All in a tangle – Dr Caroline Leaf tries to explain Alzheimer disease

In her latest blog post, Dr Caroline Leaf attempted to tackle the complex topic of Alzheimer disease.

Alzheimer disease is an important topic.  It’s the most common progressive neurodegenerative disease worldwide and accounts for 60 to 80% of dementia cases. It causes a spectrum of memory impairment from forgetting where the car keys are through to forgetting to eat or drink.  According to the 2018 report by the Alzheimer’s Association, an estimated 5.7 million Americans are diagnosed with Alzheimer dementia, costing their economy $277 billion in 2018 [1]. That’s a staggering economic cost, but the human cost is higher.  Alzheimer’s exacts a great emotional toll on someone’s family and friends, both in terms of carer stress, and in seeing the person they love gradually slip away as the disease slowly erodes their personality until there’s nothing left.

There are two main forms of Alzheimer disease, an early onset type which accounts for about 5% cases, and a late onset type which accounts for the rest.  Early onset Alzheimer disease occurs before the age of 65. It’s also called Familial Alzheimer disease because it’s caused by one of three autosomal dominant genes (if you have a copy of the gene, then you will get the disease).  Late onset Alzheimer disease, as the name suggests, occurs late, after the age of 65.  It’s more complex and is associated with a mix of both genetic, lifestyle and environmental risk factors.

The neurobiology of Alzheimer disease is complicated.  Essentially, the symptoms of Alzheimer disease result from the death of too many nerve cells in the parts of the brain that manage memory and planning, but scientists are still trying to establish exactly why the nerve cells die.  There are a number of pieces of the jigsaw already in place.

For example, scientists know that amyloid plaques and neurofibrilliary tangles are part of the disease process.  These result from genetic changes to a number of enzymes which are critical to the nerve cells maintaining their structural integrity. It was first thought that these particular cell changes were critical factors to the nerve cells dying, but there are a number of other contributing factors that are also involved, such as changes to the metabolism of the nerve cells [2], inflammation of the brain, changes in the brain’s immune function, and changes to nerve cell responses to insult or injury (technically, endocytosis and apotosis, just in case you were wondering)[3].

In fact, it may be that the plaques and tangles are not the cause of the damage but are simply present while the other causes such as neuro-inflammation are doing all of the damage in the background.  This is possible as there are a small group of people that have cellular changes of plaques and tangles, but who do not have the clinical signs of dementia.  This was one of the discoveries in the Nun Study.  We’ll talk more about the Nun Study later in the post.

Whether it’s the plaques and tangles doing the damage or not, most of these changes are happening well and truly before a person ever shows any symptoms. In fact, by the time a person has some mild cognitive impairment, the plaques have reached their maximum level and the tangles are close behind.  This makes Alzheimer disease clinically challenging.  It would be ideal if we could start treatment early in the course of the disease before the damage has been established, but right now, the fact is that by the time a person is showing signs of memory loss, the damage to the cells is already done.

This begs the question, can we reduce our risk of Alzheimer disease?  There’s no good treatment for it, and even if there was, prevention is always better that cure.  So what causes Alzheimer disease in the first place?

There are a number of factors which contribute to the development of Alzheimer disease, some of which we can change, but some of which we can’t.

Unmodifiable Risk Factors

  1. Aging

Aging is the greatest risk factor for late onset Alzheimer disease.  The older you get, the more likely you are to get the disease.  Statistically, late onset Alzheimer disease will affect 3% of people between the ages 65–74, 17% of people aged 75–84 and 32% of people that are aged 85 years or older [1].

That’s not to say that Alzheimer disease and normal aging are the same. Everything shrinks and shrivels as you get older and the brain is no exception.  And it’s true that Alzheimer disease and normal aging share some similarities in the parts of the brain most affected.  However, these occur much more rapidly in Alzheimer disease compared to normal aging [4].

So, while aging is a necessary and significant risk factor for late onset Alzheimer disease, aging alone is not sufficient to cause Alzheimer disease.

Also, normal aging of the brain is not dementia.  And forgetting things is not dementia.  Everyone forgets things.  My teenage children forget lots of things I tell them.  They don’t have dementia.  Getting old doesn’t mean getting senile.  Some elderly people remain as sharp as a tack until the rest of their body gives up on them.

  1. Genetics

There are a number of genes which have been associated with Alzheimer disease.

As I alluded to earlier, early onset Alzheimer disease is strongly hereditary, with three different autosomal dominant genes that lead to its development.  They are known as APP, PSEN1and PSEN2genes[5].  The APPgene encodes for a protein is sequentially cleaved into peptides which then aggregate and form amyloid plaques.  PSEN1and PSEN2encode subunits of one of the enzymes which breaks up the amyloid protein.  Then there is a problem with one of the genes, the breakdown of the amyloid proteins is limited and the amyloid plaques start to accumulate at a much earlier age.

For late onset Alzheimer disease, there are 21 associated gene variants which are either splice variants, or single nucleotide polymorphisms (SNPs), and while they don’t cause Alzheimer disease, they increase the risk when they interact with other risk factors.  Each of the genes is important to one of the five main biological processes that influence the cellular structure and function of nerve cells.

(taken from Eid A, Mhatre I, Richardson JR. Gene-environment interactions in Alzheimer’s disease: A potential path to precision medicine. Pharmacol Ther. 2019;199:173-87)

The risk that any of these genes confers for developing Alzheimer disease is ultimately dependent on other risk factors, but one of the most well-known of the genes related to Alzheimer disease is the gene APOE4.  Apolipoprotein (APO) is a lipid carrier and is significantly involved in cholesterol metabolism.  In humans, it’s expressed as either E2, E3 or E4 variants.  The E4 variant has a much lower affinity for lipoproteins than its siblings, and if you have the APOE4, you have much poorer cholesterol metabolism – in your liver cells and in your brain cells.  Again, this fact may not seem important now but it will be more important later in the post.

If you inherit a copy of the APOE4 gene from your mother and your father, you have an 8 – 12 times greater risk of developing Alzheimer disease than another person without both copies of the gene.

  1. Family history

So if there are genes that can send your risk of Alzheimer disease through the roof, then it follows that having a family history of Alzheimer disease is a risk factor.

Individuals who have a first-degree relative, such as a parent, brother or sister who was diagnosed with Alzheimer disease are predisposed to develop the disease with a 4–10 times increased risk, compared to individuals who do not [6].

Of course, family history is not all to do with genetic risk factors, but it’s usually a combination of both genetics and share home environment between parents and siblings, hence why the risk conferred is not as high as APOE4, but is still very high.

  1. Ethnicity

Early studies suggested that Alzheimer disease was more common in certain races, although the thought was that the risk was related to social and economic conditions common to those races, and not to specific genes.

Recently, better genetic studies have linked a few genes with some races.  For example, there is a link with genes such as APOE4 which is twice as likely in African-American’s than other races, or a higher rate of mutations in the CLU gene amongst Caucasians [7].

  1. Gender

There is a strong gender difference for Alzheimer disease.  Overall, women are twice as likely to develop Alzheimer disease than men are.

There are a few possible reasons why this might be so.  Inflammatory mechanisms might play a part, as does the function of the part of the cell called mitochondria.  Hormonal differences might make some differences as well, specifically in relation to the oestrogen or the cell receptors for oestrogen.

There are also some gender differences in the way other genes play out.  For example, it’s known that women with the APOE4 gene will experience a faster cognitive decline than men with the same gene [8].  Sorry ladies.

Modifiable Risk Factors

So whether we like it or not, there are some risk factors for Alzheimer disease that we can’t change.  We can’t change our genes, our race, or our gender.  We can’t get any younger either.

What about the risk factors for Alzheimer disease that we might be able to change?

  1. Education

There’s some correlation between how much education someone has had and their risk of Alzheimer disease.

