January 30, 2025
2 min read
Key takeaways:
- Higher total, low-density lipoprotein cholesterol variability was linked to rapid declines in cognitive function.
- More research is required to accurately link causation between lipid variability and dementia.
Tracking lipid variability may be a reliable method of predicting dementia and cognitive decline among community-dwelling older adults, according to new research from Neurology.
“Dementia and cognitive decline are major health issues disproportionately affecting older adults and have an insidious onset,” Zhen Zhou, PhD, postdoctoral research fellow at Monash University, Melbourne, Australia, and colleagues wrote. “Dyslipidemia at midlife has been identified as a risk factor of cognitive decline and dementia later in life.”
As lipid metabolism and dysregulation in older adults is influenced by a range of physical and cognitive factors, Zhou and fellow researchers sought to investigate associations between lipid variability and risk for cognitive decline and dementia in community-dwelling older adults.
They culled data from a pair of clinical trials: ASPirin in Reducing Events in the Elderly (ASPREE), a randomized, double-blind, placebo-controlled study of low-dose aspirin that included 19,114 participants aged 65 years and older from Australia and the United States who were free of dementia and major cognitive impairment; and ASPREE-eXTension, the ongoing observational portion of the trial. Participants in both trials were monitored for up to 11 years.
The post hoc analysis of these studies included 9,846 individuals (median age, 73.9 years; 55% women). At baseline and subsequent annual follow ups, participants had to fast overnight before blood samples were collected to analyze levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and triglycerides.
The primary analysis endpoint was all-cause dementia, the diagnosis of which was made by an expert panel, along with secondary endpoints of cognitive impairment with no dementia (CIND) as well as alterations in various cognitive function domains including global, memory, processing speed, verbal fluency, as well as a composite z score taken from results of the whole cognitive battery between baseline to the end of follow up.
The researchers split results into two separate models, with the second model adjusted for age, sex, BMI, health and other sociodemographic characteristics.
According to the results, 509 incident dementia and 1,760 CIND events were recorded over a median follow-up of 5.8 and 5.4 years.
The analysis revealed that higher TC and LDL-c variability was associated with more rapid declines in global cognition, episodic memory, psychomotor speed and composite z score; however, evidence for an association between HDL-c and triglyceride variability with dementia and cognitive change was relatively weak.
Hazard ratios that compared the highest and lowest quartiles of TC and LDL-c variability were 1.6 (95% CI, 1.23–2.08) and 1.48 (95% CI, 1.15–1.91) for dementia and 1.23 (95% CI, 1.08–1.41) and 1.27 (95% CI, 1.11–1.46) for CIND.
Patients from the highest quartile of TC variability recorded a higher incidence rate of dementia than the lowest (cases per 1,000 person years: 11.3 in Q4 vs. 7.1 in Q1), while the risk for dementia in the second, third and fourth quartiles was increased by 37%, 44% and 60%, respectively, than the first quartile.
“Our study suggests that cholesterol variability may represent a novel biomarker or risk factor for identifying older individuals at risk of dementia, outperforming the actual lipid values,” Zhou and colleagues wrote.
In a related editorial, Erin L. Ferguson, MPH, a doctoral student in the department of epidemiology and biostatistics at the University of California, San Francisco, and colleagues stated that more research into identifying genetic determinants of lipid variability is required to properly assess causation between dyslipidemia and dementia.
“We believe that determining the causality of these relationships is the largest opportunity for future research,” they wrote.
Reference:
Ferguson EL, et al. Neurology. 2025;doi:10.1212/WNL.0000000000213355.