old man and his bags

Reversing Cognitive Decline Through Diet and Lifestyle Part 1

Imagine reading a page in a book and then feeling like you have to start over as you have no memory of what you’ve just read or driving home from work and suddenly forgetting where you live. Instances like these can be the hallmarks of cognitive decline that leads to dementia and Alzheimer’s disease.

In a previous post I introduced the small scale study that claims, for the first time, to have reversed the cognitive decline in early stage Alzheimer’s sufferers.  In this post I want to take a look at the how they went about doing this and look at the reasoning behind each intervention.

At the outset I should make clear, as does the author of the paper, that this is a very small study that consisted of only 10 participants. The evidence, so far, is anecdotal which means further clinical trials are needed to either prove or disprove the results. Having said that, the results themselves were impressive with 9 of the 10 participants seeing huge improvements and sustaining them over the two and half year period of the study.

What I have attempted here is to flesh out the original protocol described in the paper with more details on the rationale behind each individual intervention, sometimes using sources provided in the source paper along with supplemental sources and evidence.

I’ve shied away from digging too deeply into the biochemistry and science as I want to make this a relatively easy and straightforward read for people regardless of their understanding of science.

As I want to make this as useful as possible I welcome any and all input, so please feel free to leave a comment below. For a summary of the program and the interventions used click here.

Guiding Principles

Having discussed the failure of single or monotherapeutics in the previous post I want to start by taking a look at the 6 guiding principles of this new multitarget approach.

  1. As with many other chronic illnesses the aim is not just to bring metabolic parameters to within normal range but to optimize them. For example,  a blood homocysteine level of 12μmol/l (micro moles per litre) may be considered within normal range but is far from optimal.
  2. Based on the idea that Alzheimer’s is caused by an imbalance of the brain’s plasticity network, the therapy needs to address as many points in that network as possible. The idea being that the combination may produce a result that is more than the sum of the single therapy approaches alone.
  3. As with other chronic diseases the underpinning network will be subject to a ‘threshold effect’. Once enough points on the network have been affected the disease causing mechanism will be halted or reversed. So even though patients might not be able to follow every point of the protocol if they hit enough bases to exceed the threshold it should be enough to produce a noticeable effect.
  4. Based on the contributing lab values the protocol is personalized. Data is analysed and different interventions are prioritized to determine a therapeutic program.
  5. The program is iterative, allowing it to be optimized and improved over time.
  6. For each point in the network, the goal is to address it in as physiological way, and as far upstream – as close to the beginning of the process – as possible.

Altogether there are 36 points within the system but not all the points need to be met to see improvements. As long as enough is done to cross a threshold limit benefits should be seen.

1. Optimize Diet

Approach

Reduce or remove simple carbohydrates from the diet, eat low glycemic, low inflammatory foods, Reduce grains from the diet.

Rationale

What’s considered a ‘good’ diet these days is a topic of endless discussion. However, the dogma of low fat, grain heavy diets has been challenged on several fronts in recent years. Mounting evidence is suggesting that animal fats, far from being the cause of atherosclerosis and heart disease, may actually be beneficial. As the evidence stacks up to exhonerate animal fat, there are more studies suggesting that simple carbohydrate consumption may lead to several disease states by promoting inflammation. Reducing simple sugars and grains may also help to minimize insulin resistance.

Regardless of the current arguments or state of research, reducing dietary sugar is an easy, sensible and practical means of improving several health markers.

Type 2 diabetes, which used to be known as adult onset diabetes is typically found in people with Alzheimer’s, so much so, that some researchers have begun to refer to AD as type 3 diabetes.

Ingesting too much sugar and eating a high carb diet can lead to a condition known as insulin resistance, whereby cells can longer uptake and use glucose (1, 2)

2. Enhance Autophagy and Ketogenesis

Approach

Fast 12 hours each night, essentially from dinner to breakfast including 3 hours prior to bedtime.

Rationale

Autophagy is a process by which the body recycles cellular clutter, essentially breaking down and cleaning out molecules that are damaged or no longer needed. Fasting has been shown to promote autophagy as cells recycle materials in the absence of food (3).

