Maintaining healthy brain function during aging

In the age of pandemics, nothing seems to be normal. As of this writing, the U.S. is fully seven months into a situation which is foreign to most Americans, if not people around the world. As statistics regarding COVID-19 come into focus, it is thought that people over the age of 70—who are less mobile and may be living in an institutional setting with limited exposure to exercise, fresh foods and social family interactions—are most at risk. That said, other factors are coming to light that place even greater emphasis on maintaining healthy body mass index (BMI), proper exercise and ample nutrition with health-giving foods and supplements. These include increased risk of developing chronic health conditions that impair quality of life and increase risk of cognitive decline.

Degenerative diseases brought on by inappropriate selections of foods and activities over the course of time, not to mention gerrymandering food supply stocks, are led by an explosion in type 2 diabetes. Many diabetics also exhibit elevated BMI levels, and this group is considered high risk in dealing with the pandemic.

Difficulties with insulin production and response is key to type 2 diabetes, which leads to elevated blood sugar levels that, in turn, contribute to glycation and oxidative damage of tissues. According to the article “How Type 2 Diabetes Affects the Brain” in The Scientist, this damage is believed to contribute to some of the cognitive effects diabetes can have on individuals, such as negative impacts on memory, learning and concentration.¹

Demographics play a significant role in incidence of diabetes in the U.S., with rates higher for people of color. These population groups have higher rates of complications from COVID-19, as well as higher risk of Alzheimer’s disease and other dementias, according to research reported at the Alzheimer’s Association International Conference in 2017. With more than 10% of Americans affected by diabetes—and recognizing the comorbidity considerations in dealing with COVID-19 infections of this subset of the population—this is clearly an issue that needs to be addressed from a policy standpoint.

Poor diet and lack of exercise leading to unhealthy weight absolutely contribute to the development of diabetes; as well as overall inflammation in the body, which can lead to cognitive dysfunction if left unchecked. Indeed, the development of beta-amyloid plaque in the neural tissues of Alzheimer’s patients is believed to be a physiologic response to chronic inflammation in the brain.

As people age, declines in melatonin production impact sleep and, in turn, inadequate sleep is tied to negative impacts on cognitive function and memory. Interestingly enough, research suggests low melatonin may also contribute to increased risk of diabetes.² Similarly, stress—also increasingly common with age, especially in current times—can affect sleep quality and duration, as well as contribute to cognitive difficulties. Both inadequate/poor quality sleep and chronic stress can tax the body’s nutrient reserves, which fuels existing inflammation and oxidative damage already associated with the aging process.

To be clear, aging is a natural process of human existence. How an individual ages is partially determined by genetic composition, and largely by one’s attitudes, commitment to healthy lifestyle adoption and recognition that nutrition plays an essential role in preservation of mental and physical capacities.

According to statistics from market research firm IRI per a 2020 article in Food Technology Magazine, in 2019, sales of specialty supplements targeting brain health grew by 24%, and those targeting sleep and mood grew by 16%. Reasons for purchasing brain health supplements range across age demographics, with older adults tending toward an interest in supporting memory function and mitochondrial health to protect against the effects of aging, as well as energy, sleep and stress support.

Nutrients to support cognitive function with age include those that help to correct deficiencies associated with poor dietary choices or options, as well as botanicals and nutrients to support individuals through environmental/external factors associated with the aging process.

Nutrients worthy of consideration in creating a defensive arsenal against brain function decay

Multivitamin/mineral

Adequate nutrient intake—vitamins, minerals and antioxidants—can help offset poor dietary options and/or choices and support cognitive function through prevention of nutrient deficiencies and optimization of nutrient intake. Micronutrients, including B vitamins, vitamins C, D, E and selenium, help to protect neural tissues against oxidative damage as well as support enzyme and metabolic pathways for cellular energy production and neural communication.³

Vitamin D

Vitamin D is an essential part of a complete multivitamin/mineral, but also important on its own, as many are found to be deficient in this fat-soluble vitamin that is vital for immune function and cognitive health. This is undoubtedly true even more so during shelter-in-place orders and limited ability to get outside for adequate sunlight exposure. Vitamin D has been shown to improve reaction times⁴ as well as cognitive function in older individuals.⁵

Vitamin E

Vitamin E is an important antioxidant, especially for neural tissues that are susceptible to oxidative stress, which increases during the aging process. Research indicates that higher vitamin E status is associated with improved cognition,⁶ and a large-scale study demonstrated that supplementation with  vitamin E helped to delay progression of Alzheimer’s disease symptoms.⁷

Vitamin E supplementation is actually more complex, however, in that while most research has centered on an identified alpha-tocopherol—the form utilized in the majority of multivitamin/mineral formulas—ample emerging science demonstrated a more complete array of isomers such as beta-, gamma- and delta-tocopherols, in addition to related isomers, such as tocotrienols found in natural settings, which arguably may provide optimum benefit in cellular protection from oxidative damage. Careful attention should be made to select natural-sourced vitamin E, given that synthetic vitamin E has some difficulties providing metabolic efficiencies of uptake and utilization versus the natural counterpart.