A meta-analysis by Larsson and colleagues which examined studies through to mid 2014 reported a statistical association of low education attainment (less than or equivalent to primary school) and increased Alzheimer disease risk.  For those with a primary education or lower, the risk of Alzheimer disease was 41 to 60 percent higher compared to someone who had better than primary school.  In a separate study, those who completed higher education (university level or above) had a lower risk of Alzheimer disease compared to those without higher education – approximately 11 percent per year of completed university level education [9].  There is some evidence that Alzheimer disease patients with higher education have a bigger part of the brain related to memory which is thought to be protective (if you have a bigger memory part of the brain, it will take longer to shrink in Alzheimer’s).

Two points to think about here.  First, these studies are not demonstrating cause and effect.  They don’t definitely prove that learning more stuff protects you from Alzheimer disease.  The statistics could simply reflect that people with the ability to learn more information had more robust nerve cells and connections to start with.

Also, while a 60 percent increase in risk sounds high, remember that the APOE4 gene carries a 1200 percent increased risk.  Comparatively speaking, the effect of education is actually quite small compared to other risk factors.

  1. Metabolic factors

Remember how we talked before about cholesterol and the APOE4 variants?  If you have both copies of the APOE4 gene, your liver cells and your brain cells aren’t good at handling lipoproteins.

Your liver cells are important in regulating your blood cholesterol.  Your brain cells are important for handling the amyloid proteins and lipids for making new nerve cell branches.

With APOE4, the liver doesn’t handle the blood cholesterol properly and you end up with high cholesterol and cholesterol plaques in the coronary arteries. When the brain cells don’t handle cholesterol properly, there is an increase in plaques and tangles and neuro-inflammation which increases the risk of Alzheimer disease.

At one stage, researchers thought that having a higher blood cholesterol was linked to Alzheimer disease but further research has shown that the results are inconsistent – some studies show a link while others show no link at all.  So all in all, there’s probably no cause and effect relationship with cholesterol and Alzheimer disease.  In fact, there’s some suggestion that high cholesterol is not a causative factor, but rather the result of Alzheimer disease [10] or simply a correlation, related to an underlying genetic or metabolic disorder which is common to both conditions.

Blood sugar was also considered to be a key factor for Alzheimer disease.  The Rotterdam Study conducted in the 1990s linked diabetes to Alzheimer disease [11], while a more recent nationwide population-based study in Taiwan showed that there was a higher incidence of dementia in diabetic patients [12].

While it may be that high blood sugar leads to Alzheimer disease, more recent research has suggested that there is a two-way interaction between Alzheimer disease and diabetes – diabetes increases the risk of Alzheimer disease, but Alzheimer disease increases the risk of diabetes.  Other scientists have recognised that there is a metabolic disease with overlapping molecular mechanisms shared between diabetes and Alzheimer disease.  These molecular mechanisms relate to less total insulin and higher insulin resistance, a mix of the pathologies seen in type 1 and type 2 diabetes – hence why one scientist called the underlying metabolic disorder “type 3 diabetes” [13].

So while cholesterol and blood sugar are linked to Alzheimer disease, it’s not clear whether aggressively lowering them would decrease the risk of Alzheimer disease or not.

  1. Lifestyle choices (food and exercise)

If it’s not clear how much our metabolic factors have on our Alzheimer disease risk, what about the food we eat?

There’s some evidence that having a healthy lifestyle reduces the risk of Alzheimer disease, but it’s not known what factors of lifestyle are the most important.  There was a study done on residents of New York City, and those who had a strict adherence to a Mediterranean diet and who participated in physical activity decreased their Alzheimer disease risk by about 35 percent [14].  That’s promising, but while there have been lots of studies into various aspects of diet and Alzheimer disease, it’s not clear what exactly works and why [15].

We can’t dismiss lifestyle changes, but more research is needed.

  1. Others

Smoking and alcohol are usually implicated in everything bad, and one would expect that their role in Alzheimer disease would be the same.  So it surprised everyone when one meta-analysis declared that smoking had a protective effect on Alzheimer disease.

The result sounded too good to be true and it probably is.  It’s likely that either smoking killed off all of the weaker people and only left those “healthier” smokers for the study population, or that smokers would have gotten Alzheimer disease had it not been for the fact that the smoking simply killed them off first.

Moral of the story – don’t take up smoking in the hope it will protect you from Alzheimer disease.  Even if it did, the lung cancer and emphysema will get you first.

Alcohol, on the other hand, was fairly neutral in broad population studies. That may be because the benefits of a small amount of wine drinking were being averaged out by the harmful effects of drinking too much hard liquor.  When the amount and type of alcohol drunk was separated out, there’s some evidence that a little bit of wine infrequently is somewhat preventative of Alzheimer disease [16].

Air pollution is a potential risk factor for Alzheimer disease.  It’s thought that the high exposure to chemicals and particulate matter in the air increases neuro-inflammation and death of the nerve cells leading to Alzheimer disease.  In a case-control study in Taiwan, individuals with the highest exposure to air pollution had a 2 to 4-fold increased risk in developing Alzheimer disease [17].

There are similar concerns about the risk of pesticide exposure and Alzheimer disease, although there are often a lot more confounders within the research itself, which makes the associations somewhat weaker.  Still, evidence is generally supportive of a link between pesticide exposure and the development of Alzheimer disease.

Risk factors – what can we learn?

In summary, there are a lot of different risk factors which are involved in Alzheimer disease, some of which can be influenced, and some which cannot.

Alzheimer disease is not a homogeneous disease that can be treated with one specific drug, but rather AD presents as a spectrum, with complex interactions between genetic, lifestyle and environmental factors.  So to really understand a person’s risk for Alzheimer disease, the interactions of these risk factors need to be understood which actually makes things exponentially harder.

That means that anyone telling you to eat this, or learn that, or do my program to reduce the risk of Alzheimer disease clearly doesn’t understand just how complicated Alzheimer disease is and has oversimplified things way too much.

Which brings us back to Dr Leaf and her blog.

I was surprised that Dr Leaf even tried to broach the subject of Alzheimer disease, because diseases like Alzheimers disprove her most fundamental assumption.  Dr Leaf has always taught that the mind is separate to the brain and is in control of the brain.  But if that were the case, the brain changes in Alzheimer disease would make no difference to a person’s cognition and memory.  Yet Dr Leaf admits throughout the entire post that the brain changes in Alzheimer disease do cause changes in the mind.

Dr Leaf can’t have it both ways.  Real cognitive neuroscientists don’t constantly contradict themselves, tripping themselves up on the most fundamental of all facts.  Dr Leaf needs to correct her most fundamental of all her assumptions and admit that the mind is a product of the physical brain and does not control the brain.

Dr Leaf also needs to stop exaggerating her “research and clinical experience”. She’s quick to point over every time she opens her mouth that she has decades of research and clinical experience, but such repeated and unjustified exaggeration is just another form of lying.  Her research was an outdated and irrelevant PhD in the late 1990’s, based on a theory which she tested on school children. Her limited clinical experience was as a therapist for children with acquired brain injuries.

Alzheimer disease affects the other end of the age spectrum and has nothing to do with acquired brain injury.  It is the absolute polar opposite of Dr Leaf’s already limited research and clinical experience.  Dr Leaf is like an Eskimo trying to build an igloo in the Sahara.

Dr Leaf’s credibility on the subject quickly evaporates with her introductory caution:

Before we go into too much detail, I want to remind you that our expectations can change the nature of our biology, including our brains! Indeed, recent research suggests just fearing that you will get Alzheimer’s can potentially increase your chance of getting it by up to 60%.

Dr Leaf doesn’t offer any proof that “Our expectations change the nature of our biology” but she does allude to “recent research” which suggests that “just fearing that you will get Alzheimer’s can potentially increase your chance of getting it by up to 60%”.  She doesn’t reference that either.  She could be referring to the research from Yale which she alludes to later in her post, although that research by Levy and colleagues didn’t mention anything about the risk of Alzheimer disease increasing by 60 percent [18].  In fact, given certain methodological weaknesses, it didn’t conclusively prove that negative beliefs about aging did anything to the brain, but that’s a topic for another day.

