… Cognitive impairment treatment… Alzheimer’s disease treatment… Natural remedies
Combatting Cognitive Impairment
Brain Degeneration
&
Alzheimer’s Disease
Brain Degeneration
&
Alzheimer’s Disease
NB this book is still being written
the text is unfinished and an proofread,
expected for completion during 2016
the text is unfinished and an proofread,
expected for completion during 2016
-from the back cover-
A healthy brain retains the ability to grow new neurones and connections between existing neurones throughout life. The ability for the brain to grow and develop new connections is called neuroplasticity. This book is how to increase and maintain your neuroplasticity using natural remedies.
-| Table of Contents |-
Chapter 1: Alzheimer’s and cognitive decline reversed for the first time.
Chapter 2: What is Dementia and Mild Cognitive Impairment?
Chapter 3: The New Science of Neuroplasticity.
Chapter 4: What Causes Alzheimer’s and Cognitive Decline?
Chapter 5: What to Target to Prevent and Reverse Alzheimer’s and Cognitive Decline.¶
Chapter 6: Treatment Plan Putting It All Together
-| Chapter 1 |-
The Breakthrough, Alzheimer’s Disease Reversed
The Breakthrough, Alzheimer’s Disease Reversed
PLEASE FORGIVE THE UNFINISHED STATE OF THIS PAGE IT IS STILL UNDER DEVELOPMENT AND THE HIGHLIGHTED TEXT IS NOT PROOFREAD, I’M SHARING THE WORK I’VE DONE SO FAR
© www.PeterSmithUK.com 2014 (updated April 2015)
Until recently age related cognitive decline seemed like something we couldn’t do anything to combat however in 2014 a study showed for the first time reversal of cognitive decline and early Alzheimer’s in humans [i].
In this ground-breaking study 10 people with memory loss associated with Alzheimer’s disease, amnesiac mild cognitive impairment or subjective cognitive impairment (in which the patient reports cognitive problems) were treated using a tailor-made functional medicine program based around identifying and targeting multiple issues affecting brain health rather than looking for one single cause.
Nine of the 10 participants experienced subjective or objective improvement in their memories within 3 to 6 months and without any adverse side-effects.
The improvements were significant enough that six of the participants that had previously had to give up work because of their cognitive decline were able to return to work. One participant that did not improve have been diagnosed with late stage Alzheimer’s disease.
The key feature in the above treatment program that makes it completely different to all other mainstream treatments is that it targeted multiple aspects of the condition at the same time (beta amyloid plaque buildup, inflammation in the brain, poor asleep, poor diet, nutritional deficiencies et al), in all some 25 parameters that influence the health of the brain were targeted. We know from other conditions such as cardiovascular disease, cancer and HIV that a single drug therapy approach is largely ineffective, for example we know that to reduce the chances of developing cardiovascular disease or cancer you don’t just take the single drug, you should do several things you should exercise, sleep well, reduce your exposure to free radicals, eat a diet rich in antioxidants, keep your cholesterol in check, consume lots of fibre etc etc. and yet thus far practically all mainstream research into a cure for dementia is focused on treating a single aspect.
About same time unaware of the above study I was working on developing a brain regeneration treatment based around boosting the brains natural production of something called BDNF which protects against shrinkage and regenerates loss of function in the brain. I was primarily doing this for people living with and recovering from mental illness (depression and bipolar syndrome which I live with myself) however I soon discovered that boosting BDNF levels also has implications for preventing and reversing cognitive decline. I first used my BDNF boosting protocol on myself and experienced regeneration in my hearing, facial recognition, mental arithmetic and tremendous improvement in my mental health.
In this book and described the breakthrough
-| Chapter 2 |-
What is Dementia?
Mild Cognitive Impairment MCI
define
Not everyone that develops MCI will go on to develop dementia or Alzheimer’s, however practically all cases of Alzheimer’s disease start with MCI.
Dementia affects 4 main areas of a person’s life:
Memory The person may be able to recall details from events in the distant past however forget events that happened just a few moments ago, a person may forget where they live, forget faces, what they were talking about, et cetera.
Orientation They may think they live in a somewhere they lived in years ago and that the current year is a year in the past.
Judgement They may for example wander outdoors in winter wearing pyjamas or misjudged traffic.
Affect They may become tearful for no apparent reason, rude, angry or even aggressive.
Dementia is a broad category of degenerative brain disease are several types of dementia including:-
Alzheimer’s disease AD,
Vascular dementia VaD
Lewy body dementia LBD,
Parkinson’s dementia PD when Parkinson’s disease combines with dementia,
Frontal-temporal dementia FTD,
ALS and other types.
Alzheimer’s disease and vascular dementia are the 2 most common types of dementia, which one is more prevalent varies from country to country.
Estimates of the risk of developing dementia vary between 20 to 40% by the time a person is 85 years old which is actually pretty high odds, the purpose of this book is to take the latest research about how to prevent and reserve dementia and present it in a easy to understand and usable format, as new information becomes available I will add updates to my website.
-| Chapter 3 |-
The New Science of Neuroplasticity
The New Science of Neuroplasticity
A healthy brain retains the ability to produce new neurones and grow new connections between existing neurones throughout life. The ability of the brain to grow and develop new connections is called neuroplasticity. This book is about how to maintain and actually increase your neuroplasticity using natural remedies.
The functional cells in the brain are called neurones, it’s now estimated there are about 86 billion neurones in the human brain. Neurones are highly active cells and each neuron has supportive helper cells supplying them with nutrients, oxygen and removing their toxic debris; these helper support cells are called glial cells. Although neurones are the functional cells involved in transmitting signals around the brain it’s important to maintain both the neurones and the glial cells for healthy brain function.
There are over 150 different kinds of neurones with different shapes and sizes. Neurones grow branches called dendrites that connect to neighbouring neurones, the point of connection is called a synapses and this is where neurotransmitters carry a signal from one neuron to its neighbour.
When we learn something new from language to juggling or even just practice something familiar like doing crossword puzzles neurones in the relevant part of the brain grow new dendrites and connections, basically that part of the brain becomes more densely interconnected. Anything and everything we do stimulates dendrites to grow, this is the principal feature of neuroplasticity.
Many people are familiar with the fact that thousands of brain cells die every day however people with healthy brains who continue to use their brains actually become more knowledgeable and wiser as they grow older, whilst it’s true that a professor in their 80s may have less neurones than a student in their 20s the professors remaining neurones will have thousands more connections to their neighbours, some neurones can grow an incredible 200,000 dendritic/synaptic connections their neighbours. So the professors brain is more densely connected and potentially vastly superior to a 20-year-olds brain.