Phosphatidylserine

Phospholipids are an integral component of cell membranes, contributing to cell fluidity as well as communication. All cells in the body contain phosphatidylserine (PS), but notably so in brain and nerve cells, where PS has been researched for its benefits in supporting memory, concentration and mood, including in patients with dementia or age-related cognitive decline.⁸ PS is supplemented in levels of 100 mg/d and up to 600 mg/d for memory or mood support. 300 mg/d given for 12 weeks to individuals ages 50 to 90 complaining of memory difficulties showed improvements in memory and other cognitive parameters.⁹

Astaxanthin

Produced by organisms such as bacteria, yeast, fungi and microalgae, astaxanthin has shown itself to be a powerful carotenoid with antioxidant¹⁰ and anti-inflammatory activity that can help support the body and impact the risk of health conditions.^{11, 12} Astaxanthin readily crosses the blood-brain barrier, making it an important adjunctive supplement to help protect and support neural tissues.¹¹

Potassium

While it is fairly common knowledge that the typical Western diet includes higher than healthy levels of sodium, and many people have been counseled by their physicians to reduce the amount of sodium taken into their diets, a useful and beneficial alternative is potassium chloride—which provides a pleasing taste to foods, as well as increases the concentration of cellular potassium needed to achieve beneficial results from multiple studies. Potassium consumption is less than half the daily recommended amount compared to sodium, which exceeds the recommended daily intake.¹³

Evidence suggests inadequate potassium intake may play a role in the development of cognitive impairment and Alzheimer’s disease.¹³ Low potassium levels are also tied to conditions such as diabetes and hypertension, each of which are associated with oxidative damage, chronic inflammation and risk of cognitive decline.¹⁴ Controlling blood pressure through potassium sparing diuretics has been shown to help prevent cognitive decline and should be considered over alternate antihypertensive medications for this very reason.^15,16

Choline compounds

A key precursor to phospholipids such as phosphatidylcholine (PC) in cell membranes, as well as a component of the neurotransmitter acetylcholine, choline has been deemed a required dietary nutrient in the U.S.¹⁷ Like PS, PC and other choline-derived phospholipids support neurotransmission.¹⁸ Clinical trials have shown choline supplementation to improve cognitive performance,^19,20 with a unique form of choline—cytidine-5’-diphosphocholine (CDP-Choline)—demonstrating benefits in supporting cognitive function, including attention and memory.^18,21

Omega-3 fatty acids

With inflammation playing a contributing role in development of degenerative disease, including age-related cognitive decline, essential fatty acids (EFAs)—notably the omega-3 fatty acid docosahexaenoic acid (DHA)—are key nutrients to help maintain cognitive function, as well as support overall health.²² Omega-3 fatty acids help to reduce inflammatory cytokines, and support cell membranes and nerve function. Research also demonstrates their role in reduction of beta-amyloid plaque development.²³

Turmeric

Known for anti-inflammatory and antioxidant benefits, with a long history of use in ayurvedic medicine, research shows turmeric provides protection of neural cells as well as support for cognitive function.²⁴ One of the main pathological findings associated with Alzheimer’s disease is inflammation and the presence of beta-amyloid plaques in the brain, believed by some to be a sort-of repair process gone awry in response to vascular damage or other degenerative impacts.²⁵ In any event, inflammation is also a key factor and risk for Alzheimer’s disease.²⁶

Curcumin, a component of turmeric, has been widely demonstrated to inhibit inflammatory pathways and reduce production of pro-inflammatory cytokines in the body. This is in addition to its potent antioxidant effects that protect neural tissues and its noted effects on beta-amyloid accumulation.^27,28 Studies on specific curcumin extracts show benefits in memory, attention as well as mood.^24,29

Ashwagandha

Ashwagandha—an adaptogen that helps to support the body through physical and mental stress—has also been researched for its role in supporting cognitive function and memory.³⁰ Ashwagandha is known traditionally in ayurvedic medicine for its role in helping the body during times of stress, which can impact sleep and cognitive function. Research shows ashwagandha’s potential benefits in improving attention, memory and information processing speed that may be attributed to its antioxidant effects, as well as its adaptogenic benefits.^30,31

Magnesium

Deficiencies of magnesium have been noted in the standard Western diet, yet magnesium is important for nerve transmission, muscle function/relaxation, as well as cardiovascular effects—each of which can contribute to a risk of chronic health conditions, including neurologic disorders. Aging is associated with reduced nutrient intake, and magnesium levels are found to be low in those with Alzheimer’s disease,³² so supplementation with this key mineral can be essential to support cognitive and overall health.

