Alongside classic supplements such as acetyl-l-carnitine, alpha-lipoic acid, omega-3, green tea, curcuma and Ginkgo biloba, we’re seeing the emergence of innovative new molecules for maintaining cognitive function. Acting at many levels – inhibiting acetylcholinesterase, eliminating beta-amyloid plaques, and combatting oxidative stress and chronic inflammation – these substances appear to offer considerable promise for the prevention and treatment of Alzheimer’s disease.
Acetylcholine is the most abundant neurotransmitter in the brain where it plays an essential role in memory. In Alzheimer’s patients, however, it is rapidly broken down by the enzyme cholinesterase, thus preventing signals from being transmitted effectively. Accumulation of beta-amyloid proteins, which reduces the number of neurons in the hippocampus, is another cause of this devastating disease.
And inflammation - while constituting the body’s first line of defence - is now also recognised by scientists as a key element in most major diseases, including Alzheimer’s.
A number of scientific studies have identified substances that offer significant support to those with mild or moderate forms of the disease. The most notable of these include acetyl-L-carnitine, alpha-lipoic acid, long-chain omega 3 fatty acids, green tea, curcuma and Ginkgo biloba
These substances variously protect against oxidative stress, delay cognitive decline, promote acetylcholine synthesis or prevent its breakdown, slow the progress of dementia, improve cognitive performance, reduce beta-amyloid plaques or encourage their elimination, and combat oxidation and inflammation.
In recent years, they have been joined by other exceptional neuro-nutritional supplements which, as clinical studies confirm, can slow the cognitive decline and loss of brain function associated with Alzheimer’s disease.
New molecules with proven effects
Galantamine to increase acetylcholine levels
Galantamine, an alkaloid found in snow drops (Galanthus nivalis) and other related plants, is one such welcome addition to the classic pro-cognitive supplements.
Two important clinical studies of Alzheimer’s patients have reported rapid and significant improvements in memory, learning, cognition and behaviour. Galantamine, which is well-tolerated, slows cognitive and functional decline by:
- Inhibiting acetylcholinesterase and thus increasing acetylcholine levels.
- Stimulating acetylcholine’s effect on brain receptors.
- Improving blood supply to the brain, and thus cognitive performance.
- Stimulating (like tobacco), a specific nicotinic receptor in the brain called alpha-7 nicotinic acetylcholine receptor, thus improving learning, memory, attention and concentration.
Galantamine has been attracting international interest for more than 20 years and is recommended in the US for Alzheimer’s disease and authorised for such by the FDA.
Derived from algae, this organic compound is similar in structure to GABA and thus has gabaergic and neuroprotective effects in the hippocampus, the specific region of the brain that controls memorisation and learning. It has been shown to reduce loss of volume of this area of the brain by around 68% compared with placebo.1
Clinical trials conducted in Europe and the US show that homotaurine binds to beta-amyloid proteins, inhibiting the formation of neurotoxic aggregates and consequent plaque deposits which result in the dysfunction and potential death of brain cells.
By reducing the toxic effect of these plaques in the brain, homotaurine supplementation thus protects memory and learning functions.
A close relative of vitamin B3, this molecule significantly increases production of NAD+. Activation of NAD+ has been linked with decreased toxicity of beta-amyloid peptides in Alzheimer’s disease. As a precursor of NAD+, nicotinamide riboside (NR) promotes the proliferation of (PGC)-1α, important regulators of beta-amyloid production.
Studies thus show that taking NR significantly stems cognitive decline.
NR supplementation could therefore benefit Alzheimer’s patients by improving cognitive function and synaptic plasticity, and by providing some protection against the generation of toxic beta-amyloid plaques in the brain2
This vitamin B1 derivative is able to cross the blood-brain barrier.
In recent research, sulbutiamine resulted in a significant improvement in daily activity in early-stage Alzheimer’s patients, especially when it was combined with an acetylcholinesterase-inhibitor. In this randomised, double-blind study using donepezil hydrochloride as the anticholinesterase agent, the combination produced better results than donepezil plus placebo.
Mouse studies have shown that standardised extracts of andrographis may significantly improve learning and memory, and reduce cognitive impairment in spatial memory performance.
The extracts were also found to reduce hyperphosphorylation of tau proteins. These proteins are abundant in the brain, where they stabilise microtubules. However, defective tau proteins that are no longer able to perform this function properly can lead to Alzheimer’s disease and other forms of dementia.
