|Year : 2022 | Volume
| Issue : 8 | Page : 1757-1758
How mind-body therapies might reduce pathological features of Alzheimer’s disease
Melanie Huttenrauch, Susana Castro-Obregón PhD
División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México (UNAM), Circuito Exterior SN, Ciudad Universitaria, CDMX, Mexico
|Date of Submission||28-Feb-2021|
|Date of Decision||08-Apr-2021|
|Date of Acceptance||05-Jun-2021|
|Date of Web Publication||07-Jan-2022|
ivisión de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México (UNAM), Circuito Exterior SN, Ciudad Universitaria, CDMX
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Huttenrauch M, Castro-Obregón S. How mind-body therapies might reduce pathological features of Alzheimer’s disease. Neural Regen Res 2022;17:1757-8
|How to cite this URL:|
Huttenrauch M, Castro-Obregón S. How mind-body therapies might reduce pathological features of Alzheimer’s disease. Neural Regen Res [serial online] 2022 [cited 2022 Jan 18];17:1757-8. Available from: http://www.nrronline.org/text.asp?2022/17/8/1757/332146
Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder that is responsible for around 60–80% of all dementia cases and currently affects around 50 million people worldwide. As the population’s life span tends to increase, current predictions suggest that by 2050, 152 million people worldwide will suffer from dementia (Balsinha, 2019). While the exact cause of AD remains obscure, various hypotheses regarding AD etiology have been described in the last decades. According to the amyloid hypothesis, the pathogenic changes related to AD start with the accumulation of amyloid-beta (Aβ) in the brain. These Aβ peptides form oligomers and insoluble amyloid plaques which are neurotoxic and trigger harmful downstream events such as the aggregation of the microtubule-associated protein Tau into neurofibrillary tangles, chronic inflammation, and brain atrophy.
Despite numerous clinical trials, to date no causal AD therapy exists. Therefore, preventive strategies that reduce the risk of developing AD are coming to the fore. Interestingly, the first pathological changes in the brain occur years to decades before the first AD symptoms arise. These early changes offer a time window for strategies that might delay or even prevent dementia symptoms. Mind-body therapies (MBTs) that are rooted in ancient eastern traditions and include practices such as yoga, meditation and mindfulness, have recently emerged as a complementary therapeutic approach for neurological diseases and conditions, as they can influence both brain structure and function. MBTs have the intention to build a connection between the brain, mind, body, and behavior to enhance the minds capacity which influences physical function and promotes overall health (Mooventhan and Nivethitha, 2017). How yoga and meditation practices affect the brain during aging and in neurodegenerative disorders has not yet been studied in detail, even though Silver Yoga or Chair Yoga has been created to meet special challenges of the senior population. During this type of yoga, adaptations of original yoga poses (asanas) are practiced sitting on a chair or using a chair for support. A limited number of studies with patients suffering from Mild cognitive impairment (MCI) or dementia mostly showed beneficial effects of MBTs on neuropsychiatric and cognitive outcomes. Nevertheless, the mechanistic link between the positive effect of MBTs and AD-related pathological processes is still missing, as there are no investigations on how yoga and meditation affect characteristic amyloid plaque and tau accumulation, neuron loss or brain growth factor level changes. However, various studies in patients with conditions other than dementia have shown that yoga and meditation can have a direct effect on parameters such as brain volume, brain-derived neurotrophic factor (BDNF), serotonin and cortisol levels as well as sleep quality, which directly or indirectly affect the pathogenesis of AD.
Neuron loss and subsequent grey matter atrophy displays one of the most prominent pathological features during the progression of AD. While the loss of < 1% of brain mass per year from the early twenties on is part of normal physiological functioning, brain atrophy rates are much higher during AD progression. Surprisingly, to date there exists no study on how yoga and meditation affect grey matter volume in patients with dementia. However, studies in MCI patients have shown that these practices have specifically positive effects on hippocampal volumes, giving evidence that MBTs positively affect brain regions vulnerable to neurodegeneration (Fotuhi et al., 2016).
On a molecular level, the neurotrophin BDNF could be a key player in decreasing brain atrophy due to yoga and meditation practices. BDNF is predominantly located within neurons of the cortex and hippocampus of the brain and regulates their survival, function, and plasticity. Therefore, this neurotrophin exerts numerous neuroprotective effects in brain areas that are first affected by AD. Interestingly, BDNF serum levels are significantly lower in AD patients when compared to healthy controls and studies with healthy individuals showed that mind-body interventions such as yoga increase serum BDNF levels (Cahn et al., 2017). Therefore, it is tempting to speculate that the upregulation of BDNF due to yogic practices is, at least partly, responsible for the observed decreased grey matter volume loss that is related to these interventions in MCI patients.