Dr Leaf made several attempts throughout the rest of the blog to portray Alzheimer disease as a disease related to toxic thoughts and poor lifestyle choices.  For example:

There is now a growing body of research that approaches the question of Alzheimer’s and the dementias as a preventable lifestyle disease, rather than a genetic or biological fault.  More and more scientists are looking at Alzheimer’s and the dementias as the result of a combination of factors, including how toxic stress and trauma are managed, the quality of someone’s thought life, individual diets and exercise, how we can be exposed to certain chemicals and toxic substances, the impact of former head injuries, and the effect of certain medications.

That statement is just a big furphy.  Yes, Alzheimer disease is the result of a complex interaction of genes and environmental factors.  Yes, there is some evidence looking at the interactions of diet and exercise, environmental exposures and former head injuries (although there’s very mixed evidence for the role of brain trauma in Alzheimer disease.  It’s not clear cut [19]).  But there is no ‘growing body of research’ that claims Alzheimer disease is not strongly genetic or biological, and there’s certainly no real scientist dumb enough to call Alzheimers a “preventable lifestyle disease”.

The evidence is pretty clear, that there are very strong genetic factors for developing Alzheimer disease.  Yes, some of them can be modified by environmental factors, but it’s foolhardy to claim that Alzheimer disease can be entirely prevented, based on the current evidence I outlined earlier.  Dr Leaf is rushing in where angels fear to tread.

Dr Leaf’s baseless exaggerations don’t stop there.

It is therefore unsurprising that professor Stuart Hammerhoff of Arizona University, who has done groundbreaking research on consciousness and memory, argues that the kind of thinking and resultant memories we build impacts our cell division and can contribute to the development of Alzheimer’s and the dementias.

Dr Leaf includes a hyperlink which when clicked, takes you to this article: https://www.theglobeandmail.com/life/health-and-fitness/health/conditions/new-theory-targets-different-origins-of-alzheimers/article4210442/.

It’s not a scientific paper, but a newspaper article which is more than seven years old.  The only thing it says about Professor Stuart Hameroff is this:

One of the co-authors, Stuart Hameroff at the Center for Consciousness Studies at the University of Arizona, has argued that microtubules may also be involved in consciousness.

That’s it.  There’s nothing else in the article about Prof Hameroff at all, nothing to back up Dr Leaf’s wild claim that our thinking and our memories alters cell division and contributes to the development of Alzheimers and dementia.  Dr Leaf is just confabulating.

Dr Leaf also claims that:

One of the many studies that have come out of this research, done by the Buck Institute for Research on Aging, showed dramatic improvement in patients diagnosed with Alzheimer’s and the dementias when they were put on an individualized lifestyle-based program that includes diet, exercise and learning.

Again, that’s a gross exaggeration.  The “research” that Dr Leaf is alluding to is a paper written by Bredesen [20].  It’s a narrative paper which describes a total of ten cases. That’s it – just ten cases. That’s nowhere near enough information to draw even the weakest of conclusions, but it gets worse.  The paper only gives a formal description of three patients and their treatments, the rest were listed in a table.  So there is even less data to draw any definitive conclusions from.  The other serious weaknesses of the paper were that the patients self-identified, and most of them didn’t have dementia at all, but instead had “amnestic mild cognitive impairment” or “subjective cognitive impairment”.  In other words, they were a little forgetful, or they only thought they were forgetful. The one subject that did have Alzheimer disease continued to rapidly deteriorate in spite of the program.

If you took Dr Leaf at her word, you would think that this treatment program was working miracles and clearly proved that Alzheimer disease could be cured by lifestyle treatment.  The study showed anything but.

Again, Dr Leaf is proving herself untrustworthy – either she knew that the study failed to demonstrate significant results and she was deliberately deceptive, or she didn’t understand that the results of the study were not conclusive, in which case she’s too ignorant to be treated as an expert.

In the same vein, Dr Leaf writes:

Another famous study, known as the “Nun Study,” followed a number of nuns over several years, showing that, although extensive Alzheimer’s markers were seen in their brains during autopsy (namely neurofibrillary plaques and tangles), none of them showed the symptoms of Alzheimer’s and the dementias in their lifetime. These nuns led lifestyles that focused on disciplined and detoxed thought lives, extensive learning to build their cognitive reserves, helping others and healthy diet and exercise, which helped keep their minds healthy even as their brains aged!

The hyperlink that Dr Leaf included was to a Wikipedia page which again, said nothing about the nuns who were apparently impervious to the effects of Alzheimers.  It did say that

Researchers have also accessed the convent archive to review documents amassed throughout the lives of the nuns in the study. Among the documents reviewed were autobiographical essays that had been written by the nuns upon joining the sisterhood; upon review, it was found that an essay’s lack of linguistic density (e.g., complexity, vivacity, fluency) functioned as a significant predictor of its author’s risk for developing Alzheimer’s disease in old age. The approximate mean age of the nuns at the time of writing was merely 22 years. Roughly 80% of nuns whose writing was measured as lacking in linguistic density went on to develop Alzheimer’s disease in old age; meanwhile, of those whose writing was not lacking, only 10% later developed the disease.

As it turns out, lots of nuns did end up with dementia after all … well that’s awkward – the page that Dr Leaf used to try and support her argument actually directly contradicted her.

Wikipedia’s entry was supported by the original journal article in the research from Riley et al [21].  And after a bit of gentle trawling of the scientific literature, I also found this article from Latimer and colleagues which said, “Interestingly, our results show very similar rates of apparent cognitive resilience (5% in the HAAS and 7% in the Nun Study) to high level neuropathologic changes” [22].

So, sure, some nuns did indeed have some plaques and tangles without showing signs of the disease, but not 100 percent of them as Dr Leaf tried to make out. In reality, it was only 7 percent of them!  And given what we know from the current research, plaques and tangles often precede clinical symptoms, so it may be that the nuns in question were on their way to cognitive impairment, but they hadn’t quite made it.  Who knows.  One thing’s for sure, the “lifestyles that focused on disciplined and detoxed thought lives” didn’t stop dementia affecting most of the nuns in the study.

Dr Leaf finishes off her post with what she thinks will help prevent Alzheimer disease. Given that she clearly doesn’t understand Alzheimer disease, we need to take what she advises with a large dose of salt.  Let’s look at what Dr Leaf suggested and see if it lines up with actual research.

Research shows that education, literacy, regular engagement in mentally-stimulating activities and so on results in an abundance of and flexibility in these neural connectionswhich help us build up and strengthen our cognitive reserves and protect our brain against the onset of Alzheimer’s and the dementias.
Like everything in life, the more you use your ability to think, the more you get better at it and the stronger your brain gets!

Rating: Half-true

Education has a small positive benefit, but the research isn’t clear if that’s cause or correlation.  So yes, stimulate your brain and see what happens.  It might not help stave off Alzheimer disease, but at least it will make the journey interesting it nothing else.

What else can you do to prevent Alzheimer’s and the dementias, or help someone already suffering cognitive decline?
1. Detoxing the brain:
I have written extensively about the importance of detoxing the brain by dealing with our thought life in a deliberate and intentional way. Our minds and brains are simply not designed to keep toxic habits and toxic trauma; we are designed to process and deal with issues. If, however, we suppress our problems, over time our genome can become damaged, which will increase the potential for cognitive decline as we age. This is why it is important to build up a strong cognitive reserves AND live a “detoxing lifestyle”, which essentially means that you make examining and detoxing your thoughts and emotions a daily habit. We want to have good stuff in our brain, yes, but we don’t want the neurochemical chaos of a bad thought life affecting our healthy cognitive reserves!

Rating: BS (“Bad Science”)

This is Dr Leaf’s favourite pseudoscientific claptrap, her neurolinguistic-programming-voodoo-nonsense that has no scientific basis whatsoever.  Skip it and move on.

2. Social connections:
Intentionally developing deep meaningful relationships can help build up our cognitive reserves against Alzheimer’s and the dementias – our brains are designed to socialize! Loneliness and social isolation, on the other hand, can seriously impact the health of our brains, making us vulnerable to all sorts of diseases, including ones associated with cognitive decline and the dementias …

Rating: Half-true

Loneliness has deleterious effects on health, but there’s nothing in the research to suggest that loneliness is a risk factor for Alzheimer disease.  Like we discussed about education and mental stimulation before, I think you should make friends and enhance your social connections.  There’s no guarantee that it will make any difference to your risk of Alzheimer disease, but it will make things fun and interesting at least.

