{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:29:05Z","timestamp":1787502545986,"version":"build-2736575974"},"reference-count":67,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T00:00:00Z","timestamp":1733875200000},"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>Background\/Objectives: Those with the genetic disorder Down syndrome are at high risk of developing Alzheimer\u2019s disease. Previous work shows group differences in magnetic resonance spectroscopy metabolite measures in adults with Down syndrome who have Alzheimer\u2019s disease-related dementia compared to those who do not. In this pilot study, we assess relationships between metabolites and measures related to dementia status in a sample of adults with Down syndrome. Methods: Seventeen adults with Down syndrome were scanned using a 3 tesla MRI scanner. Magnetic resonance spectroscopy scans focused on the hippocampus and dorsal lateral prefrontal cortex. Metabolites of interest, including myo-inositol and N-acetyl-aspartate, were correlated with scores on the Dementia Questionnaire for People with Learning Disabilities, cortical thickness, and a measure of cognitive ability. In addition, cortical thickness was compared to an age- and sex-matched cohort of 17 previously scanned adults without Down syndrome. Results: Metabolite measures were not significantly related to cognitive\/behavioral measures or to cortical thickness in this small cohort. Participants with Down syndrome showed widespread increases in cortical thickness compared to controls, even after accounting for potential differences in grey matter\/white matter contrast. Conclusions: Metabolite values were not related to two continuous measures that have previously been associated with dementia status in those with Down syndrome.<\/jats:p>","DOI":"10.3390\/brainsci14121241","type":"journal-article","created":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T06:44:05Z","timestamp":1733899445000},"page":"1241","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Assessing the Relationship of Brain Metabolites to Cortical Thickness and Dementia Symptoms in Adults with Down Syndrome: A Pilot Study"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1504-7130","authenticated-orcid":false,"given":"Katherine A.","family":"Koenig","sequence":"first","affiliation":[{"name":"Imaging Sciences, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7989-3897","authenticated-orcid":false,"given":"Pallab K.","family":"Bhattacharyya","sequence":"additional","affiliation":[{"name":"Imaging Sciences, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"88","DOI":"10.3109\/13506120208995241","article-title":"Intraneuronal Abeta42 accumulation in Down syndrome brain","volume":"9","author":"Mori","year":"2002","journal-title":"Amyloid"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/s41582-018-0132-6","article-title":"Dementia in Down syndrome: Unique insights for Alzheimer disease research","volume":"15","author":"Lott","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1006\/nbdi.1996.0003","article-title":"Sequence of deposition of heterogeneous amyloid beta-peptides and APO E in Down syndrome: Implications for initial events in amyloid plaque formation","volume":"3","author":"Lemere","year":"1996","journal-title":"Neurobiol. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"439","DOI":"10.3233\/JAD-170390","article-title":"PET Imaging of Tau Pathology and Relationship to Amyloid, Longitudinal MRI, and Cognitive Change in Down Syndrome: Results from the Down Syndrome Biomarker Initiative (DSBI)","volume":"60","author":"Rafii","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Sullivan, K.D., Evans, D., Pandey, A., Hraha, T.H., Smith, K.P., Markham, N., Rachubinski, A.L., Wolter-Warmerdam, K., Hickey, F., and Espinosa, J.M. (2017). Trisomy 21 causes changes in the circulating proteome indicative of chronic autoinflammation. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-13858-3"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"84489","DOI":"10.18632\/oncotarget.21060","article-title":"Aberrations in circulating inflammatory cytokine levels in patients with Down syndrome: A meta-analysis","volume":"8","author":"Zhang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3653","DOI":"10.1093\/brain\/awaa326","article-title":"Evolution of neuroinflammation across the lifespan of individuals with Down syndrome","volume":"143","author":"Iulita","year":"2020","journal-title":"Brain"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.4049\/jimmunol.1901166","article-title":"An Altered Relationship between Soluble TREM2 and Inflammatory Markers in Young Adults with Down Syndrome: A Preliminary Report","volume":"204","author":"Weber","year":"2020","journal-title":"J. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/S1474-4422(15)70016-5","article-title":"Neuroinflammation in Alzheimer\u2019s disease","volume":"14","author":"Heneka","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1016\/j.ajpath.2011.05.047","article-title":"Reactive glia not only associates with plaques but also parallels tangles in Alzheimer\u2019s disease","volume":"179","author":"Mielke","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Garcia, O., and Flores-Aguilar, L. (2022). Astroglial and microglial pathology in Down syndrome: Focus on Alzheimer\u2019s disease. Front. Cell. Neurosci., 16.","DOI":"10.3389\/fncel.2022.987212"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1159\/000111347","article-title":"Multinuclear NMR studies on the energy metabolism of glial and neuronal cells","volume":"15","author":"Brand","year":"1993","journal-title":"Dev. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1007\/s11481-013-9460-x","article-title":"Magnetic resonance spectroscopy to assess neuroinflammation and neuropathic pain","volume":"8","author":"Chang","year":"2013","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/nbm.1186","article-title":"Myo-inositol: A marker of reactive astrogliosis in glial tumors?","volume":"21","author":"Hattingen","year":"2008","journal-title":"NMR Biomed."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.18632\/aging.102677","article-title":"Down syndrome and Alzheimer\u2019s disease: Common molecular traits beyond the amyloid precursor protein","volume":"12","author":"Gomez","year":"2020","journal-title":"Aging"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s40478-021-01300-9","article-title":"Developmental deficits and staging of dynamics of age associated Alzheimer\u2019s disease neurodegeneration and neuronal loss in subjects with Down syndrome","volume":"10","author":"Wegiel","year":"2022","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.mito.2020.07.007","article-title":"Mitochondrial pathways in human health and aging","volume":"54","author":"Bornstein","year":"2020","journal-title":"Mitochondrion"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1523\/JNEUROSCI.13-03-00981.1993","article-title":"Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types","volume":"13","author":"Urenjak","year":"1993","journal-title":"J. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Schuff, N., Meyerhoff, D.J., Mueller, S., Chao, L., Sacrey, D.T., Laxer, K., and Weiner, M.W. (2006). N-Acetylaspartate as a marker of neuronal injury in neurodegenerative disease. N-Acetylaspartate, Springer. A Unique Neuronal Molecule in the Central Nervous System.","DOI":"10.1007\/0-387-30172-0_17"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.pneurobio.2006.12.003","article-title":"N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology","volume":"81","author":"Moffett","year":"2007","journal-title":"Prog. Neurobiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"101503","DOI":"10.1016\/j.arr.2021.101503","article-title":"Mitochondrial dysfunction, oxidative stress, neuroinflammation, and metabolic alterations in the progression of Alzheimer\u2019s disease: A meta-analysis of in vivo magnetic resonance spectroscopy studies","volume":"72","author":"Song","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0925-4927(98)00010-9","article-title":"Metabolic brain mapping in Alzheimer\u2019s disease using proton magnetic resonance spectroscopy","volume":"82","author":"Lazeyras","year":"1998","journal-title":"Psychiatry Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1002\/mrm.1910330619","article-title":"Role of increased cerebral myo-inositol in the dementia of Down syndrome","volume":"33","author":"Shonk","year":"1995","journal-title":"Magn. Reason. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1176\/ajp.156.12.1879","article-title":"High brain myo-inositol levels in the predementia phase of Alzheimer\u2019s disease in adults with Down\u2019s syndrome: A 1H MRS study","volume":"156","author":"Huang","year":"1999","journal-title":"Am. J. Psychiatry"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1001\/archpsyc.62.12.1360","article-title":"Hippocampal Myo-inositol and Cognitive Ability in Adults With Down Syndrome: An In Vivo Proton Magnetic Resonance Spectroscopy Study","volume":"62","author":"Beacher","year":"2005","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/j.nicl.2016.06.001","article-title":"1H-MRS metabolites in adults with Down syndrome: Effects of dementia","volume":"11","author":"Lin","year":"2016","journal-title":"NeuroImage Clin."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1002\/ana.26178","article-title":"Metabolite Signature of Alzheimer\u2019s Disease in Adults with Down Syndrome","volume":"90","author":"Montal","year":"2021","journal-title":"Ann. Neurol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.neuroimage.2011.03.073","article-title":"Down syndrome with and without dementia: An in vivo proton Magnetic Resonance Spectroscopy study with implications for Alzheimer\u2019s disease","volume":"57","author":"Lamar","year":"2011","journal-title":"NeuroImage"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0028-3932(96)00055-3","article-title":"Long-term memory in mental retardation: Evidence for a specific impairment in subjects with Down\u2019s syndrome","volume":"35","author":"Carlesimo","year":"1997","journal-title":"Neuropsychologia"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1111\/1467-8624.00522","article-title":"The neuropsychology of Down syndrome: Evidence for hippocampal dysfunction","volume":"74","author":"Pennington","year":"2003","journal-title":"Child Dev."