The ability to think and remember are essential to life. Reasoning helps us to make the many decisions we face each day, and memory helps us both function (language, names, faces, etc.) and preserve meaningful events in our lives. If the degeneration of these abilities is the curse of aging, natural products may well be the antidote, as numerous nutrients, herbs and specialty ingredients are proving beneficial to cognitive function.

In many ways, the brain controls everything in the body, including operational functions such as heart rate and muscle contraction. However, its role in cognitive processes is its most recognizable activity, often simplified as the ability to think and organize thoughts. Perception, reasoning, problem-solving, learning and remembering all owe their abstract activities to billions of nerves, bundled for maximum performance.

Brain cells are the heart of the neuron and connect to their surroundings via dendrites and axons. Axons carry electrochemical nerve impulses/messages and are often covered in myelin, a fatty sheath that aids nerve transmissions. Neurotransmitters, including glutamic acid and gamma-aminobutyric acid (GABA), are chemical hormones that help deliver these messages.

There are numerous threats to the structures and function of the complex brain. The organ is mostly water and fat, yet operates at mysterious proficiency, given its primary components typically don't mix well. However, with fat the major nutrient in the brain, oxidation becomes cerebral enemy number one.

Oxidation Equals Aging

As described by a research team at University of Kentucky, Lexington, significantly increased levels of lipid peroxidation and protein, DNA and RNA oxidation have been found in vulnerable regions of the brain of both early- and late-stage patients suffering cognitive impairment.¹ In fact, this oxidation has been linked to progression of Alzheimer's disease (AD), the granddaddy of cognitive degeneration.

This pathology opens the door for antioxidant supplementation. Researchers have reported an antioxidant-rich diet may counteract oxidative damage and decreased motor and cognitive performance linked to increased risk of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), AD and fellow degenerative condition Parkinson's disease(PD).²

This has borne true, as research has linked low peripheral levels of various antioxidant nutrients—vitamins C, A and E and carotenoids (lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene and beta-carotene)—to cognitive impairment.³ Of this group, vitamin E has shown particular efficacy against cognitive disorder related to oxidation. Nano-sized alpha-tocotrienol may cross the blood-brain barrier to protect the brain.⁴

The vitamin-esque nutrient coenzyme Q10 (CoQ10) is another protective antioxidant, addressing free radicals produced during oxidative phosphorylation in the inner mitochondrial membrane.⁵ Complicating the aging process in the brain, CoQ10 levels decline with age, potentially contributing to beta-amyloid deposits, which disrupts signal transmission by synaptic receptors and leads to decreased learning and memory functions. Intervention with CoQ10 appears to limit amyloid beta peptide toxicity in brain cells;⁶ co-supplementation with vitamin E has shown promise in improving cognitive performance.⁷

Beyond nutrients, botanical antioxidants might be useful in preserving brain function. From the herb turmeric comes curcumin, or curcuminoids, which offers both antioxidant and anti-inflammatory properties important to cognition. An extract of curcumin has inhibited neurological oxidative stress in animal models,⁸ and also appears to help hinder beta amyloid formation and progression.⁹

Also from the botanical world, pine bark extract has brought its powerful antioxidant hammer down on free radicals, improving cognitive function as well as related issues such as circulation and vascular function. In 2008, two different extracts of pine bark made inroads on memory capability in aging people. Maritime pine bark extract from France (as Pycnogenol, from Horphag) addressed the oxidation theory of aging and neurological degeneration by significantly inhibiting the oxidation of nerve membranes and improving memory after three months of supplementation in elderly patients.¹⁰ Previously, this extract was found to improve attention, concentration and motor-visual coordination in attention deficit hyperactive disorder (ADHD).¹¹

Similarly, New Zealand pine bark extract (as Enzogneol, from ENZO Nutraceuticals) improved cognitive performance in middle-age men after only five weeks of supplementation.¹² Computer-based cognitive testing showed rapid improvements in performance on both spatial working memory (SWM) and immediate recognition memory (IRM) tasks. Researchers noted performance on these tests normally declines with age, while the Enzogneol group's results indicated a far younger performance than their age range would have normally predicted. Follow-up worked revealed the extract seemed to improve the way different brain regions interacted or talked to each other, possibly explaining the performance increase on the cognitive tasks.

Overall, the researchers suggested the antioxidant effects and improvements in blood circulation may have driven the test results. The researchers left open the possibility that some phenolic constituents or metabolites entering the brain may directly influence nervous signal transduction.

