{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T20:00:39Z","timestamp":1773432039069,"version":"3.50.1"},"reference-count":70,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T00:00:00Z","timestamp":1742947200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>\nObjective\n<\/jats:title>\n<jats:p>Frailty has emerged as prevalent condition in ageing. While frailty has been assessed through physical and functional criteria, recent studies have explored the link between cognitive decline and frailty, which remains complex and warrants further investigation. Our aims were to compare differences at the brain level between robust and frail older people without dementia and to explore possible associations between brain measures and cognitive performance assessed with neuropsychological tests.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>\nMethods\n<\/jats:title>\n<jats:p>Using data from the \u201cCAM-Cam\u201d project that recruited a community dwelling population, we identified robust and frail participants based on the Rockwood Frailty index. Magnetic Resonance Imaging was performed to probe the interplay between physical frailty and cognitive health. The main aims were: (i) to identify differences in cognitive performance using the\u00a0Cattell Culture Fair test and the Tip of the Tongue test and (ii) to assess voxel-wise group-related effects, using a general linear model design to investigate potential differences between our two study groups (\u201cfrail\u201d and \u201crobust\u201d).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>\nResults\n<\/jats:title>\n<jats:p>Our findings revealed significantly smaller grey matter volume in frail individuals, primarily localized in cerebellar areas and in the right supramarginal gyrus. Diffusion magnetic resonance imaging scans showed diminished axial diffusivity values in frail participants, particularly in the corticospinal tract. Resting-state functional MRI showed increased functional connectivity values within the Default Mode Network (DMN) in frail individuals, relative to the robust group in parietal and cerebellar portions of the DMN. Moreover, we observed significant correlations between cognitive score and brain measures for our study groups.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>\nConclusions\n<\/jats:title>\n<jats:p>The associations between cognitive test scores and anatomical and functional patterns in the\u00a0brain highlight the complex interconnections between physical and cognitive aspects of frailty. This study brings novel insights into the early neurobiological markers associated with physical frailty in a cognitively healthy population.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0320492","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T20:56:10Z","timestamp":1743022570000},"page":"e0320492","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Neural correlates of frailty in cognitively healthy adults: A multimodal imaging study"],"prefix":"10.1371","volume":"20","author":[{"given":"Ilaria","family":"Parrotta","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenza","family":"Maistrello","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgio","family":"Arcara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dante","family":"Mantini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Lazzaro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8752-0978","authenticated-orcid":true,"given":"Sonia","family":"Montemurro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1513-5269","authenticated-orcid":true,"given":"Nicola","family":"Filippini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,3,26]]},"reference":[{"issue":"3","key":"pone.0320492.ref001","doi-asserted-by":"crossref","first-page":"e033870","DOI":"10.1136\/bmjopen-2019-033870","article-title":"Willingness, perceived barriers and motivators in adopting mobile applications for health-related interventions among older adults: a scoping review protocol","volume":"10","author":"NA Ahmad","year":"2020","journal-title":"BMJ Open"},{"issue":"9","key":"pone.0320492.ref002","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/s41569-018-0064-2","article-title":"Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty","volume":"15","author":"L Ferrucci","year":"2018","journal-title":"Nat Rev Cardiol"},{"issue":"9782","key":"pone.0320492.ref003","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1016\/S0140-6736(11)60844-1","article-title":"World report on disability","volume":"377","year":"2011","journal-title":"Lancet"},{"issue":"34","key":"pone.0320492.ref004","doi-asserted-by":"crossref","first-page":"e30169","DOI":"10.1097\/MD.0000000000030169","article-title":"Risk factors for frailty in older adults","volume":"101","author":"X Wang","year":"2022","journal-title":"Medicine (Baltimore)"},{"key":"pone.0320492.ref005","doi-asserted-by":"crossref","first-page":"74","DOI":"10.11606\/S1518-8787.2018052000497","article-title":"Factors associated with frailty in older adults: a longitudinal study","volume":"52","author":"JRS Fhon","year":"2018","journal-title":"Rev Saude Publica"},{"key":"pone.0320492.ref006","first-page":"1","article-title":"Frailty: What is it?","author":"M Proietti","year":"2020","journal-title":"Adv Exp Med Biol"},{"key":"pone.0320492.ref007","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.3389\/fneur.2019.01255","article-title":"Frailty Syndromes in Persons With Cerebrovascular Disease: A Systematic Review and Meta-Analysis","volume":"10","author":"K Palmer","year":"2019","journal-title":"Front Neurol"},{"issue":"24","key":"pone.0320492.ref008","first-page":"e3269","article-title":"Neuropathologic burden and the degree of frailty in relation to global cognition and dementia","volume":"95","author":"LMK Wallace","year":"2020","journal-title":"Neurology"},{"key":"pone.0320492.ref009","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.2147\/CIA.S165085","article-title":"Muscle weakness, cognitive impairment and their interaction on altered balance in elderly outpatients: results from the TRIP observational study","volume":"13","author":"F Lauretani","year":"2018","journal-title":"Clin Interv Aging"},{"issue":"1","key":"pone.0320492.ref010","doi-asserted-by":"crossref","first-page":"e12353","DOI":"10.1002\/dad2.12353","article-title":"Combination of gait speed and grip strength to predict cognitive decline and dementia","volume":"14","author":"SG Orchard","year":"2022","journal-title":"Alzheimers Dement (Amst)"},{"key":"pone.0320492.ref011","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jns.2016.07.055","article-title":"Does mild cognitive impairment always lead to dementia? 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