Autophagy can be a double edged sword, with too much being as bad as too little. Studies also show that damage to autophagic pathways are implicated in a number of brain diseases (4) but fasting may help to swing the balance in favour of the beneficial aspects (5). Another study looking at time restricted feeding (another way of saying fasting) in mice found a range of positive benefits to a number of biological markers, which most likely translate to the brain, too (6).

Fasting for between 10 and 16 hours promotes the use of fat stores and the production of ketone bodies which have been shown to be neuroprotective. Evidence suggests that ketogenesis – the production of ketone bodies- which brain cells can use as fuel enhances the production of a number of neurotrophic (brain cell growing) factors like Brain Derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF) whilst reducing signs of oxidative damage (7)

Yet another issue with Alzheimer’s and other systemic diseases is that of glucose intolerance, with evidence suggesting a strong link between diabetes type 2 and dementia (8) and it appears that high glucose concentrations may inhibit the degradation of the APP protein leading to a build up of amyloid beta fragments (9)

Neuroinflammation is also thought to play a large part in Alzheimer’s and other neurodegenerative diseases (10).

3. Reduce Stress

Approach

Each approach is personalized and can be any practice that helps the individual to relax- yoga, meditation, listening to or playing music etc.

Rationale

Increasing evidence seems to suggest that stress can have a direct, measurable influence of several health markers. Things like chronic stress, low socioeconomic status, caring for a sick spouse etc tend to activate specific patterns of genes in what’s known as the conserved transcriptional response to adversity (CTRA). CTRA promotes the expression of a number of pro-inflammatory genes, that may be beneficial for short periods of stress or adversity but have a negative impact on health if activated for a prolonged period including the promotion of diseases such as cancer, cardiovascular disease and Alzheimer’s (11).

Interestingly, the same paper talks about how levels of happiness may oppose the CTRA pattern of expression which may lead to better overall well-being. Hedonistic happiness, generally defined as being subjective with the idea that increased pleasure and reduced stress results in happiness, was linked to reduced expression of CTRA. Eudaimonic happiness, which includes aspects like having a sense of control or autonomy, life having meaning or purpose, feelings of belongingness and social contribution etc was associated with with significantly lower expression of CTRA.

Evidence also suggests that practices such as mindfulness, tai chi, yoga and cognitive-behavioral stress management can reduce pro-inflammatory gene expression in people experiencing stress (11, 12)

4. Optimize Sleep

Approach

Aim for 7-8 hours of sleep a night. 0.5mg melatonin can be taken just before bedtime. Tryptophan can also be supplemented 3 times a week (500mg) if individual has problems waking during the night. Sleep apnea should also be excluded.

Rationale

Recent research suggests that when we sleep the space between brain cells increases allowing fluid to flow through the brain and wash away all the harmful proteins and compounds that have built-up throughout the day. Wakefulness suppresses this, so an imbalance in the sleep cycle or lack of sleep will prevent the thorough flushing out of harmful molecules that may build up over time. Here’s a link to a paper detailing the mechanism (13) and here’s a link to an easier piece in the New York Times discussing the same findings  (Goodnight. Sleep Clean.)

There are a great many reasons why supplementing with melatonin is beneficial to the brain which I won’t go into in any great length here, but here are a few of the reasons.

Melatonin upregulates antioxidative defense systems including many of the body’s own powerful antioxidants; superoxide dismutase, glutathione peroxidase and glutathione.

Melatonin also binds and inactivates iron; which is known to build up in the brains of Alzheimer sufferers. This binding suppresses a process known as the Fenton reaction and so prevents the overproduction of damaging reactive oxygen species.

Melatonin has also been shown to reverse chronic and acute inflammation processes with inflammation implicated in Alzheimer’s and many other diseases besides.

Melatonin helps to protect the mitochondria through a number of mechanisms. Again loss of mitochondrial function plays a role in Alzheimer’s and several other conditions.

Melatonin is protective against β-amyloid peptides which are known to form plaques and contribute directly to Alzheimer’s. By reducing the generation of the β-amyloid it also reduces neuronal death more effectively than other antioxidants.