In other words it’s the number of connections between neurons that’s more important in maintaining intelligence and mental function than the number of neurones themselves; thanks to neuroplasticity we can not only compensate for the perfectly normal death of neurones but actually grow smarter.
Loss of function in the brain isn’t only due to death of neurones it can also be that the dendrites on the remaining neurones shrink, you can imagine the neuron looking like a tree that’s had its branches trimmed; the good news about neurones in this condition is that like a trimmed tree they are still very much alive and can be stimulated to regrow new dendrites and synapses. Later on I’m going to tell you how to boost the production of the growth stimulating protein (BDNF) that stimulates dendrites to grow. Not only does this protein stimulate new growth but it also protects existing neurones from shrinkage and death.
For some reason in the brains of people with cognitive decline and Alzheimer’s disease neurones are dying and dendrites are shrinking more quickly than normal and the brains ability to compensate for this by growing new dendrites and cells is diminished; the result is degeneration and loss of function.
Exactly what causes this is unknown at this time, in my opinion there is unlikely to be one single cause and so looking for a single drug treatment is unlikely to be successful, and for the same reason that I believe the work of Dr Bredesen was effective because it targeted many aspects of brain health the same time.
Interestingly neuroplasticity can work in any direction so when we practise meditation we can grow and develop the calm, happy, contented, forgiving and compassionate parts of our brain conversely when we focus on depressive or anxious thinking it grows and develops the parts of the brain that engender that type of thinking.
When you first hear about neuroplasticity is easy to get carried away and imagine that we can completely grow a new brain, unfortunately however this is not possible our genetics does impose finite limitations on what is possible. With regard to cognitive decline and Alzheimer’s our concern is to prevent loss of neuroplasticity.
The pictures opposite[ii] are great illustrations of the brains ability to change. These are images of real neurons from rats either kept in a standard cage with little stimulation or from rats living in a more stimulating activity enriched environment. In the first picture you can clearly see an increased number of dendrite branches in the cell on the right from the brain of a rat living in an enriched environment compared to the cell on the left of a rat living in an under-stimulated environment.
The second picture shows close-ups of the dendrites, the images are in pairs on the left of each pair is from a rat housed in a standard environment and on the right we see the effects of just 3 weeks living in an enriched more stimulating environment. We can clearly see more tiny little buds called dendrite spines on the neurones on the rat living in an enriched stimulating environment, each of these dendrite spines forms a synapse connection with a dendrite branch from a neighbouring neuron, imagine millions of neurones sprouting hundreds of millions of new dendrite branches and spines, the result is a much more densely networked and connected brain.
By using the techniques below you could produce even better results than the rats in this experiment, the only thing that changed for them was the amount of external stimulating activity, but for optimum results you can combine focused brain training exercise with a diet, exercise and supplement protocol to increase BDNF levels at the same time.
INTRODUCE BDNF
So What is BDNF ?
BDNF is a protein naturally produced in our brain, it’s a desirable thing you want more of it. You can think of BDNF acting like a plant rooting-fertiliser it stimulates roots to grow and branch out; as well as stimulating new growth BDNF also protects brain cells from damage and stimulates them to make new connections (synapses).
- BDNF protects brain cells from death from stress, toxins and free radicals etc. it prolongs the life of brain cells.
- BDNF stimulates the growth of completely new brain cells something that used to be thought impossible.
- BDNF protects the dendrites from shrinking.
- Not only does BDNF protect dendrites from shrinking but it also stimulates neurones to sprout and grow new dendritic connections (synapses) with their neighbours.
- BDNF levels are suppressed by the stress hormone cortisol.
- Mild cognitive impairment[iii] [iv]
- Alzheimer’s[v]
- Depression
- Bipolar syndrome
- OCD
- and possibly chronic fatigue syndrome
Brain scans of people with cognitive decline and Alzheimer’s disease show shrinkage in both the grey matter and white matter of the brain {ref}. Furthermore a slower rate of cognitive decline is observed in patients with Alzheimer’s disease and higher levels of BDNF[vi]. The good news is many natural remedies have proven BDNF boosting and brain regenerated effects
Part of the physiology of bipolar syndrome (I have bipolar syndrome type II) is hyperactivity in the body’s stress responses (HPA axis) which simultaneously causes an increase in the production of inflammation in the brain and a decrease in the production of protective BDNF. Chronic inflammation combined with decreased protection from BDNF can take a toll on the health of the brain and by my mid 40s I noticed signs of mild cognitive impairment (MCI) with a decline in my hearing, facial recognition and ability to do mental arithmetic; remembering faces and mental arithmetic had been always been things I was good at.
My ongoing research into more effective ways to treat mental health problems both my own and my patients led me to BDNF; discovering that BDNF not only offered the potential to improve my mental health condition but it also had the potential to combat the MCI I was starting to notice was very exciting, I remember immediately thinking what is this BDNF and how I get a hold of it.
I was delighted to discover that there was quite a bit of research identifying natural remedies that have BDNF boosting properties and I decided to experiment on myself and see what would happen if I took all the known natural remedies boots BDNF at the same time combined with another course of relaxation brain training and an anti-inflammatory diet
Originally my focus was entirely developing a new technique to treat the underlying physiology of bipolar syndrome however I was delighted to experience the unexpected side-effects of full reversal in my mild cognitive impairment. Within a few months my facial recognition felt completely normal how it used to be, doing mental arithmetic felt like something I could do whereas it had become something I felt was beyond me, although still feel I need to do a bit more practice on the latter to fully regrow the neural pathways associated with this ability and the improvements in my hearing were dramatic. Not only did I notice my hearing returned to normal but seems to have improved to become better than it was in my 20s! I believe this to be so because while I was on my BDNF boosting prescription I started to understand for the first time the lyrics of many songs that I’ve been listening to since my 20s (in the 1980s) but previously never understood the words; unfortunately understanding the lyrics has ruined many of the songs I’ve been happily listening to since the 1980s. Nothing else has changed, I have not for example upgraded my hi-fi since 1997 and so I believe I’m hearing the lyrics for the first time because boosting BDNF has upgraded my brain.
Following my personal success I began using the technique in my practice in 2014 initially for my patients with intractable mental health problems and problems resulting from long-term prescription medication use, it quickly began to change lives and today I routinely recommend BDNF boosting prescriptions.
