Delaying and slowing cognitive decline

Professor of Neurology, Dale Bredesen, along with medical colleagues from 15 other clinics, recently published a paper describing 100 patients with cognitive decline who had well documented, quantified improvements in cognition using his targeted, multi-component programme.¹

These new results expand on Professor Bredesen’s earlier published case studies of 10 patients, 9 of whom showed sustained subjective and objective improvement in cognition, using his approach that involves identifying and addressing underlying contributors and causes.^2,3

According to The Alzheimer’s Society, 225,000 people will develop dementia this year, that’s one every 3 minutes; there are currently 850,000 people with dementia in the UK, with numbers set to rise to over 1 million by 2025.

The pathology begins many years before a diagnosis. More than 30% of people aged 85 years have Alzheimer’s and the pathology began between the ages of 55 and 65.⁴

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Drug therapy for neurodegenerative diseases has failed because drugs do not address the multifactorial nature of these conditions. As a consequence, despite huge spending worldwide on drug research, there is still no effective treatment for Alzheimer’s disease. Professor Bredesen suggests several reasons for this failure:

1. Attempting to treat without identifying the underlying cause/s and contributors
2. Assuming a single cause, attempting to treat with a monotherapy
3. Targeting the mediators (e.g. β-amyloid peptides) instead of the root causes (e.g. pathogens, toxins, and insulin resistance etc.) and
4. Treatment is typically initiated late in the pathophysiological process

Accumulated research is showing that Alzheimer’s disease is far more complex than previously thought.  To effect an improvement, dozens of biological mechanisms may need to be brought back into balance. Thus he has developed a personalised, multiphasic programme based on each individual’s genetics, biochemistry and a full case history. The programme addresses nutrition (diet and supplements to optimise nutritional status), fasting, gut health, optimising sleep, reduction of stress, physical activity, brain training, removal/avoidance of toxins and optimisation of hormones.

His work has also identified that Alzheimer’s disease can be sub-divided into a number of subtypes:

1a) Inflammatory/infectious (hot) – These people have biomarkers of systemic inflammation including increased C-reactive protein (C-RP), interleukin 6 (IL-6) and nuclear factor kappaβ (NF-kβ) and are often becoming insulin resistant with high blood circulating insulin. Inflammation drives metabolic dysfunction. The inflammation may be sterile or may be associated with infectious agents.

1b) Glycotoxic – People in this subtype present with features of both type 1 inflammatory Alzheimer’s disease and type 2, atrophic. This subtype may be characterised by people with insulin resistance/type 2 diabetes, moving from an inflammatory presentation towards an atrophic one.

2) Atrophic (cold Alzheimer’s) – These people do not have markers of inflammation but of low trophic support (low insulin production – insulin is trophic for neuronal and synapse formation), low hormones, low vitamin D, low TNF-alpha (tumour necrosis factor-alpha) and IL-6. Other metabolic abnormalities are often present along with atrophy (shrinkage) of the hippocampus (the area of the brain important for memory consolidation).

3) Toxic – Distinctly different – tends to affect younger people (45-65 years of age), often non-amnestic but instead these people present with dyscalculia or aphasia or executive dysfunction. Often zinc deficient and generally toxic. Mycotoxins or metals such as mercury are often contributory. Lyme’s disease may be found. Cortical atrophy may occur ahead of hippocampal atrophy.

4) Vascular – This subtype is characterised by impaired/reduced blood flow, and damage to the vascular system within the brain. Underlying cardiovascular disease/diabetes is implicated in this subtype.

5) Traumatic – Traumatic brain injury is a risk factor for Alzheimer’s disease. Pathogenic mechanisms that may occur after injury to the brain involve proteins known to contribute to the pathological hallmarks of Alzheimer’s.

Key elements addressed as part of The Bredesen Protocol

Extensive biochemical testing helps to identify the sub-type of Alzheimer’s and this along with consideration of an individual’s genetics, case history and specific test results is used to produce a personalised, therapeutic programme that includes consideration of:

Nutrition – a low glycaemic load diet in order to prevent the development of hypoglycaemia and/or insulin resistance (and conversely to increase insulin sensitivity) is central to the programme; a Mediterranean, Paleo or Ketogenic diet depending on the patient.

