Fluctuating Cholesterol Levels Linked to Increased Dementia and Cognitive Decline Risk in Older Adults: Study Finds

Participants with the highest variability in total cholesterol levels had a 60% higher risk of developing dementia (HR 1.60) and a 23% higher risk of experiencing cognitive decline without dementia (HR 1.23), according to Zhen Zhou, PhD, from Monash University in Melbourne, Australia, and co-authors in a study published in Neurology.

Older adults' lipid metabolism is influenced by biological aging, functional decline, reduced physiological reserve, and nutrient intake. Disruptions in lipid metabolism can have detrimental effects on brain health. In this context, the researchers examined the relationship between year-to-year intraindividual lipid variability and the subsequent risk of cognitive decline and dementia in community-dwelling older adults.

For this purpose, the researchers analyzed data from the ASPirin in Reducing Events in the Elderly (ASPREE) trial, a randomized study involving 19,114 participants aged 65 and older, free of dementia and major cognitive impairment. The post-trial follow-up, ASPREE-eXTension, extends up to 11 years. This post hoc analysis focused on participants with lipid measurements at baseline and in years 1, 2, and 3. Variability in lipid levels, including total cholesterol, LDL-C, HDL-C, and triglycerides, was quantified. Cox regression assessed associations with dementia and cognitive impairment, while a mixed model examined cognitive changes across four domains over time.

The study led to the following findings:

• The analysis included 9,846 participants, with a median age of 73.9 years, and 54.9% were female.
• Over a median follow-up of 5.8 and 5.4 years, 509 incident dementia and 1,760 CIND events were recorded.
• The hazard ratios for dementia comparing the highest and lowest quartiles of total cholesterol (TC) and LDL-C variability were 1.60 and 1.48, respectively.
• The hazard ratios for CIND were 1.23 for TC variability and 1.27 for LDL-C variability.
• Higher TC and LDL-C variability were linked to faster declines in global cognition, episodic memory, psychomotor speed, and the composite score.
• There was no significant association between HDL-C and triglyceride variability with dementia or cognitive decline.

The findings showed that greater variability in total cholesterol and low-density lipoprotein cholesterol was linked to an increased risk of dementia, cognitive impairment without dementia (CIND), and faster cognitive decline in community-dwelling older adults, independent of average lipid levels.

The researchers suggested that monitoring the variability of total cholesterol and low-density lipoprotein cholesterol could be a novel biomarker for predicting incident dementia and cognitive decline in older adults.

"To confirm these findings and further explore whether lipid variability can identify high-risk individuals or directly influence cognitive decline and dementia risk in this population, additional large-scale, well-designed prospective cohort studies in older adults are warranted," they concluded.

Reference:

Zhou Z, Moran C, Murray AM, Zoungas S, Magnussen C, Chong TT, Shah RC, Sheets KM, Nelson M, Zhu C, Tonkin AM, Talic S, Ernst ME, Orchard SG, McNeil JJ, Wolfe R, Woods RL, Neumann JT, Qiu P, Ryan J. Association of Year-to-Year Lipid Variability With Risk of Cognitive Decline and Dementia in Community-Dwelling Older Adults. Neurology. 2025 Feb 25;104(4):e210247. doi: 10.1212/WNL.0000000000210247. Epub 2025 Jan 29. PMID: 39879572; PMCID: PMC11774555.