If you’re interested in treatments for mental health problems including depression, bipolar syndrome and OCD I have an alternative book on boosting BDNF for these problems.
While studying the scientific research on BDNF as it related to mental illness I repeatedly I repeatedly came across research relating BDNF to cognitive impairment and Alzheimer’s disease.
It was seeing improvements in cognitive performance of my patients and experiencing first-hand reversal of MCI in myself together with the breakthrough reversal of cognitive impairment with Dr Bredesen’s treatment that gave rise to this book.
I’d like to make a disclaimer here so that you can make an informed decision:
My BDNF boosting brain regenerating technique has not been scientifically tested and therefore from a scientific point of view all the improvements I’m claiming are purely anecdotal; furthermore the breakthrough study by Dr Bredesen only involved 10 people and was not placebo-controlled.
All the techniques and remedies used in both Dr Bredesen’s and my BDNF boosting treatments are natural and safe, however you are responsible for your own health and must consult with your doctor before considering discontinuing any prescription medication or combining it with any of the treatments discussed in this book. The information in this book is for people that don’t want to wait for further scientific study into these methods, but instead want to go ahead with self-help personal experimentation. Unfortunately scientific investigation into the use of naturally remedies and holistic functional medicine techniques progresses at a snails pace because it never attracts the same financial backing that research into patentable and potentially profitable drugs attracts; it’s entirely possible that because of this simple economics the techniques described in this book may never become mainstream.
Originally I developed my BDNF boosting brain regenerating protocol to treat brain degeneration associated with mental health problems (depression, bipolar syndrome et al) which is my main speciality.
Part of the physiology of bipolar syndrome (I have bipolar syndrome type II) is hyperactivity in the body’s stress responses which simultaneously causes a decrease in the production of protective BDNF and an increase in the production of inflammation in the brain. Chronic inflammation combined with decreased protection from BDNF can take a toll on the health of the brain and in my mid 40s I noticed mild cognitive impairment with a decline in my hearing, facial recognition and ability to do mental arithmetic; remembering faces and mental arithmetic had been always been things I was good at. When combined all the known natural remedies to boost BDNF with relaxation techniques and a healthy anti-inflammation diet within a few months I restored my hearing, facial recognition and mental arithmetic abilities although I need a bit more practice on the latter to fully regrow this ability.
Originally my focus was entirely developing a new technique to treat the underlying physiology of bipolar syndrome however I was of course delighted to experience the completely unexpected side-effects of reversal in my mild cognitive impairment.
I introduced the technique in my practice in 2014 for my patients with mental health problems and it quickly began to change lives.
As I continued to study the scientific research on BDNF as it related to mental illness I repeatedly came across scientific research also relating BDNF to cognitive impairment and Alzheimer’s disease.
It was seeing and experiencing first-hand reversal of cognitive impairment in myself or my patients together with the breakthrough reversal of cognitive impairment with Dr Bredesen’s treatment that gave rise to this book.
I’d like to make a disclaimer here so that you can make an informed decision:
My BDNF boosting brain regenerating protocol has not been scientifically tested and therefore from the scientific point of view all the improvements I’m claiming are purely anecdotal; furthermore the breakthrough study by Dr Bredesen only involved 10 people and was not placebo-controlled. All the techniques and remedies used in both Dr Bredesen’s and my BDNF boosting treatments are natural and safe, however you are responsible for your own cells and must consult with your doctor before considering discontinuing any prescription medication or combining it with any of the treatments discussed in this book. The information in this book is for people that don’t want to wait for further scientific study into these methods, but instead want to go ahead with self-help personal experimentation. Unfortunately scientific investigation into the use of naturally remedies and holistic functional medicine techniques progresses at a snails pace because it never attracts the same financial backing that research into patentable and profitable drugs attracts; because of this simple economics the techniques described in this book they never become mainstream.
N.B. Boosting BDNF may also assist the recovery from brain injury or stroke and recovery form drug withdrawal.
Cognitive Decline Alzheimer’s and BDNF
under construction
My expertise lies in mental illness and I have not attempted to treat Alzheimer’s or cognitive decline however in researching the role of BDNF and neuroplasticity for mental health problems I constantly found scientific literature alluding to their significant role in Alzheimer’s and cognitive decline, BDNF protects brain cells from degeneration and increases the brain’s capacity to regenerate and make new connections. In the past I deliberately avoided commenting on Alzheimer’s and cognitive decline because I didn’t feel there was anything useful or practical to say either in terms of treatment or prevention apart from intermittent fasting and not overeating is the best prevention. In 2014 this situation changed when for the first time cognitive decline was reversed in humans [vii] by a Dr Bredesen using what mainstream medicine describes as a novel approach but interestingly for me the approach was individualised functional medicine which is what I do. I now think finally there are some currently available techniques we that may help at least the early stages of cognitive decline and Alzheimer’s. I would suggest combining the techniques used by Dr Bredesen with my BDNF boosting protocols to increase neuroplasticity. At the moment I’m engaged in writing up my therapeutic methods for mental health problems however at some point in the future (2016) I’ll be putting up pages on nondrug approaches to cognitive decline.
N.B. Boosting BDNF may also assist the recovery from brain injury or stroke and recovery form drug withdrawal.
BDNFs other roles in the Body
BDNF performs many other functions in the body outside the brain. It is involved in stabilising blood sugar and insulin metabolism, preventing insulin resistance and type II diabetes, IBS, healing the intestines and intestinal movement.
See Blood Sugar and Mental Health.
BDNF Isn’t Snake Oil
When you first hear about BDNF and neuroplasticity it’s easy to get carried away and think that you could completely grow a new brain, unfortunately however boosting BDNF is not out to be a miracle cure for Alzheimer’s disease
Unfortunately boosting BDNF is not a breakthrough miracle cure for Alzheimer’s disease however I personally experienced a complete reversal of the mild cognitive impairment and developed in my late 40s within a few months of boosting my BDNF levels.
Lots of research is going into the relationship between BDNF and Alzheimer’s disease, higher levels of BDNF exert a protective effect against beta-amyloid[viii], conversely beta-amyloid plaque appears to impair BDNF’s ability to maintain the synapses[ix]; it seems that at least for some people having higher levels of BDNF is associated with a reduced risk of progressing on to develop Alzheimer’s [insert reference], it also seems to slow down the progression of Alzheimer’s [insert reference].
I believe adding my BDNF protocol to Dr Bredesen’s protocol offers the best treatment currently available for these conditions; I will be constantly updating the information on my website whenever I come across something new regarding brain ageing.
