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Cognitive Decline & Phytomedicine

Cognitive Decline & Phytomedicine
 

Posted: February 2023
Author: Katie Donnelly, Adv Dip HSc Naturopathy


Alterations in cognitive function and relative decline occur for numerous reasons, from lifestyle choices and ageing to chronic illness, stress, genetic predisposition, medication use, or microbial infection. These factors can contribute to alterations in glial cells and the ability to maintain homeostasis of the central nervous system.1

A relationship has also been established between chronic illness and deterioration in cognitive function, which can lead to the development of more advanced neurodegeneration. Contributing factors primarily identify the impact of systemic inflammation and oxidative stress (OS) on neuron health, as predisposed by endogenous and exogenous influences. This also impacts psychological well-being.

Increasing research has identified a specific role for phytotherapy in supporting renewed cognition and preventing the development or symptom intensity in secondary disease states.

Chronic disease and cognitive decline
Chronic conditions including cardiovascular disease (CVD), hypertension, chronic obstructive pulmonary disease, and metabolic syndrome are directly associated with alterations in cognition and mental well-being.2,3

In CVD alone, the probability of mild cognitive impairment developing into Alzheimer’s disease is significantly increased, along with memory decline.4 Changes in microglia and astrocytes have also been noted after myocardial infarction, triggering increased hypothalamus-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) response. This altered formation becomes wider with shorter processes, and a shift to pro-inflammatory signalling occurs in some glial cells. This move from homeostatic monitoring to cytokine production has been identified in Parkinson’s disease, Alzheimer’s disease, and dementia.5

The correlation between conditions highlights the role of herbal medicine as a treatment option. Ginkgo biloba (ginkgo) is commonly utilised to support cognition and working memory, particularly where ageing is a contributing factor, reducing neuroinflammation and inflammatory markers. The cellular regeneration, free radical scavenging, and mitochondria support from ginkgolides, kaempferol, and quercetin, also protect against further CVD development.6

Similarly, individuals with diabetes mellitus showed a 50 per cent increase in the likelihood of developing dementia. Hyperglycaemia and hypertension were associated factors, with a higher incidence of amyloid-beta plaque development evident in those with insulin resistance.7

The terpenoid safranal in Crocus sativus (saffron) has shown beneficial actions on renal tissue in cases of Type-2 diabetes and in cognitive decline. Animal model studies identified a reduction in tissue damage, lowered nitric oxide, tumour necrosis factor-alpha, and interleukin-1-beta (Il-1β). Lowered levels of hippocampus protein displacement were also noted. Carotenoids, primarily crocins and crocetin, reduce cyclo-oxygenase, prostaglandins and reactive oxygen species (ROS), and are associated with normalising mood dysregulation.8

The bi-directional communication between the gastrointestinal system (GI) microbiome and the CNS is another influencing factor. Noted associations between anxiety, depression, and brain fog are supported by studies identifying changes to neurotransmitters, cellular communication, and inflammatory markers in individuals with low GI microbial diversity.9

This is further identified in phytomedicine, with Panax ginseng (Korean ginseng), well utilised for cognition, also reducing the intensity of ulcerative colitis and Crohn’s disease in recent studies. A reduction in tumour necrosis factor-alpha, Il-1β, Il-12, and Il-6 were identified in animal model studies, and are linked to reduced irritable bowel symptoms.10 Ginsenoside saponins also improved nuclear factor-erythroid 2-p45 derived factor 2 (Nrf2) interaction, reduced cellular apoptosis, and regulated the presence and removal of amyloid-beta.11

Cellular stress
Alongside systemic inflammation, mitochondrial cellular respiration contributes to oxidative stress (OS) measured by the presence of marker 8-hydroxydeoxyguanosine. This is an identifying factor in endogenous gene mutation and tumour development through altered cell processes.12 The high oxygen needs, lipid composition and presence of metal ions in the central nervous system make the brain particularly susceptible to OS damage. Resulting apoptosis and cellular mutation are noted factors in cognitive decline.