Like sulbutiamine, this particularly bioavailable form of magnesium is able to cross the blood-brain barrier. Recent animal studies have shown it increases synaptic density and thus improves cognitive function and memory capacity. In addition, it reduces toxic beta-amyloid plaques in the hippocampus and frontal cortex, even at very advanced stages of the disease, producing a slight increase in life expectancy 3
This natural alkaloid extracted from the traditional Chinese plant Huperzia serrata promotes growth of nerve cells and inhibits acetylcholine breakdown by blocking the action of acetylcholinesterase. Huperzine A was thus shown to improve memory, cognition and behaviour in over half of the Alzheimer’s patients to whom it was administered.
is a substance recognised for stimulating the growth of axons, stabilising nerve cell membranes and increasing production of acetylcholine. It is used in the prevention and treatment of neurological problems including Alzheimer’s disease.
Other promising substances
Fullerene C60 could be considered useful in treating Alzheimer’s as it counters aggregation of beta-amyloid proteins and degeneration of pyramidal neurons in the hippocampus 4
Extracted from loquat leaves, ursolic acid inhibits acetylcholinesterase and may thus have a preventive effect against Alzheimer’s disease5
Comprising proline and glycine, this dipeptide was developed in Russia and patented in 1995. It is prescribed there and in neighbouring countries as a nootropic and neuroprotector. In studies, it has shown promise against Alzheimer’s disease by repairing damaged cells and receptor sites6
Also known as choline alfoscerate or alpha-GPC, this compound is naturally present in the brain where it increases production of acetylcholine. It may thus prove beneficial in combatting cognitive problems. It may also be regarded as a nootropic, improving the ability to respond better to life’s challenges by aiding motivation and decision-making, and in particular, by improving cognitive and neurosensory processes as a whole, likesarcosine
, which is chemically similar to resveratrol
, reduces lipid peroxidation and has a neuroprotective effect7
. It improves overall concentration and short- and long-term memory, and a mouse study has shown that it may have a protective effect against Alzheimer’s and age-related cognitive decline through its potential to combat inflammation in the brain.
PQQ is extraordinarily effective at protecting brain cells from oxidative damage and neurotoxicity induced by mercury and other toxins. It improves performance in memory tests and interacts positively with the brain’s neurotransmitter systems. Some studies have shown that it protects nerve cells against oxidative damage induced by beta-amyloid proteins associated with Alzheimer’s disease.
1-Analyse Post-hoc d’une phase 3 (78 semaines) d’une recherche nord-américaine sur des patients atteints de la maladie d’Alzheimer (intensité de la maladie : légère à modérée) et âgés de 50 ans ou plus
2- Gong B, Pan Y, Vempati P, Zhao W, Knable L, Ho L, Wang J, Sastre M, Ono K, Sauve AA, Pasinetti GM. Nicotinamide riboside restores cognition through an upregulation of proliferator-activated receptor-γ coactivator 1α regulated β-secretase 1 degradation and mitochondrial gene expression in Alzheimer's mouse models. Neurobiol Aging. 2013 Jun;34(6):1581-8. doi: 10.1016/j.neurobiolaging.2012.12.005. Epub 2013 Jan 9.
3- Li, W., Yu J., Liu Y., Huang x., Abumaria N., Zhu X., Huang X., Xiong W., Ren C. , Liu X. G. , Chui D., and Liu G. Elevation of Brain Magnesium Prevents and Reverses Cognitive Deficits and Synaptic Loss in Alzheimer’s Disease Mouse Model. J Neurosci, 2013. 33(19): p8423-41
4- Makarova EG1, Gordon RY, Podolski IY. Fullerene C60 prevents neurotoxicity induced by intrahippocampal microinjection of amyloid-beta peptide. J Nanosci Nanotechnol. 2012 Jan;12(1):119-26.
5- Chung YK1, Heo HJ, Kim EK, Kim HK, Huh TL, Lim Y, Kim SK, Shin DH. Inhibitory effect of ursolic acid purified from Origanum majorana L on the acetylcholinesterase. Mol Cells. 2001 Apr 30;11(2):137-43.
6- Ostrovskaya RU, Belnik AP, Storozheva ZI. Noopept efficiency in experimental Alzheimer disease (cognitive deficiency caused by beta-amyloid25-35 injection into Meynert basal nuclei of rats). Bull Exp Biol Med. 2008 Jul;146(1):77-80.
7- Porquet D, Casadesús G, Bayod S, Vicente A, Canudas AM, Vilaplana J, Pelegrí C, Sanfeliu C, Camins A, Pallàs M, Del Valle J. Dietary resveratrol prevents Alzheimer's markers and increases life span in SAMP8. Age (Dordr). 2012 Nov 7.