Other conditions involving BDNF
It’s not my area of speciality but low levels of BDNF have been observed in schizophrenia and eating disorders implying it may play a role.
Boost BDNF to Help You Study
Not only can you boost BDNF to repair damaged brain pathways you can also use the BDNF boosting protocol any time you want to develop a new mental ability to accelerate the rate at which the brain make new connections, I’ve no experience of using it with learning languages, improving maths abilities etc if you do let me know he get on; what I’m proposing however is that let’s say you had depression in the past and you’ve already done the BDNF protocol once along with taken remedies to rebalance your neurotransmitters and you’ll now feeling much better but you still have for example low self-esteem you could then redo the BDNF boosting protocol whilst at the same time undergoing intensive therapy and or using meditations that promote positive self-esteem at the same time. The therapy/meditation will stimulate the development of new positive self-esteem pathways in the brain and the extra BDNF will increase the results.
I’m only just beginning to experiment with this possibility but what I’m hoping is that the combination of boosting BDNF at the same time as performing brain training therapy exercises and meditations to target qualities we want more of in a life may be a useful therapy enabling us to literally sculpt our brain to become better at doing the things we want more of in a life.
-| Chapter 4 |-
What Causes Brain Degeneration?
What Causes Brain Degeneration?
More often than not mainstream medicine research tends to focus on treating one single aspect of a condition at a time, unfortunately however degenerative diseases such as dementia and Alzheimer’s disease often turn out to be complex, multifactorial and not caused by a single factor that can easily be targeted.
If you look at the history of cardiovascular disease for example every time research attempted to treat or prevent heart disease by reducing a single factor such as cholesterol or homocysteine the results have been disappointing and yet we know that if you combine the right diet with exercise, stress management and certain supplements we can significantly reduce the risk of cardiovascular disease. The same can be said with regard to current research into how to prevent and treat the current epidemic of diabetes.
So far treatments that target just one single aspect dementia or Alzheimer’s disease at a time, reducing amyloid beta or inflammation for example have failed to produce any effective treatments.
I think we can say with some certainty that it’s a mistake to think that there’s a single simple cause for the brain degeneration seen in cognitive decline, dementia and Alzheimer’s. An analogy might be if you analysed how a coastal town was destroyed by a hurricane you would discover that some destruction was caused by the force of the wind alone ripping off roofs for example that then with the roof gone there was water ingress resulting in water damage, a lot of damage was also caused indirectly by the wind hurtling objects such as glass pieces of wood around, downed power lines and gas leaks can cause fires and explosions, another component is the storm surge whereby the sea rises causing destructive flooding. So there’s a lot of individual destructive forces at play within a hurricane.
In the brain as in other parts of the body destructive forces can compound together for example AB formation causes mitochondrial dysfunction (see below) and mitochondrial dysfunction increases the formation of oxidative free radicals which promotes the formation of AB, this creates a vicious circle leading to increased brain cell death[x].
Another way of addressing the problem is even if there is a single cause for the condition in the meantime until we discover a single cause we can achieve a lot by combating all the manifestations of the condition we can influence, so we can reduce amyloid beta formation, reduce inflammation, improve mitochondrial dysfunction, reduce oxidative stress, improve the zinc/copper balance; we can also do all the things that enhance and maintain brain health such as: boosting BDNF levels, physical exercise, brain stimulation, optimising sleep, feeding our brain the building blocks to grow synapses and manufacturer acetylcholine.
I’ll discuss each of these and more in chapter XXX What to Target to Promote Brain Regeneration and Combat Dementia, but first let’s briefly review some of the mainstream and less mainstream individual theories about what causes brain degeneration.
Build-up of Amyloid Beta Plaque
A prominent feature of Alzheimer’s disease is the accumulation in the brain of clumps of an insoluble protein called amyloid beta (AB) which causes cellular damage to key areas of the brain such as the hippocampus involved in memory and spatial navigation. A lot of research has gone into finding ways to prevent and reverse the build-up of AB unfortunately treatment aimed at reducing AB on its own has turned out to be disappointing. Nevertheless it is worth targeting and fortunately there are some natural ways to do it.
Build-up of Tangled Tau Protein
Our neurones contain important tube structures called microtubules which function as transporting conveyor belts for nutrients and other small cell structures, the microtubules also gives the cell some internal structural scaffolding. The microtubules are maintained and secured in place by a proteins called tau proteins. In the brains of people with Alzheimer’s disease the tau proteins clump together into what are called neurofibrillary tangles or NFTs with can be seen in brain scans. When the tau protein malfunctions and forms insoluble tangle it results in break down and collapse of the important microtubules which causes the cell to die.
The tangles of tau protein form inside brain cells whereas clumps of amyloid beta protein form outside or between brain cells.
We may be able to combat the formation of both AB and NFTs by enhancing by enhancing autophagy[xi] (cellular housecleaning see later) and diminish their detrimental effects with intermittent fasting and calorie restriction techniques[xii][xiii].
Mitochondrial Dysfunction
Mitochondria are tiny structures within our cells whose main function is to turn the energy stored in food (glucose for example) into a form that our cells can use for energy; the process of making usable energy involves splitting stable oxygen molecules into single oxygen atoms which are potentially dangerous free radicals. Healthy mitochondria are designed to handle single oxygen atoms safely however dysfunctional mitochondria do not always properly control oxygen free radicals which can then be released as reactive oxygen free radicals that damage anything they touch.
It is thought that mitochondrial dysfunction which increases with age acts as an initial trigger for AB production, then AB itself further accelerates mitochondrial dysfunction and oxidative stress setting up a vicious circle resulting in cell death[xiv].
Oxidative stress from mitochondrial dysfunction occurs early in the development of Alzheimer’s disease and prior to the formation of amyloid beta toxicity[xv] implying that at least in part Alzheimer’s disease is a cascade of damage originating from mitochondrial dysfunction. This is not a universally accepted theory and there is still debate about whether mitochondrial dysfunction is a cause for a consequence of Alzheimer’s disease, with the multi-targeted treatment approach however we target mitochondrial health as just one of many targets; there are several things we can take and do to combat mitochondrial dysfunction which I’ll discuss in the next chapter.
Oxidative Stress
You probably already have an understanding that there are very reactive chemicals called free radicals both produced in our cells and ingested in our diet which cause considerable damage inside our bodies. In Alzheimer’s disease oxidative stress both increases the formation of AB and AB intensifies the damaging effects of free radicals, in other words AP and oxidative stress interact with each other and intensify their mutual damaging effects. A significant source of oxidative stress in Alzheimer’s disease is the mitochondrial dysfunction discussed above.
