This article explores factors contributing to the development of neurodegenerative disease and lifestyle and herbal approaches to mitigate risk and limit progression.
Neurodegenerative conditions such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), Huntington’s disease, spinal muscular atrophy and spinocerebellar ataxia are associated with progressive loss of neuronal functions (1). The prevalence of these conditions has been on the rise worldwide (2, 3). The World Health Organisation (WHO) estimates that soon neurodegenerative conditions will overtake cancer to become the second leading cause of death, after cardiovascular disease (4).
One of the primary drivers of the rise in neurodegenerative diseases is the ageing population. As life expectancy increases globally, the prevalence of age-related conditions, including Alzheimer’s and Parkinson’s, rises accordingly. Epidemiological data consistently show a strong correlation between age and the risk of developing neurodegenerative disorders (5, 6).
Several lifestyle factors have been linked to an increased risk of neurodegeneration. These include sedentary behaviour, poor diet, smoking and excessive alcohol consumption and (7). Studies have highlighted the importance of adopting healthy lifestyle choices in reducing the risk of cognitive decline and neurodegenerative diseases (7, 8, 9).
While ageing and lifestyle factors contribute significantly to the rise in neurodegeneration, genetic predisposition also plays a crucial role (6). Epidemiological studies have identified several genetic variants associated with an elevated risk of Alzheimer’s, Parkinson’s, and other neurodegenerative disorders. However, it’s essential to recognise that genetic predisposition alone does not determine disease onset, and interactions with environmental factors are often involved (6, 7).
Exposure to heavy metals, such as lead, mercury, and aluminium, has been implicated in the pathogenesis of neurodegenerative diseases (10). These metals can accumulate in the brain over time, leading to oxidative stress, neuroinflammation, and neuronal damage (10).
Exposure to heavy metals, such as lead, mercury, cadmium, and arsenic, can significantly contribute to the pathogenesis of neurodegeneration (11). Heavy metals can generate reactive oxygen species (ROS) through Fenton-like reactions. ROS cause oxidative damage to cellular components like proteins, lipids, and DNA. This oxidative stress can lead to neuronal injury and cell death, contributing to neurodegeneration (7, 12).
Heavy metals can also trigger inflammatory responses in the brain by activating microglia, the resident immune cells of the central nervous system. Chronic inflammation can lead to neuronal damage and contribute to the progression of neurodegenerative diseases. Some heavy metals can disrupt the blood brain barrier (BBB), allowing toxic substances to enter the brain more easily. Once inside, these substances can induce neuronal damage and contribute to neurodegeneration (13).
Heavy metals can impair mitochondrial function, which is crucial for energy production and maintaining cellular homeostasis. Mitochondrial dysfunction leads to energy depletion and an increase in ROS production, further exacerbating oxidative stress and neuronal damage (14). Certain heavy metals have been shown to promote the aggregation of proteins such as amyloid-beta and tau, which are characteristic features of Alzheimer’s disease and other neurodegenerative disorders (15). Protein aggregation disrupts cellular function and can lead to neuronal dysfunction and death.
Moreover, heavy metals can interfere with neurotransmitter systems, such as dopamine, glutamate, and GABA, disrupting neuronal communication and leading to neurodegenerative changes (16).
Epidemiological studies have demonstrated a correlation between lead exposure and cognitive decline in both children and adults (17, 18). Even low levels of lead exposure have been associated with an increased risk of neurodegenerative disorders later in life. Mechanistically, lead interferes with neurotransmitter function, disrupts calcium homeostasis, and promotes the generation of reactive oxygen species (ROS), contributing to neuronal dysfunction and death.
Mercury exposure, primarily through contaminated seafood or dental amalgams, has been linked to neurodegenerative diseases such as Alzheimer’s and Parkinson’s (19, 20). Epidemiological evidence suggests that chronic exposure to mercury can impair neuronal function, disrupt mitochondrial activity, and induce neuroinflammation (21). Additionally, mercury has been shown to facilitate the aggregation of amyloid-beta and tau proteins, characteristic features of Alzheimer’s pathology.
