Lets Face the Music of Time
OnIn 1936 Irving Berlin composed his masterpiece ‘Let’s face the music and dance’ for the Astaire and Rogers movie ‘Follow the Fleet’. The melancholic text refers nominally to Fred’s latest heartbreak, but the song’s genius derives from the way it captured the zeitgeist and made it danceable. The specter of war was looming, and people who were awake knew what was coming. In that same year my (Jewish) grandmother Isabelle, who knew full well that London would be bombed, took her family to Wales where my mother and her siblings sat out the war in safety. My grandfather, whose physics research was deemed essential to the war effort, remained in London until his labs were doodle-bugged. Beckie lived on well into her nineties, and until her last few days was physically active and mentally very acute. She died, mercifully quickly, of a series of strokes.
The threat of war looms again today. Driven by the ZioCons and their client states Saudi Arabia and the USA, in a pathological and destructive response to the burgeoning New Silk Roads and the ongoing global financial collapse, I can feel the tug of the impending rapids. But before we face the madness, let’s dip into dementia.
Stroke is still a major killer, but it has been eclipsed by the neuro-degenerative diseases. Globally, the incidence of dementia more than doubled between 1990 and 2016 (1) and is projected to double again by 2050 (2).
In the UK, the numbers of cases of dementia have risen by 7.4% in the last year alone (2), and in the over 65’s the incidence is now around 7% (3). The average age of onset has fallen by 15 years since 1980 (4), which helps to explain why neurodegenerative deaths in the over-75’s have increased 300% in men, and 500% in women (5, 6).
Although the idea that dementias will double by 2050 is frightening, it is clearly not true. It assumes that current demographic trends will continue, and numbers of elderly will grow in line with life expectancy – but this is not what is happening. Life expectancy is falling in the USA and in the UK, due in part to neurodegenerative disease. It is also falling in bellwether groups in India and China, and will continue to fall everywhere that processed foods dominate. The incidence of dementia will undoubtedly continue to increase in older subjects, due to neurotoxic effects of the modern diet and lifestyle, but the numbers of the very elderly will surely fall as our nutritional standards and health care systems go into long-term decline.
We do not, however, have to continue to go down this road. Dementia is not a normal or essential part of ageing.
A minority of cases are driven by genetic factors which can’t be changed (yet), but most appear to be driven by lifestyle factors, which can be. For example, important risk factors such as diabetes can be reversed with lifestyle programs of exercise, and calorie and carbohydrate restriction (7). The related vascular complications that predispose to multiple stroke dementia (hypertension, atheromatous disease and vascular calcification), can all be managed and modified using pharmaco-nutritional tools.
But we can go further.
Just as diabetes was formerly considered an intrinsically progressive condition but is now seen as reversible, so too is Alzheimer’s. Recently, convincing evidence has emerged that early onset Alzheimer’s or its can be reversed, also via pharmaconutritional programs. Dale Bredesen, who I had the great pleasure of meeting when his first study was published, calls the approach MEND.
One patient had well documented mild cognitive impairment, abnormal neuropsychological testing, and hippocampal volume reduced to 17th percentile. After 10 months on the MEND protocol, his hippocampal volume had increased to 75th percentile, with a reversal of cognitive decline. Another patient had well documented early Alzheimer’s disease and markedly abnormal neuro-psychological testing. After 22 months on the MEND protocol he showed marked improvement in his neuropsychological testing, with some improvements reaching three standard deviations from his earlier testing.
To quote Dale, ‘The approach is personalized, responsive to suboptimal metabolic parameters that reflect a network imbalance in synaptic establishment and maintenance vs. reorganization, and progressive in that continued optimization is sought through iterative treatment and metabolic characterization.’
While this is inherently more logical and clearly far more effective than any pharma strategy, personalised approaches are not cheap and cannot be easily duplicated. This severely limits their usefulness when dealing with the global pandemic of dementia. So for those who cannot afford or access personalised treatment, here is an abbreviated list of do-it-yourself recommendations to keep your brain working better for longer. They are presented in no particular order, and take into account the major sub-types of dementia and the several sub-sets of Alzheimer’s (11).
