disease and Facial Soft-Tissue Markers in the Alzheimer\u2019s Disease Continuum"],"prefix":"10.3390","volume":"16","author":[{"given":"Caterina","family":"Bernetti","sequence":"first","affiliation":[{"name":"Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"},{"name":"Research Unit of Diagnostic Imaging, Department of Medicine and Surgery, Universit\u00e0 Campus Bio-Medico di Roma, 00128 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7204-4091","authenticated-orcid":false,"given":"Gianfranco","family":"Di Gennaro","sequence":"additional","affiliation":[{"name":"CRUISE Research Center, Science of Health Department, Magna Gr\u00e6cia University, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Roberti","sequence":"additional","affiliation":[{"name":"CRUISE Research Center, Science of Health Department, Magna Gr\u00e6cia University, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milena","family":"Ricci","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"},{"name":"Research Unit of Diagnostic Imaging, Department of Medicine and Surgery, Universit\u00e0 Campus Bio-Medico di Roma, 00128 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8264-0625","authenticated-orcid":false,"given":"Francesco","family":"Pipitone","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"},{"name":"Research Unit of Diagnostic Imaging, Department of Medicine and Surgery, Universit\u00e0 Campus Bio-Medico di Roma, 00128 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Profilo","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"},{"name":"Research Unit of Diagnostic Imaging, Department of Medicine and Surgery, Universit\u00e0 Campus Bio-Medico di Roma, 00128 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Motolese","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"},{"name":"Research Unit of Neurology, Department of Medicine and Surgery, Universit\u00e0 Campus Bio-Medico di Roma, 00128 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4517-3477","authenticated-orcid":false,"given":"Rosalinda","family":"Calandrelli","sequence":"additional","affiliation":[{"name":"Radiology and Neuroradiology Unit, Department of Imaging, Radiation Therapy and Hematology, Universit\u00e0 Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli\u2014IRCCS, 00168 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7248-3916","authenticated-orcid":false,"given":"Fabio","family":"Pilato","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"},{"name":"Research Unit of Neurology, Department of Medicine and Surgery, Universit\u00e0 Campus Bio-Medico di Roma, 00128 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Di Lazzaro","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"},{"name":"Research Unit of Neurology, Department of Medicine and Surgery, Universit\u00e0 Campus Bio-Medico di Roma, 00128 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno","family":"Beomonte Zobel","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"},{"name":"Research Unit of Diagnostic Imaging, Department of Medicine and Surgery, Universit\u00e0 Campus Bio-Medico di Roma, 00128 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0149-0801","authenticated-orcid":false,"given":"Carlo Augusto","family":"Mallio","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"},{"name":"Research Unit of Diagnostic Imaging, Department of Medicine and Surgery, Universit\u00e0 Campus Bio-Medico di Roma, 00128 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1016\/S0140-6736(20)32205-4","article-title":"Alzheimer\u2019s disease","volume":"397","author":"Scheltens","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1007\/s00415-018-9016-3","article-title":"Magnetic resonance imaging in Alzheimer\u2019s disease and mild cognitive impairment","volume":"266","author":"Chandra","year":"2019","journal-title":"J. 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