Blood cholesterol levels are measured as a routine part of primary care. Since high cholesterol has been linked to increased risk for cardiovascular disease and dementia, knowing our cholesterol levels provides valuable information about our relative risk for these chronic diseases. High cholesterol levels get flagged and typically prompt discussions about ways to lower low-density lipoprotein (LDL)-cholesterol, such as diet, exercise, and medication. It is less common, however, to track changes in our cholesterol levels over time. New research suggests that, especially as we get older, monitoring changes in cholesterol levels from year to year may be just as important for assessing risk as the cholesterol level itself.
The relationship between cholesterol levels and disease risk is strongest during middle age. Observational studies have found that this relationship starts to weaken with age, particularly after age 65, such that a high cholesterol level alone becomes a less reliable indicator of dementia risk [1]. Instead, fluctuations in cholesterol levels that are not tied to the initiation, cessation, or adjustment of lipid-lowering medications may be a better indicator of risk during late life.
A study following nearly 10,000 relatively healthy adults aged 65 and older for approximately five years found that individuals with the highest total cholesterol or LDL-cholesterol variability were at a higher risk for cognitive impairment and dementia [2]. The risk increased progressively with the degree of visit-to-visit variability.
Similar associations have been found in other large observational studies. A study following over 11,000 adults aged 60 and older in the US for around 13 years found that those with the highest amount of cholesterol variability over time had a 19% higher risk for Alzheimer’s disease and related dementias [3]. Another study following nearly 132,000 middle-aged to older adults in Korea for approximately eight years found that the risk for dementia was 15% higher in those with the greatest degree of visit-to-visit variability in total cholesterol levels [4].
While the association between cholesterol variability and cognitive impairment is most prominent during late life, there is evidence that cholesterol variability can impact cognitive function and trajectories starting in young adulthood. A study following over 3,000 young adults for 20 years, found that those with higher variability in cholesterol levels over this period showed worse performance on cognitive tests during midlife [5].
Across studies, this relationship between cholesterol variability and dementia risk was not affected by the continuous and stable use of lipid-lowering therapies. It is not yet clear whether fluctuations stemming from non-adherence to medication also impact risk [2].
The mechanisms underlying this association are not yet completely understood, but may be a reflection of problematic changes in vascular health and function. Similar to the shared associations for high LDL-cholesterol with the risk for cardiovascular disease and dementia, variability in cholesterol levels has also been associated with increased risk for cardiovascular disease and mortality [6]. Fluctuating lipid levels could contribute to the growth and destabilization of atherosclerotic plaques in blood vessels [2]. Higher visit-to-visit variability in LDL-cholesterol has been found to be associated with a reduction in blood flow to the brain and a higher load of vascular damage in the brain [7].
The variability in cholesterol levels may also reflect the loss of the ability to properly regulate lipids in the body [2]. Lipids, particularly cholesterol, play an essential role in brain function, thus a dysregulation of cholesterol could negatively impact cognition. High cholesterol variability may then be an indicator of frailty, which itself is associated with increased risk for dementia [2].
To have a more comprehensive assessment of your dementia risk profile, it is important to measure your cholesterol levels on an annual basis, follow any changes that occur over time, and discuss the results with your health care provider.
Betsy Mills, PhD, is a member of the ADDF's Aging and Alzheimer's Prevention program. She critically evaluates the scientific evidence regarding prospective therapies to promote brain health and/or prevent Alzheimer's disease, and contributes to CognitiveVitality.org. Dr. Mills came to the ADDF from the University of Michigan, where she served as the grant writing manager for a clinical laboratory specializing in neuroautoimmune diseases. She also completed a Postdoctoral fellowship at the University of Michigan, where she worked to uncover genes that could promote retina regeneration. She earned her doctorate in neuroscience at Johns Hopkins University School of Medicine, where she studied the role of glial cells in the optic nerve, and their contribution to neurodegeneration in glaucoma. She obtained her bachelor's degree in biology from the College of the Holy Cross. Dr. Mills has a strong passion for community outreach, and has served as program presenter with the Michigan Great Lakes Chapter of the Alzheimer's Association to promote dementia awareness.
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