{
  "abstract": "Associations of lipid profiles, including qualitative and functional high-density lipoprotein (HDL) traits, and cholesterol-related biomarkers with incident dementia and Alzheimer’s disease (AD), remain unclear. In this regard, older adults at high cardiovascular risk are at particularly high risk of developing dementia. The aim is to evaluate whether these biomarkers are associated with the incidence of dementia and AD in older adults at high cardiovascular (CV) risk. In a case–cohort study, we selected 106 incident dementia cases (82 AD) and a random subcohort of 201 non-cases. We quantified (baseline and at one-year), lipid profile; HDL-mediate cholesterol efflux capacity in a model of human neurons; HDL-mediated anti-inflammatory protection in a model of brain endothelial cells; 24S-hydroxycholesterol and apolipoprotein E. Multivariable-adjusted Cox models were addressed. HDL cholesterol was inversely associated, whereas triglycerides directly associated, with dementia and AD incidence. Higher HDL-mediated cholesterol efflux was inversely associated with dementia (HR 0.64, 95% confidence interval (CI) 0.45–0.91) and AD (HR 0.52, 0.35–0.76). Greater HDL-mediated endothelial protection was associated with lower dementia and AD incidence (HR 0.68, 95% CI 0.47 to 0.99 and HR 0.61, 95% CI 0.41 to 0.91, respectively). A one-year increase in 24S-hydroxycholesterol was associated with a higher incidence of any dementia (HR 2.38, 1.33–4.27) and AD (HR 2.24, 1.11–4.53). Enhanced HDL functional properties ex vivo, in preclinical models using human brain cells, together with lower levels of 24S-hydroxycholesterol, are inversely associated with the incidence of dementia and AD, highlighting these factors as promising prognostic targets in older adults at high CV risk.",
  "abstract_shown": true,
  "affiliations": [
    "Hospital del Mar Research Institute (IMIM), 08003 Barcelona, Spain",
    "Blanquerna School of Health Sciences, University Ramon Llull, 08025 Barcelona, Spain",
    "Consorcio CIBER, M.P. Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, 28029 Madrid, Spain",
    "August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain",
    "CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain",
    "Department of Preventive Medicine, University of Valencia, 46010 Valencia, Spain",
    "Department of Preventive Medicine and Public Health, Universidad de Navarra, 31008 Pamplona, Spain",
    "Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain",
    "Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA",
    "Unitat de Alimentació, Nutrició, Desenvolupament i Salut Mental, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, 43201 Reus, Spain",
    "Institut d’Investigació Sanitària Pere Virgili (IISPV), 43204 Reus, Spain",
    "Internal Medicine Service, Hospital Clínic, 08036 Barcelona, Spain",
    "Department of Cardiology, Hospital Universitario de Álava, 01004 Vitoria, Spain",
    "Department of Preventive Medicine, University of Málaga, 29071 Malaga, Spain",
    "Research Group on Nutritional Epidemiology & Cardiovascular Physiopathology, Health Research Institute of the Balearic Islands, University Hospital Son Espases, 07120 Palma de Mallorca, Spain",
    "Research Unit, Department of Family Medicine, Distrito Sanitario Atención Primaria Sevilla, 41013 Sevilla, Spain",
    "Research Group in Nutritional Epidemiology and Cardiovascular Pathophysiology, Instituto de Investigación Sanitaria Illes Balears (IdISBa), 35016 Las Palmas de Gran Canarias, Spain",
    "Servicio Canario de Salud, Centro Hospitalario Universitario Insular Materno Infantil, 35016 Las Palmas de Gran Canarias, Spain",
    "Lipids and Vascular Risk Unit, Internal Medicine, Hospital Universitario de Bellvitge Institut d’Investigació Biomèdica de Bellvitge, 08907 Hospitalet de Llobregat, Spain",
    "Faculty of Medicine and Health Sciences, Universitat de Barcelona, 08036 Barcelona, Spain",
    "Cognitive and Behavioural Neurology Unit, Department of Neurology, Hospital del Mar, 08003 Barcelona, Spain",
    "Polyphenol Research Group, Department of Nutrition, Food Science and Gastronomy, Faculty of Pharmacy and Food Sciences, INSA-UB, University of Barcelona, 08921 Barcelona, Spain",
    "CIBER, M.P. Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, 28029 Madrid, Spain",
    "Primary Care Research Unit Metropolitana Sud, Institut Català de la Salut, 08820 El Prat de Llobregat, Spain",