Beta-alanine and carnosine

Carnosine is a powerful antioxidant, with high concentrations in the brain as well as muscle, and has been shown to support cognitive function in individuals exposed to high levels of oxidative stress.^33,34 However, carnosine levels decline with age and under stress, and are impacted by dietary choices. Supplementation with beta-alanine, the rate-limiting precursor to carnosine synthesis in the body, helps to ensure adequate levels of carnosine not only for cognitive and muscular function, but also for overall antioxidant and cellular support.

Research shows beta-alanine’s benefits for supporting mental acuity, learning and overall cognitive health well into the senior years.^35,36 Researchers found in a recent study that SR CarnoSyn, a patented form of sustained release beta-alanine, promoted significantly better spatial learning abilities than a control group, as well as reduced anxiety. The study also investigated the mechanism of action for this benefit and found that the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus (the section of the brain that plays a major role in learning and memory) was higher in rats  supplemented with SR CarnoSyn, even among older rats with naturally lower BDNF expression.³⁷

Aging gracefully with one’s full complement of intellectual capacity, sound memory recall and a quick wit should be the normal expectation for adults. Unfortunately, for a variety of reasons cited above, that is not always the case. But with the aforementioned arsenal of aids readily available to deploy, along with healthy course-correction choices in daily life, the golden years can filled with great joy and contentment.

Mark A. LeDoux is founder, chairman and CEO of Natural Alternatives International Inc. (NAI), an organization established in 1980 with facilities in the U.S. and Switzerland engaged in the research, design and manufacture of nutritional supplement programs and products for multinational clients. He is a proud member and leader of many industry organizations.

References

1 Kim DJ et al. “Hyperglycemia reduces efficiency of brain networks in subjects with Type 2 Diabetes.” PLoS ONE. 2016;11(6):e0157268.

2 McMullan CJ et al. “Melatonin secretion and the incidence of type 2 diabetes.” JAMA. 2013;309(13):1388-1396.

3 McCleery J et al. “Vitamin and mineral supplementation for preventing dementia or delaying cognitive decline in people with mild cognitive impairment.” Cochrane Database Syst Rev. 2018;11:CD011905.

4 Dhesi JK et al. “Vitamin D supplementation improves neuromuscular function in older people who fall.” Age Aging. 2004;33(6):589-595.

5 Devere R. “Cognitive consequences of vitamin D deficiency.” Pract Neurol. 2014;25-28.

6 La Fata G, Weber P, Mohajeri MH. “Effects of vitamin E on cognitive performance during ageing and in Alzheimer’s disease.” Nutrients. 2014;6(12):5453-5472.

7 Dysken MW et al. “Effect of vitamin E and memantine on functional decline in Alzheimer’s disease: The TEAM-AD VA Cooperative Randomized Trial.” JAMA. 2014;311(1):33-44.

8 Kidd P. “A review of nutrients and botanicals in the integrative management of cognitive dysfunction.” Altern Med Rev. 1999;4(3):144-161.

9 Richter Y et al. “The effect of soybean-derived phosphatidylserine on cognitive performance in elderly with subjective memory complaints: A pilot study.” Clin Int Aging. 2013;8:557-563.

10 Nakagawa K et al. “Antioxidant effect of astaxanthin on phospholipid peroxidation in human erythrocytes.” Brit J Nutr. 2011;105(11):1563-1571.

11 Galasso C et al. “On the neuroprotective role of astaxanthin: New perspectives?” Mar Drugs. 2018;16(8):247.

12 Grimming B et al. “Neuroprotective mechanisms of astaxanthin: A potential therapeutic role in preserving cognitive function in age and neurodegeneration.” GeroScience. 2017;39:19-32.

13 Cisternas P et al. “The increased potassium intake improves cognitive performance and attenuates histopathological markers in a model of Alzheimer’s disease.” Biochimica et Biophysica Acta. 2015;1852(12):2630-2644.