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Goldman-Rakic, P.S. (1990). Cellular and circuit basis of working memory in prefrontal cortex of nonhuman primates. Prog. Brain Res., 85.","DOI":"10.1016\/S0079-6123(08)62688-6"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1111\/j.1365-2788.2010.01262.x","article-title":"Executive function in adolescents with Down Syndrome","volume":"54","author":"Lanfranchi","year":"2010","journal-title":"J. Intellect. Disabil. Res."},{"key":"ref_33","first-page":"621","article-title":"Morphology of Alzheimer disease","volume":"108","author":"Braak","year":"1990","journal-title":"Fortschritte Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.nicl.2018.01.024","article-title":"A longitudinal study of brain anatomy changes preceding dementia in Down syndrome","volume":"18","author":"Pujol","year":"2018","journal-title":"NeuroImage Clin."},{"key":"ref_35","first-page":"e12288","article-title":"Cortical atrophy and amyloid and tau deposition in Down syndrome: A longitudinal study","volume":"14","author":"Padilla","year":"2022","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.neurobiolaging.2019.02.018","article-title":"Delineating the topography of amyloid-associated cortical atrophy in Down syndrome","volume":"80","author":"Mak","year":"2019","journal-title":"Neurobiol. Aging"},{"key":"ref_37","first-page":"e12044","article-title":"Promising outcome measures of early Alzheimer\u2019s dementia in adults with Down syndrome","volume":"12","author":"Zigman","year":"2020","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1111\/j.1365-2788.1996.tb00642.x","article-title":"Further evaluation of the Dementia Questionnaire for Persons with Mental Retardation (DMR)","volume":"40","author":"Evenhuis","year":"1996","journal-title":"J. Intell. Disabil. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1186\/s13195-022-01064-x","article-title":"Neural correlates of episodic memory in adults with Down syndrome and Alzheimer\u2019s disease","volume":"14","author":"Benejam","year":"2022","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1016\/S0140-6736(20)30689-9","article-title":"Clinical and biomarker changes of Alzheimer\u2019s disease in adults with Down syndrome: A cross-sectional study","volume":"395","author":"Fortea","year":"2020","journal-title":"Lancet"},{"key":"ref_41","unstructured":"Evenhuis, H.M., Kengen, M.M.F., and Eurlings, H.A.L. (2006). Dementia Questionnaire for People with Intellectual Disabilities, Harcourt Assessment B.V.. [2nd ed.]."},{"key":"ref_42","unstructured":"Wechsler, D. (1997). WAIS-III\/WMS-III Technical Manual, The Psychological Corporation."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1002\/mrm.1910290613","article-title":"Automatic, localized in vivo adjustment of all first- and second-order shim coils","volume":"29","author":"Gruetter","year":"1993","journal-title":"Magn. Reson. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1002\/hbm.10062","article-title":"Fast robust automated brain extraction","volume":"17","author":"Smith","year":"2002","journal-title":"Hum. Brain Mapp."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1109\/42.906424","article-title":"Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm","volume":"20","author":"Zhang","year":"2001","journal-title":"IEEE Trans. Med. Imaging"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"S208","DOI":"10.1016\/j.neuroimage.2004.07.051","article-title":"Advances in functional and structural MR image analysis and implementation as FSL","volume":"23","author":"Smith","year":"2004","journal-title":"Neuroimage"},{"key":"ref_47","unstructured":"Deelchand, D. (2024, September 01). MRSpa: Magnetic Resonance Signal Processing and Analysis. Available online: https:\/\/www.cmrr.umn.edu\/downloads\/mrspa\/."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1002\/mrm.1910300604","article-title":"Estimation of metabolite concentrations from localized in vivo proton NMR spectra","volume":"30","author":"Provencher","year":"1993","journal-title":"Magn. Reson. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/j.neuroimage.2006.01.021","article-title":"An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest","volume":"31","author":"Desikan","year":"2006","journal-title":"NeuroImage"},{"key":"ref_50","unstructured":"(2024, September 15). Freesurfer. Available online: https:\/\/surfer.nmr.mgh.harvard.edu\/."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"60","DOI":"10.3102\/10769986025001060","article-title":"On the Adaptive Control of the False Discovery Rate in Multiple Testing With Independent Statistics","volume":"25","author":"Benjamini","year":"2000","journal-title":"J. Educ. Behav. Stat."