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Can Phosphatidylserine Reverse Cognitive Decline and Cognitive Impairment and Prevent Dementia?

Cognitive decline and phosphatidylserine

A happy, health brain that works well is full of brain cells that can efficiently connect or ‘talk’ with each other. The way brain cells connect is called a synapse, and all the cells in our brains and central nervous system use synapses to allow us to think, move, learn and remember. However, as we age our brain cells (aka neurons) start to die off, and the neurons that survive get less healthy and slowly lose their ability to connect to the other neurons surrounding them.

The older we get the more unhealthy our neurons become, and as some point most people start to notice some minor symptoms such as their short term memory not being as sharp as it once was, or struggling to remember names and faces that were once familiar. This is a natural part of ageing and is known as cognitive decline, it’s obviously not great, but doesn’t hugely affect our lives. However, if we allow the degeneration to continue we reach the next stage beyond this known as cognitive impairment. It’s a little more serious, and means people are living well below their potential, but they can still live relatively normally and independently. Although, when things progress beyond the point, to where people can no longer live a unaided life, and have problems completing simple everyday tasks, we reach the stage of dementia. 60%-80% of cases of dementia are Alzheimer’s.

Cell Membranes and Cognitive Decline

As scientific researchers are discovering there is no one cause for dementia, so unfortunately there is no one cure either. Despite this, there is one key characteristic that is present and steadily worsens at all the stages from cognitive decline to dementia, and that a change in the structure of the membranes that surround and protect our brain cells.

Our cell membranes are made up of 2 layers of lipids, known as the lipid bilayer, and as our cells decline the composition of the lipid bilayer changes. They should be plump, fluid, malleable and flexible, which allows them to adjust to efficiently receive the synapse signal from other cells, as well as being permeable, allowing all of the proteins, enzymes, nutrients, oxygen and glucose etc that needs to get in and out of the cell to do so. However, as the membranes lose their plumpness and fluidity they become harder, so they are less permeable and less able to adjust to receive synaptic signals. You can think of it as an orange which starts off plump and juicy, but as it loses moisture it becomes dryer and harder.

phosphatidylserine membrane
The Phospholipid Bilayer of Cell Membranes

The lipid bilayers are made up of Phosphatidylcholine, Phosphatidylenolmine, Sphingomylin (a combination of Phosphatidylcholine and Phosphatidylenolmine), Phosphatidylserine and the omega 3 fatty acid DHA. Whilst Phosphatidylcholine, Phosphatidylenolmine are very important to the membrane integrity they seem to be more about the structural integrity of the membrane perhaps a little like the steel frame of a building, whereas the phosphatidylserine and the DHA allow extra fluidity and flexibility. Although not quite the same, you can think of them like windows in the building that the people inside can open to feel the fresh air.

As we age the phosphatidylserine content of the membranes decrease and the cholesterol content increases (1,3), and this change is key to increasing the hardness and reducing the fluidity and flexibility of the cell membrane. This causes a reduction in enzymic activity and the proteins and other nutrients aren’t as able to easily get in and out of the cell, and the cells simply can’t efficiently communicate with other cells (1,4,5). Effectively, we can no longer properly open the windows to get the fresh air.

Thankfully, we can prevent this decline in phosphatidylserine levels by taking a simple phosphatidylserine supplement. Phosphatidylserine supplements are easily absorbed (as long as you take them with food containing fat!), and also easily cross the blood brain barrier into the brain so they can absorbed into our neuronal membranes (6).

Once in the neuronal membranes phosphatidylserine can slow, halt, or even reverse the structural, and biochemical changes that have occurred, and restore flexibility and fluidity to brain cell membranes. This supports cognitive functions, allows us to form new short term memories, consolidate long term ones, as well as retrieve memories and create completely new ones. It also improves our ability to learn, focus and concentrate, as well as our our ability to reason and solve problems. We can improve our language skills and our ability to communicate, as well as locomotor functions, especially our rapid reactions and reflexes (6).

Phosphatidylserine supplementation also supports the release of Nerve Growth Factor a hormone that stimulates growth of new healthy nerve cells and the cleaning up of old and damaged ones (7). Phosphatidylserine also protects membranes from free radicals and oxidative damage, and stimulates an increase in our own antioxidant defence systems (8).

Research on Phosphatidyserine and Cognitive Decline and Cognitive Impairment

In open label trials (i.e ones where both the subjects and researchers know that the subjects are receving phosphatidylserine, as opposed to double blind placebo trials where neither party are sure whether it is phosphatidylserine or a placebo), older individuals with mild cognitive decline supplemented with 300mg of Phospahtidylserine (100mg, 3 times a day) for 60 days. At the end of the 60 day period the subjects significantly improved their performance on tests of verbal learning, verbal recall, verbal fluency, visual learning, attention, communication skills, initiative, socialisation and self sufficiency (9,10).

Another study extended the supplementation period to 90 days and found very similar results, but also found the subjects improved their ability to recall names and recognise faces (11). Another group of older adults with more severe cognitive decline achieved significant improvements in verbal learning, verbal recall, attention span and ability to concentrate, vigilance, initiative, socialisation and self sufficiency following supplementation with the same dose of 100mg of phosphatidylserine 3 times a day.