3.  Sleep:
Dr. Lisa Genova, a neuroscientist, wrote the book Still Alice (this was also made into a movie), which describes the impact of the early onset of Alzheimer’s. She believes that buildup of plaques and tangles associated with Alzheimer’s can be averted, since it takes about 10 to 20 years before a tipping point is reached and cognitive decline becomes symptomatic. We all build plaques and tangles, but it takes at least a decade for them to actually affect our ability to remember, so there is hope!
There are things we can do to prevent this buildup, and sleep is an important one. During a slow-wave, deep sleep cycle, the glial cells rinse cerebrospinal fluid throughout our brains, which clears away a lot of the metabolic waste that accumulates during the day, including amyloid beta associated with the dementias. Bad sleeping patterns, however, can cause the amyloid beta to pile up and affect our memory. Essentially, sleep is like a deep cleanse for the brain!

Rating: What?

Dr Leaf’s advice here isn’t necessarily BS, it’s just plain confusing as she takes two unrelated chunks of information and tries to conflate them.

I don’t know if Dr Lisa Genova is a neuroscientist, or if she thinks the build-up of plaques and tangles can be averted or not.  The science as I outlined earlier in the post shows that the rise in plaques and tangles predate clinical symptoms, so you don’t know if you have them or not.  If that’s the case, how can you hope to reverse them.  Science is working on it, but it’s not there yet.

Irrespective, Dr Leaf doesn’t present any evidence to support her statement that sleep clears amyloid proteins.  And neither is there any evidence that sleep has a significant impact on the development of Alzheimer disease.

I think it’s good general advice to try and get a reasonable amount of good quality sleep so you can wake up refreshed.  Whether it changes your Alzheimer disease risk, who knows.

2. Diet:
We can now say with a good degree of certainty that consuming highly processed, sugar-, salt-, and fat-laden foods contributes to increased levels of obesity, cardiovascular disease, diabetes, stroke, allergies, autism, learning disabilities, and autoimmune disorders and Alzheimer’s! Some of the ways modern, highly processed and refined foods can contribute to Alzheimer’s and the dementias include added, highly-processed sugars, which cause your insulin to spike and the enteric nervous system of your gut to secrete an abnormal amount of amyloid protein. This will start destroying the blood-brain barrier, and can contribute to the formation of the amyloid plaques of Alzheimer’s disease. Some researchers now even refer to Alzheimer’s as type III diabetes!

Rating: Complete and utter BS

High sugar and high fat foods is certainly a contributing factor to obesity and to diabetes, and indirectly to cardiovascular disease and stroke. That’s where the intelligence in Dr Leaf’s statement comes to a grinding halt.  The rest of it is just a stream of fictitious nonsense without any basis in reality.

The western diet does not contribute to allergies, and it’s scientifically impossible for it to contribute to autism since autism is a genetic condition which expresses itself during foetal development, and I am yet to see a foetus chow down on a cheeseburger.  But wait, there’s more – learning disabilities, and autoimmune disorders too, and of course, Alzheimer disease.  Who cares that there’s no definitive trials to clearly prove that Alzheimer disease is in any way connected to our diets.

But apparently it’s the evil sugar which causes insulin to make the gut nervous system secrete amyloid proteins which destroy the blood brain barrier. When you put enough medical terms in a sentence, you would fool about 99 percent of people.  But looking past the random string of medical jargon, it’s clear that Dr Leaf is deluded.  The structural damage in Alzheimer disease comes from the nerve cell’s poor lipid metabolism, most of which comes from a gene which codes for a lipid carrying protein. Lipids have nothing to do with sugar. Besides, who cares if the enteric nervous system secretes amyloid … the enteric nervous system is in the gut [23], not the brain.  Even her inconsistencies are inconsistent.

Dr Leaf’s throw-away line at the end, “Some researchers now even refer to Alzheimer’s as type III diabetes!” is ignorant or intentionally misleading.  We’ve already established that the name “Type 3 diabetes” referred to the fact that scientists have recognised a metabolic disease with overlapping molecular mechanisms shared between diabetes and Alzheimer disease, not that Alzheimer disease is a metabolic disorder. Alzheimer disease is not because of too much sugar or bad lifestyle choices.

5. Exercise:
There is extensive research on the importance of exercise as a preventative tool against Alzheimer’s and the dementias. A number of studies show that people who exercise often improve their memory performance, and show greater increase in brain blood flow to the hippocampus, the key brain region that deals with converting short-term memory to long-term memory, which is particularly affected by Alzheimer’s disease.

Rating: Plausible

I don’t know what the state of the research is, but the study discussed earlier in the post about lifestyle changes did show improvement in risk for those who exercised.  And out of all of Dr Leaf’s pronouncements, at least this one has scientific plausibility.

Exercise promotes a growth factor in the brain called BDNF.  BDNF does stimulate the growth of new nerve cell branches.  Growth of new nerve cell branches results in improved mood.  It’s not entirely implausible to think that it would help with new memory formation and an enhanced hippocampus.

How much it really prevents Alzheimer disease is not clear, but given that exercise is universally good for you, I think it should be first on the list, not the last.

Dr Leaf – in a tangle

So in summary, Alzheimer disease is a complex multifactorial disease with a number of factors that affect its development, some of which can be changed, while others cannot.

Dr Leaf doesn’t understand this.  Her reading of the literature about Alzheimer disease is limited and skewed by her biased assumptions about toxic thinking and lifestyle.  Sure, there are some risk factors for Alzheimer disease which may be related to lifestyle and which may be modifiable, but Dr Leaf has failed to synthesise that information into the broader understanding of Alzheimer disease.

So some of her advice is helpful.  Most of it is not.  If you’re concerned that you or a loved one might have early memory loss, please don’t listen to Dr Leaf – see a real doctor instead and get the right advice.

References

[1]        Alzheimer’s A. 2018 Alzheimer’s disease facts and figures. Alzheimers Dement 2018;14(3):367-429.

[2]        Area-Gomez E, Schon EA. On the Pathogenesis of Alzheimer’s Disease: The MAM Hypothesis. FASEB J 2017 Mar;31(3):864-67.

[3]        Eid A, Mhatre I, Richardson JR. Gene-environment interactions in Alzheimer’s disease: A potential path to precision medicine. Pharmacol Ther 2019 Jul;199:173-87.

[4]        Toepper M. Dissociating Normal Aging from Alzheimer’s Disease: A View from Cognitive Neuroscience. J Alzheimers Dis 2017;57(2):331-52.

[5]        Dai MH, Zheng H, Zeng LD, Zhang Y. The genes associated with early-onset Alzheimer’s disease. Oncotarget 2018 Mar 13;9(19):15132-43.

[6]        Cupples LA, Farrer LA, Sadovnick AD, Relkin N, Whitehouse P, Green RC. Estimating risk curves for first-degree relatives of patients with Alzheimer’s disease: the REVEAL study. Genet Med 2004 Jul-Aug;6(4):192-6.

[7]        Nordestgaard LT, Tybjaerg-Hansen A, Rasmussen KL, Nordestgaard BG, Frikke-Schmidt R. Genetic variation in clusterin and risk of dementia and ischemic vascular disease in the general population: cohort studies and meta-analyses of 362,338 individuals. BMC medicine 2018 Mar 14;16(1):39.

[8]        Altmann A, Tian L, Henderson VW, Greicius MD, Investigators AsDNI. Sex modifies the APOE‐related risk of developing Alzheimer disease. Annals of neurology 2014;75(4):563-73.

[9]        Larsson SC, Traylor M, Malik R, et al. Modifiable pathways in Alzheimer’s disease: Mendelian randomisation analysis. Bmj 2017 Dec 6;359:j5375.

[10]      Rantanen K, Strandberg A, Pitkälä K, Tilvis R, Salomaa V, Strandberg T. Cholesterol in midlife increases the risk of Alzheimer’s disease during an up to 43-year follow-up. European Geriatric Medicine 2014;5(6):390-93.