The Cholinergic Hypothesis
The neurotransmitter acetylcholine is involved in many aspects of memory and cognition and the cholinergic hypothesis of Alzheimer’s disease is that as we age we produce insufficient amounts of acetylcholine and degeneration of the cholinergic neurones.
Drugs treatment aimed at boosting acetylcholine levels can provide symptomatic improvement however they do not halt or cure the condition, nevertheless there are the natural remedies that can be used to boost acetylcholine levels and help maintain more youthful levels.
Inflammation in the Brain
Whatever the type or origin of dementia inflammation in the brain is always found to be present. How much inflammation causes the condition or just accelerates it is still a matter of scientific debate and investigation. I believe that a strong scientific case can be argued that inflammation in the brain is at least responsible for accelerating neurodegeneration even if it doesn’t start it in the first place, furthermore if we do not reduce inflammation our brain will be unable to maintain and regenerate itself; therefore reducing neuro-inflammation must be achieved at least to pave the way for other aspects of the integrated treatment to be effective.
There are some studies however that showed that reducing inflammation may not influence the course of the condition but these studies looked at the role of targeting inflammation in isolation and not as part of an integrated brain health improving strategy which I believe fails to properly investigate the significance of the role of inflammation in neurodegeneration.
Glutamate Excitotoxicity
The most abundant excitatory or stimulating neurotransmitter in the brain is glutamate. Glutamate is necessary for normal brain functioning however when too much glutamate lingers in the synapses it becomes toxic to the neurones causing cell death and brain degeneration, this is called excitotoxicity. Excitotoxicity from excessive glutamate activity is becoming recognised as a degenerative process involved in a number of neurological disorders including temporal lobe epilepsy and stroke/ischaemia, in Alzheimer’s disease glutamate excitotoxicity can damage the hippocampus.
Excitotoxicity is promoted by AB, NFT’s, mitochondrial dysfunction, oxidative stress and low intracellular zinc and is considered to be part of neurodegenerative processes that occur in Alzheimer’s disease.
Some mainstream drug therapies are aimed at targeting excitotoxicity, but once again on their own they have not produced the hoped-for breakthrough. With the holistic functional medicine approach to we combat excitotoxicity by combating the things that promote it in the first place and specific supplements.
Inorganic Copper from Water Pipes
Is Poisonous Inorganic Copper from Water Pipes the cause of the Alzheimer’s Epidemic?
See copper pipes and Alzheimer's disease
Zinc Dis-Homeostasis Hypothesis and Zinc deficiency
Zinc is the most abundant mineral in the brain and has numerous functions, the properties of zinc that concern us here are:
- Adequate zinc is needed to maintain your neuroplasticity.
- When sufficient zinc is available inside our neurones it reduces glutamate excitotoxicity which is a good thing.
- Zinc together with copper and iron builds and stabilises protein including AB protein which could be a bad thing.
- Zinc reduces copper absorption from the intestines and antagonises copper in our cells which can reduce copper neuro-toxicity[xviii].
- Excessive exposure to stress responses (HPA-axis activity see later) can cause excessive toxic levels of the zinc to be excreted into the synapses.
Firstly zinc is not evenly distributed in the body or even within the brain itself right down to the microscopic level, it’s nonsensical to simply refer to “zinc levels”, when looking at the effects of zinc on health one has be specific which zinc levels are being measured, is it zinc in the blood, in the brain, inside the cell (intracellular) or outside the cell (extracellular). Measurement of zinc levels in the blood tells us very little about the levels of zinc in the brain, as we age the level of zinc in our blood declines but the level in the brain seem to remain stable, however as I’ll explain below the distribution of zinc in the brain can become disharmonious in Alzheimer’s disease.
There’s evidence showing that dietary zinc deficiency decreases cognitive function[xix], that supplementing zinc decreases the rate of cognitive decline in Alzheimer’s disease[xx][xxi] and improves memory, understanding, communication and social contact[xxii][xxiii]; so at first glance it looks like zinc is a neuro-protective thing and that supplementing zinc is beneficial. It’s possible that one of the ways that supplementing zinc is beneficial is that it inhibits the absorption of neuro-toxic inorganic copper but when you look closely at how zinc is behaving in the brain it presents a complicated picture.
You can find studies showing zinc has neurotoxic effects, but the doses of zinc used to produce neuro-toxic effects were ridiculously high (insert ref) several times higher is than anything I would ever prescribe and bear no relation whatsoever to what any sensible human diet or nutritional supplement regime would deliver. Another discovery is that
At ordinary levels inside a healthy brain zinc is neuro-protective not neuro-toxic, however inside the brain of someone with Alzheimer’s the picture is more complicated. Zinc is highly concentrated in AB suggesting it’s a partner in the process of AB formation, [xxiv] furthermore research has shown that depleting zinc with zinc binding (chelating) compounds could help to dissolve AB plaques[xxv], human trials with this approach are currently underway[xxvi]. Dissolving AB plaque with zinc chelation will not however correct the faulty process causing AB to form in the first place and depleting zinc could potentially increase glutamate excitotoxicity damage elsewhere. Hearing this rather puts one off the idea of taking zinc supplements however zinc doesn’t build AB on its own, AB formation also needs copper and iron and it looks like keeping zinc levels high reduces AB formation because high zinc antagonises copper and iron levels[xxvii].
The zinc dis-homeostasis hypothesis of Alzheimer’s disease:
It’s appears that in Alzheimer’s the process that forms AB sequesters zinc from inside our neurones where it’s needed and concentrates it in the AB plaque that forms outside the neurones. The resultant intracellular zinc deficiency can mean that inadequate levels of zinc are secreted along with the neurotransmitter glutamate into the synapses to shut off glutamate activity causing glutamate excitotoxicity which results in destruction of the synapses neuron.
This is called the zinc dis—homeostasis hypothesis of Alzheimer’s disease and there are trials of pharmaceutical agents underway that could remove zinc from AB and redistributed back to the inside of our neurones[xxviii].
In conclusion with our current state of knowledge it looks what we want to do with regard to zinc and the health of our brain is:
1/ Avoid inorganic copper as completely as you can, not just because it’s neuro-toxic but also because it antagonises and depletes zinc.
2/ Maintain a high intake of zinc with diet and supplements, this will do 2 things firstly it reduces iron and copper levels and AB needs all 3 minerals (zinc, iron and copper) to form and secondly maintaining high zinc levels inside our cells enables the glutamate neurones to calm down excessive glutamate activity (glutamate excitotoxicity).
