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However, less is known about the relationship with cortical microstructural characteristics [i.e. cortical mean diffusivity (cMD)] even though these are sensitive to preclinical phases of Alzheimer\u2019s disease. We studied a sample of 964 cognitively healthy adults (age: 40\u201382 years; 52% females) with available structural and diffusion MRI data. The preclinical Alzheimer\u2019s cognitive composite was used as the cognition measure, and plasma concentrations of neurodegenerative-related (i.e. phosphorylated tau 181 and neurofilament light) and inflammatory (i.e. high-sensitivity C-reactive protein) biomarkers were assessed, together with apolipoprotein \u025b4 status. Neuroimaging data was preprocessed using FreeSurfer and FSL, and a homemade surface-based approach was used to obtain cMD maps. A two-class generalized linear model was used as the main statistical analysis. We identified a significant negative association between both cortical measures (cMD and CTh) and age. cMD associations were more extensive at earlier ages (&amp;lt;50 years), while CTh associations were greater at older ages (&amp;gt;50 years). cMD was positively correlated with cognition and with both neurodegenerative-related biomarkers in prefrontal regions, while the association was negative and more widespread for the inflammatory biomarker. CTh was positively correlated with cognition in more restricted areas than cMD and only negatively correlated with neurofilament light. Also, cMD presented lower levels in apolipoprotein \u025b4 carriers compared to non-carriers, while no results were found for CTh. Correlating cMD with CTh resulted in a regional pattern of negative and positive correlations, differencing somatosensory and associative areas, respectively. Altogether, we show that cMD can capture microstructural cortical changes occurring across adulthood into older age before CTh alterations. Indeed, it seems more sensitive to age-related cognitive decline and pathological and inflammatory processes related to risk profiles, showing an opposite trend to CTh in relation to neurodegenerative biomarker levels. Furthermore, our results suggest a pattern relating the two cortical metrics perhaps reflecting a cortical organization pattern.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf511","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T12:48:49Z","timestamp":1767962929000},"source":"Crossref","is-referenced-by-count":0,"title":["Cortical mean diffusivity detects early age-related changes and associates with cognition and plasma biomarkers"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0659-6978","authenticated-orcid":false,"given":"Oriol","family":"Perera-Cruz","sequence":"first","affiliation":[{"name":"Department of Medicine, Faculty of Medicine and Health Sciences and Institute of Neurosciences, University of Barcelona , Barcelona 08036 ,","place":["Spain"]},{"name":"August Pi I Sunyer Institute of Biomedical Research (IDIBAPS) , Barcelona 08036 ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Sol\u00e9-Padull\u00e9s","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine and Health Sciences and Institute of Neurosciences, University of Barcelona , Barcelona 08036 ,","place":["Spain"]},{"name":"August Pi I Sunyer Institute of Biomedical Research (IDIBAPS) , Barcelona 08036 ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8884-136X","authenticated-orcid":false,"given":"L\u00eddia","family":"Mulet-Pons","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine and Health Sciences and Institute of Neurosciences, University of Barcelona , Barcelona 08036 ,","place":["Spain"]},{"name":"August Pi I Sunyer Institute of Biomedical Research (IDIBAPS) , Barcelona 08036 ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5066-3476","authenticated-orcid":false,"given":"Mar\u00eda","family":"Cabello-Toscano","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine and Health Sciences and Institute of Neurosciences, University of Barcelona , Barcelona 08036 ,","place":["Spain"]},{"name":"August Pi I Sunyer Institute of Biomedical Research (IDIBAPS) , Barcelona 08036 ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel M","family":"Morse","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine and Health Sciences and Institute of Neurosciences, University of Barcelona , Barcelona 08036 ,","place":["Spain"]},{"name":"August Pi I Sunyer Institute of Biomedical Research (IDIBAPS) , Barcelona 08036 ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kilian","family":"Abellaneda-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Guttmann Institute, Institut Universitari de Neurorehabilitaci\u00f3 adscrit a la Universitat Aut\u00f2noma de Barcelona , Badalona 08916 ,","place":["Spain"]},{"name":"Department of Medicine, Universitat Aut\u00f2noma de Barcelona , Bellaterra, Cerdanyola del Vall\u00e8s 08193 ,","place":["Spain"]},{"name":"Fundaci\u00f3 Institut d\u2019Investigaci\u00f3 en Ci\u00e8ncies de la Salut Germans Trias i Pujol , Badalona 08916 ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8647-3703","authenticated-orcid":false,"given":"Rub\u00e9n","family":"Perell\u00f3n-Alfonso","sequence":"additional","affiliation":[{"name":"August Pi I Sunyer Institute of Biomedical Research (IDIBAPS) , Barcelona 08036 ,","place":["Spain"]},{"name":"Guttmann Institute, Institut Universitari de Neurorehabilitaci\u00f3 adscrit a la Universitat Aut\u00f2noma de Barcelona , Badalona 08916 ,","place":["Spain"]},{"name":"Fundaci\u00f3 Institut d\u2019Investigaci\u00f3 en Ci\u00e8ncies de la Salut Germans Trias i Pujol , Badalona 