Well known as a potent antioxidant, Camellia sinensis (green tea) has been shown to normalise mitochondrial function. The epigallocatechin gallate, from catechins, is thought to be a primary factor in counteracting oxidative damage by bonding with metal ions and acting as a neuroprotective by preventing amyloid-beta development. Anti-inflammatory actions from polyphenol components also contribute to reduced nuclear factor kappa-beta signalling and support dopamine regulation.13

Recent research also supports the use of Curcuma longa (turmeric) for CNS protection and symptomatic reduction in cases of Alzheimer’s disease and Parkinson’s disease. Traditionally used as an anti-inflammatory and antioxidant, C. longa displays preventative actions against lipopolysaccharide damage, neuroinflammation, and tumour development. Also noted was the maintenance of the blood-brain barrier and reduced prevalence of mitochondrial ROS cell apoptosis.14

Lifestyle factors in cognitive decline
Chronic stress is a factor in increased inflammation via consistent HPA and SNS stimulation and release of hormones, glucocorticoid steroids, and inflammatory markers. Unregulated inflammation increases OS, a contributing factor in cognitive decline and neuron degenerative disease.

Animal model studies focused on the impact of chronic stress on cognitive behaviour and identified alterations to the hippocampus, based on neurotransmitter presence and brain-derived neurotrophic factor (BDNF), influencing regeneration ability. This increases the likelihood of depression, anxiety, and insomnia development.15

Melissa officinalis (lemon balm) has been traditionally used in regulating the stress response, reducing anxiety, depression, and encouraging sleep. This is supported by more recent studies that showed notable improvements in stress regulation.16 It has also demonstrated significant free radical scavenging properties, as measured by interaction with 2,2-Diphenyl-1-picrylhydrazyl in vitro. This was of particular relevance to neuroprotective and neuro-regenerative actions in animal model studies, with phenolic acids quercetin, gallic acid and rutin displaying potent antioxidant actions.17
Recent studies have also reiterated the importance of sufficient sleep and regular exercise in preventing dementia development. Of particular focus was the re-alignment of circadian rhythms, reduction in sleep disruption and improvement in sleep phases for maintaining cognitive function.18 Separate studies identified a reduction in the development of amyloid-beta plaques and neurofibrillary tangles, synonymous with Alzheimer’s disease, in animals who engaged in regular exercise, mentally challenging tasks, and social interaction.19

This is further supported by herbal supplementation with Polygonum multiflorum (polygonum), which initiated improvements in memory, mood and cognition. Improved serotonin and BDNF levels were also noted, with reduced monoamine oxidase presence.20

Other factors noted for cognitive well-being included low alcohol intake, avoiding cigarette smoke, and daily food intake. Dietary considerations included consuming increased vegetables, fresh fruits, fatty fish, and lowered salt, sugar, and processed foods.21