Although the role of aluminium in neurodegeneration remains controversial, epidemiological studies have indicated a potential link between aluminium exposure and cognitive impairment (22). Aluminium can accumulate in the brain, particularly in regions affected by Alzheimer’s disease pathology. It exerts neurotoxic effects by promoting oxidative stress, disrupting neurotransmitter balance, and facilitating the formation of amyloid plaques (22).
Emerging evidence suggests that chronic exposure to organophosphates may contribute to the development of neurodegenerative conditions. Organophosphates are a class of chemicals commonly used as pesticides, insecticides, and nerve agents (23).
Epidemiological studies have identified an association between pesticide exposure, particularly organophosphates, and an increased risk of neurodegenerative disorders (23, 24). Agricultural workers and individuals living in proximity to pesticide-treated areas are at higher risk (25). Organophosphates inhibit acetylcholinesterase, leading to the accumulation of acetylcholine and overstimulation of cholinergic pathways in the brain, which can result in neurotoxicity (24).
Organophosphates can also induce oxidative stress and neuroinflammation, contributing to neuronal damage and dysfunction. These chemicals generate ROS and disrupt antioxidant defence mechanisms, leading to cellular damage and mitochondrial dysfunction (25). As mentioned before, chronic inflammation can exacerbate neurodegeneration by activating microglia and promoting the release of pro-inflammatory cytokines.
It is important to remember that the consequences of neurodegeneration extend beyond individual health outcomes, and can also impact healthcare systems, economies, and society as a whole. Neurodegenerative conditions impose a substantial burden on healthcare systems worldwide, as people suffering with neurodegenerative conditions generally need extensive medical care, long-term support, and specialised services (26).
What can we do?
There are lifestyle factors and herbs that can be helpful in preventing and slowing down the progression of neurodegenerative conditions.
Herbs
Ashwagandha (Withania somnifera) is an adaptogenic herb traditionally used in Ayurvedic medicine. It has been shown to have neuroprotective effects, including reducing oxidative stress, inflammation, and improving cognitive function. Ashwagandha powder is an effective herbal preparation that can be taken daily for neuroprotection (27).
Bacopa (Bacopa monnieri) is another herb commonly used in Ayurvedic medicine for cognitive enhancement. It has been shown to improve memory and cognitive function, possibly by enhancing neurotransmitter activity and reducing oxidative stress in the brain. Numerous studies have shown its neuroprotective effects in Alzheimer’s and Parkinson’s disease models (28, 29).
Ginkgo (Ginkgo biloba) is one of the most widely used herbs for cognitive enhancement and neuroprotection. It has antioxidant and anti-inflammatory properties that may help protect against neuronal damage and improve cognitive function (30). It also improves cerebral blood flow, having vasodilatory and blood thinning properties. A meta-analysis found ginkgo to be more effective in older people than in younger healthy subjects (31).
Gotu kola (Centella asiatica) has been traditionally used in Ayurvedic and traditional Chinese medicine for cognitive enhancement and neuroprotection (32). It has antioxidant and anti-inflammatory properties that could protect against neurodegeneration, particularly ischaemic dementia (33).
Green tea (Camellia sinensis) contains catechins such as epigallocatechin gallate (EGCG), which have antioxidant and neuroprotective properties. Studies have suggested that green tea consumption may help protect against neurodegenerative conditions like Alzheimer’s and Parkinson’s disease (34).
Lion’s mane (Hericium erinaceus) mushroom has been studied for its potential neuroprotective effects. It contains compounds that may stimulate nerve growth factor (NGF) production, promote neurogenesis, and protect against neuronal damage (35).
Rhodiola (Rhodiola rosea) is another adaptogenic herb that has been studied for its potential neuroprotective effects. It may help reduce oxidative stress, improve mood, and enhance cognitive function, making it a promising candidate for supporting brain health (36).
Please note, rhodiola is critically endangered in the wild, so do not use unless from cultivated sources or from certified, sustainable wild collection sold with appropriate guarantees and certification.
Rosemary (Rosmarinus officinalis) is an aromatic herb that contains compounds like carnosic acid and rosmarinic acid, which have antioxidant and anti-inflammatory properties. Some studies have suggested that rosemary extract may help protect against neurodegenerative conditions by reducing oxidative stress and inflammation in the brain (37).
