Cholesterol is confusing, the science can be complicated and online opinions varied. I was recently asked about cholesterol and brain health, the question along the lines of “I read that the elderly are protected against dementia and Alzheimer's by higher levels of cholesterol. Should I no longer be worried about my cholesterol levels? Isn’t the brain made from cholesterol and we all need it anyway? "
Good questions. We dug a little deeper and found one much cited 2018 study, by the prestigious Icahn School of Medicine at Mount Sinai, that perhaps prompted this question. The actual study results are not quite what our friend understood from the headline and make for a good case how the media pick up on stories and results get misinterpreted.
Please note, if you have immediate questions and concerns about your health and cholesterol levels, always consult with your medical practitioner most familiar with your personal medical history and circumstances.
To answer the question: is the brain made out of cholesterol, do we need cholesterol?
Cholesterol is an essential part of all cellular function. It forms the membrane of every cell and the backbone of many key hormones. Our bodies make the required amount of cholesterol that we need for cellular function; ingested dietary cholesterol is not required, nor (for most) a problem.
The brain contains 25% of the body's entire amount of cholesterol.
The body also produces LDL and HDL cholesterol, those that are measured in health screenings.
Are there studies that show a negative relationship between LDL cholesterol and brain health?
Yes, this relationship is well studied. If you are interested in the science, at the bottom of the page I have shared relevant published studies, including meta-analyses.
What does the balance of evidence show regarding cholesterol and brain health?
The overall picture is that high cholesterol, certainly in mid-life, contributes to cognitive decline / dementia in later life. Not only directly affecting vascular health, leading to mini-strokes and so forth, but also contributing to the creation of the amyloid plaques that cause dementia.
What about the 2018 study, the link between the elderly, higher cholesterol and positive brain health?
The study did indeed show a correlation between high LDL cholesterol and brain health, specifically in the very elderly - those aged 85-94. But the study does not conclude that 'cholesterol is neuroprotective' as some headlines have shown.
The study population was over the age of 85. Most people in the US (or anywhere) are already deceased by this age. So what is happening with these very elderly, lucky few with high LDL cholesterol? Does this single 2018 study negate the previous body of evidence?
The study’s own authors conclude that “…these results suggest that oldest-old individuals who are cognitively intact despite having high risk would be particularly informative for genetic and other studies seeking protective factors.” That is, further research needs to be done.
Further clarifying the conclusion, Dr David Reynolds, Chief Scientific Officer of Alzheimer’s Research UK commented "The finding that high cholesterol in people over 85 may be linked to better cognitive function, probably reflects the genetic makeup of people who survive to this advanced age rather than the amount of cholesterol in their blood."
We know that genes play a role in people’s response to cholesterol in other areas. Some people have high cholesterol due to genetics. Another scenario relates to dietary cholesterol. The old thinking was that dietary (ingested) cholesterol raised blood cholesterol, so the advice was to "avoid cholesterol". Based on later findings, this statement was retracted as it was not found to be the case. Confusing. More recent studies demonstrate that for a small number of people, about 15% of the population - so called hyper absorbers - dietary cholesterol raises serum cholesterol. This population needs to be careful with what they eat.
A recent (2023) meta-analysis, studying over 1.2m people (authors Wee and Sukudom) on the role of cholesterol and dementia concludes that there is "a compelling relationship between midlife dyslipidemia and increased risk of dementia and MCI. Efforts to reduce midlife cholesterol have the potential to decrease the total incidence and prevalence of dementia over time."
When it comes to reducing cholesterol levels, diet should be a key area of focus. Says Felicia Koh (MA Human Nutrition), The Whole Health Practice's co-founder and nutritionist:
A neuroprotective diet is high in fibre and low in saturated fat, high in omega-3s, rich in whole foods and antioxidant polyphenols. Whether you enjoy Mediterranean or Asian flavours, eat right and don't worry about the occasional indulgence!
What does this mean when it comes to the plate? On a daily basis eat a whole food diet, avoid processed foods. Enjoy small portions of lean meat, oily fish, nuts and seeds, colourful vegetables, dark leafy grains, beans and whole grains, herbs and spices. Be mindful of your alcohol intake.
Other proven cholesterol lowering measures include regular physical activity and stress reduction.
Final Thoughts
Since 2018 there have been other studies that demonstrate the same correlation as found by the Mt. Sinai team. Since 2018 there have also been a wealth of new studies (see below) that further demonstrate a negative relationship between high cholesterol and brain health. These add to the weight of the evidence that managing one's exposure to dietary saturated fat (that raises cholesterol) and even, for some, dietary cholesterol, is an important factor in the promotion of long term health.
For most people, improving health is about finding motivation and prioritising self-care with an ultimate goal of taking action. If you want to take effective and targeted steps that fit into your unique lifestyle, The Whole Health Practice is here to help.
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Stay Healthy,
Alastair
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Update 05 October 2023: see the results of the Swedish AMORIS cohort study, demonstrating a correlation between cholesterol and longevity but showing a similar conclusion to this brain health study.