Reference List

  1. Ruffini N, Klingenberg S, Schweiger S, Gerber S. Common Factors in Neurodegeneration: A Meta-Study Revealing Shared Patterns on a Multi-Omics Scale. Cells [Internet]. 2020 Dec 8;9(12):2642. Available from: https://doi.org/10.3390/cells9122642
  2. von Cederwald BF, Josefsson M, Wåhlin A, Nyberg L, Karalija N. Association of Cardiovascular Risk Trajectory With Cognitive Decline and Incident Dementia. Neurology [Internet]. 2022 May; 98 (20) e2013-e2022; Available from: https://doi.org/10.1212/WNL.0000000000200255
  3. Ranzini L, Schiavi M, Pierobon A, Granata N, Giardini A. From Mild Cognitive Impairment (MCI) to Dementia in Chronic Obstructive Pulmonary Disease. Implications for Clinical Practice and Disease Management: A Mini-Review. Front. Psychol. [Internet]. 2020 Feb; 11. Available from: https://doi.org/10.3389/fpsyg.2020.00337
  4. Farnsworth von Cederwald B, Josefsson M, Wåhlin A, Nyberg L, Karalija N. Association of Cardiovascular Risk Trajectory With Cognitive Decline and Incident Dementia. Neurology [Internet]. 2022 May;98(20) e2013-e2022. Available from: https://doi.org/10.1212/WNL.0000000000200255
  5. Wang M, Pan W, Xu Y, Zhang J, Wan J, Jiang H. Microglia-Mediated Neuroinflammation: A Potential Target for the Treatment of Cardiovascular Diseases. J Inflamm Res [Internet]. 2022 May; 15: 3083–3094. Available from: https://doi.org/10.2147/JIR.S350109
  6. Barbalho SM, Direito R, Laurindo LF, Marton LT, Guiguer EL, Goulart R de A, et al. Ginkgo biloba in the Aging Process: A Narrative Review. Antioxidants [Internet]. 2022;11:525. Available from: https://doi.org/10.3390/antiox11030525
  7. Varghese SM, Joy N, John AM, George G, Chandy GM, Benjamin AV. Sweet Memories or Not? A Comparative Study on Cognitive Impairment in Diabetes Mellitus. Front. Public Health [Internet]. 2022 Feb; 10. Available from: https://doi.org/10.3389/fpubh.2022.822062
  8. El Midaoui A, Ghzaiel I, Vervandier-Fasseur D, Ksila M, Zarrouk A, Nury T, et al. Saffron (Crocus sativus L.): A Source of Nutrients for Health and for the Treatment of Neuropsychiatric and Age-Related Diseases. Nutrients [Internet]. 2022;14:597. Available from: https://doi.org/10.3390/nu14030597
  9. Radjabzadeh D, Bosch JA, Uitterlinden AG, et al. Gut microbiome-wide association study of depressive symptoms. Nat Commun [Internet]. 2022;13(7128). Available from: https://doi.org/10.1038/s41467-022-34502-3
  10. Kang Z, Zhonga Y, Wu T, et al. Ginsenoside from ginseng: a promising treatment for inflammatory bowel disease. Pharmacol [Internet]. 2021; 73: 700–711. Available from: https://doi.org/10.1007/s43440-020-00213-z
  11. Li J, Huang Q, Chen J, Qi H, Liu J, Chen Z, Zhao D, Wang Z, Li X. Neuroprotective Potentials of Panax Ginseng Against Alzheimer’s Disease: A Review of Preclinical and Clinical Evidences. Front. Pharmacol [Internet]. 2021 June;12. Available from: https://doi.org/10.3389/fphar.2021.688490
  12. Sharifi-Rad M, Kumar NVA, Zucca P, et al. Lifestyle, Oxidative Stress, and Antioxidants: Back and Forth in the Pathophysiology of Chronic Diseases. Front. Physiology [Internet]. 2020 July;11. Available from: https://doi.org/10.3389/fphys.2020.00694
  13. Li C, Lin J, Yang T, Shang H. Green Tea Intake and Parkinson's Disease Progression: A Mendelian Randomization Study. Front Nutr [Internet]. 2022 May 26;9:848223. Available from: https://doi.org/10.3389/fnut.2022.848223
  14. Benameur T, Giacomucci G, Panaro MA, Ruggiero M, Trotta T, Monda V, Pizzolorusso I, Lofrumento DD, Porro C, Messina G. New Promising Therapeutic Avenues of Curcumin in Brain Diseases. Molecules [Internet]. 2021 Dec 31;27(1):236. Available from: https://doi.org/10.3390/molecules27010236
  15. Janke KL, Cominski TP, Kuzhikandathil EV, Servatius RJ, Pang KC. Investigating the Role of Hippocampal BDNF in Anxiety Vulnerability Using Classical Eyeblink Conditioning. Front Psychiatry [Internet]. 2015 Jul 24;6:106. Available from: https://doi.org/10.3389/fpsyt.2015.00106
  16. Habib H, Javid AZ, Haghighizadeh MH, et al. The effects of Melissa officinalis supplementation on depression, anxiety, stress, and sleep disorder in patients with chronic stable angina. Clinical Nut [Internet]. 2018 Aug; 26:47-52. Available from: https://doi.org/10.1016/j.clnesp.2018.04.015
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  18. Sewell KR, Erickson KI, Rainey-Smith SR, et al. Relationships between physical activity, sleep and cognitive function: A narrative review. Neuro & Beh Sci [Internet]. 2021 Nov;130:369-378. Available from: https://doi.org/10.1016/j.neubiorev.2021.09.003
  19. Mehla J, Deibel SH, Karem H, et al. Dramatic impacts on brain pathology, anxiety, and cognitive function in the knock-in APPNL-G-F mouse model of Alzheimer disease following long-term voluntary exercise. Alz Res Therapy [Internet].2022;14: 143. Available from: https://doi.org/10.1186/s13195-022-01085-6
  20. Bashir MI, Abdul Aziz NHK, Noor DAM. Antidepressant-like Effects of Polygonum minus Aqueous Extract in Chronic Ultra-Mild Stress-Induced Depressive Mice Model. Behavioral Sciences [Internet]. 2022;12:196. Available from: https://doi.org/10.3390/bs12060196
  21. Clare L, Wu YT, Teale JC, MacLeod C, Matthews F, Brayne C, Woods B. Potentially modifiable lifestyle factors, cognitive reserve, and cognitive function in later life: A cross-sectional study. PLoS Med [Internet]. 2017 Mar 21;14(3):e1002259. Available from: https://doi.org/10.1371/journal.pmed.1002259
 
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