Cognitive and Memory Preservation

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.