Bring chronic inflammation under control. This can be achieved most effectively with long chain omega 3’s, stabilized and chaperoned by lipophilic polyphenols. Use blended prebiotic fibers to achieve gram-positive dominance in the large bowel, lipophilic phytonutrients to stabilize deep abdominal adipose tissue, and mixed fucoidans and funorans to manage periodontal disease. To avoid immuno-inadequacy, combine the above with 1-3, 1-6 beta glucans and the lactoperoxidase-critical factors thiocyanate and iron.
Include phosphatidyl phospholipids in the daily diet, as these are essential building blocks for cell membranes (brain is a heavily membrane dependent organ); together with a broad-spectrum micro- and phyto-nutrient support program.
Normalize insulin sensitivity. Metformin, or alternatively a standardized extract of Gynestemma pentaphyllum, can be very helpful here; but one has to start with dietary management, weight-loss if appropriate and physical exercise. Which is where we start to wheel back to dance.
A recent and very comprehensive review concluded that exercise has a neuro-protective effect in mild cognitive impairment and Alzheimer’s disease (12).
The effects of aerobic exercise and general fitness seem to mainly impact brain structures sensitive to neurodegeneration such as the hippocampal/parahippocampal region, precuneus, anterior cingulate and prefrontal cortex. Short courses of exercise have more of an effect on the hippocampus, although they presumably have a more global effect if sustained.
The brain-trophic effects of exercise are not restricted to the elderly; for example, professional athletes have more grey matter in certain parts of the brain than their non-active controls (13). This is hard to reconcile with the fabled stupidity of, for example, professional soccer players, but can be explained by the fact that their enhanced grey matter is preferentially dedicated to motor skills and to reward-related areas (!). This, together with their excess of testosterone, early exposure to stardom and lack of a proper education, helps to explain their frequently boorish behaviour. There are honourable exceptions, naturally.
Footballers aside, there is little doubt that physical exercise improves cognition, especially spatial and executive function, in both young and old subjects (14-16). The improved cognition is a reflection of enhanced brain health and connectivity, and is to be expected given the brain’s inherent plasticity. A well-known example of this adaptive plasticity is found among London taxi drivers, whose work is sedentary but whose hippocampal structures develop as they acquire their huge spatial knowledge (‘The Knowledge’) of The Great Wen (17).
Exercise and particularly aerobic exercise improves cardiovascular function and creates the conditions for improved oxygenation of the brain, together with reduced inflammatory stress (18). More specifically, it also up-regulates the synthesis of brain-derived neurotrophic factor (BDNF) (19). BDNF is a nerve growth factor known to promote nerve growth and survival, and functional and structural plasticity in the hippocampus (20). It is perhaps no accident that taxi drivers of old learned The Knowledge while cycling through the roads and backstreets of London!
Times change, and the trainee drivers’ shift to mopeds (and the universal availability of GPS systems) has created a generation of taxidermists who – in my experience – do not seem to know London as well as the old-timers did. Before aggrieved taxi drivers start sending in irate email, I concede that only a very few are taxidermists.
Preclinical studies have found that exercise, particularly aerobic endurance exercise, creates reproducible changes in the structure and function of the brain. Compared to their sedentary counterparts, mice or rats that run voluntarily on wheels show increased branching in hippocampal neurons, increased neurogenesis, and improved performance in at least some tests of cognitive function (21-23). There is more than one link between physical activity and increased neurogenesis, as mentioned above, but BDNF is probably the most important of these.
BDNF has multiple roles. Essential for neuronal and brain health,
‘In challenging environments food is scarce, competition within and among species for energy is high, and hazards such as predation also enter into the energy equation on both the acquisition and expenditure sides. Such environments demand higher levels of processing and retention (memory) of information from the environment, particularly sights, sounds, and odours. The underlying activity in neuronal circuits involves BDNF production and signalling, which promotes synaptic plasticity, the growth of dendrites, neurogenesis and learning.’