Like BDNF, levels of the neurotransmitter serotonin are significantly lower under AD conditions when compared to healthy controls, and serotonin receptor expression has been shown to be decreased in various AD brain areas (Garcia-Alloza et al., 2004). While it was not clear for a long time whether changes in the serotonergic system are a cause or a product of AD-related brain changes, it is now known that these changes occur at very early stages of AD pathogenesis, as they are already present in MCI patients. Serotonin is produced in the raphe area of the brain stem and stored in raphe nuclei. Raphe nuclei project serotonergic signals to the hippocampus, the amygdala, and the prefrontal cortex, which regulate learning and memory function. While no study so far investigated the effect of MBTs on serotonin in cognitively impaired people, in healthy individuals and patients of chronic lower back pain, yoga has shown to increase serotonin plasma and serum levels (Lee et al., 2014). Interestingly, in vitro studies have shown that serotonin has a direct impact on the toxic amyloid beta peptides that accumulate to insoluble Aβ plaques in AD brains. One study showed that serotonin destabilizes both amyloid beta oligomers and fibrils (Hornedo-Ortega et al., 2018). As oligomers and fibrils have been shown to be the neurotoxic versions of Aβ, serotonin therefore might protect against Aβ-induced neuronal death. Another in vitro study demonstrated that serotonin receptor activation induces the non-amyloidogenic processing of the amyloid beta precursor protein, leading to the secretion of a peptide variant with neuroprotective and neurotrophic properties (Shen et al., 2011). Accordingly, serotonin release upon yogic practices might affect harmful Aβ species and therefore protect from their neurotoxic effects.
Sleep problems are among the lifestyle factors that are associated with a greater risk to develop dementia. Around 40% of all AD patients suffer from sleep disturbances. Already at early timepoints of disease progression, sleep problems become present and evolve simultaneously to the accumulation of cerebral amyloid beta depositions. A direct bidirectional relationship between sleep and Aβ has been demonstrated in numerous studies. Just recently it was shown that only one night of sleep deprivation significantly increases the accumulation of beta amyloid in human brains (Ooms et al., 2014). One hypothesis to explain this phenomenon is an increased activity of the glymphatic system during the night. This clearing system is supposed to transport amyloid beta peptides from the interstitial fluid out of the brain to maintain a balance between its synthesis, clearance, and re-uptake. As studies in rodent models have shown that the glymphatic system is more active during sleep, sleep disturbances might diminish the efficient clearance of Aβ (Xie et al., 2013). Studies in individuals with subjective cognitive decline as well as healthy older adults and individuals with other medical conditions than dementia have repeatedly shown that MBTs have a positive effect on sleep. Therefore, the cerebral clearance of beta amyloid and less toxic Aβ species production might be promoted by an improved night sleep due to yogic practices in dementia patients.
Next to sleep disturbances, persistent high levels of the steroid hormone cortisol are associated with an increased risk to develop dementia. In AD patients, cortisol plasma concentrations have repeatedly shown to be dysregulated. After crossing the blood brain area, cortisol activates glucocorticoid receptors in various areas of the brain, with the hippocampus being particularly responsive as it contains a high concentration of these receptors. As demonstrated in both humans and animal models, an increased secretion of cortisol and its downstream signaling events is associated with an abnormal accumulation of Aβ, resulting in synaptic dysfunction and neurodegenerative processes. The exact molecular mechanism behind the increased amyloid deposition due to stress remains elusive, however, initial studies showed that Aβ production is stimulated by cortisol (Dong and Csernansky, 2009). In dementia patients, no study has investigated the relationship between stress levels and disease progression yet. However, other individuals with chronic stress that practiced yoga and meditation showed a measurable decrease in cortisol levels as well as lower subjective stress levels, depression, and anxiety (Danucalov et al., 2013). Accordingly, AD patients might benefit from yogic practices by a downregulation of cortisol levels and subsequent decrease of cortisol induced Aβ production and deposition.
