Defying Genetics and Alzheimer’s Disease with Lifestyle and Nutrition

September 14, 2023

Here we continue from Part 1 of this two-part series on genetics and Alzheimer’s disease, this time diving into how we can take action to minimize the effects of APOE-e4 and other pliable genetic risk factors. 

Can APOE-e4 Carriers Control Their Risk? 

For almost all of us, genetic factors only govern a part of our risk of developing Alzheimer’s disease.  That is, genetic factors alone do not determine our cognitive fate.  Not everyone who carries one allele or even two alleles of APOE-e4 will get Alzheimer’s; and on the other hand, many people who are non-carriers of APOE-e4 do indeed get Alzheimer’s.  What makes that difference?   

The difference can be found in how our genes are affected by lifestyle, diet, and environment – and these effects can be quite dramatic.  For example, on average, Italian APOE-e4 carriers living in the south of the country survive into their late 90s, just as often as non-carriers.  But members of the same cohort who migrated to the United States are less likely to live as long.1  Thus, we can see a big geographic difference in how APOE-e4 plays-out in people who live in the villages and islands of southern Italy versus the go-go-fast food cities of the United States.   

This underscores the impact of non-genetic factors, and we can see this even more clearly in another geography:  Nigerians and West Africans quite commonly carry APOE-e4, but the rate of Alzheimer’s is comparatively low in Nigeria, and being a carrier of APOE-e4 in that cohort is not a significant risk factor.1  The same trend is found in East Africans.2  Whereas, people of African descent in the US have twice the incidence of Alzheimer’s disease.  Researchers have linked this disparity in-part to the fact that Nigerians consume only one-quarter as much sugar as Americans, another indicator of the power of diet, nutrition, and lifestyle.1  

Diving into Modifiable Risk Factors 

Unlike genetic risk factors, which are called ‘non-modifiable’ (i.e. can’t be changed), it is clear now that there are modifiable risk factors, like lifestyle and nutrition choices, that are crucial for mitigating the risk of Alzheimer’s, even in the presence of APOE-e4.3  An example of the power of modifiable risk factors is  shown in how the presence of diabetes increases Alzheimer’s risk by 2 times.4  Since diabetes is widely considered to be caused by various lifestyle factors, like excess sugar and low physical activity, it is clear that modifiable risk factors can have just as big an effect (or even greater) than genetics.  Researchers have found eleven other factors that can become tools in the arsenal of those trying to reduce their Alzheimer’s risk, including becoming educated about the risks, controlling hypertension, and guarding against hearing impairment and traumatic brain injury (by keeping headphone volume down, and by wearing a helmet while cycling, for example).5     

You can read more about these modifiable risk factors here.  Also, research is showing that these behaviors can lead to benefits particularly for APO-e4 carriers, along with non-carriers.6,7 

Let’s briefly review seven remaining factors. 

Social Connectedness 

Social contact was found to be important as it provides a sense of purpose and the chance to learn from and enjoy the company of others.  In essence, these are our relationships.  Opportunities for greater social connection include joining clubs, having regular visits with friends and family, and volunteering.  Social isolation is indeed found to be linked to worsened symptoms of Alzheimer’s.8 

Regular Exercise  

There is an established link between low levels of physical activity and reduced cognitive function. Exercise promotes blood flow to the brain, as well as the growth of new neurons.  Aerobic exercise is a great way to combat this risk factor, but taking a brisk, daily walk or taking an at-home yoga class are beneficial, too.  Reducing obesity can have a huge impact on your Alzheimer’s risk; losing as little as 2kg (4.4lbs) can help attention and memory.5  

Reduce Smoking and Alcohol, and Air Pollution 

Unsurprisingly, smoking, and excessive alcohol consumption have detrimental effects on brain health.  Alcohol is a well-known neurotoxin with strong links to cognitive decline through neuro-inflammation while smoking is known to increase dementia risk.9  Also, consider the effects of air pollution, which can worsen cognitive decline and encourage the build-up of amyloid-beta in the brain, and how to reduce it if you live in an urban area.10 

Train Your Brain 

Cognitive fitness helps guard against neurodegeneration.  Examples include puzzles, memory games, playing music, learning new languages and skills, and travel.11  These activities can help support neuroplasticity (the brain’s ability to reshape itself in response to change) and your cognitive reserve (the brain’s nimbleness at handling change and aging without reduced function).12 

Manage Mental Health and Stress 

While occasional feelings of stress are not likely harmful to health, chronic stress, anxiety, and depression can negatively affect cognition. Depression is a significant factor for the emergence of Alzheimer’s disease.13  After speaking with your healthcare provider about your concerns, there are many interventions that can help to manage stress levels, including deep breathing, meditation, and working with a trained therapist. 