‘Such individuals will be lean, alert, and cognitively sharp when living in an environment where there are major challenges for energy acquisition. This same physical and cognitive phenotype can be achieved by self-imposed energy restriction and exercise routines in humans.’
‘In unchallenging environments, energy is readily available and there are few hazards to obtaining the energy. The time that would otherwise be used for food acquisition is used for reproduction and work to obtain other types of resources that provide an advantage to the individuals and their families. Because energy intake is increased and physical activity reduced in such an environment, BDNF signaling is reduced in neurons in the brain. Reduced BDNF signaling enhances food intake, reduces insulin sensitivity, deconditions the cardiovascular system, reduces cognitive abilities, and increases vulnerability to age-related diseases.’
If you think that sounds like modern times, you’re right. And now let’s sashay from the running track, finally, onto the dance floor.
As mentioned above, programs of physical activity reverse some of the signs of brain ageing in older people.
A recent study, carried out by researchers at the Center for Neurodegenerative Diseases in Magdeburg, took this further (25, 26). The Magdeburg team wanted to know whether exercise that involved learning might exert even more protective effects. They compared repetitive endurance exercise with a challenging course of dance lessons including Latin, Jazz and ballroom. These complex activities combine structured movement, music involvement, interaction with a partner, cognition and memory.
Endurance training and dancing both increased hippocampal volume, but only dancing lead to significant behavioral improvement, in terms of improved balance. This is important in the elderly, among whom falls are a common cause of debility, medical dependency and death. Another team, from the University of Electronic Science and Technology of China, found that dance lessons also improved empathy (27). Serious dancers already know this.
Because in nutrition everything connects, including the brain and the gut, let me end with the microbiome. If you eat enough prebiotic fibers, your learning improves even more (28). For those interested in such things, butyrate produced when prebiotic fibers are consumed reduces inflammation in the brain (29) and acts, more specifically, at GABA receptors (30), to make learning easier.
So take your partner and your prebiotics in hand, face the music, and dance. Hell, bought to you by the elites, is coming.
REFERENCES
- http://ghdx.healthdata.org/gbd-2016
- https://www.who.int/features/factfiles/dementia/en/
- https://www.alzheimers.org.uk/news/2018-07-19/new-data-shows-rise-deaths-caused-dementia
- https://www.alzheimers.org.uk/sites/default/files/migrate/downloads/dementia_uk_update.pdf
- Pritchard C, Rosenorn-Lanng E, Silk A, Hansen L. Controlled population-based comparative study of USA and international adult [55-74] neurological deaths 1989-2014. Acta Neurol Scand. 2017 Dec;136(6):698-707.
- Pritchard C, Rosenorn-Lanng E. Neurological deaths of American adults (55-74) and the over 75’s by sex compared with 20 Western countries 1989-2010: Cause for concern. Surg Neurol Int 23-Jul-2015;6:123
- Lim EL, Hollingsworth KG, Aribisala BS, Chen MJ, Mathers JC, Taylor R. Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas & liver triacylglycerol. Diabetologia. 2011;54:2506–2514.
- Bredesen DE. Reversal of cognitive decline: A novel therapeutic program. Aging (Albany NY) 2014;6:707–17.
- Kurakin A, Bredesen DE. Dynamic self-guiding analysis of Alzheimer’s disease. Oncotarget. 2015;6:14092–14122.
- Bredesen DE, Amos EC, Canick J, Ackerley M, Raji C, Fiala M, Ahdidan J. Reversal of cognitive decline in Alzheimer’s disease. Aging (Albany NY). 2016 Jun;8(6):1250-8.
- Bredesen DE. Metabolic profiling distinguishes three subtypes of Alzheimer’s disease. Aging (Albany NY) 2015;7:595–600.
- Haeger A, Costa AS, Schulz JB, Reetz K. Cerebral changes improved by physical activity during cognitive decline: A systematic review on MRI studies. Neuroimage Clin. 2019;23:101933.