Consideration is given to nutrients needed for brain health and, in addition to ensuring dietary sources, these may be supplemented:

• Essential fatty acids – the brain is 60% fat. The omega-3 fatty acids DHA and EPA are important for brain health
• Antioxidants – with lipids comprising the main structural components of the brain, along with the brain’s high metabolic rate (resulting in the production of free radicals), the brain is particularly susceptible to oxidative stress. This is coupled with the fact that the brain’s natural antioxidant capacity declines with age
• Vitamin A – concentrations of vitamin A have been reported as lower in cerebrospinal fluid and plasma of Alzheimer’s patients. Vitamin A’s role in maintenance of mucous membranes, including supporting integrity of the gut lining, is important for reducing inflammation
• B vitamins are need for energy production, methylation and homocysteine reduction
• Vitamin D receptors are widely expressed in the brain and serum vitamin D deficiency has been linked to cognitive impairment
• Magnesium is a cofactor for more than 300 enzymes. In the brain it acts as a modulator of synaptic plasticity. Magnesium’s roles in energy (i.e. ATP) production and insulin signalling are also important in the brain
• Zinc deficiency has been shown to affect neurogenesis and increase neuronal apoptosis (cell death) which can lead to learning and memory deficits. Zinc deficiency is seen in particular in the ‘toxic’ sub-type of Alzheimer’s

Supplements – in addition to essential vitamin and mineral micronutrients there are many other supplemental nutrients and herbals that are being researched and used to support brain health including curcumin, glutathione, ashwagandha, Bacopa, gotu kola and others.

Gut health – there is a link via several mechanisms between gut health and brain health. For example, compromised gut barrier function or ‘leaky gut’, may underpin chronic low grade inflammation.

Stress reduction – persistently high levels of the stress hormone cortisol can cause death of brain cells. Stress also affects brain function through a number of other mechanisms.

Optimising sleep – sleep is when cell maintenance and repair occurs. Good quality sleep supports the production of the peptide brain derived neurotrophic factor (BDNF) which promotes growth and regeneration of new nerve cells.

Physical activity – exercise increases blood flow to the brain and thus the delivery of oxygen and nutrients. Moderate exercise upregulates anti-inflammatory pathways and increases BDNF.

Brain training – challenging and stretching the brain allows new connections to be created and maintained.

Other research

Research by others also supports a multimodal approach and some studies are discussed in a recent review by Lancaster University who appraised evidence for the effectiveness of multimodal non-pharmacological interventions for improving cognitive function in twenty-one group studies and five case studies.⁵ The inclusion criteria was adults with a primary diagnosis of dementia in an age range of 54-93. The 26 studies included used two or more different modes of intervention and measured a cognitive outcome. Modes included a range of cognitive therapies, psychological therapies, exercise and nutrition.

The results have important implications for dementia treatments as 92% of included studies demonstrated statistical improvement, stability or decrease of decline.  Studies that personalised the multimodal approach resulted in the greatest outcomes.

Can a similar approach be used for prevention?

A personalised, multiphasic programme can be used by healthy individuals wanting to prevent Alzheimer’s disease and, as Professor Bredesen discovered, it seems to be a protocol that will optimise every area of health.

A review this year by Klimova & Valis⁴ included 12 randomised controlled trials of healthy people, aged 50+ which focussed on nutritional interventions as a strategy to delay cognitive decline. They concluded that nutritional interventions had a positive impact with interactions between more than one nutrient being most effective, they also concluded that multi-domain interventions that included nutrition alongside other aspects – exercise, cognitive training and vascular risk monitoring resulted in more significant effects.

Two US Alzheimer Prevention Clinics are using a comprehensive approach for people at risk of Alzheimer’s disease.⁶ Clinical management decisions are based on clinical history and on what they refer to as the “ABCs” of Alzheimer’s prevention.