Sage (Salvia officinalis) is also an aromatic herb that has constituents with antioxidant and anti-inflammatory properties that can help protect against neurodegeneration (37). It has been traditionally used to improve memory and cognitive function, and a double blind randomised clinical trial showed it was effective for mild to moderate Alzheimer’s disease (38).
Turmeric (Curcuma longa) contains the phytochemical curcumin, which has been studied for its potential neuroprotective effects (39). Turmeric has antioxidant and anti-inflammatory properties that by reducing oxidative stress and neuroinflammation could slow down neurodegeneration (40).
Some antioxidant supplements such as co-enzyme Q10 can be helpful in restoring mitochondrial dysfunction, which is one of the many mechanisms contributing to neurodegeneration. There are studies showing the positive impact of coQ10 administration in some neurodegenerative conditions (41, 42).
Lifestyle factors
Lifestyle factors, such as regular exercise, a balanced diet, adequate sleep, and cognitive stimulation, play an important role in preventing and managing neurodegenerative conditions.
A balanced diet
Consuming a balanced diet rich in fruits, vegetables, whole grains, lean proteins, and healthy fats can provide essential nutrients and antioxidants that support brain health. Antioxidants such as curcumin, blueberry polyphenols, resveratrol, polyunsaturated fatty acids such as flaxseed oil or omega 3 in fatty fish can increase healthy neuronal proliferation (43).
Physical activity
Engaging in regular physical activity is crucial for maintaining brain health. Exercise has been shown to improve blood flow to the brain, stimulate the release of growth factors that promote neuronal health, and reduce the risk of neurodegenerative conditions (44, 45).
Cognitive stimulation
Cognitive stimulation is also important. Keeping the brain active and engaged through activities such as reading, puzzles, learning new skills, and social interaction can help maintain cognitive function and build cognitive reserve, which may delay the onset of cognitive decline (45). Maintaining strong social connections and participating in meaningful social activities can also provide cognitive stimulation, emotional support, and a sense of belonging, all of which are beneficial for brain health (46, 47).
More sleep and relaxation
Chronic stress and inadequate sleep can have detrimental effects on brain health and may contribute to neurodegeneration. Practising stress-reduction techniques such as mindfulness meditation, deep breathing exercises, yoga, and spending time in nature can help mitigate the effects of stress on the brain (48, 49).
The rise of neurodegeneration represents a complex interplay of demographic, lifestyle, environmental, and genetic factors. Epidemiological studies have provided valuable insights into the trends and risk factors associated with these conditions, showing that the incidence of neurodegenerative conditions is increasing, and shedding light on important environmental factors that are contributing to it. Heavy metals, such as lead, mercury, and aluminium, as well as organophosphate pesticides, have been implicated in the pathogenesis of neurodegenerative diseases, highlighting the importance of environmental exposures in disease development.
References
- Zaib S, Javed H, Khan I, et al. Neurodegenerative diseases: their onset, epidemiology, causes and treatment. ChemSelect. 2023;8(20):e202300225.
- Feigin VL, Nichols E, Alam T, et al. Global, regional, and national burden of neurological disorders, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019;18(5):459-480.
- Vos T, Lim SS, Abbafati C, et al. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396(10258):1204-1222.
- Gammon K. Neurodegenerative disease: brain windfall. Nature. 2014;515(7526):299-300.
- Mayeux R. Epidemiology of neurodegeneration. Annu Rev Neurosci. 2003;26:81-104.
- Bertram L, Tanzi RE. The genetic epidemiology of neurodegenerative disease. J Clin Invest. 2005;115(6):1449-1457.
- Niedzielska E, Smaga I, Gawlik M, et al. Oxidative stress in neurodegenerative diseases. Mol Neurobiol. 2016;53(6):4094-4125.
- Popa-Wagner A, Dumitrascu DI, Capitanescu B, et al. Dietary habits, lifestyle factors and neurodegenerative diseases. Neural Regen Res. 2020;15(3):394-400.