[11]      Ott A, Stolk R, Van Harskamp F, Pols H, Hofman A, Breteler M. Diabetes mellitus and the risk of dementia: The Rotterdam Study. Neurology 1999;53(9):1937-37.

[12]      Huang C-C, Chung C-M, Leu H-B, et al. Diabetes mellitus and the risk of Alzheimer’s disease: a nationwide population-based study. PloS one 2014;9(1):e87095.

[13]      de la Monte SM. Type 3 diabetes is sporadic Alzheimer׳s disease: mini-review. European Neuropsychopharmacology 2014;24(12):1954-60.

[14]      Scarmeas N, Luchsinger JA, Schupf N, et al. Physical activity, diet, and risk of Alzheimer disease. JAMA : the journal of the American Medical Association 2009 Aug 12;302(6):627-37.

[15]      Hu N, Yu J-T, Tan L, Wang Y-L, Sun L, Tan L. Nutrition and the risk of Alzheimer’s disease. BioMed research international 2013;2013.

[16]      Heymann D, Stern Y, Cosentino S, Tatarina-Nulman O, Dorrejo JN, Gu Y. The Association Between Alcohol Use and the Progression of Alzheimer’s Disease. Curr Alzheimer Res 2016;13(12):1356-62.

[17]      Wu YC, Lin YC, Yu HL, et al. Association between air pollutants and dementia risk in the elderly. Alzheimers Dement (Amst) 2015 Jun;1(2):220-8.

[18]      Levy BR, Ferrucci L, Zonderman AB, Slade MD, Troncoso J, Resnick SM. A culture-brain link: Negative age stereotypes predict Alzheimer’s disease biomarkers. Psychol Aging 2016 Feb;31(1):82-8.

[19]      Kokiko-Cochran ON, Godbout JP. The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease. Front Immunol 2018;9:672.

[20]      Bredesen DE. Reversal of cognitive decline: a novel therapeutic program. Aging (Albany NY) 2014 Sep;6(9):707-17.

[21]      Riley KP, Snowdon DA, Desrosiers MF, Markesbery WR. Early life linguistic ability, late life cognitive function, and neuropathology: findings from the Nun Study. Neurobiology of aging 2005 Mar;26(3):341-7.

[22]      Latimer CS, Keene CD, Flanagan ME, et al. Resistance to Alzheimer Disease Neuropathologic Changes and Apparent Cognitive Resilience in the Nun and Honolulu-Asia Aging Studies. J Neuropathol Exp Neurol 2017 Jun 1;76(6):458-66.

[23]      Costa M, Brookes SJH, Hennig GW. Anatomy and physiology of the enteric nervous system. Gut 2000;47(suppl 4):iv15-iv19.

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Cutting through the Paleo hype

Paleo-Diet-Meal-Plan1

Fad diets come and go. One of the most popular fad diets of recent times is Paleo.

The Palaeolithic diet, also called the ‘Stone Age diet’, or simply ‘Paleo’, is as controversial as it is popular. It’s been increasing in popularity over the last few years, and has had some amazing claims made of it by wellness bloggers and celebrity chefs. Advocates like ‘Paleo’ Pete Evans of MKR fame, claim that the Palaeolithic diet could prevent or cure poly-cystic ovarian syndrome, autism, mental illness, dementia and obesity [1].

So what does the published medical literature say? Is there really good research evidence to support the vast and extravagant claims of Paleo?

About 10 months ago, I started reviewing the medical research to try and answer that very question. My review of the medical literature turned up some interesting results, and so rather than post it just as a blog, I thought I would submit it to a peer-reviewed medical journal for publication. After a very nervous 9-month gestation of submission, review, and resubmission, my article was published today in Australian Family Physician [2].

So, why Paleo, and what’s the evidence?

Why Paleo?

The rationale for the Palaeolithic diet stems from the Evolutionary Discordance hypothesis – that human evolution ceased 10,000 years ago, and our stone-age genetics are unequipped to cope with our modern diet and lifestyle, leading to “diseases of civilization” [3-9]. Thus, only foods that were available to hunter-gatherer groups are optimal for human health – “could I eat this if I were naked with a sharp stick on the savanna?” [10] Therefore meat, fruits and vegetables are acceptable, but grains and dairy products are not [11].

Such views have drawn criticism from anthropologists, who argue that that there is no blanket prescription of an evolutionarily appropriate diet, but rather that human eating habits are primarily learned through behavioural, social and physiological mechanisms [12]. Other commentators have noted that the claims of the Palaeolithic diet are unsupported by scientific and historical evidence [13].

So the Palaeolithic diet is probably nothing like the actual palaeolithic diet. But pragmatically speaking, is a diet sans dairy and refined carbohydrates beneficial, even if it’s not historically accurate?

Published evidence on the Palaeolithic Diet

While the proponents of the Palaeolithic diet claim that it’s evidence based, there are only a limited number of controlled clinical trials comparing the Palaeolithic diet to accepted diets such as the Diabetic diet or the Mediterranean diet.

Looking at the studies as a whole, the Palaeolithic diet was often associated with increased satiety independent of caloric or macronutrient composition. In other words, gram for gram, or calorie for calorie, the Paleo diets tended to make people fuller, and therefore tend to eat less. Of course, that may have also been because the Paleo diet was considered less palatable and more difficult to adhere to [14]. A number of studies also showed improvements in body weight, waist circumference, blood pressure and blood lipids. Some studies showed improvements in blood sugar control, and some did not.

The main draw back of clinical studies of Paleo is that the studies were short, with different designs and without enough subjects to give the studies any statistical strength. The strongest of the studies, by Mellburg et al, showed no long-term differences between the Palaeolithic diet and a control diet after two years [15].

The other thing to note is that, in the studies that measured them, there was no significant difference in inflammatory markers as a result of consuming a Palaeolithic diet. So supporters of Paleo don’t have any grounds to claim that Paleo can treat autoimmune or inflammatory diseases. No clinical study on Paleo has looked at mental illness or complex developmental disorders such as autism.

Other factors also need to be considered when thinking about Paleo. Modelling of the cost of the Palaeolithic diet suggests that it is approximately 10% more expensive than an essential diet of similar nutritional value, which may limit Paleo’s usefulness for those on a low income [16]. Calcium deficiency also remains a significant issue with the Palaeolithic diet, with the study by Osterdahl et al (2008) demonstrating a calcium intake about 50% of the recommended dietary intake [17]. Uncorrected, this could increase a patients risk of osteoporosis [18].

To Paleo or not to Paleo?

The bottom line is the Paleo diet is currently over-hyped and under-researched. There are some positive findings, but these positive findings should be tempered by the lack of power of these studies, which were limited by their small numbers, heterogeneity, and short duration.

If Paleo is to be taken seriously, larger independent trials with consistent methodology and longer duration are required to confirm the initial promise in these early studies. But for now, claims that the Palaeolithic diet could treat or prevent conditions such as autism, dementia and mental illness are not supported by clinical research.

If you’re considering going on the Palaeolithic diet, I would encourage you to talk with an accredited dietician or your GP first, and make sure that it’s right for you. Or you could just eat more vegetables and drink more water, which is probably just as healthy in the long run, but without the weight of celebrity expectations.