08916 ,","place":["Spain"]},{"name":"Unit for Cognitive Neuroscience, Institute of Neurosciences, University of Barcelona , Barcelona 08035 ,","place":["Spain"]},{"name":"Centre for Biomedical Research on Mental Health (CIBERSAM), Instituto de Salud Carlos III , Madrid 28029 ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriele","family":"Cattaneo","sequence":"additional","affiliation":[{"name":"Guttmann Institute, Institut Universitari de Neurorehabilitaci\u00f3 adscrit a la Universitat Aut\u00f2noma de Barcelona , Badalona 08916 ,","place":["Spain"]},{"name":"Fundaci\u00f3 Institut d\u2019Investigaci\u00f3 en Ci\u00e8ncies de la Salut Germans Trias i Pujol , Badalona 08916 ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Solana-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Guttmann Institute, Institut Universitari de Neurorehabilitaci\u00f3 adscrit a la Universitat Aut\u00f2noma de Barcelona , Badalona 08916 ,","place":["Spain"]},{"name":"Fundaci\u00f3 Institut d\u2019Investigaci\u00f3 en Ci\u00e8ncies de la Salut Germans Trias i Pujol , Badalona 08916 ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanessa","family":"Alviarez-Schulze","sequence":"additional","affiliation":[{"name":"Guttmann Institute, Institut Universitari de Neurorehabilitaci\u00f3 adscrit a la Universitat Aut\u00f2noma de Barcelona , Badalona 08916 ,","place":["Spain"]},{"name":"Fundaci\u00f3 Institut d\u2019Investigaci\u00f3 en Ci\u00e8ncies de la Salut Germans Trias i Pujol , Badalona 08916 ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nuria","family":"Bargall\u00f3","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine and Health Sciences and Institute of Neurosciences, University of Barcelona , Barcelona 08036 ,","place":["Spain"]},{"name":"August Pi I Sunyer Institute of Biomedical Research (IDIBAPS) , Barcelona 08036 ,","place":["Spain"]},{"name":"Centre for Biomedical Research on Mental Health (CIBERSAM), Instituto de Salud Carlos III , Madrid 28029 ,","place":["Spain"]},{"name":"Neuroradiology Section, Radiology Department, Diagnostic Image Center, Hospital Clinic of Barcelona, University of Barcelona , Barcelona 08036 ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1340-638X","authenticated-orcid":false,"given":"Juan","family":"Fortea","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Institut d\u2019Investigacions Biom\u00e8diques Sant Pau-Hospital de Sant Pau , Barcelona 08025 ,","place":["Spain"]},{"name":"Barcelona Down Medical Center, Fundaci\u00f3 Catalana de S\u00edndrome de Down , Barcelona 08029 ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josep M","family":"Tormos","sequence":"additional","affiliation":[{"name":"Guttmann Institute, Institut Universitari de Neurorehabilitaci\u00f3 adscrit a la Universitat Aut\u00f2noma de Barcelona , Badalona 08916 ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Traslacional San Alberto Magno, Universidad Cat\u00f3lica de Valencia San Vicente M\u00e1rtir , Val\u00e8ncia 46001 ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alvaro","family":"Pascual-Leone","sequence":"additional","affiliation":[{"name":"Hinda and Arthur Marcus Institute for Aging Research and Deanna and Sidney WolkCenter for Memory Health, Hebrew SeniorLife, Harvard Medical School , Boston, MA 02131 ,","place":["USA"]},{"name":"Department of Neurology, Harvard Medical School , Boston, MA 02115 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3930-4354","authenticated-orcid":false,"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, Institute of Neuroscience and Physiology, University of Gothenburg , Gothenburg 41390 ,","place":["Sweden"]},{"name":"Department of Neurodegenerative Disease, UCL Institute of Neurology , London LN WC1N3BG ,","place":["UK"]},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital , M\u00f6lndal 43180 ,","place":["Sweden"]},{"name":"Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health , Madison, WI 53792 ,","place":["USA"]},{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison , Madison, WI 53792 ,","place":["USA"]},{"name":"UK Dementia Research Institute at UCL , London W1B 3HH ,","place":["UK"]},{"name":"Hong Kong Center for Neurodegenerative Diseases, InnoHK , Tseung Kwan O, Hong Kong ,","place":["China"]},{"name":"Centre for Brain Research, Indian Institute of Science , Bangalore, Karnataka 560012 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6776-6559","authenticated-orcid":false,"given":"L\u00eddia","family":"Vaqu\u00e9-Alc\u00e1zar","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine and Health Sciences and Institute of Neurosciences, University of Barcelona , Barcelona 08036 ,","place":["Spain"]},{"name":"August Pi I Sunyer Institute of Biomedical Research (IDIBAPS) , Barcelona 08036 ,","place":["Spain"]},{"name":"Sant Pau Memory 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,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,1,10]]},"reference":[{"issue":"11","key":"2026022505161610400_fcaf511-B1","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/S1474-4422(17)30299-5","article-title":"Global, regional, and national burden of neurological disorders during 1990\u20132015: A systematic analysis for the Global Burden of Disease Study 2015","volume":"16","author":"Feigin","year":"2017","journal-title":"Lancet Neurol"},{"issue":"10452","key":"2026022505161610400_fcaf511-B2","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/S0140-6736(24)01296-0","article-title":"Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission","volume":"404","author":"Livingston","year":"2024","journal-title":"The 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