Memory Upgrade

“Memory is the diary that we all carry about with us.” Oscar Wilde used this line in “The Importance of Being Earnest” as a response to character Cecily's incessant journaling. Like Cecily, a good memory helps us "keep the wonderful secrets of life." However, like old pages, the neurons and other structures of the brain responsible for memory can deteriorate over time. This threatens to lock memories away, forever bound to an unreachable, dead region of the brain.

While antioxidants such as pine bark extract may help improve performance memory, other botanicals can influence memory by other mechanisms.

Ginkgo biloba is a vasodilator used as a stroke treatment in China and Europe, and has been popular globally as a memory aid supplement. Prior animal studies showed ginkgo administration curbs cognitive deficiencies and improves spatial and non-spatial memory.^13,14 Chinese studies have upheld ginkgo's benefits to spatial learning and memory.^15,16 More recently, Oregon Health & Science University researchers reported Ginkgo biloba supplementation may help protect the memory of people aged 85 and older.¹⁷ When adjusting for compliance, they found subjects who reliably took the ginkgo supplements had a 70-percent lower risk of developing mild memory problems than those who took placebo.

Brain enzymes related to cognitive function are the likely target of green oat extract (as Neuravena, from Frutarom). A pair of 2007 studies confirmed earlier in vitro conclusions that green oat administration increases brain activity and improves learning performance. One trial found Neuravena stimulates the dopaminergic transmitter system, which affects motivation and depression, and inhibits enzyme monoaminoxidase B, which is responsible for degradation of the neurotransmitter dopamine.¹⁸ Researchers noted the increased brain activity attributed to the green oat extract was comparable to that achieved by dementia drugs. The other trial concluded green oat administration enhanced stress coping abilities and alertness, in addition to improving general learning performance and speed of learning.¹⁹

Both trials were conducted on animals, but 2008 saw results of a human trial out of Switzerland, in which Neuravena's benefit to brain activity, mental fitness and stress resistance were confirmed.²⁰ Men and women taking the green oat extract daily experienced improved concentration, learning and memory, as well as an overall stimulation of brain activity.

Vinpocetine is isolated from the leaves of the lesser periwinkle (Vinca minor) and has shown significant benefits to memory preservation. Its mechanism in brain health may involve increased blood flow to the brain via reduction in flow resistance in cerebral vessels and improved platelet aggregation.^21,22 Both animal and human trials have shown vinpocetine can increase short-term memory as well as reaction time.^23,24

A Matter of Fat

Memory enhancement is not just for botanicals. As fat is the most prevalent macronutrient in the brain (18 percent), far ahead of protein (1 percent), it is no surprise a group of lipid-based ingredients is taking the brain health segment by storm.

Among omega-3 fatty acids, long-chain docosahexaenoic acid (DHA) represents most of the fatty acid content in the brain and appears to be most beneficial to the developing brain. DHA from breast milk helps neural development in infants, so it is no surprise DHA is a popular addition to infant formula. Supporting this use, several studies have shown pregnant women with higher DHA have children with higher IQ scores, while increased DHA intake by infants has a positive impact on mental processing and development.^25,26,27

In adults, DHA is important for nerve health and function, as well as healthy neurological function. Consumption of fish, which is rich in DHA, has long been linked to improved IQ and lower risk of dementia.^28,29 In a study on omega-3 supplementation, adults with early-stage AD taking an fish oil concentrate high in DHA (as EPAX 1050G, from EPAX AS) experienced less memory decline, while those taking placebo suffered memory decline.³⁰ In another trial of AD patients, DHA supplementation markedly reduced beta amyloid accumulation and oxidative damage, in addition to correcting synaptic deficits and improving cognitive function.³¹

One proposed mechanism of DHA's action in the brain is counteraction of neuron-inflammation. In 2007, Ohio State University researchers reported DHA metabolizes in the body to resolvins and neuroprotectins, inflammatory mediators with a key role in helping DHA "prevent neuroinflammation by inhibiting transcription factor NFkappaB, preventing cytokine secretion, blocking the synthesis of prostaglandins, leukotrienes, and thromboxanes, and modulating leukocyte trafficking."³²

DHA is an integral partner of phosphatidylserine (PS), a phospholipid found in the membranes of cells, including neuronal cells. In fact, half of the body's PS is in the brain. Research shows greater DHA in the brain increases PS levels,³³ and, together, the DHA-PS pairing affects cell signaling and proliferation.³⁴

Humans produce PS, but the levels decline with age. As a supplement, PS was originally sourced from cow brains and contained other substances such as DHA and miscellaneous brain compounds. PS is now sourced from soybeans, which do not yield DHA. However, PS is available in combination with DHA. Alternately, scientists have researched PS from fish liver and squid skin, both result in PS with DHA content.

