Blood lipid levels provide valuable information about chronic disease risk. Similar to cholesterol, elevated blood levels of triglycerides are associated with higher risk for cardiovascular disease. Triglyceride levels have also been associated with the risk for cognitive decline, but this relationship is more nuanced, as it may be impacted by factors such as age, sex, and race.
Lipids, or fats, play a variety of roles in the body, but their major role is the storage of energy. The predominant way the body stores its excess energy is in the form of triglycerides [1]. This class of lipids is comprised of glycerol and three fatty acids. There are numerous types of triglycerides, which can have different properties, depending on the combination of fatty acids. Consuming excess calories can lead to a buildup of triglycerides in the body. Blood triglyceride levels over 150 mg/dL are considered elevated and put one at higher risk for cardiovascular disease [1].
Numerous studies have found that elevated levels of blood triglycerides at midlife are associated with higher risks of cognitive impairment in late life [2]. However, there is variability across studies, which may stem from differences in the demographics of the study populations. A large study including 125,727 participants from two longitudinal studies of the Danish general population found that individuals at the 50th percentile of non-fasting triglycerides (median 89 mg/dL) had a lower risk for dementia and stroke compared with those with higher triglyceride levels [3]. In a more racially diverse cohort in the US including 16,170 participants without a history of stroke, the relationship between elevated fasting triglycerides (≥150 mg/dL) and cognitive impairment was only statistically significant in white women [4].
The mechanisms underlying this relationship have not been established, but several have been proposed, including the aggravation of atherosclerotic vascular damage, disruption of the blood-brain-barrier, and the promotion of amyloid pathology [2].
Preclinical and human biomarker studies suggest that, in early stages, triglycerides may facilitate the accumulation of toxic amyloid species in the brain. A longitudinal study in adults with normal cognitive function found that individuals with high triglycerides in midlife were more likely to have evidence of brain amyloid accumulation 20 years later [5].
The relationship between triglyceride levels and cognition can change with age and in the context of dementia. In contrast to what is observed in midlife (ages 40-60), several studies have found that triglyceride levels in the normal to mildly elevated range were associated with lower risk for cognitive decline in older adults (>65 years old) [2; 6]. The most comprehensive of these studies found that those with the lowest triglyceride levels (<62 mg/dL) were at the highest risk for dementia, suggesting that very low levels are a marker of risk in this population rather than high levels conferring protection [6]. Very low triglyceride levels in older adults could be an indicator of poor nutrition, and frailty, which are also risk factors for dementia [6]. Some studies have found that classes of triglycerides which are thought to play important roles in the brain are reduced in dementia patients [7]. Therefore, inadequate triglyceride levels may impair brain function.
To have a comprehensive assessment of your risk profile, make sure to have your triglyceride levels measured as part of your annual physical exam, and discuss the results with your health care provider. If your levels are flagged as elevated, discuss options to manage them, such as diet, exercise, and medication.
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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