    "Institut Universitari de Recerca en Atenció Primària Jordi Gol i Gurina, 08007 Barcelona, Spain"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 24,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Mireia Malcampo",
      "orcid": "0000-0002-1916-4537"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Álvaro Hernáez"
    },
    {
      "affs": [
        0
      ],
      "name": "Javier Hernando-Redondo",
      "orcid": "0000-0002-6777-1649"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Emilio Ros",
      "orcid": "0000-0002-2573-1294"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Dolores Corella",
      "orcid": "0000-0002-2366-4104"
    },
    {
      "affs": [
        4,
        6,
        7,
        8
      ],
      "name": "Miguel Ángel Martínez-González",
      "orcid": "0000-0002-3917-9808"
    },
    {
      "affs": [
        4,
        9,
        10
      ],
      "name": "Jordi Salas-Salvadó",
      "orcid": "0000-0003-2700-7459"
    },
    {
      "affs": [
        3,
        4,
        11
      ],
      "name": "Ramon Estruch",
      "orcid": "0000-0003-1260-4445"
    },
    {
      "affs": [
        4,
        12
      ],
      "name": "Juan Timiraos"
    },
    {
      "affs": [
        13
      ],
      "name": "Enrique Gómez-Gracia"
    },
    {
      "affs": [
        4,
        14
      ],
      "name": "Miquel Fiol"
    },
    {
      "affs": [
        4,
        15
      ],
      "name": "José Lapetra",
      "orcid": "0000-0002-3873-5737"
    },
    {
      "affs": [
        4,
        16,
        17
      ],
      "name": "Lluis Serra-Majem",
      "orcid": "0000-0002-9658-9061"
    },
    {
      "affs": [
        4,
        18,
        19
      ],
      "name": "Antoni Riera-Mestre",
      "orcid": "0000-0001-9411-804X"
    },
    {
      "affs": [
        4,
        18
      ],
      "name": "Xavier Pintó",
      "orcid": "0000-0002-2216-2444"
    },
    {
      "affs": [
        0,
        20
      ],
      "name": "Albert Puig-Pijoan"
    },
    {
      "affs": [
        4,
        6,
        7
      ],
      "name": "Miguel Ruiz-Canela",
      "orcid": "0000-0002-7684-2787"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "José V. Sorlí",
      "orcid": "0000-0002-0130-2006"
    },
    {
      "affs": [
        4,
        9,
        10
      ],
      "name": "Nancy Babio",
      "orcid": "0000-0003-3527-5277"
    },
    {
      "affs": [
        4,
        21
      ],
      "name": "Rosa Maria Lamuela-Raventós",
      "orcid": "0000-0002-1287-4560"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Olha Khymenets"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Aleix Sala-Vila"
    },
    {
      "affs": [
        0,
        22,
        23,
        24
      ],
      "name": "Olga Castañer"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Montserrat Fitó"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/63swzpk8dxtcp.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27209197",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13705062/?tool=EBI",
  "id": "63swzpk8dxtcp",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/20/9197",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2738|Dementia and Cognitive Impairment Research"
    ]
  ],
  "openalex": "W7222675964",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13705062/pdf/?tool=EBI",
  "pmcid": "PMC13705062",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/63swzpk8dxtcp.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:57Z",
      "native_id": "10.3390/ijms27209197",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/20/9197"
    },
    {
      "first_seen": "2026-10-30T12:21:31Z",
      "native_id": "PMC:PMC13705062",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13705062"
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  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2738|Dementia and Cognitive Impairment Research",
      "subfield": "psychiatry"
    }
  ],
  "title": "HDL Functionality, Cholesterol-Related Biomarkers and Incidence of Dementia: A Case–Cohort Study in Older Adults at High Cardiovascular Risk",
  "title_text": "HDL Functionality, Cholesterol-Related Biomarkers and Incidence of Dementia: A Case–Cohort Study in Older Adults at High Cardiovascular Risk",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:31Z",
  "url": "https://research.draconitic.com/paper/63swzpk8dxtcp",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}