Comparison of the current Australian Dietary Guidelines Recommendations [19] to the Palaeolithic diet [17]

Australian Dietary Guidelines The Palaeolithic Diet
Enjoy a wide variety of nutritious foods from these five groups every day:  
Plenty of vegetables, including different types and colours, and legumes/beans Ad libitum fresh vegetables and fruits
Fruit
Grain (cereal) foods, mostly wholegrain and/or high cereal fibre varieties, such as bread, cereals, rice, pasta, noodles, polenta, couscous, oats, quinoa and barley All cereals / grain products prohibited, including maize and rice
Lean meats and poultry, fish, eggs, tofu, nuts and seeds, and legumes/beans Ad libitum lean meats and poultry, fish, eggs, tofu, nuts and seeds, but all legumes prohibited
Milk, yoghurt, cheese and/or their alternatives, mostly reduced fat (reduced fat milks are not suitable for children under 2 years) All dairy products prohibited
And drink plenty of water. Ad libitum water (mineral water allowed if tap water unavailable)

References

[1]        Duck S. Paleo diet: Health experts slam chef Pete Evans for pushing extreme views. Sunday Herald Sun. 2014 December 7.
[2]        Pitt CE. Cutting through the Paleo hype: The evidence for the Palaeolithic diet. Australian Family Physician 2016 Jan/Feb;45(1):35-38.
[3]        Konner M, Eaton SB. Paleolithic nutrition: twenty-five years later. Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition 2010 Dec;25(6):594-602.
[4]        Eaton SB, Eaton SB, 3rd, Konner MJ. Paleolithic nutrition revisited: a twelve-year retrospective on its nature and implications. European journal of clinical nutrition 1997 Apr;51(4):207-16.
[5]        Eaton SB, Konner M. Paleolithic nutrition. A consideration of its nature and current implications. The New England journal of medicine 1985 Jan 31;312(5):283-9.
[6]        Kuipers RS, Luxwolda MF, Dijck-Brouwer DA, et al. Estimated macronutrient and fatty acid intakes from an East African Paleolithic diet. The British journal of nutrition 2010 Dec;104(11):1666-87.
[7]        Eaton SB, Konner MJ, Cordain L. Diet-dependent acid load, Paleolithic [corrected] nutrition, and evolutionary health promotion. The American journal of clinical nutrition 2010 Feb;91(2):295-7.
[8]        O’Keefe JH, Jr., Cordain L. Cardiovascular disease resulting from a diet and lifestyle at odds with our Paleolithic genome: how to become a 21st-century hunter-gatherer. Mayo Clinic proceedings 2004 Jan;79(1):101-08.
[9]        Eaton SB, Eaton SB, 3rd, Sinclair AJ, Cordain L, Mann NJ. Dietary intake of long-chain polyunsaturated fatty acids during the paleolithic. World review of nutrition and dietetics 1998;83:12-23.
[10]      Audette RV, Gilchrist T. Neanderthin : eat like a caveman to achieve a lean, strong, healthy body. 1st St. Martin’s Press ed. New York: St. Martin’s, 1999.
[11]      Lindeberg S. Paleolithic diets as a model for prevention and treatment of Western disease. American journal of human biology : the official journal of the Human Biology Council 2012 Mar-Apr;24(2):110-5.
[12]      Turner BL, Thompson AL. Beyond the Paleolithic prescription: incorporating diversity and flexibility in the study of human diet evolution. Nutrition reviews 2013 Aug;71(8):501-10.
[13]      Knight C. “Most people are simply not designed to eat pasta”: evolutionary explanations for obesity in the low-carbohydrate diet movement. Public understanding of science 2011 Sep;20(5):706-19.
[14]      Jonsson T, Granfeldt Y, Lindeberg S, Hallberg AC. Subjective satiety and other experiences of a Paleolithic diet compared to a diabetes diet in patients with type 2 diabetes. Nutrition journal 2013;12:105.
[15]      Mellberg C, Sandberg S, Ryberg M, et al. Long-term effects of a Palaeolithic-type diet in obese postmenopausal women: a 2-year randomized trial. European journal of clinical nutrition 2014 Mar;68(3):350-7.
[16]      Metzgar M, Rideout TC, Fontes-Villalba M, Kuipers RS. The feasibility of a Paleolithic diet for low-income consumers. Nutrition research 2011 Jun;31(6):444-51.
[17]      Osterdahl M, Kocturk T, Koochek A, Wandell PE. Effects of a short-term intervention with a paleolithic diet in healthy volunteers. European journal of clinical nutrition 2008 May;62(5):682-85.
[18]      Warensjo E, Byberg L, Melhus H, et al. Dietary calcium intake and risk of fracture and osteoporosis: prospective longitudinal cohort study. BMJ 2011;342:d1473.
[19]      National Health and Medical Research Council. Australian Dietary Guidelines. Canberra: National Health and Medical Research Council; 2013.

Does our attitude towards aging increase Alzheimer Dementia?

“I think I’m forgetting something …”
Does our attitude towards aging increase Alzheimer Dementia?

For the last few years, I’ve worked as a doctor for a number of my local nursing homes.  On my morning rounds, I would literally reintroduce myself to every second patient, because even though I’d seen them every week for the previous few months, they still couldn’t remember who I was.

And it’s not just because I have a less than memorable face.  Most of my nursing home residents had dementia.

While there are many different causes for dementia, the one first described by Mr Alzheimer in the (early 1900’s) is the best known and most feared.  It is also the most common, and is a significant drain on the nation’s economy as well as the quality of life in the twilight of years.

Recently, an article was published by a group of researchers from Yale University in the US which claimed to show that the attitude a person had towards aging contributes to their chances of Alzheimer Disease.  I first saw it yesterday on the social media feed of Dr Caroline Leaf, communication pathologist and self-titled cognitive neuroscientist.  Dr Leaf is known for her scientifically dubious assumptions that the mind changes the brain, not the other way around, and has previously publically stated that dementia was caused by toxic thinking.  This article seems to vindicate her assumptions.

Screen Shot 2015-12-10 at 6.08.55 PM

However, this article also made it onto Facebook’s trending list ands was picked up by news site all over the world (such as this article in the Australian http://goo.gl/RavbMl), so the interest wasn’t just from Dr Leaf, but also from the broader public.  And I can understand why.  No one wants to ‘grow old and senile’, or to ‘lose our marbles’.  Any potential cure or prevention for Alzheimer Dementia is worth paying attention to.

I admit, the headline intrigued me too, both personally and professionally.  I wasn’t aware that one’s attitude towards aging would contribute to Alzheimers, since Alzheimers is predominantly genetic, and the other associated risk factors have more to do with physical health (like diabetes, high blood pressure etc).  Psychological stress is a risk factor for Alzheimers in mice, but good evidence in humans has been lacking [1].

So, does negative attitudes to aging really cause stress which then leads to Alzheimers as the report suggested, or is there a much better explanation?

The scientific article that the news reports were based on is A Culture-Brain Link: Negative Age Stereotypes Predict Alzheimer’s Disease Biomarkers [2].  This study was done in two stages.  Volunteers were recruited from a larger study called the Baltimore Longitudinal Study of Aging.  At entry point, the participants answered a questionnaire about their attitudes towards aging.  This was about 25 years before the participants were actively studied.

The first study examined the change in volume of a part of the brain called the hippocampus (which plays an essential part in our memory system).  The second part of the study examined the volunteers’ brains at autopsy for markers of Alzheimer Dementia, namely ‘plaques’ and ‘tangles’.  The number of plaques tangles were combined to form a single composite score, which was then compared to the baseline attitude towards aging score.

In the first study, the researchers reported that those people who held negative views of aging were more likely to have a smaller hippocampus which more rapidly decreased in size over time.

In the second study, the researchers reported that those people who held negative views of aging were more likely to have more plaques and tangles in their brain.

On the surface, this seems to suggest that people who hold negative views on aging contribute to the development of Alzheimer Dementia, and certainly this is how the different news agencies seemed to interpret the outcomes of the study.  Though on deeper palpation, a number of questions arise about how the researchers did the study and chose to interpret the results.

For example, the aging attitude survey was only done once, which means there’s a 25 year gap or longer between the questionnaire and the active studies. That’s a long time, and the attitudes of the volunteers may have improved or worsened in that time, but that doesn’t seem to have been considered

Levy and her researchers also report that the average size of the hippocampus changed significantly when they averaged the size of the left and the right hippocampus.  But when they analyzed the two sides separately, there was no significant change over time.  So this makes me wonder about the validity of their analysis too – if the volume of each side separately doesn’t change much at all, then how can the average volume of the two sides change so much?

I’m not much of a statistician, but I wonder if the secret’s in their modeling.  They used a linear regression model to compare their data to their hypothesis, a legitimate statistical method, but which involves adjustment for other variables.  If you do enough adjusting, you can get a significant result statistically, but according to their numbers, their Cohen’s d was 0.29, which is considered a weak effect overall.