14 Chatterjee R et al. “Potassium and risk of Type 2 Diabetes.” Expert Rev Endocrinol Metab. 2011;6(5):665-672.

15 Casey J. “Potassium-sparing diuretics might reduce risk of Alzheimer’s disease.” Nat Rev Neurol. 2006;2(6):293.

16 Tschanz JT et al. “The Cache County Study on memory in aging: Factors affecting risk of Alzheimer’s disease and its progression after onset.” Int Rev Psychiatry. 2013;25(6):673-685.

17 Sanders LM, Zeisel SH. “Choline: Dietary requirements and role in brain development.” Nutr Today. 2007;42(4):181-186.

18 Secades JJ. “Citicholine in the treatment of cognitive impairment.” J Neurol Exp Neurosci. 2019;5(1):14-25.

19 Buchman A et al. “Verbal and visual memory improve after choline supplementation in long-term total parenteral nutrition: A pilot study.” JPEN. 2001;25(1):30-35. 

20 Naber M, Colzato L, Hommel B. “Improved human visuomotor performance and pupil constriction after choline supplementation in a placebo-controlled double-blind study.” Scientific Reports. 2015;5:13188. 

21 Nakazaki E et al. “Effect of citicholine on memory function in healthy older adults: A randomized, double-blind, placebo-controlled clinical trial.” Curr Dev Nutr. 2020;4(S2):1227.

22 Yurko-Mauro K, Alexander DD, Van Elswyk MR. “Docosahexaenoic acid and adult memory: A systematic review and meta-analysis.” PLoS One. 2015;10(3):e0120391.

23 Lee BY et al. “Effect of varying concentrations of docosahexaenoic acid on amyloid beta (1-42) aggregation: An atomic force microscopy study.” Molecules. 2018;23(12):3089.

24 Seddon N et al. “Effects of curcumin on cognitive function – A systematic review of randomized controlled trials.” Explor Res Hypothesis Med. 2019;4(1):1-11. 

25 Kokjohn TA, Maarouf CL, Roher AE. “Is Alzheimer’s disease amyloidosis the result of a repair mechanism gone astray?” Alzheimers Dement. 2012;8(6):574–583.

26 Kinney JW et al. “Inflammation as a central mechanism in Alzheimer’s disease.” Alzheimers Dement (N Y). 2018;4:575-590.

27 Mishra S, Palanivelu K. “The effect of curcumin (turmeric) on Alzheimer’s disease: An overview.” Ann Indian Acad Neurol. 2008;11(1):13-19.

28 Small GW et al. “Memory and brain amyloid and tau effects of a bioavailable form of curcumin in non-demented adults: A double-blind, placebo-controlled 18-month trial.” Am J Geriat Psych. 2018;26(3):266-277.

29 Cox KHM et al. “Further evidence of benefits to mood and working memory from lapidated curcumin in healthy older people: A 12-week, double-blind, placebo-controlled, partial replication study.” Nutrients. 2020;12(6):1678.

30 Choudhary D, Bhattacharyya S, Bose S. “Efficacy and safety of Ashwagandha (Withania somnifera (L.) Dunal) root extract in improving memory and cognitive functions.” J Diet Suppl. 2017;14(6):1-14. 

31 Pingali U, Pilli R, Fatima N. “Effect of standardized aqueous extract of Withania somnifera on tests of cognitive and psychomotor performance in healthy human participants.” Pharmacognosy Res. 2014;6(1):12-18.

32 Kirkland AE, Sarlo GL, Holton KF. “The role of magnesium in neurological disorders.” Nutrients. 2018;10(6):730.

33 Rokicki J et al. “Daily carnosine and anserine supplementation alters verbal episodic memory and resting state network connectivity in healthy elderly adults.” Front Aging Neurosci. 2015;7:219.

34 Hipkiss HR. “Glycotoxins: Dietary and metabolic origins; Possible amelioration of neurotoxicity by carnosine, with special reference to Parkinson’s disease.” Neurotox Res. 2018;34(1):164-172.

35 Furst T et al. “Beta-alanine supplementation increased physical performance and improved executive function following endurance exercise in middle aged individuals.” J Int Soc Sports Nutr. 2018;15(1):32.

36 Hoffman JR, Varanoske A, Stout JR. “Effects of Beta-alanine supplementation on carnosine elevation and physiological performance.” Adv Food Nutr Res. 2018;84:183-206.

37 Hoffman JR, Gepner Y, Cohen H. “Beta-alanine supplementation reduces anxiety and increases eurotrophin expression in both young and older rats.” Nutr Res. 2018;62.