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3758\/BF03193146","article-title":"G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences","volume":"39","author":"Faul","year":"2007","journal-title":"Behav. Res. Methods"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1111\/j.1468-3148.1997.tb00006.x","article-title":"Dementia Questionnaire for Persons with Mental Retardation (DMR): Modified Criteria for Adults with Down\u2019s Syndrome","volume":"10","author":"Prasher","year":"1997","journal-title":"J. Appl. Res. Intellect. Disabil."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1212\/WNL.0b013e31822dc7e1","article-title":"Magnetic resonance spectroscopy, \u03b2-amyloid load, and cognition in a population-based sample of cognitively normal older adults","volume":"77","author":"Kantarci","year":"2011","journal-title":"Neurology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/1866-1955-6-42","article-title":"Hippocampal glutamate-glutamine (Glx) in adults with Down syndrome: A preliminary study using in vivo proton magnetic resonance spectroscopy (1H MRS)","volume":"6","author":"Tan","year":"2014","journal-title":"J. Neurodev. Disord."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"310","DOI":"10.5409\/wjcp.v12.i5.310","article-title":"Brain metabolic profile assessed by magnetic resonance spectroscopy in children with Down syndrome: Relation to intelligence quotient","volume":"12","author":"Elmahdy","year":"2023","journal-title":"World J. Clin. Pediatr."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1111\/jir.12901","article-title":"Identifying dementia in Down syndrome with the Severe Impairment Battery, Brief Praxis Test and Dementia Scale for People with Learning Disabilities","volume":"65","author":"Wallace","year":"2021","journal-title":"J. Intellect. Disabil. Res."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Paiva, A.F., Nolan, A., Thumser, C., and Santos, F.H. (2020). Screening of Cognitive Changes in Adults with Intellectual Disabilities: A Systematic Review. Brain Sci., 10.","DOI":"10.20944\/preprints202009.0739.v1"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"101874","DOI":"10.1016\/j.nicl.2019.101874","article-title":"Structural magnetic resonance imaging demonstrates abnormal cortical thickness in Down syndrome: Newborns to young adults","volume":"23","author":"Levman","year":"2019","journal-title":"NeuroImage Clin."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4043","DOI":"10.1002\/hbm.24230","article-title":"Down syndrome is accompanied by significantly reduced cortical grey\u2013white matter tissue contrast","volume":"39","author":"Bletsch","year":"2018","journal-title":"Hum. Brain Mapp."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1111\/jon.12259","article-title":"Age-Related Cortical Thickness Reduction in Non-Demented Down\u2019s Syndrome Subjects","volume":"26","author":"Romano","year":"2016","journal-title":"J. Neuroimaging"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.neurobiolaging.2017.01.009","article-title":"The Down syndrome brain in the presence and absence of fibrillar \u03b2-amyloidosis","volume":"53","author":"Annus","year":"2017","journal-title":"Neurobiol. Aging"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.neuroimage.2009.06.074","article-title":"Age-associated alterations in cortical gray and white matter signal intensity and gray to white matter contrast","volume":"48","author":"Salat","year":"2009","journal-title":"NeuroImage"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"6527","DOI":"10.1002\/alz.14146","article-title":"Characterization of white matter hyperintensities in Down syndrome","volume":"20","author":"Zsadanyi","year":"2024","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/1866-1955-5-19","article-title":"Dementia in Down\u2019s syndrome: An MRI comparison with Alzheimer\u2019s disease in the general population","volume":"5","author":"Mullins","year":"2013","journal-title":"J. Neurodev. Disord."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.ridd.2009.01.010","article-title":"Diagnosing Alzheimer\u2019s dementia in Down syndrome: Problems and possible solutions","volume":"30","year":"2009","journal-title":"Res. Dev. Disabil."},{"key":"ref_67","first-page":"e12184","article-title":"Markers of early changes in cognition across cohorts of adults with Down syndrome at risk of Alzheimer\u2019s disease","volume":"13","author":"Aschenbrenner","year":"2021","journal-title":"Alzheimer\u2019s Dement."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/14\/12\/1241\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:52:15Z","timestamp":1760115135000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/14\/12\/1241"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,11]]},"references-count":67,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["brainsci14121241"],"URL":"https:\/\/doi.org\/10.3390\/brainsci14121241","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,11]]}}}