Then there’s the question of clinical significance.  Even if the hippocampus did shrink in those who thought aging was negative two decades ago, was the shrinkage enough to contribute to the cognitive impairment seen in Alzheimer Dementia?  When compared to other studies, probably not.  Looking at Levy’s graph, the “negative” attitudes group changed about 150mm3 over the 10 year follow up period, or about 5%.  A recent study also showed that the the hippocampal size of subjects with mild memory loss is about 12% less than a healthy age matched control [3].

The same problems are seen in study 2 – Levy and her researchers reported an increase in the number of plaques and tangles in the “aging is bad” group.  But her numbers are small, and not statistically strong.  And again, the question of clinical significance arises.  Plaques and tangles represent biomarkers of Alzheimer Dementia, not necessarily a diagnosis.  Normal aging brains without dementia also have plaques and tangles, and it’s the number of tangles that seem more significant for developing cognitive impairment [4, 5], not the combined score that they used in this study.

And when all is said and done, all Levy and colleagues have shown is a correlation between attitude to aging and changes in the brain.  But correlation does not equal causation.  Just because two things are associated does not mean that one causes the other.  There maybe another variable or factor that causes both observations to co-occur.

In Levy’s case, the common connecting cause could easily be neuroticism, which they discussed as a co-variant but did not say if or how they corrected for it.  The other thing they did not examine in this study is the ApoE gene subtypes, which contribute significantly to the onset of Alzheimer Dementia [6].  The action of ApoE subtypes in the brain may contribute to both negative attitudes and Alzheimers changes?

The bottom line is that Levy’s study shows a weak correlation between a single historical sample of attitude towards aging, and some changes in the brain that are known to be markers for Alzheimer Dementia some three decades later.

They’ve certainly NOT shown that stress, or a person’s attitude to aging, in anyway causes Alzheimer Dementia.  They did not correct for genetics in this study which is the major contributor to the risk of developing Alzheimers.  So the results mean very little as it stands, and further research is required to delineate the cause and effect relationship here.

So don’t stress.  It’s not definitely proven that how you view the aging process determines your risk of dementia.  There will be those like Dr Leaf who will trot out this cherry-picked little titbit of information in the future to try and justify their pretense that thought can change our brain and impact our mental health, but what the press release says and what the study shows appear to be two different things altogether.

References

[1]       Reitz C, Brayne C, Mayeux R. Epidemiology of Alzheimer disease. Nat Rev Neurol 2011 Mar;7(3):137-52.
[2]       Levy BR, Slade MD, Ferrucci L, Zonderman AB, Troncoso J, Resnick SM. A Culture-Brain Link: Negative Age Stereotypes Predict Alzheimer’s Disease Biomarkers. Psychology and Aging 2015;30(4).
[3]       Apostolova LG, Green AE, Babakchanian S, et al. Hippocampal atrophy and ventricular enlargement in normal aging, mild cognitive impairment (MCI), and Alzheimer Disease. Alzheimer Dis Assoc Disord 2012 Jan-Mar;26(1):17-27.
[4]       Nelson PT, Alafuzoff I, Bigio EH, et al. Correlation of Alzheimer disease neuropathologic changes with cognitive status: a review of the literature. J Neuropathol Exp Neurol 2012 May;71(5):362-81.
[5]       Jansen WJ, Ossenkoppele R, Knol DL, et al. Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis. JAMA : the journal of the American Medical Association 2015 May 19;313(19):1924-38.
[6]       Liu CC, Kanekiyo T, Xu H, Bu G. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol 2013 Feb;9(2):106-18.

My patient, Kev

I meet a lot of people in my job. Some are not particularly memorable, and some I truly wish to forget. But every now and then, I meet a person who’s memorable for all the right reasons. Kev was one of those people.

Once upon a time, Kev was a business man, a corporate manager who started in the postal service in his late teens, but got more experience and moved into the Commonwealth Bank, where he quickly moved through their ranks and became a regional manager. Towards the end of his career, he moved industries to become the CEO of one of the smaller private hospitals in Brisbane in the 1980’s.

After he retired, his wife developed dementia, and he cared for her at home for many years, before he became too weak. They both moved into a nursing home, but his wife succumbed a couple of years later.

When I met Kev in early 2013, he was dying. His heart and his lungs were failing, and he couldn’t walk ten metres without gasping or needing oxygen. He was gaunt and frail, and extremely thin. I was worried that if he fell, he might snap.

But his intellect remained untouched by the disease ravaging the rest of his body. He was quick-witted, jovial, and always polite. He was the consummate professional – always showing respect, and earning it. I could see why he was so good as a businessman. He was a pleasure to be around – so much so that I spent extra time with him every week just chatting, when I should have been finishing off my work.

In the week before he died, the last time I saw him, as I sat in his room listening to some more of his stories, he looked me in the eye and said,

“Don’t sweat the small stuff. You don’t have to do everything. Let people flow in the things they can do. There are more important things in life.”

He smiled as he looked at the photos on his wall of his wife and kids.

I smiled and shook his hand. “I’ll see you later, Kev”, I said. I never did see him again.

I still remember him now, skinny and breathless, but with a big smile on his face and a sparkle in his eyes every time I entered his room. And I remember his advice on living a life driven by values.

New Years Day is a time to start afresh, a celebration of new beginnings, a focal point to take stock and refocus. But if we’ve learnt anything at all from our previous attempts at New Years resolutions, it is that they don’t work. Don’t be mislead by the occasional partial successes. I sometimes hit a golf ball straight, but that still doesn’t mean my golf swing is any good. New Years resolutions are the same – they are fundamentally flawed, in spite of the accidental successes that we sometimes have.

The truth is that etherial statements, or short term goals for self-improvement don’t help us. We don’t need New Years resolutions, we need New Years re-evaluations.

Values are different to goals. A goal is like a destination, where as a value is like a direction. Our individual values are like the direction of the breeze. It’s easier to sail with the breeze of our values than against it.

We often get goals and values confused. Goal orientation means that we move from place to place, sometimes travelling in the same direction as our values, but sometimes against them. When we live according to our values, the goals seem to set themselves as we live according to what we truly believe in, what truly motivates us.

A few things can acts as guides to help us learn what our values are. What are your passions or what makes you mad? Is it justice, or injustice? Is it relationships? Is it children, or family? The environment? What is it that gets your juices flowing?

Another way of understanding your values is to do the eulogy exercise. It’s a little morbid, perhaps. But simply, the eulogy exercise involves writing your own eulogy. What is it that you want others to remember you for? What do you want your epitaph to say?

The eulogy exercise helps us to plan our lives with the end in mind. When you’re on your death bed, will you regret not finishing that report, or will you regret whether you lived according to your values, your deepest desires. Putting your values into perspective makes it much easier to let things go that aren’t truly important. It’s a lesson I’m continually working at too.

May 2014, and the rest of your life, be about the important things. Don’t sweat the small stuff.

I hope you have a happy new year.

Cheers, Kev.

Autism Series 2013 – Part 2: The History Of Autism

“We can chart our future clearly and wisely only when we know the path which has led to the present.” Adlai E. Stevenson

I always thought history was boring, and I must admit, If you want to put me to sleep, start reading early Australian history to me. “Convicts … first fleet … zzzzzz.”

But as Stevenson wrote, the key to the future is the past. With autism, I don’t want to see a future as checkered as its past. In this series of essays, I want to help our community see a future in which autism is recognised and appreciated for its strengths. To properly lay the groundwork, I want to look at the history of autism. This will help provide context for the current understanding of autism, which will then give a framework for understanding the autistic person, and for a glimpse into the future as new research unfolds.