In summary, here we propose that yoga and meditation practices might act as a barrier for neurodegenerative processes and diminish the progression of AD by affecting specific pathological characteristics of the disease [Figure 1]. Studies with healthy individuals and patients with conditions other than dementia clearly show that yogic practices can have positive effects on sleep, stress levels, BDNF and serotonin levels as well as brain volume. As both in vitro and/or in vivo studies have shown that sleep, stress levels and serotonin directly act on Aβ, it is tempting to speculate that yoga and meditation might slow down disease progression in AD patients. Clearly, both long- and short-term clinical studies with dementia patients are necessary to proof this hypothesis and to clarify the relationship between MBTs and the molecular pathways implicated in AD progression.
|Figure 1: Mind-body therapies could reduce Alzheimer's disease progression.|
By reducing chronic stress, yoga practice leads to reduced cortisol levels, and increase in BDNF and serotonin levels. Simultaneously, yoga practice improves sleep, potentially promoting glymphagtic clearance of Aβ. See text for details. Aβ: Amyloid-beta; BDNF: brain-derived neurotrophic factor.
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We acknowledge the technical assistance given by Dr. Beatriz Aguilar from División de Neurociencias, Instituto de Fisiología Celular, UNAM, Mexico.
SCO’s research work is supported by grant UNAM-PAPIIT IN209221. MH was a Feodor Lynen Fellow, awarded by the Alexander von Humboldt Foundation.
©Article author(s) (unless otherwise stated in the text of the article) 2022. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
| References|| |
Balsinha C, Gonçalves-Pereira M, Iliffe S, Freitas JA, Grave J (2019) Health-care delivery for older people with dementia in primary care. In: Primary care mental health in older people (de Mendonça Lima C, Ivbijaro G, eds), pp 311-329. Berlin: Springer.
Cahn BR, Goodman MS, Peterson CT, Maturi R, Mills PJ (2017) Yoga, meditation and mind-body health: increased BDNF, cortisol awakening response, and altered inflammatory marker expression after a 3-month yoga and meditation retreat. Front Hum Neurosci 11:315.
Danucalov MA, Kozasa EH, Ribas KT, Galduroz JC, Garcia MC, Verreschi IT, Oliveira KC, Romani de Oliveira L, Leite JR (2013) A yoga and compassion meditation program reduces stress in familial caregivers of Alzheimer’s disease patients. Evid Based Complement Alternat Med 2013:513149.
Dong H, Csernansky JG (2009) Effects of stress and stress hormones on amyloid-beta protein and plaque deposition. J Alzheimers Dis 18:459-469.
Fotuhi M, Lubinski B, Trullinger M, Hausterman N, Riloff T, Hadadi M, Raji CA (2016) A personalized 12-week “Brain Fitness Program” for improving cognitive function and increasing the volume of hippocampus in elderly with mild cognitive impairment. J Prev Alzheimers Dis 3:133-137.
Garcia-Alloza M, Hirst WD, Chen CP, Lasheras B, Francis PT, Ramirez MJ (2004) Differential involvement of 5-HT(1B/1D) and 5-HT6 receptors in cognitive and non-cognitive symptoms in Alzheimer’s disease. Neuropsychopharmacology 29:410-416.
Hornedo-Ortega R, Da Costa G, Cerezo AB, Troncoso AM, Richard T, Garcia-Parrilla MC (2018) In vitro effects of serotonin, melatonin, and other related indole compounds on amyloid-beta kinetics and neuroprotection. Mol Nutr Food Res doi: 10.1002/mnfr.201700383.
Lee M, Moon W, Kim J (2014) Effect of yoga on pain, brain-derived neurotrophic factor, and serotonin in premenopausal women with chronic low back pain. Evid Based Complement Alternat Med 2014:203173.
Mooventhan A, Nivethitha L (2017) Evidence based effects of yoga in neurological disorders. J Clin Neurosci 43:61-67.
Ooms S, Overeem S, Besse K, Rikkert MO, Verbeek M, Claassen JA (2014) Effect of 1 night of total sleep deprivation on cerebrospinal fluid beta-amyloid 42 in healthy middle-aged men: a randomized clinical trial. JAMA Neurol 71:971-977.
Shen F, Smith JA, Chang R, Bourdet DL, Tsuruda PR, Obedencio GP, Beattie DT (2011) 5-HT(4) receptor agonist mediated enhancement of cognitive function in vivo and amyloid precursor protein processing in vitro: a pharmacodynamic and pharmacokinetic assessment. Neuropharmacology 61:69-79.
Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, O’Donnell J, Christensen DJ, Nicholson C, Iliff JJ, Takano T, Deane R, Nedergaard M (2013) Sleep drives metabolite clearance from the adult brain. Science 342:373-377.
C-Editors: Zhao M, Zhao LJ, Qiu Y; T-Editor: Jia Y