In the '90s, research on soy-PS in cognition suggested improved memory, learning, concentration, word recall and mood in middle-aged and elderly subjects with dementia or age-related cognitive decline.³⁵ However, 2001 Dutch research found no benefit on memory or cognition from PS supplementation in elderly patients with prior memory complaints.³⁶ Then, in 2008, Nachum Vaisman, M.D., Sourasky Tel-Aviv Medical Center, Israel, reported elderly subjects taking soy-derived PS (as Sharp-PS, from Enzymotec) for 12 weeks demonstrated improved memory and attention, as gauged by a computer assessment battery.³⁷

Chemi Nutra reported its SerinAid® PS was studied at the University of Guadalajara in Mexico, demonstrating an ability to reduce the incidence of memory loss that accompanies hormone replacement therapy (HRT) in women. PS even improved some emotional parameters associated with HRT in these women.

Part of the role PS plays in brain function may be in boosting production of neurotransmitters such as acetylcholine (ACL), which is involved in synaptic plasticity, a mechanism of memory and learning. A few natural ingredients for improved cognition and memory are precursors of ACL.

Glycerophosphocholine (GPC) is one such ACL precursor that has shown a modest improvement of cognitive dysfunction in neurodegenerative and vascular dementia.³⁸ GPC combined with a cholinesterase inhibitor not only increases ACL levels in the brain but also helps in cases of altered cholinergic nuuerotransmission.³⁹ GPC may also provide neuroprotection in cases of vascular brain damage.⁴⁰ In a review of 13 trials on dementia disorders of degenerative or vascular origin, GPC (also known as choline alphocerate) was found to match or best clinical improvements achieved by reference drug or placebo.⁴¹ A 2003 multicenter, double blind, randomized, placebo-controlled trial involving GPC administration in patients affected by mild to moderate Alzheimer-like dementia resulted in cognitive improvements in the treatment group after 90 and 180 days of supplementation.⁴²

Citicoline, another lipid precursor to ACL, has a positive effect on memory, especially short-term memory, according to Italian researchers.⁴³ Also known as CDP-choline and cytidine diphosphate choline (cytidine 5-diphosphocholine), citicoline has shown cholinergic and neuroprotective actions, according to a 2008 monograph in Alternative Medicine Review, which further noted citicoline as a supplement promotes structural integrity and functionality of the neuronal membranes involved in membrane repair.⁴⁴ Overall, citicoline supplementation may help to improve cognitive deficits, stroke rehabilitation, brain and spinal cord injuries and neurological diseases.

In the brain cell membranes of older human subjects, citicoline (as Cognizin, from Kyowa Hakko) stimulated synthesis of phosphatidylcholine,⁴⁵ another brain cell phospholipid that has shown its own ability as a supplement to produce ACL and improve memory.⁴⁶

In a double blind, placebo-controlled, randomized clinical trial, 12 weeks of Cognizin administration in 30 patients with mild to moderate senile dementia of the Alzheimer's type, the citicoline ingredient improved cognitive performance, most notably in those with mild dementia.⁴⁷ Researchers noted the citicoline treatment also increased cerebral blood flow and bioelectrical brain activity.

In a 2006 review, a pair of Spanish researchers stated administering citicoline orally is about the same as intravenous delivery, in terms of absorption.⁴⁸ They explained once absorbed, "citicoline is widely distributed throughout the body, crosses the blood-brain barrier and reaches the central nervous system (CNS), where it is incorporated into the membrane and microsomal phospholipid fraction." From there, citicoline prompts the biosynthesis of structural phospholipids in neuronal membranes, increases brain metabolism and affects neurotransmitter levels. They added citicoline has been shown to increase norepinephrine and dopamine levels in the central nervous system, resulting in a neuroprotective effect in hypoxic and ischemic conditions, and improving learning and memory performance in animal models of brain aging.

In a Spanish study, elderly subjects with memory deficits and without dementia were administered 1,000 mg/d or 500 mg/d of citicoline alone (as Cognizin, from Kyowa Hakko) or 300 mg/d of citicoline plus 90 mg/d of nimpdipine for four weeks.⁴⁹ Citicoline treatment improved memory in free recall tests, but not in recognition tests. However, there was also a significant improvement in word recall, immediate object recall and delayed object recall after citicoline treatment. And three subgroups of treatment also experienced enhanced memory activity following citicoline intervention at multiple doses.