A – anthropometrics – % body fat, lean muscle mass, waist to hip ratio

B – blood biomarkers – genetic analysis, lipid profile, inflammatory, metabolic and nutritional biomarkers

C – cognition – neuropsychological testing

Interventions are then personalised and may include targeted cardiovascular risk factor management, physical exercise, nutrition, sleep, cognitive engagement, social interaction, sense of purpose, stress management and oral hygiene. Preliminary results have demonstrated improvements in cognition and biomarkers of Alzheimer’s risk.

So where does the UK stand in their health prevention strategy?

In the UK, we are spending £97bn of public money on treating disease and only £8bn preventing it across the UK.

However, the Health and Social Care Secretary Matt Hancock recently announced a green paper focused on prevention that aims to stop people from slipping into poor health.  The paper, entitled “Prevention is better than cure” argues for a shift towards primary and community care services, which help people stay well. The paper states that there will be an extra £20.5 billion a year by the end of the next five years, offering an opportunity to change the focus of health and social care onto prevention; and discusses that with an ageing society and people living with multiple complex conditions it is imperative that this rebalancing happens.

The paper points out the significant challenges: rising levels of obesity, mental illness, age-related conditions like dementia, and a growing, ageing and diversifying population, often living with multiple, long-term conditions such as diabetes, asthma and arthritis. For example, in 2017 there were almost 3.7 million people who had been diagnosed with diabetes in the UK⁷ and diabetes accounts for about 10% of the NHS budget and 80% of these costs are due to complications.⁸

It looks hopeful that a shift is starting and that the importance of prevention and the need for focussing proactively on a health prevention strategy is now recognised. Will this mean more services which target the root causes of poor health and promote the health of the whole individual, rather than treating single pathways with drug monotherapy?  Let’s hope so.

The Brain Health Programme

Delivered by Cytoplan,The Brain Health Programme has been designed to provide individuals with the knowledge and practical tools required to optimise wellbeing, memory and mood.

The Programme comprises six interactive workshops, led by qualified Nutritional Therapists, which include talks, activities and discussion to show individuals how to make, and sustain, lifelong food and lifestyle choices to protect and promote the health of the brain.  The workshops cover topics such as nutrition, optimising gut health, stress management, improving sleep, physical activity and brain training.

The Brain Health Programme is suitable for anyone wishing to learn how to support their mental health and wellbeing and reduce their risk of cognitive decline.

Visit The Brain Health Programme website here.

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If you have any questions regarding the topics that have been raised, or any other health matters please do contact me (Jackie) by phone or email at any time.

jackie@cytoplan.co.uk, 01684 310099

Jackie Tarling and the Cytoplan Editorial Team

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References

1. Bredesen DE. Reversal of Cognitive Decline: 100 Patients. 2018. doi:10.4172/2161-0460.1000450.
2. Bredesen DE. Reversal of cognitive decline: A novel therapeutic program. Aging (Albany NY). 2014;6(9):707-717. doi:10.18632/aging.100690.
3. Bredesen D, Amos E, Canick J, et al. Reversal of cognitive decline in Alzheimer’s disease. Aging (Albany NY). 2016;8(6):1250-1258. doi:10.18632/aging.100981.
4. Klímová B, Vališ M. Nutritional Interventions as Beneficial Strategies to Delay Cognitive Decline in Healthy Older Individuals. Nutrients. 2018;10(7):905. doi:10.3390/nu10070905.
5. Chalfont G, Milligan C, Simpson J. A mixed methods systematic review of multimodal non-pharmacological interventions to improve cognition for people with dementia. Dementia. September 2018:147130121879528. doi:10.1177/1471301218795289.
6. Isaacson RS, Ganzer CA, Hristov H, et al. The clinical practice of risk reduction for Alzheimer’s disease: A precision medicine approach. Alzheimer’s Dement. November 2018. doi:10.1016/j.jalz.2018.08.004.
7. Diabetes.org.uk. Diabetes Prevalence 2017 (November 2017) | Diabetes UK. https://www.diabetes.org.uk/professionals/position-statements-reports/statistics/diabetes-prevalence-2017. Published 2017. Accessed November 26, 2018.
8. UK D. THE COST OF DIABETES.; 2014.

Last updated on 20th November 2020 by cytoffice