If you are interested in learning more about Alzheimer's, cognitive health and how to minimise risk, read The Alzheimer's Solution by Drs Sherzai, co-directors of the Brain Health and Alzheimer's Prevention Program at Loma Linda University Medical Center.
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The 2018 study:
Silverman JM, Schmeidler J. Outcome age-based prediction of successful cognitive aging by total cholesterol. Alzheimers Dement. 2018 Jul;14(7):952-960. doi: 10.1016/j.jalz.2018.01.009. Epub 2018 Mar 5. PMID: 29514768; PMCID: PMC6050071.
Related Studies
Manuello, J., Min, J., McCarthy, P. et al. The effects of genetic and modifiable risk factors on brain regions vulnerable to ageing and disease. Nat Commun 15, 2576 (2024). https://doi.org/10.1038/s41467-024-46344-2
Wee J, Sukudom S, Bhat S, Marklund M, Peiris NJ, Hoyos CM, Patel S, Naismith SL, Dwivedi G, Misra A. The relationship between midlife dyslipidemia and lifetime incidence of dementia: A systematic review and meta-analysis of cohort studies. Alzheimers Dement (Amst). 2023 Mar 8;15(1):e12395. doi: 10.1002/dad2.12395. PMID: 36911359; PMCID: PMC9993469.
Gong J, Harris K, Peters SAE, Woodward M. Serum lipid traits and the risk of dementia: A cohort study of 254,575 women and 214,891 men in the UK Biobank. EClinicalMedicine. 2022 Oct 6;54:101695. doi: 10.1016/j.eclinm.2022.101695. PMID: 36247924; PMCID: PMC9561731.
Wingo AP, Vattathil SM, Liu J, Fan W, Cutler DJ, Levey AI, Schneider JA, Bennett DA, Wingo TS. LDL cholesterol is associated with higher AD neuropathology burden independent of APOE. J Neurol Neurosurg Psychiatry. 2022 Jun 30;93(9):930–8. doi: 10.1136/jnnp-2021-328164. Epub ahead of print. PMID: 35772923; PMCID: PMC9380478.
Norwitz NG, Feldman D, Soto-Mota A, Kalayjian T, Ludwig DS. Elevated LDL Cholesterol with a Carbohydrate-Restricted Diet: Evidence for a "Lean Mass Hyper-Responder" Phenotype. Curr Dev Nutr. 2021 Nov 30;6(1):nzab144. doi: 10.1093/cdn/nzab144. PMID: 35106434; PMCID: PMC8796252.
Barone Gibbs B, Hivert MF, Jerome GJ, Kraus WE, Rosenkranz SK, Schorr EN, Spartano NL, Lobelo F; American Heart Association Council on Lifestyle and Cardiometabolic Health; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology. Physical Activity as a Critical Component of First-Line Treatment for Elevated Blood Pressure or Cholesterol: Who, What, and How?: A Scientific Statement From the American Heart Association. Hypertension. 2021 Aug;78(2):e26-e37. doi: 10.1161/HYP.0000000000000196. Epub 2021 Jun 2. PMID: 34074137.
Helgadottir A, Thorleifsson G, Alexandersson KF, Tragante V, Thorsteinsdottir M, Eiriksson FF, Gretarsdottir S, Björnsson E, Magnusson O, Sveinbjornsson G, Jonsdottir I, Steinthorsdottir V, Ferkingstad E, Jensson BÖ, Stefansson H, Olafsson I, Christensen AH, Torp-Pedersen C, Køber L, Pedersen OB, Erikstrup C, Sørensen E, Brunak S, Banasik K, Hansen TF, Nyegaard M, Eyjolfssson GI, Sigurdardottir O, Thorarinsson BL, Matthiasson SE, Steingrimsdottir T, Bjornsson ES, Danielsen R, Asselbergs FW, Arnar DO, Ullum H, Bundgaard H, Sulem P, Thorsteinsdottir U, Thorgeirsson G, Holm H, Gudbjartsson DF, Stefansson K. Genetic variability in the absorption of dietary sterols affects the risk of coronary artery disease. Eur Heart J. 2020 Jul 21;41(28):2618-2628. doi: 10.1093/eurheartj/ehaa531. PMID: 32702746; PMCID: PMC7377579.
Sáiz-Vazquez O, Puente-Martínez A, Ubillos-Landa S, Pacheco-Bonrostro J, Santabárbara J. Cholesterol and Alzheimer's Disease Risk: A Meta-Meta-Analysis. Brain Sci. 2020 Jun 18;10(6):386. doi: 10.3390/brainsci10060386. PMID: 32570800; PMCID: PMC7349210.
Blom K, Emmelot-Vonk MH, Koek HL. The influence of vascular risk factors on cognitive decline in patients with dementia: a systematic review. Maturitas. 2013 Oct;76(2):113-7. doi: 10.1016/j.maturitas.2013.06.011. Epub 2013 Jul 10. PMID: 23849703.
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