More recently, neuroscientists at Massachusetts Institute of Technology, Cambridge, produced animal study results showing long-term dietary CDP-choline supplementation can counteract the hippocampal-dependent memory impairment caused by impoverished environmental conditions.⁵⁰ The researchers linked the benefits to citicoline's membrane phospholipid boosting but noted long-term supplementation is required for the desired benefit.

B Smarter

Citicoline is a form of B vitamin, a group of nutrients that has exhibited some importance in brain health, relative to cognition and memory. Vitamin B9, or folic acid, has been indicated as a key nutrient in risk of both stroke and neural tube birth defects, so it is little surprise this vitamin delivers cognitive and memory benefits as well. In fact, folic acid deficiency in mice led to neurodegeneration and brain dysfunction.⁵¹

In a 2008 study report, outpatients with probable Alzheimer's disease were treated concurrently with cholinesterase inhibitors plus either folic acid or a placebo.⁵² Researchers discovered the response to cholinesterase (promotes healthy neuronal function) in patients with AD may be improved by the use of folic acid.

Low folate and raised homocysteine have been correlated to cognitive impairment in both the general population and in people with brain-related disease, including Alzheimer's, Parkinson's and even multiple sclerosis.

A 2007 trial published in The Lancet concluded folic acid supplementation for three years in a cross-section of the general population in the Netherlands significantly improved aspects of cognitive function that decline with age.⁵³ The folic acid treatment group had improved memory, information processing speed and sensorimotor speed, compared to the placebo group.

Italian researchers studying elderly people in Northern Italy found subclinical folate deficiency may be a risk factor for the cognitive decline that is associated with aging and possibly contributes to Alzheimer’s as well as other dementia developments.⁵⁴

A 2008 review confirmed folate's role in improving cognitive function in Alzheimer's, noting folic acid enhances plasma concentrations of DHA and fellow omega-3 fatty acid eicosapentaenoic acid (EPA), which are both beneficial in dementia and Alzheimer's disease.⁵⁵ Undurti Das, M.D., explained the two omega-3s up-regulate gene expression related to neurogenesis, neurotransmission and connectivity; improve endothelial nitric oxide (eNO) generation; enhance brain acetylcholine levels; and suppress the production of pro-inflammatory cytokines.

Folate isn't the end all and B-all when it comes to cognitive function. A Swedish population-based study of patients at various stages of Alzheimer's disease showed vitamin B12 and folate were more crucial to cognitive performance in pre-clinical patients compared to full-blown Alzheimer's patients.⁵⁶

In patients with mild to moderate Alzheimer's and normal levels of both folate and vitamin B12, Taiwanese researchers found intervention with a multivitamin containing vitamin B6, B12 and folate led to decreased homocysteine, concentrations but no statistically significant difference in cognitive function.⁵⁷

However, researchers from India reported abnormal mental test scores among subjects with vitamin B12 deficiency neurological syndromes were improved with vitamin B12 supplementation.⁵⁸

A 2008 trial report out of University of Oxford, England, concluded low B12 status among elderly subjects is a modifiable cause of brain atrophy and cognitive impairment.⁵⁹ One of the study's authors, David Smith, Ph.D., published a 2008 review of B vitamins, homocysteine and dementia. Citing an estimated 4.6 million new cases of dementia worldwide each year, he noted 77 cross-sectional studies on more than 34,000 subjects have shown associations between cognitive decline/dementia and homocysteine and B vitamins.⁶⁰

Market Outlook

Adding to the figures on dementia, five million Americans suffer from Alzheimer's, a figure that threatens to balloon to 16 million by mid-century. According to the Natural Marketing Institute (NMI), 44 percent of the adult American population report losing brain/mental capacity is among their biggest fears, with Boomers and the elderly the most fearful.

Fortunately, many consumers see diet and lifestyle improvements as ways to allay such fears, as NMI found nearly two-thirds of American adults maintain a healthy lifestyle in order to have a healthy mind. Interestingly, they count increased stress and lack of sleep/energy as the major causes of mental deficiency. While many invest faith and hope in medical advancements relative to dementia, Alzheimer's and the other cognitive impairments of aging, there are numerous natural nutrients, herbs and specialty ingredients churning out positive research outcomes on cognitive function and memory preservation.

References on the next page...

References for "Cognitive and Memory Preservation"

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