Quality Sleep 

Sleep quantity and sleep quality both play a role in cognitive health throughout life.  In fact, poor-quality sleep is linked to increased amounts of amyloid-beta plaque build-up in the brain.5  Most adults function best on 7 or more hours of sleep per night, though advancing age, medical conditions, and other lifestyle factors may make it difficult to get enough quality sleep.  If you frequently struggle with sleep, first speak with your healthcare provider to identify any possible medical causes (e.g. sleep apnea).  You can then practice good sleep hygiene, which includes developing a calming and screen-free bedtime routine, going to bed and waking up at the same time each day, and limiting caffeine and alcohol intake. 

Defying Genetics by Eating Right  

Nutrients to focus on with APOE4

We’ve seen how the APOE-e4 allele helps to govern fat processing and inflammation.  These two risk factors can be meaningfully influenced by dietary choices, and research has shown strong links between the Mediterranean diet and a lowered risk of dementia.14  APOE-e4 carriers should consider their intake of a group of nutrients that scientists believe may significantly reduce the risk of developing dementia.   

There are two healthy omega-3 fatty acids found in cold water fish, like salmon, mackerel, and sardines: EPA and DHA.  The latter is especially important for brain structure and for reducing inflammation.  APOE-e4 carriers actually need more DHA than most people because of differences in their brain metabolism.  So, consider eating more than the recommended two portions of fish per week.     

You might also want to supplement your DHA intake, emphasizing phosphatidylcholine-DHA (PC-DHA), which is a type of phospholipid omega-3.  PC-DHA may be absorbed more efficiently into the brains of APOE-e4 carriers15 because it can bypass hurdles in the blood-brain barrier that are more common with APOE-e4.16  

Quercetin, an antioxidant found in onions and capers, has been shown to reduce the activity of MMP-9, an enzyme found in elevated amounts in the brains of Alzheimer’s sufferers.17  More famously, another antioxidant, resveratrol, which is found in red wine, can also reduce the impact of MMP-9.  It might also help to counteract the disturbed metabolism of sugar in the brain often found in APOE-e4 carriers.  This isn’t a reason to reach for a bottle, however; you would need to drink a truly catastrophic eight barrels of wine per day to achieve levels of resveratrol intake clinical studies showing meaningful bioavailability (i.e. in amounts and form that the body can use).  This makes resveratrol a conundrum, requiring extremely high doses in supplement form.  On the other hand, supplementation of nutrients in the same family with similar longevity-promoting evidence as resveratrol, like pterostilbene (which is also abundant grapes and berries), may be an alternative.18  

There are also three vitamins that can help protect APOE-e4 carriers. Vitamin D3 and Vitamin K can help regulate the effects of MMP-9 and can help with cholesterol metabolism.  The presence of B-vitamins, especially B12, can control levels of homocysteine, an amino acid that is a risk factor for Alzheimer’s when its levels rise.  Synergistically, B-vitamins also help the body make the most efficient use of DHA.1  

Finally, choline is a building block for neurotransmitters, and it helps to regulate the activity of microglia, the brain’s immune cells, possibly reducing their inflammatory effects.19  Usefully, choline forms part of PC-DHA, the version of DHA that could be helpful for APOE-e4 carriers mentioned earlier.20   

RELEVATE®: Nutritional Supplementation for Brain Health    

To receive this broad spectrum of neuroprotective nutrients in thoughtfully designed forms and dosages, consider a dietary supplementation with RELEVATE.  It contains brain beneficial nutrients most commonly lacking in the American diet, including nutrients specifically selected that may address challenges with APOE-e4 carriers, like PC-DHA and quercetin. 

You can explore more APOE4 specific nutrient recommendations by downloading our FREE e-guide on “Living with APOE4: Strategies to Reduce Risk”, click here to get the guide.  