- Taubert M, Wenzel U, Draganski B, Kiebel SJ, Ragert P, Krug J, Villringer A. Investigating Neuroanatomical Features in Top Athletes at the Single Subject Level. PLoS One. 2015 Jun 16;10(6):e0129508.
- Gates N, Singh MAF, Sachdev PS, Valenzuela M. The effect of exercise training on cognitive function in older adults with mild cognitive impairment: a meta-analysis of randomized controlled trials. Am. J. Geriatr. Psychiatr. 2013;21(11):1086–1097.
- Hess NCL, Dieberg G, Mcfarlane JR, Smart NA. The effect of exercise intervention on cognitive performance in persons at risk of, or with, dementia: a systematic review and meta-analysis. Health. Aging Res. 2014:1–10.
- Zheng G, Xia R, Zhou W, Tao J, Chen L. Aerobic exercise ameliorates cognitive function in older adults with mild cognitive impairment: a systematic review and meta-analysis of randomised controlled trials. Br. J. Sports Med. 2016;50(23):1443–1450.
- Maguire EA, Woollett K, Spiers HJ. London taxi drivers and bus drivers: a structural MRI and neuropsychological analysis. Hippocampus. 2006;16(12):1091-101.
- Safdar A, Saleem A, Tarnopolsky MA. The potential of endurance exercise-derived exosomes to treat metabolic diseases. Nat Rev Endocrinol. 2016 Sep; 12(9):504-17.
- Leech KA, Hornby GT. High-Intensity Locomotor Exercise Increases Brain-Derived Neurotrophic Factor in Individuals with Incomplete Spinal Cord Injury. J Neurotrauma. 2017 Mar 15; 34(6): 1240–1248.
- Park H, Poo M-M. Neurotrophin regulation of neural circuit development and function. Nature Reviews Neuroscience. 2013;14:7–23.
- Cotman CW, Berchtold NC, Christie LA. Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends Neurosci. 2007;30:464–472.
- van Praag H, Kempermann G, Gage FH. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat. Neurosci. 1999;2:266–270.
- Farmer J, Zhao X, van Praag H, et al. Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male Sprague-Dawley rats in vivo. Neuroscience. 2004;124:71–79.
- Rothman SM, Griffioen KJ, Wan R, Mattson MP. Brain-derived neurotrophic factor as a regulator of systemic and brain energy metabolism and cardiovascular health. Ann N Y Acad Sci. 2012 Aug; 1264(1): 49–63.
- Rehfeld K, Müller P, Aye N, Schmicker M, Dordevic M, Kaufmann J, Hökelmann A, Müller NG. Dancing or Fitness Sport? The Effects of Two Training Programs on Hippocampal Plasticity and Balance Abilities in Healthy Seniors. Front Hum Neurosci. 2017; 11: 305.
- Rehfeld K, Lüders A, Hökelmann A, Lessmann V, Kaufmann J, Brigadski T, Müller P, Müller NG. Dance training is superior to repetitive physical exercise in inducing brain plasticity in the elderly. PLoS One. 2018; 13(7): e0196636.
- Gujing L, Hui H, Xin L, Lirong Z, Yutong Y, Guofeng Y, Jing L, Shulin Z, Lei Y, Cheng L, Dezhong Y. Increased Insular Connectivity and Enhanced Empathic Ability Associated with Dance/Music Training. Neural Plast. 2019 May 6;2019:9693109
- Intlekofer KA, Berchtold NC, Malvaez M, Carlos AJ, McQuown SC, Cunningham MJ, Wood MA, Cotman CW. Exercise and sodium butyrate transform a subthreshold learning event into long-term memory via a brain-derived neurotrophic factor-dependent mechanism. Neuropsychopharmacology. 2013;38:2027-2034.
- Matt SM, Allen JM, Lawson MA, Mailing LJ, Woods JA, Johnson RW. Butyrate and Dietary Soluble Fiber Improve Neuroinflammation Associated With Aging in Mice. Front Immunol. 2018 Aug 14;9:1832.
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