3/ Combat AB formation in the first place and use remedies to break it down to combat AB sequestering zinc from the inside of our neurones causing zinc deficiency inside our neurones further contributing to glutamate excitotoxicity and cell death.
4/ Train your brain how to switch off stress-responses to reduce increased HPA activation causing excessive toxic levels of zinc to flood the synapses.
GSK3 Hypothesis
You’ve probably never heard of GSK3 (glycogen synthase kinase 3) it’s a naturally occurring enzyme in the body only discovered in 1980. The simple way to think of GSK3 is that over-activity of GSK3 increases chronic static inflammation and this can cause degeneration in various places throughout the body, increasing the risk of developing type II diabetes, cancer, mood disorders most notably bipolar syndrome possibly multiple sclerosis as well as both familial and non-familial Alzheimer’s disease[i].
Over-activity of GSK3 promotes inflammation in the brain, the formation of tau protein, the formation of AB causes and memory impairment[ii] therefore we want to combat and control over-activity of GSK3; actually GSK3 comes in 2 forms: GSK3 alpha and GSK3 beta, it’s the GSK3 beta or GSK3 B that we want to inhibit whilst the GSK3 alpha may actually protect us from cancer and ageing.
The only useful agent I know of to inhibit unhealthy GSK3 B over-activity is lithium, fortunately we can inhibit GSK3 B without having to use the very high doses of lithium carbonate prescribed to control bipolar mania which is notorious for producing toxic side-effects.
[i] Neurochem Res. Author manuscript; available in PMC 2007 Sep 6. : Neurochem Res. 2007; 32(4-5): 577–595. Published online 2006 Aug 30. doi: 10.1007/s11064-006-9128-5 PMCID: PMC1970866 NIHMSID: NIHMS24923 Glycogen Synthase Kinase-3 (GSK3): Inflammation, Diseases, and Therapeutics Richard S. Jope, Christopher J. Yuskaitis, and Eléonore Beurel
[ii] J Neurochem. 2008 Mar;104(6):1433-9. Epub 2007 Dec 18. The GSK3 hypothesis of Alzheimer's disease. Hooper C1, Killick R, Lovestone S.Author information. PMC3073119
-| Chapter 5 |-
What to Target to
Promote Brain Regeneration
and Combat Dementia
What to Target to
Promote Brain Regeneration
and Combat Dementia
In the last section I introduced you to a number of things found to be faulty in the brains of people with Alzheimer’s disease and beginning to go faulty in the brains of people with mild cognitive impairment, I also introduced some additional theories about what may cause of neurodegeneration. In this chapter we go into how we can combat these things and construct a brain healthy diet and lifestyle.
You’ll see how the functional medicine multi pronged approach works and how some simple key treatment strategies can have multiple beneficial effects, for example intermittent fasting increases autophagy which in turn reduces mitochondrial dysfunction which in turn reduces oxidative stress in the buildup of amyloid plaque which further reduces oxidative stress furthermore intermittent fasting reduces high blood sugar which also reduces mitochondrial dysfunction and inflammation, then there’s the Mediterranean diet which acts on many beneficial levels reducing oxidative stress and diabetes risk. Many of the key remedies work on many levels curcumin for example is anti-inflammatory, combats AB?, Combats diabetes, increases BDNF, quenches free radicals et cetera; resveratrol…
To the functional medicine with thinking it’s not good medicine to allow someone to carry on eating high GI carbohydrates which pushes up their blood sugar and mitochondrial dysfunction and carry on eating excessive amounts of calories especially late at night which shuts off their autophagy and carry on eating a diet that promotes inflammation then use drug treatments to singularly target AB and inflammation.
Remember dementia and Alzheimer’s our new diseases arising from changes we’ve made to our diet and lifestyle in the 20th century…
-| Chapter 6 |-
Treatment and Prevention
[under development]
Treatment and Prevention
[under development]
-| Chapter x |-
Reverse Cognitive Decline with Dr Bredesen Functional Medicine Treatment:
The table below summarises Dr Bredesen’s approach
Reverse Cognitive Decline with Dr Bredesen Functional Medicine Treatment:
The table below summarises Dr Bredesen’s approach
Goal | Approach | Rationale and References |
Optimise diet: exclude high GI carbohydrates, minimise inflammation |
Follow a low GI Mediterranean style diet low in grains and excluding wheat. |
Minimise inflammation, minimise insulin resistance. |
Enhance autophagy, ketogenesis |
Fast 12 hr each night, including 3hr prior to bedtime | Reduce insulin levels, reduce aβ. |
reduce stress personalised | – yoga or meditation or music, etc. | reduction of cortisol, crf, stress axis. |
optimise sleep |
8 hr sleep per night; melatonin 0.5mg; trp 500mg 3x/wk if awakening. exclude sleep apnea. |
(front Biosci 2014, https://dx.doi.org/10.2741/4217) |
Exercise | 30-60 per day, 4-6 days/wk | (curr Alzheimer res.2014, doi: 10.2174/1567205011666140618102224. frontiers in aging neuroscience 2014, doi: 10.3389/fnagi.2014.00061) |
Brain stimulation | posit or related | (J am Geriatr soc 2009, doi: 10.1111/j.1532-5415.2008.02167) |
homocysteine <7 | B12, Mthf, P5P; TMG if necessary | (neurology 2010, doi: 10.1212/Wnl.0b013e3181f88162.) |
serum B12 >500 | B12 | (neurology 2009, doi: 10.1212/01.wnl.0000341272.48617.b0. |
CRP <1.0; a/G >1.5 | anti-inflammatory diet; curcumin; dha/epa; optimise hygiene |
critical role of inflammation in ad |
fasting insulin <7; hgba1c <5.5 | diet as above | type ii diabetes-ad relationship |
hormone balance optimise | ft3, ft4, e2, t, progesterone, pregnenolone, cortisol |
[5, 42]( eMBo Mol Med. 2013, https://dx.doi.org/10.1002/emmm.201202307 neurology 2009, doi: 10.1212/01.wnl.0000341272.48617.b0.) |
Gi health | repair if needed; | prebiotics and probiotics avoid inflammation, autoimmunity |