References

  1. Norwitz, Nicholas G et al. “Precision Nutrition for Alzheimer's Prevention in ApoE4 Carriers.” Nutrients vol. 13,4 1362. 19 Apr. 2021, doi:10.3390/nu13041362
  2. Kalaria, R. N., Ogeng’o, J. A., Patel, N. B., Sayi, J. G., Kitinya, J. N., Chande, H. M., Matuja, W. B., Mtui, E. P., Kimani, J. K., Premkumar, D. R. D., Koss, E., Gatere, S., & Friedland, R. P. (1997). Evaluation of Risk Factors for Alzheimer’s Disease in Elderly East Africans. Brain Research Bulletin, 44(5), 573–577. https://doi.org/10.1016/S0361-9230(97)00310-9
  3. Jia, J., Zhao, T., Liu, Z., Liang, Y., Li, F., Li, Y., Liu, W., Li, F., Shi, S., Zhou, C., Yang, H., Liao, Z., Li, Y., Zhao, H., Zhang, J., Zhang, K., Kan, M., Yang, S., Li, H., … Cummings, J. (2023). Association between healthy lifestyle and memory decline in older adults: 10 year, population based, prospective cohort study. BMJ, 380. https://doi.org/10.1136/BMJ-2022-072691
  4. Athanasaki, Athanasia et al. “Type 2 Diabetes Mellitus as a Risk Factor for Alzheimer's Disease: Review and Meta-Analysis.” Biomedicines vol. 10,4 778. 27 Mar. 2022, doi:10.3390/biomedicines10040778
  5. Livingston, G., et al. (2020). Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. The Lancet, 396(10248), 413–446. https://doi.org/10.1016/S0140-6736(20)30367-6/ATTACHMENT/5F8C54CB-A837-4EBA-AC5D-9F2EF488E625/MMC1.PDF
  6. Kolli, A., Zhou, Y., Chung, G., Ware, E. B., Langa, K. M., & Ehrlich, J. R. (2022). Interactions between the apolipoprotein E4 gene and modifiable risk factors for cognitive impairment: a nationally representative panel study. BMC Geriatrics, 22(1), 1–7. https://doi.org/10.1186/S12877-022-03652-W/FIGURES/1
  7. Rosenich, E., Bransby, L., Yassi, N., Fripp, J., Laws, S. M., Martins, R. N., Fowler, C., Rainey-Smith, S. R., Rowe, C. C., Masters, C. L., Maruff, P., & Lim, Y. Y. (2022). Differential Effects of APOE and Modifiable Risk Factors on Hippocampal Volume Loss and Memory Decline in Aβ− and Aβ+ Older Adults. Neurology, 98(17), e1704–e1715. https://doi.org/10.1212/WNL.0000000000200118
  8. Hsiao, Ya-Hsin et al. “Impact of social relationships on Alzheimer's memory impairment: mechanistic studies.” Journal of biomedical science vol. 25,1 3. 11 Jan. 2018, doi:10.1186/s12929-018-0404-x
  9. Livingston, Gill et al. “Dementia prevention, intervention, and care.” Lancet (London, England) vol. 390,10113 (2017): 2673-2734. doi:10.1016/S0140-6736(17)31363-6
  10. Power, Melinda C et al. “Exposure to air pollution as a potential contributor to cognitive function, cognitive decline, brain imaging, and dementia: A systematic review of epidemiologic research.” Neurotoxicology vol. 56 (2016): 235-253. doi:10.1016/j.neuro.2016.06.004 
  1. Chan, Dennis et al. “Lifestyle activities in mid-life contribute to cognitive reserve in late-life, independent of education, occupation, and late-life activities.” Neurobiology of aging vol. 70 (2018): 180-183. doi:10.1016/j.neurobiolaging.2018.06.012
  2. Stern, Yaakov. “Cognitive reserve in ageing and Alzheimer's disease.” The Lancet. Neurology vol. 11,11 (2012): 1006-12. doi:10.1016/S1474-4422(12)70191-6
  3. Sáiz-Vázquez, Olalla et al. “Depression as a Risk Factor for Alzheimer's Disease: A Systematic Review of Longitudinal Meta-Analyses.” Journal of clinical medicine vol. 10,9 1809. 21 Apr. 2021, doi:10.3390/jcm10091809
  4. Shannon, O. M., et al. (2023). Mediterranean diet adherence is associated with lower dementia risk, independent of genetic predisposition: findings from the UK Biobank prospective cohort study. BMC Medicine, 21(1), 1–13. https://doi.org/10.1186/S12916-023-02772-3/FIGURES/3
  5. Patrick, Rhonda P. “Role of phosphatidylcholine-DHA in preventing APOE4-associated Alzheimer's disease.” FASEB journal : official publication of the Federation of American Societies for Experimental Biology vol. 33,2 (2019): 1554-1564. doi:10.1096/fj.201801412R
  6. Patrick, Rhonda P. “Role of phosphatidylcholine-DHA in preventing APOE4-associated Alzheimer's disease.” FASEB journal : official publication of the Federation of American Societies for Experimental Biology vol. 33,2 (2019): 1554-1564. doi:10.1096/fj.201801412R
  7. Lorenzl,, Albers, D. S., Relkin, N., Ngyuen, T., Hilgenberg, S. L., Chirichigno, J., Cudkowicz, M. E., & Beal, M. F. (2003). Increased plasma levels of matrix metalloproteinase-9 in patients with Alzheimer’s disease. Neurochemistry International, 43(3), 191–196. https://doi.org/10.1016/S0197-0186(03)00004-4
  8. Lange, Klaus W, and Shiming “Resveratrol, pterostilbene, and dementia.” BioFactors (Oxford, England) vol. 44,1 (2018): 83-90. doi:10.1002/biof.1396
  9. Velazquez, Ramon et al. “Choline as a prevention for Alzheimer's disease.” Aging vol. 12,3 (2020): 2026-2027. doi:10.18632/aging.102849
  10. Chouinard-Watkins, Raphaël et al. “DHA Esterified to Phosphatidylserine or Phosphatidylcholine is More Efficient at Targeting the Brain than DHA Esterified to Triacylglycerol.” Molecular nutrition & food research vol. 63,9 (2019): e1801224. doi:10.1002/mnfr.201801224
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