HDL Functionality, Cholesterol-Related Biomarkers and Incidence of Dementia: A Case–Cohort Study in Older Adults at High Cardiovascular Risk

@article{malcampo2026functionality,
  title = {{HDL Functionality, Cholesterol-Related Biomarkers and Incidence of Dementia: A Case–Cohort Study in Older Adults at High Cardiovascular Risk}},
  author = {Mireia Malcampo and Álvaro Hernáez and Javier Hernando-Redondo and Emilio Ros and Dolores Corella and Miguel Ángel Martínez-González and Jordi Salas-Salvadó and Ramon Estruch and Juan Timiraos and Enrique Gómez-Gracia and Miquel Fiol and José Lapetra and Lluis Serra-Majem and Antoni Riera-Mestre and Xavier Pintó and Albert Puig-Pijoan and Miguel Ruiz-Canela and José V. Sorlí and Nancy Babio and Rosa Maria Lamuela-Raventós and Olha Khymenets and Aleix Sala-Vila and Olga Castañer and Montserrat Fitó},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = oct,
  doi = {10.3390/ijms27209197},
  url = {https://www.mdpi.com/1422-0067/27/20/9197},
  note = {CC BY 4.0},
}

TY  - JOUR
TI  - HDL Functionality, Cholesterol-Related Biomarkers and Incidence of Dementia: A Case–Cohort Study in Older Adults at High Cardiovascular Risk
AU  - Mireia Malcampo
AU  - Álvaro Hernáez
AU  - Javier Hernando-Redondo
AU  - Emilio Ros
AU  - Dolores Corella
AU  - Miguel Ángel Martínez-González
AU  - Jordi Salas-Salvadó
AU  - Ramon Estruch
AU  - Juan Timiraos
AU  - Enrique Gómez-Gracia
AU  - Miquel Fiol
AU  - José Lapetra
AU  - Lluis Serra-Majem
AU  - Antoni Riera-Mestre
AU  - Xavier Pintó
AU  - Albert Puig-Pijoan
AU  - Miguel Ruiz-Canela
AU  - José V. Sorlí
AU  - Nancy Babio
AU  - Rosa Maria Lamuela-Raventós
AU  - Olha Khymenets
AU  - Aleix Sala-Vila
AU  - Olga Castañer
AU  - Montserrat Fitó
PY  - 2026
DA  - 2026/10/01
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27209197
UR  - https://www.mdpi.com/1422-0067/27/20/9197
AB  - 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.
SN  - 1422-0067
ER  -