reduction of amyloid-beta | curcumin, ashwagandha | ( J pharmacol exp ther 2008,doi: 10.1124/jpet.108.137455; J Biol chem 2013, doi: 10.1074/jbc.M112.393751; pnas 2012, doi: 10.1073/pnas.1112209109.) |
cognitive enhancement | Bacopa monniera, Mgt | (neuropsychiatr dis treat. 2014, doi: 10.2147/ndt.s51092; J neurosci 2013, doi: 10.1186/s13041-014-0065-y.) |
25oh-d3 = 50-100ng/ml | Vitamins d3, K2 | (neurology 2014, doi: 10.1212/Wnl.0000000000000755.) |
increase nGf | h. erinaceus or alcar | (Biol pharm Bull 2008; 31:17271732; exp Gerontol. 1994; 29:5566.) |
provide synaptic structural components |
citicoline, dha | (alzheimer’s & dementia 2008, doi: 10.1016/j.jalz.2007.10.005.) |
optimise antioxidants | Mixed tocopherols and tocotrienols, se, blueberries, nac, ascorbate, α-lipoic acid |
(plos one 2010, doi: 10.1371/journal.pone.0014015.) |
optimise Zn:fcu ratio | depends on values obtained | (international J alzheimer’s disease 2013, doi: 10.1155/2013/586365.) |
ensure nocturnal oxygenation | exclude or treat sleep apnea | (J neurol neurosurg psychiatry 2014, doi: 10.1136/jnnp-2013-307544.) |
optimise mitochondrial function |
coQ or ubiquinol, α-lipoic acid, pQQ, nac, alcar, se, Zn, resveratrol, ascorbate, thiamine |
(Bland J. the disease delusion: conquering the causes of illness for a healthier, longer and happier life. 2014; United states: harper Wave.) |
increase focus | pantothenic acid | acetylcholine synthesis requirement |
increase sirt1 function | resveratrol | (pnas 2013, doi: 10.1073/pnas.1314145110.) |
exclude heavy metal toxicity | evaluate hg, pb, cd; chelate if indicated | cns effects of heavy metals |
Mct effects | coconut oil or axona | (nutrition & Metabolism 2009, doi: 10.1186/1743-7075-6-31.) |
CHO, carbohydrates; Hg, mercury; Pb, lead; Cd, cadmium; MCT, medium chain triglycerides; PQQ, polyquinoline quinone; naC, n-acetyl cysteine; CoQ, coenzyme Q; aLCar, acetyl-L-carnitine; DHa, docosahexaenoic acid; MgT, magnesium threonate; fT3, free triiodothyronine; fT4, free thyroxine; E2, estradiol; T, testosterone; Me-B12, methylcobalamin; MTHF, methyltetrahydrofolate; P5P, pyridoxal-5-phosphate; TMG, trimethylglycine; Trp, tryptophan
ashwagandha reverses aZ pathology? the reference trail made easy
The references here are well worth following up.
For example, one refers to a staggering paper published in 2012 in the high-end journal PnaS (Proceedings of the national academy of Sciences uSa), which describes how a 30-day course of treatment with an extract of the root of Withania somnifera (the ayurvedic herb ashwagandha) rEVErSED alzheimer’s pathology in the brains of middle-aged and old alzheimer’s disease transgenic mice.
Similarly, the references on curcumin are powerful: if you read them, we bet you’ll get some! and we’re making it easier for you to find abstracts and full papers online with our new citation/referencing style we are rolling out for the new year. you’ll find all the references online on the CaM website – www.cam-mag.com/references – where the doi numbers are “live”. Where an article does have a Digital Object Identifier, that will link direct to the abstract – usually on PubMed. If the article is available in full and free, PubMed will give you that link to click. a doi also works if you just tap it into a search engine.
-| Chapter X |-
My BDNF Brain Regenerating Treatment
-| Chapter X |-
Brain Regenerating Remedies
-| Chapter x |-
How to Stay Healthy and
Live Longer
1/ Protect your DNA
As we age the ends or tips of our DNA called telomeres breakdown and become shorter, this leads us more vulnerable to disease. Surprisingly we can protect our telomeres with resveratrol, meditation and intermittent fasting.
2/ Have Active Friends
Both having more friends or a social network has been shown to extend life but also choose friends pursue an active lifestyle, an outdoor walking, swimming or bowling club for example.
3/ Habitually take a siesta
4/ Follow a Mediterranean Diet
5/ practice intermittent fasting and do not overeat
6/ drink a little alcohol every day
7/ Find something spiritual for you
References: [Sorry the reference links the text do not work properly, the numbers are however correct]
[i] Aging (Albany NY). 2014 Sep; 6(9): 707–717. Published online 2014 Sep 27. PMCID: PMC4221920 Reversal of cognitive decline: A novel therapeutic program Dale E. Bredesen.
[ii] Journal of Cerebral Blood Flow & Metabolism (2002) 22, 89–96; doi:10.1097/00004647-200201000-00011 Neuronal Plasticity and Dendritic Spines: Effect of Environmental Enrichment on Intact and Postischemic Rat Brain Supported by grants from the Swedish Medical Research Council (14X-4968) Swedish Brain Foundation, The Royal Swedish Academy of Sciences (12533), and the Russian RFFI (98–04–49550). Barbro B Johansson, Pavel V Belichenko
[iii] Front Aging Neurosci. 2014 Apr 15;6:69. doi: 10.3389/fnagi.2014.00069. eCollection 2014. A large, cross-sectional observational study of serum BDNF, cognitive function, and mild cognitive impairment in the elderly. Shimada H1, Makizako H1, et.al.
[iv] Neurobiology of Learning and Memory xxx (2008) xxx–xxx BDNF is a novel marker of cognitive function in ageing women: The DR’s EXTRA Study Pirjo Komulainen, Maria Pedersen, Tuomo Hänninen, et.al.
[v] Neurobiology of Learning and Memory xxx (2008) xxx–xxx BDNF is a novel marker of cognitive function in ageing women: The DR’s EXTRA Study Pirjo Komulainen, Maria Pedersen, Tuomo Hänninen, et.al.
[vi] Int J Neuropsychopharmacol. 2011 Apr;14(3):399-404. doi:10.1017/S1461145710001008. Epub 2010 Sep 22. Higher BDNF serum levels predict slower cognitive decline in Alzheimer's disease patients. Laske C1, Stellos K, et al.
[vii] Reversal of cognitive decline: A novel therapeutic program Dale E. Bredesen, Mary S. Easton Center for Alzheimer's Disease Research, Department of Neurology, University of California, Los Angeles, CA 90095; 2 Buck Institute for Research on Aging, Novato, CA 94945.