Supplementing melatonin in Alzheimer’s significantly slows down cognitive impairment and decreases brain atrophy (shrinkage). A study of 14 patients at various stages of the disease who were given melatonin supplements for between 22 and 35 months showed significantly decreased ‘sundowning’ – a term used to describe the agitated state of AD sufferers often seen around early evening. Throughout the study period the patients also experienced no cognitive or behavioural deterioration. Furthermore giving melatonin to Alzheimer sufferers has been found to improve both sleep and circadian rhythm issues.

Melatonin also displays impressive anti-fibrillogenic activity even in the presence of apolipoprotein e4 (Apoe4) and disrupts the neurotoxic synergistic relationship between Apoe4 and β-amyloid.

For a thorough run-down of the myriad of beneficial effects you can read the open access paper ‘Role of melatonin supplementation in neurodegenerative disorders’ published online in Frontiers in Bioscience here (14)

Melatonin levels were found to be significantly decreased in patients with Alzheimer’s compared to aged matched control subjects.

Sleep apnea, a condition in which breathing halts or has been linked to the development of a number of neurodegenerative diseases including Alzheimer’s. Some estimates put the figure of people who have some form of sleep apnea at between 9-24%(15, 16)

5. Exercise

Approach

30-60 minutes a day 4-6 times a week

Rationale

Numerous studies show that exercise has positive impact on both the body and brain.

Exercise most likely benefits the brain in multiple ways
improving things like blood pressure by decreasing hypertension which is thought to be contributing factor to neurodegeneration. (below link)Regular exercise also bring benefits in terms of improved insulin sensitivity, lower levels of inflammatory molecules like interleukin-6 and C-reactive protein, serum homocysteine etc. (17)

In animals models that express greatly increased amounts of β-amyloid and tau proteins – which are directly involved in with Alzheimer’s disease – exercise appeared to reduce the build-up of both these harmful proteins (17)

Studies also show that older adults with greater levels of fitness have better levels of brain connectivity and activity compared with adults with lower levels of fitness. People who are also more active in mid and later life tend to have lower incidence of cognitive decline, too. (17) It’s also thought that exercise may boost certain neurotrophic factors – substances that promote brain cell growth – like insulin like growth factor 1 and brain derived neurotrophic factor BDNF.

People who carry a gene variant known as apolipoprotein-E ε4 (APOE ε4) have an increased risk of developing Alzheimer’s. Fortunately, studies have shown that vigorous exercise and other changes to lifestyle can offset much of the risk that APOE ε4 carriers have (18)

At present there is much we don’t know about all the effects of exercise on the body as one study recently showed changes within 4,000 different genes following three months of exercise (19) Despite the many unknowns it’s a safe bet say that done correctly exercise has many real and positive impacts on both the body and in turn the brain.

Recommendations

Exercise programs should ideally consist of a mix of both aerobic and resistance exercises.

Aerobic exercise

There are many ways to improve aerobic fitness though 150 minutes of moderate aerobic exercise per week (30 minutes, 5 days/week) or 60 minutes of vigorous-intensity aerobic exercise (20 minutes, 3 days/week) is recommended. Short bouts of aerobic exercise in the 6–10-minute range can also be beneficial to people with limited exercise capacity.

To significantly increase VO2 max in healthy older adults, aerobic exercise intensity should be equal to or greater than 60% of their pre-training VO2 max with measurable results becoming apparent within 16 weeks but the emphasis here should be on building up to a level that is consistently achievable, after all, the benefit is derived from exercise being on going.

Resistance exercise

Long term resistance training has multiple benefits beyond brain health relating to mobility, increased strength, bone and joint health.

Resistance exercise needs to be approached with the aid of a good and sympathetic  coach as individual starting levels will vary greatly and will need to take into account overall level of fitness, joint and mobility issues and injuries etc. The overall aim, however, should be to follow a program that aims to progressively increase physical strength beyond that of the starting original base condition. Sadly, all too often I see individuals undertaking resistance programs that see no progress even over a number of years, this is often to do with the fact that individuals or trainers don’t make the training progressively more difficult which it should be in order to really reap the benefits.

In the next installment I’ll look at brain stimulation, optimizing homocysteine levels, serum B12 levels, C-reactive protein, albumin-globulin ratio, lowering fasting insulin and glycated hemoglobin levels.

Part 2

Got a question or maybe something to add? Leave a comment and let me know!