The autistic spectrum has been present for as long as humans have. But to our knowledge, one of the first specific descriptions of someone who met the characteristics of the autistic spectrum was in the mid 1700’s. In 1747, Hugh Blair was brought before a local court to defend his mental capacity to contract a marriage. Blair’s younger brother successfully had the marriage annulled to gain Blair’s share of inheritance. The recorded testimony describes Blair as having the classic characteristics of autism, although the court described him at the time as lacking common sense and being afflicted with a “silent madness”.[1]

Isolated case reports appeared sporadically in medical journals. John Haslam reported a case in 1809, although with modern interpretation, the child probably had post-encephalitis brain damage rather than true autism. Henry Maudsley described a case of a 13 year old boy with Aspergers traits in 1879. There were no other reports of children with autism in the early literature, although at the turn of the 19th century, Jean Itard reported on the case of an abandoned child found roaming in the woods like a wild animal. This child, called Victor, displayed many features of autism, although he may have simply had a speech disorder. Either diagnosis was obscured by the effects of severe social isolation.[1]

Others described syndromes which shared autistic features, but without describing autism itself. The names given to each syndrome reveals how autistic features were regarded in the 19th century: Dementia Infantalis, Dementia Praecocissima, Primitive Catatonia of Idiocy.[1]

Around 1910, Eugen Bleuger was a Swiss psychiatrist who was researching schizophrenic adults (and as an aside, Bleuger was the person to first use the term ‘schizophrenia’). Bleuger used the term ‘autismus’ to refer to a particular sub group of patients with schizophrenia, from the Greek word “autos,” meaning “self”, describing a person removed from social interaction, hence, “an isolated self.”[2]

But it wasn’t until the 1940’s that the modern account of autism was articulated, when two psychiatrists in different parts of the world first documented a handful of cases. Leo Kanner documented eleven children who, while having variable presentations, all shared the same pattern of an inability to relate to people, a failure to develop speech or an abnormal use of language, strange responses to objects and events, excellent rote memory, and an obsession with repetition and sameness[3].

Kanner thought that the condition, which he labelled ‘infantile autism’, was a psychosis[1] – in the same family of disorders as schizophrenia, although separate to schizophrenia itself[2]. He also observed a cold, distant or anti-social nature of the parents relationship towards the child or the other parent. He thought this may have contributed (although he added that the traits of the condition were seen in very early development, before the parents relationship had time to make an impact)[3]. True to the influence of Freud on early 20th century psychiatry, Kanner said of the repetitive or stereotyped movements of autistic children, “These actions and the accompanying ecstatic fervor strongly indicate the presence of masturbatory orgastic gratification.”[3]

Despite the otherwise reserved, cautious discussion of possible causes of this disorder, the link with schizophrenia and “refrigerator mothers” took hold in professional and lay communities alike. In the 1960s and 70s, treatments for autism focused on medications such as LSD, electric shock, and behavioral change techniques involving pain and punishment. During the 1980s and 90s, the role of behavioral therapy and the use of highly controlled learning environments emerged as the primary treatments for many forms of autism and related conditions.[2]

Unbeknown to Kanner, at the same time as his theory of ‘infantile autism’ was published in an English-language journal, a German paediatrician called Hans Asperger published a descriptive paper of four boys in a German language journal. They all shared similar characteristics to the descriptions of Kanner’s children, but were functioning at a higher level. They shared some aggression, a high pitched voice, adult-like choice of words, clumsiness, irritated response to affection, vacant gaze, verbal oddities, prodigious ability with arithmetic and abrupt mood swings. Asperger was the first to propose that these traits were the extreme variant of male intelligence[4].

But the full impact of Asperger wasn’t felt until 1981, when British psychiatrist Lorna Wing translated Aspergers original paper into English. By this time, autism had become a disorder of its own according to the DSM-III, the gold-standard reference of psychiatric diagnosis, but it was still largely defined by the trait of profound deficit. Aspergers description of a ‘high-functioning’ form of autism resonated amongst the autism community, and a diagnosis of Aspergers Syndrome became formally recognised in the early 1990’s with the publication of the DSM-IV.

The most recent history of autism comes in two parts. The first was the revision of the DSM-IV. For the first time, rather than two separate diagnoses, Autism and Aspergers have been linked together as a spectrum and collectively known as the Autism Spectrum Disorders (although autism self-advocates prefer the term ‘conditions’ to ‘disorders’).

The second part is a highly controversial chapter that will stain the history of autism research and scientific confidence, into the next few decades. Chris Mooney, in a piece for Discover Magazine, sums it up nicely:

“The decade long vaccine-autism saga began in 1998, when British gastroenterologist Andrew Wakefield and his colleagues published evidence in The Lancet suggesting they had tracked down a shocking cause of autism. Examining the digestive tracts of 12 children with behavioral disorders, nine of them autistic, the researchers found intestinal inflammation, which they pinned on the MMR (measles, mumps, and rubella) vaccine. Wakefield had a specific theory of how the MMR shot could trigger autism: The upset intestines, he conjectured, let toxins loose in the bloodstream, which then traveled to the brain. The vaccine was, in this view, effectively a poison.”[5]

Inflamed by a post-modern distrust of science and a faded memory of what wild-type infectious diseases did to children, the findings swept through the internet and social media and lead to a fall in vaccination rates (from about 95% to below 80% at its lowest)[6].

But the wise words, “Be sure your sins will find you out”, still hold true, even in modern science. In 2010, Wakefield was found guilty of Serious Professional Misconduct by the British General Medical Council, and was struck off the register of medical practitioners in the UK. In the longest ever hearing into such allegations, the GMC considered his conduct surrounding the research project, the medical treatment of his child subjects, and his failure to disclose his various conflicts of interest to be dishonest and professionally and clinically unethical[7]. There is evidence that he also selectively chose his subjects to confound the results, misrepresented the time course of their symptoms related to the vaccinations, misrepresented their diagnosis of autism, and altered the reports of their bowel tests[8, 9].

For the record, this isn’t a comment on the science of Wakefield’s rise and fall, but the history. I am not suggesting that the proposed autism/vaccination link should be discounted solely on the basis of Wakefield’s scientific fraud. Rigorous science has already done that. The science for and against the proposed link between autism and vaccinations deserves special attention, and will be discussed in a future post. Rather, lessons need to be learned from what is one of the most destructive cons in the recent history of medicine.

The losers of this hoax are twofold. Thousands of children have unnecessarily suffered from preventable infectious disease because of a fear of vaccines that has turned out to be unfounded, and those who actually have autism miss out on actual funding because it was syphoned off into Wakefield’s pockets and into research disproving his rancid theory. As the editorial in the BMJ stated, “But perhaps as important as the scare’s effect on infectious disease is the energy, emotion, and money that have been diverted away from efforts to understand the real causes of autism and how to help children and families who live with it.”[6]

As with all good history, there are lessons for the future. Autism is still largely misunderstood. The vacuum of definitive scientific knowledge is slowly being filled, gradually empowering people with autism and the people that interact with them to truly understand and communicate. Each breakthrough and revision of the diagnosis has lead to more sophisticated and more humane ways of living with autism. But there is still a need for caution – people will use the gaps in knowledge and the pervasive distress that can come from the diagnosis, to manipulate and exploit for their own ends.

I’ll continue with the series in the next week or so, looking at the modern “epidemic” of autism.

REFERENCES:

1. Wolff, S., The history of autism. Eur Child Adolesc Psychiatry, 2004. 13(4): 201-8.
2. WebMD: The history of autism. 2013  [cited 2013 August 14]; Available from: http://www.webmd.com/brain/autism/history-of-autism.
3. Kanner, L., Autistic disturbances of affective contact. Acta Paedopsychiatr, 1968. 35(4): 100-36.
4. Draaisma, D., Stereotypes of autism. Philos Trans R Soc Lond B Biol Sci, 2009. 364(1522): 1475-80.
5. Mooney, C., Why Does the Vaccine/Autism Controversy Live On?, in Discover2009, Kalmbach Publishing Co: Waukesha, WI.
6. Godlee, F., et al., Wakefield’s article linking MMR vaccine and autism was fraudulent. BMJ, 2011. 342: c7452.
7. General Medical Council. Andrew Wakefield: determination of serious professional misconduct, 24 May 2010. http://www.gmc-uk.org/Wakefield_SPM_and_SANCTION.pdf_32595267.pdf
8. Deer, B., How the case against the MMR vaccine was fixed. BMJ, 2011. 342: c5347.
9. Deer, B., More secrets of the MMR scare. Who saw the “histological findings”? BMJ, 2011. 343: d7892.