[viii] Protective effect of BDNF against beta-amyloid induced neurotoxicity in vitro and in vivo in rats S. Arancibia, , M. Silhol, F. Moulière, J. Meffre, I. Höllinger, T. Maurice, L. Tapia-Arancibia. Neurobiology of Disease Volume 31, Issue 3, September 2008, Pages 316–326
[ix] β-Amyloid impairs axonal BDNF retrograde trafficking Wayne W. Poona, Mathew Blurton-Jonesa, Christina H. Tub, Leila M. Feinberga, Meredith A. Chabriera, Joe W. Harrisc, Noo Li Jeonc, Carl W. Cotmana. Neurobiology of Aging Volume 32, Issue 5, May 2011, Pages 821–833
[x] Mol Neurobiol. 2012 Aug;46(1):186-93. doi:10.1007/s12035-012-8307-4. Epub 2012 Jul 26. From mitochondrial dysfunction to amyloid beta formation: novel insights into the pathogenesis of Alzheimer's disease. Leuner K, Müller WE, Reichert AS. PMID: 22833458
[xi] PLoS One. 2011;6(9):e25416. doi: 10.1371/journal.pone.0025416. Epub 2011 Sep 28. Inducing autophagy by rapamycin before, but not after, the formation of plaques and tangles ameliorates cognitive deficits. Majumder S1, Richardson A, Strong R, Oddo S.
[xii] Neurobiology of Disease Volume 26, Issue 1, April 2007, Pages 212–220 Cover image Intermittent fasting and caloric restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzheimer's disease. Veerendra Kumar Madala Halagappaa, et al.
[xiii] Brain. 2012 Jul; 135(7): 2169–2177. Published online 2012 Jun 9. doi: 10.1093/brain/aws143 PMCID: PMC3381726. Stimulation of autophagy reduces neurodegeneration in a mouse model of human tauopathy Véronique Schaeffer,1 Isabelle Lavenir, Sefika Ozcelik, et al.
[xiv] Med Hypotheses. 2004;63(1):8-20. A "mitochondrial cascade hypothesis" for sporadic Alzheimer's disease. Swerdlow RH, Khan SM. PMID:15193340
[xv] Neurobiol Aging. 2009 Oct;30(10):1574-86. doi: 10.1016/j.neurobiolaging.2007.12.005. Epub 2008 Mar 4. Mitochondrial dysfunction: an early event in Alzheimer pathology accumulates with age in AD transgenic mice. Hauptmann S, Scherping I, et al.
[xvi] Alzheimer’s disease causation by copper toxicity and treatment with zinc George J. Brewer Department of Human Genetics, University of Michigan Health System, Ann Arbor, MI, USA PMID: 24860501 [PubMed] PMCID: PMC4030141
[xvii] J Trace Elem Med Biol. 2012 Jun;26(2-3):89-92. doi: 10.1016/j.jtemb.2012.04.019. Epub 2012 Jun 4. Copper toxicity in Alzheimer's disease: cognitive loss from ingestion of inorganic copper. Brewer GJ1.
[xviii] J Alzheimers Dis. 2014 Jan 1; 41(1): 179–192. PMCID: PMC4051494 NIHMSID: NIHMS582165 Oral zinc reduces amyloid burden in Tg2576 mice. C. Harris, K. Voss, et al.
[xix] Int J Alzheimers Dis. 2011; 2011: 492686. Published online 2011 Sep 22. doi: 10.4061/2011/492686 PMCID: PMC3178199 Paradigm Shift in Treatment of Alzheimer's Disease: Zinc Therapy Now a Conscientious Choice for Care of Individual Patients Tjaard U. Hoogenraad
[xx] Int J Alzheimers Dis. 2013; 2013: 586365. Published online 2013 Oct 10. doi: 10.1155/2013/586365 PMCID: PMC3810325 Zinc Deficiency and Zinc Therapy Efficacy with Reduction of Serum Free Copper in Alzheimer's Disease George J. Brewer
[xxi] Constantinidis J. The hypothesis of zinc deficiency in the pathogenesis of eurofibrillary tangles. Med Hypoth 1991; 35: 319-23.
[xxii] Constantinidis J. Treatment of Alzheimer’s by zinc compounds. Drug Develop Res 1992; 27: 1-14.
[xxiii] S Afr Med J. 1997 Sep;87(9):1116-9. Zinc and platelet membrane microviscosity in Alzheimer's disease. The in vivo effect of zinc on platelet membranes and cognition. Potocnik FC1, van Rensburg SJ, et al.
[xxiv] The Role of Zinc inAlzheimer’sDisease. Nicole T.Watt, Isobel J.Whitehouse, and NigelM. Hooper Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Clarendon Way, Leeds LS2 9JT, UK rights Correspondence should be addressed to Nigel M. Hooper, n.m.hooper@leeds.ac.uk
[xxv] R. A. Cherny, J. T. Legg, C. A. McLean et al., “Aqueous dissolution of Alzheimer’s disease Aβ amyloid deposits by biometal depletion,” The Journal of Biological Chemistry, vol. 274, no. 33, pp. 23223–23228, 1999. (Cited from: The Role of Zinc inAlzheimer’sDisease Nicole T.Watt, Isobel J.Whitehouse, and NigelM. Hooper Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Clarendon Way, Leeds LS2 9JT, UK Correspondence should be addressed to Nigel M. Hooper, International Journal of Alzheimer’s Disease Volume 2011, Article ID 971021, 10 pages doi:10.4061/2011/971021)
[xxvi] R. A. Cherny, C. S. Atwood, M. E. Xilinas et al., “Treatment with a copper-zinc chelator markedly and rapidly inhibits β-amyloid accumulation in Alzheimer’s disease transgenic mice,” Neuron, vol. 30, no. 3, pp. 665–676, 2001. (Cited from: The Role of Zinc inAlzheimer’sDisease Nicole T.Watt, Isobel J.Whitehouse, and NigelM. Hooper Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Clarendon Way, Leeds LS2 9JT, UK Correspondence should be addressed to Nigel M. Hooper, International Journal of Alzheimer’s Disease Volume 2011, Article ID 971021, 10 pages doi:10.4061/2011/971021)
[xxvii] J Alzheimers Dis. 2014 Jan 1; 41(1): 179–192. PMCID: PMC4051494 NIHMSID: NIHMS582165 Oral zinc reduces amyloid burden in Tg2576 mice. C. Harris, K. Voss, et al.
[xxviii] The Zinc Dyshomeostasis Hypothesis of Alzheimer’s Disease Travis J. A. Craddock, Jack A. Et al.