A double blind study on both women and men aged over 60 with mild memory loss and 300mg of phosphatidylserine a day for 90 days, found the group that supplemented with phosphatidylserine had significant improvements in short term recall, immediate memory, vocabulary skills, word recall, attention span and vigilance. Whilst the placebo group received no benefit (14).

phospahtidylserine and cognitive impairment2 more double blind studies looked at people with more severe cognitive impairment (14), and mild degenerative dementia (15) and found they had significantly improved verbal recall and overall cognitive functioning, and significantly reduced withdrawal and apathy compared to the placebo group following phosphatidylserine supplementation. The considerable success of phosphatidylserine to support brain function and stop cognitive decline in clinical trials was recognised by the FDA who have stated, “consumption of phosphatidylserine may reduce the risk of dementia in the elderly” and “consumption of phosphatidylserine may reduce the risk of cognitive dysfunction in the elderly” (16).

However, it should be noted that phosphatidylserine is not a magic pill, and is best suited for people looking to prevent cognitive decline or with mild to moderate stages of cognitive impairment. For example, another trial focused on patients with Alzheimers who supplemented with 400mg per day of phosphatidylserine. They found that although supplementation along with a 16 week cognitive training program produced much greater improvements in neuropsychological tests than just the cognitive training program alone, phosphatidylserine wasn’t able to stop progress of the disease. The researchers found that 4 months later despite continued supplementation with phosphatidylserine performance had worsened (17). Although it does leave open the possibility of future studies in Alzheimers patients with higher dosages of phospahtidylserine.

For anyone looking to help or prevent cognitive decline we recommend trying phosphatidylserine at 100mg 3 times a day. Click Here for more information.

References:

(1) Cenacchi T, Bertoldin T, Farina C, Fiori MG, Crepaldi G. Cognitive decline in the elderly: a double blind, placebo-controlled multicenter study on efficacy of phosphatidylserine administration. Aging Clin Exp Res 1993;5:123–33.

(2) Crook TH, Tinklenberg J, Yesavage J, Petrie W, Nunzi MG, Massari DC. Effects of phosphatidylserine in age-associated memory impairment. Neurology 1991;41:644–9.

(3) Crook T, Petrie W, Wells C, Massari DC. Effects of phosphatidylserine in Alzheimer’s disease. Psychopharmacol Bull 1992;28:61–6.

(4) Cohen SA, Muller WE. Age-related alterations of NMDA-receptor properties in the mouse forebrain: partial restoration by chronic phosphatidylserine treatment. Brain Res 1992;584:174–80.

(5) Marra C, Silveri MC, Gainotti G. Predictors of cognitive decline in the early stage of probable Alzheimer’s disease. Dement Geriatr Cogn Disord 2000;11:212–8.

(6) Michael J. Glade Ph.D., Kyl Smith D.C., Phosphatidylserine and the human brain, Nutrition 31 (2015) 781–786

(7) De Simone R., Ajmone-Cat M.A., Tirassa P., Minghetti L. Apoptotic PC12 cells exposing phosphatidylserine promote the production of anti-inflammatory and neuroprotective molecules by microglial cells. Journal of Neuropathology and Experimental Neurology. 2003 Feb;62(2):208-16.

(8) Chaung HC, Chang CD, Chen PH, Chang CJ, Liu SH, Chen CC. Docosahexaenoic acid and phosphatidylserine improves the antioxidant activities in vitro and in vivo and cognitive functions of the developing brain. Food Chem 2013;138:342–7

(9) Sinforiani E, Agostinis C, Merlo P, Gualtieri S, Mauri M, Mancuso A. Cognitive decline in ageing brain. Therapeutic approach with phosphatidylserine. Clin Trials J 1987;24:115–25.

(10) Caffara P, Santamaria V. The effects of phosphatidylserine in patients with mild cognitive decline. An open trial. Clin Trials J 1987;24:109–14.

(11) Schreiber S, Kampf-Sherf O, Gorfine M, Kelly D, Oppenheim Y, Lerer B. An open trial of plant-source derived phosphatidylserine for treatment of age-related cognitive decline. Isr J Psychiatry Relat Sci 2000;37:302–7.

(12) Granata Q, DiMichele J. Phosphatidylserine in elderly patients. An open trial. Clin Trials J 1987;24:99–103.

(13) Allegro L, Favaretto V, Ziliotto G. Oral phosphatidylserine in elderly patients with cognitive deterioration. An open study. Clin Trials J
1987;24:104–8.

(14) Cenacchi T, Bertoldin T, Farina C, Fiori MG, Crepaldi G. Cognitive decline inthe elderly: a double blind, placebo-controlled multicenter study on efficacy of phosphatidylserine administration. Aging Clin Exp Res
1993;5:123–33.

(15) Villardita C, Grioli S, Salmeri G, Nicoletti F, Pennisi G. Multicentre clinical trial of brain phosphatidylserine in elderly patients with intellectual deterioration. Clin Trials J 1987;24:84–93.

(16) Taylor CL. Letter regarding phosphatidylserine and cognitive dysfunction and dementia. Bethesda, MD: US Food and Drug Administration; 2003.

(17) Heiss WD, Kessler J, Mielke R, Szelies B, Herholz K. Long-term effects of phosphatidylserine, pyritinol, and cognitive training in Alzheimer’s disease. Dementia 1994;5:88–98