A large study of nearly 10 000 adults in their 70s reveals that unexplained year-to-year changes in cholesterol levels might serve as an early warning sign for dementia risk. The research, conducted over six years, found that people with the most variable cholesterol levels showed a 60% higher risk of developing dementia than those with stable levels.
In their study presented at the American Heart Association’s Scientific Sessions 2024, and which is yet to undergo peer review, the scientists found that in older adults, particularly, annual changes in cholesterol levels could increase the risk of dementia and cognitive decline.
All participants in the research were enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE project), a large study run in Australia and the United States to investigate low-dose aspirin and health in older adults.
Of the 9 846 participants, all in their 70s, 87% lived in Australia and the rest in the US. MedicalNewsToday reports that all were free of dementia at the start of the study, and 32% were on cholesterol-lowering medications, on which they remained throughout the study.
For the three years of the study, they underwent annual tests of their total cholesterol, LDL-C, HDL-C and triglycerides – another fatty substance that comes from diet and is found in the blood.
The researchers split them into four groups based on how much their cholesterol levels fluctuated, from highest to lowest fluctuations.
They then monitored the participants for six years for development of dementia and cognitive decline. An expert panel analysed the results of cognitive tests, self-reported cognitive problems, and medical reports of dementia diagnosis or prescription of dementia medication.
The researchers then compared the numbers with dementia and cognitive decline in the highest and lowest fluctuating cholesterol groups.
Changing cholesterol levels and dementia
During the six-year follow up, 509 people developed dementia and 1 760 developed cognitive decline without dementia. The researchers found associations between fluctuating levels of total cholesterol and LDL-C and dementia, but not with fluctuating HDL-C or triglycerides.
People with the highest fluctuations in total cholesterol levels had a 60% higher likelihood of dementia, and a 23% increase in cognitive decline, compared with those with the most stable cholesterol levels.
Those with the highest fluctuations in LDL-C had a 48% higher risk of dementia and a 27% higher risk of cognitive decline.
They also experienced more rapid declines in overall cognitive health, memory and reaction speed.
Biomarker for dementia diagnosis?
Lead author Zhen Zhou, PhD, a postdoctoral research fellow in the School of Public Health and Preventive Medicine at Monash University in Melbourne, Australia, said: “Oder people with fluctuating cholesterol levels unrelated to whether they were taking lipid-lowering medications, particularly those experiencing big year-to-year variations, may warrant closer monitoring and proactive preventive interventions.”
Zhou called for further studies. “That would help us understand the relationship between cholesterol variability and dementia risk. Are cholesterol variability levels a real risk factor, a precursor or a biomarker of dementia risk?”
In their study abstract, the authors suggested that “tracking the variability of TC (total cholesterol) and LDL-C measured annually may serve as a novel biomarker for higher risk of incident dementia and cognitive decline in older adults”.
The study had some limitations, including that cholesterol readings can vary for many reasons, and the connection between cholesterol variability and dementia risk may be affected by these unanalysed factors.
In addition, participants were mostly white adults (96%), so, the findings may not apply to people in other population groups.
As an observational study, it cannot prove a cause-and-effect relationship between cholesterol fluctuations and dementia risk.
However, Clifford Segil, DO, a neurologist at Providence Saint John’s Health Centre in California, who was not involved in the study, was not fully persuaded by the findings.
He told MNT that: “Monitoring annual cholesterol levels is part of annual physical exams and lipids are directly related to the risk of having a heart attack and stroke. It does not seem, after reading this, that it will be useful in clinical practice, any time soon, to monitor annual lipid profiles or cholesterol levels, with regard to assessing the risk for a patient to develop dementia.
“LDL, or bad cholesterol, and total cholesterol levels are not accepted risk factors in developing dementia but are followed very closely to prevent heart attacks or strokes.”
See more from MedicalBrief archives:
Lancet adds to dementia risk factors list
Up to 13% of dementia cases may be misdiagnosed – US cohort study
WHO issues its first guidelines on reducing dementia risk
‘Protective effect of obesity’ against dementia challenged in 2 studies