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 in older adults at high cardiovascular risk.
Higher HDL cholesterol was inversely associated, and triglycerides directly associated, with incident dementia and Alzheimer's disease in older adults at high cardiovascular risk.
Higher HDL-mediated cholesterol efflux capacity, measured in a human neuron model, was associated with lower incidence of dementia and AD.
Greater HDL-mediated anti-inflammatory protection of brain endothelial cells was associated with lower incidence of dementia and AD.
A one-year increase in 24S-hydroxycholesterol was associated with a higher incidence of dementia and AD.
The study evaluated lipid and cholesterol-related biomarkers, including HDL functionality, apolipoprotein E and 24S-hydroxycholesterol, in relation to dementia in a population at high cardiovascular risk.
This study followed older adults at high risk of heart disease and compared those who developed dementia (106 people, 82 with Alzheimer's disease) with a random group of 201 who did not. The researchers measured not only standard cholesterol levels but also how well a person's HDL ("good") cholesterol worked in laboratory tests using human brain cells. Higher HDL cholesterol and lower triglycerides were linked to a lower chance of developing dementia and Alzheimer's disease. HDL that was better at removing cholesterol from neurons, and better at protecting brain blood-vessel cells from inflammation, was also linked to lower dementia risk. In addition, people whose blood levels of 24S-hydroxycholesterol, a cholesterol by-product from the brain, rose over one year had a higher risk of dementia. This research suggests that how well HDL functions, and not just how much is present, may relate to dementia risk, and that these measures could eventually help identify people at higher risk. The findings show associations in a fairly small study of high-risk older adults and do not prove that changing these markers would prevent dementia.
Malcampo M, Hernáez &, Hernando-Redondo J, Ros E, Corella D, Martínez-González M, et al.. (2026). HDL Functionality, Cholesterol-Related Biomarkers and Incidence of Dementia: A Case-Cohort Study in Older Adults at High Cardiovascular Risk.. International journal of molecular sciences. https://doi.org/10.3390/ijms27209197