- Santiago JA, Potashkin JA. Physical activity and lifestyle modifications in the treatment of neurodegenerative diseases. Front Aging Neurosci. 2023;15:1185671.
- Cicero CE, Mostile G, Vasta R, et al. Metals and neurodegenerative diseases: a systematic review. Environ Res. 2017;159:82-94.
- Chen P, Miah MR, Aschner M. Metals and neurodegeneration. F1000Res. 2016;5:F1000 Faculty Rev-366.
- Jomova K, Vondrakova D, Lawson M, Valko M. Metals, oxidative stress and neurodegenerative disorders. Mol Cell Biochem. 2010;345(1-2):91-104.
- Yokel RA. Blood-brain barrier flux of aluminum, manganese, iron and other metals suspected to contribute to metal-induced neurodegeneration. J Alzheimers Dis. 2006;10(2-3):223-253.
- Shcherbatykh I, Carpenter DO. The role of metals in the etiology of Alzheimer’s disease. J Alzheimers Dis. 2007;11(2):191-205.
- Bakulski KM, Seo YA, Hickman RC, et al. Heavy metals exposure and Alzheimer’s disease and related dementias. J Alzheimers Dis. 2020;76(4):1215-1242.
- He B, Wang Y, Li S, et al. A cross–sectional survey of preschool children: Exploring heavy metal exposure, neurotransmitters, and neurobehavioral relationships and mediation effects. Ecotoxicol Environ Saf. 2021;220:112391.
- Chandramouli K, Steer CD, Ellis M, Emond AM. Effects of early childhood lead exposure on academic performance and behavior of school age children. Arch Dis Child. 2009;94(11):844-848.
- Naicker N, Richter L, Mathee A, Becker P, Norris SA. Environmental lead exposure and socio-behavioral adjustment in the early teens: the birth to twenty cohort. Sci Total Environ. 2012;414:120-125.
- Bates MN. Mercury amalgam dental fillings: an epidemiologic assessment. Int J Hyg Environ Health. 2006;209(4):309-316.
- Chin-Chan M, Navarro-Yepes J, Quintanilla-Vega B. Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases. Front Cell Neurosci. 2015;9:124.
- Zahir F, Rizwi SJ, Haq SK, Khan RH. Low dose mercury toxicity and human health. Environ Toxicol Pharmacol. 2005;20(2):351-360.
- Campbell A. The potential role of aluminium in Alzheimer’s disease. Nephrol Dial Transplant. 2002;17 Suppl 2:17-20.
- Sarailoo M, Afshari S, Asghariazar V, Safarzadeh E, Dadkhah M. Cognitive impairment and neurodegenerative diseases development associated with organophosphate pesticides exposure: a review study. Neurotox Res. 2022;40(5):1624-1643.
- Sánchez-Santed F, Colomina MT, Hernández EH. Organophosphate pesticide exposure and neurodegeneration. Cortex. 2016;74:417-426.
- Parrón T, Requena M, Hernández AF, Alarcón R. Association between environmental exposure to pesticides and neurodegenerative diseases. Toxicol Appl Pharmacol. 2011;256(3):379-385.
- Checkoway H, Lundin JI, Kelada SN. Neurodegenerative diseases. IARC Sci Publ. 2011;(163):407-419.
- Sandhir R, Sood A. Neuroprotective potential of Withania somnifera (ashwagandha) in neurological conditions. In: Benzie IFF, Wachtel-Galor S, eds. Herbal Medicine: Biomolecular and Clinical Aspects. 2nd ed. CRC Press/Taylor & Francis; 2011:373-387.
- Abdul Manap AS, Vijayabalan S, Madhavan P, et al. Bacopa monnieri, a neuroprotective lead in Alzheimer disease: a review on its properties, mechanisms of action, and preclinical and clinical studies. Drug Target Insights. 2019;13:1177392819866412.
- Singh B, Pandey S, Rumman M, Mahdi AA. Neuroprotective effects of Bacopa monnieri in Parkinson’s disease model. Metab Brain Dis. 2020;35(3):517-525.
- Ahlemeyer B, Krieglstein J. Neuroprotective effects of Ginkgo biloba extract. Cell Mol Life Sci. 2003;60(9):1779-1792.
