It’s fair to say we carry many objectives regarding our wellbeing and health – to get more fit, lose weight, or better manage finances are common objectives. One is the management and maintenance of cognition. Memory and cognitive function becomes more significant with age. Many people seek natural support for the improvement of memory, and some therapeutic agents have more evidence than others for their ability to support cognition and memory.
Acetylcholine is a neurotransmitter with many biological roles. It is necessary for skeletal muscle activation, parasympathetic nervous system balance, and also for the processes of learning and memory.[1],[2] Acetylcholine is not the only chemical that plays a role in memory and cognition. Memory and cognition is also affected by other neurotransmitters including histamine,[3] gamma-aminobutyric acid (GABA),[4] dopamine, and glutamate,[5] as well as hormones,[6] chemical mediators of inflammation known as cytokines,[7] blood sugar regulation[8] and many other biological factors.
Medications which inhibit the breakdown of acetylcholine, called cholinesterase inhibitors, have been shown to be efficacious for mild to moderate Alzheimer’s disease. Benefits associated with the use of cholinesterase inhibitors for individuals with Alzheimer’s dementia include improvements in cognitive function, as well as other measures associated with activities of daily living and behaviour.[9]
Phosphatidylcholine is a phospholipid that comprises a majority of cellular membranes and is a precursor for the formation of choline and acetylcholine. Choline is essential for brain development and influences cognitive function in later life. High amounts of phosphatidylcholine can be found in food sources such as egg yolks, milk, meat and fish. Individuals who avoid consumption of all animal products may be at risk of inadequate choline intake, although some vegetables such as broccoli and brussel sprouts provide some of this nutrient.[10] In animal studies, supplementation of egg-sourced phosphatidylcholine was shown to improve memory as well as increase brain choline and acetylcholine concentrations.[11]
Natural cholinesterase inhibitors also exist. One natural cholinesterase inhibitor is huperzine A, derived from the club moss species Huperzia serrata. Huperzine A is a reversible inhibitor of acetylcholinesterase, and also has other neuroprotective properties including regulation of beta-amyloid precursor protein metabolism, and protection against beta-amyloid-mediated oxidative stress and apoptosis.[12],[13] Clinical trials utilizing huperzine A for a period of 8 to 12 weeks in patients with dementia have shown improvements in cognition with improved Mini-Mental State Examination scores of 1-5 points,[14] while studies in healthy young adults demonstrated the action of huperzine A as an acetylcholinesterase inhibitor.[15]
Acetyl-l-carnitine has been proposed as a neuroprotective agent because of its ability to confer improved mitochondrial function, which also plays a central role in the pathogenesis of diseases such as Alzheimer’s.[16] Acetyl-L-carnitine also is a precursor of acetylcholine. Formation of acetylcholine from acetyl-L-carnitine is dependent on concentration of acetyl-L-carnitine and requires the presence of coenzyme A, which is synthesized from pantothenate and cysteine.[17] Therapies combining the use of acetyl-L-carnitine in conjunction with an acetylcholinesterase inhibitor have been shown to improve response rate of acetylcholinesterase treatment.[18]
Other natural substances also have been shown to have a therapeutic effect in neurodegenerative diseases. This includes ginkgo, omega-3 fatty acids, alpha lipoic acid, curcuminoids, rosmarinic acid, and resveratrol.[19],[20],[21] Some of these substances may support cognitive function by acting as antioxidants or anti-inflammatories, while others may improve circulation and cellular or mitochondrial function. For the majority of these substances it is likely that there are multiple affects that may support cognitive function. In some cases, they may have synergistic effects[22] similarly to the use of acetyl-l-carnitine in combination with a cholinesterase inhibitor.
References
[1] Hasselmo ME. The role of acetylcholine in learning and memory. Curr Opin Neurobiol. 2006 Dec;16(6):710-5. View Full Paper
[2] Blokland A. Acetylcholine: a neurotransmitter for learning and memory? Brain Res Brain Res Rev. 1995 Nov;21(3):285-300. View Abstract
[3] Köhler CA, et al. Histaminergic mechanisms for modulation of memory systems. Neural Plast. 2011;2011:328602. View Full Paper
[4] McQuail JA, et al. Molecular aspects of age-related cognitive decline: the role of GABA signaling. Trends Mol Med. 2015 Jul;21(7):450-60. View Abstract
[5] Papenberg G, et al. Dopamine and glutamate receptor genes interactively influence episodic memory in old age. Neurobiol Aging. 2014 May;35(5):1213.e3-8. View Abstract
[6] Hogervorst E. Effects of gonadal hormones on cognitive behaviour in elderly men and women. J Neuroendocrinol. 2013 Nov;25(11):1182-95. View Abstract
[7] Tarkowski E, et al. Cerebral pattern of pro- and anti-inflammatory cytokines in dementias. Brain Res Bull. 2003 Aug 15;61(3):255-60. View Abstract
[8] Watson GS, Craft S. Modulation of memory by insulin and glucose: neuropsychological observations in Alzheimer’s disease. Eur J Pharmacol. 2004 Apr 19;490(1-3):97-113. View Abstract
[9] Birks J. Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD005593. View Abstract
[10] Linus Pauling Institute. Micronutrient Information Center: Choline. Accessed December 9, 2015. View Full Paper
[11] Chung SY, et al. Administration of phosphatidylcholine increases brain acetylcholine concentration and improves memory in mice with dementia. J Nutr. 1995 Jun;125(6):1484-9. View Full Paper
[12] Zhang HY, et al. Non-cholinergic effects of huperzine A: beyond inhibition of acetylcholinesterase. Cell Mol Neurobiol. 2008 Feb;28(2):173-83. View Abstract
[13] Xiao XQ, et al. Huperzine A and tacrine attenuate beta-amyloid peptide-induced oxidative injury. J Neurosci Res. 2000 Sep 1;61(5):564-9. View Abstract
[14] Desilets AR, et al. Role of huperzine a in the treatment of Alzheimer’s disease. Ann Pharmacother. 2009 Mar;43(3):514-8. View Abstract
[15] Morasch KC, et al. Physiological and neurobehavioral effects of cholinesterase inhibition in healthy adults. Physiol Behav. 2015 Jan;138:165-72. View Abstract
[16] Moreira PI, et al. Mitochondria: a therapeutic target in neurodegeneration. Biochim Biophys Acta. 2010 Jan;1802(1):212-20. View Full Paper
[17] White HL, et al. Acetyl-L-carnitine as a precursor of acetylcholine. Neurochem Res. 1990 Jun;15(6):597-601. View Abstract
[18] Bianchetti A, et al. Effects of acetyl-L-carnitine in Alzheimer’s disease patients unresponsive to acetylcholinesterase inhibitors. Curr Med Res Opin. 2003;19(4):350-3. View Abstract
[19] Bigford GE, et al. Supplemental substances derived from foods as adjunctive therapeutic agents for treatment of neurodegenerative diseases and disorders. Adv Nutr. 2014 Jul 14;5(4):394-403. View Full Paper
[20] Liu J. The effects and mechanisms of mitochondrial nutrient alpha-lipoic acid on improving age-associated mitochondrial and cognitive dysfunction: an overview. Neurochem Res. 2008 Jan;33(1):194-203. View Abstract
[21] Birks J, et al. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev. 2002;(4):CD003120. View Abstract
[22] Shinto L, et al. A randomized placebo-controlled pilot trial of omega-3 fatty acids and alpha lipoic acid in Alzheimer’s disease. J Alzheimers Dis. 2014;38(1):111-20. View Full Paper