- Liu H, Ye M, Guo H. An updated review of randomized clinical trials testing the improvement of cognitive function of Ginkgo biloba extract in healthy people and Alzheimer’s patients. Front Pharmacol. 2020;10:509513.
- Sabaragamuwa R, Perera CO, Fedrizzi B. Centella asiatica (Gotu kola) as a neuroprotectant and its potential role in healthy ageing. Trends Food Sci Technol. 2018;79:88-97.
- Pramastya H, Anggadiredja K, Fidriany I. Neuroprotective effect of Gotu kola (Centella asiatica L urban) in cerebral ischemic rat model. In: Proceedings of the 3rd International Conference on Mathematical, Computational and Statistical Sciences (MCSS-2010). 2010:77-90.
- Weinreb O, Mandel S, Amit T, Youdim MB. Neurological mechanisms of green tea polyphenols in Alzheimer’s and Parkinson’s diseases. J Nutr Biochem. 2004;15(9):506-516.
- Lai PL, Naidu M, Sabaratnam V, et al. Neurotrophic properties of the Lion’s mane medicinal mushroom, Hericium erinaceus (Higher Basidiomycetes) from Malaysia. Int J Med Mushrooms. 2013;15(6).
- Lee Y, Jung JC, Jang S, et al. Anti-inflammatory and neuroprotective effects of constituents isolated from Rhodiola rosea. Evid Based Complement Alternat Med. 2013;2013:514049.
- Faridzadeh A, Salimi Y, Ghasemirad H, et al. Neuroprotective potential of aromatic herbs: rosemary, sage, and lavender. Front Neurosci. 2022;16:909833.
- Akhondzadeh S, Noroozian M, Mohammadi M, et al. Salvia officinalis extract in the treatment of patients with mild to moderate Alzheimer’s disease: a double blind, randomized and placebo‐controlled trial. J Clin Pharm Ther. 2003;28(1):53-59.
- Cole GM, Teter B, Frautschy SA. Neuroprotective effects of curcumin. Mol Targets Ther Uses Curcumin Health Dis. 2007:197-212.
- Darvesh AS, Carroll RT, Bishayee A, et al. Curcumin and neurodegenerative diseases: a perspective. Expert Opin Investig Drugs. 2012;21(8):1123-1140.
- Yang X, Zhang Y, Xu H, et al. Neuroprotection of coenzyme Q10 in neurodegenerative diseases. Curr Top Med Chem. 2016;16(8):858-866.
- Shults CW. Coenzyme Q10 in neurodegenerative diseases. Curr Med Chem. 2003;10(19):1917-1921.
- Poulose SM, Miller MG, Scott T, Shukitt-Hale B. Nutritional factors affecting adult neurogenesis and cognitive function. Adv Nutr. 2017;8(6):804-811.
- Meeusen R. Exercise and the brain. In: 13th ISEI symposium. 2017:24-28.
- Hannan AJ. Environmental enrichment and brain repair: harnessing the therapeutic effects of cognitive stimulation and physical activity to enhance experience‐dependent plasticity. Neuropathol Appl Neurobiol. 2014;40(1):13-25.
- Colonnello V, Petrocchi N, Farinelli M, Ottaviani C. Positive social interactions in a lifespan perspective with a focus on opioidergic and oxytocinergic systems: Implications for neuroprotection. Curr Neuropharmacol. 2017;15(4):543-561.
- Mahalingam G, Samtani S, Lam BCP, et al. Social connections and risk of incident mild cognitive impairment, dementia, and mortality in 13 longitudinal cohort studies of aging. Alzheimers Dement. 2023;19(11):5114-5128.
- Kline SA, Mega MS. Stress-induced neurodegeneration: the potential for coping as neuroprotective therapy. Am J Alzheimers Dis Other Demen. 2020;35:1533317520960873.
- Iranzo A, Santamaria J. Sleep in neurodegenerative diseases. In: Kushida CA, ed. Sleep Medicine: A Comprehensive Guide to Its Development, Clinical Milestones, and Advances in Treatment. Springer; 2015:271-283.