More evidence that insulin plays a role in the development of dementia

Last month one of my posts was devoted to some research which found a link between weight accumulation around the mid-riff (abdominal obesity) and an increased risk of dementia. In this post, I also explored some of the mechanisms which might explain this association. At the heart of these suggested mechanisms is the hormone insulin. As I wrote in the post, high levels of insulin may possibly increase the production of a substance called ‘amyloid beta’ which is found in the brains of individuals with Alzheimer’s disease. Also, impaired glucose tolerance (difficulty handling sugar in the system) and its potential end result – type 2 diabetes – have been linked with reduced mental functioning through a variety of other mechanisms.

I reckoned at that time that the available evidence suggests that insulin may indeed play a role in the development of dementia and cognitive decline, and I advised individuals wanting to protect themselves from such issues to get control over blood sugar and insulin levels. In general terms, this means eating a diet low in foods that tend to disrupt blood sugar control such as most forms of bread, potato, rice, pasta and breakfast cereals.

Since I wrote that post, more evidence has come to light which suggests that blood sugar and insulin metabolism may be a key underlying process in dementia.

The research, published on-line this week in the journal Neurology, assessed about 2300 Swedish men [1]. At age 50, these men underwent a ‘glucose tolerance test’ (they were ‘dosed’ with glucose and their insulin and sugar levels were monitored subsequently). The men were assessed again at 70 and 82 years of age for a variety of things including presence of Alzheimer’s disease and what is known as ‘vascular dementia’ (dementia caused by problems with the circulation to the brain).

Analysis of the data collected in this study revealed two main things:

1. Impaired glucose tolerance was associated with a significantly increased risk of vascular dementia.

2. A ‘blunted’ insulin response (thought by the authors to be a sign of inadequate insulin secretion) was found to be associated with an increased risk of Alzheimer’s disease.

Finding number 1 is in keeping with previous work mentioned above and in my previous blog last month. However, finding 2 is not.

Just to recap, I previously suggested that HIGH levels of insulin may lead to high levels of amyloid-beta in the brain and therefore enhanced risk of Alzheimer’s disease. This more recent study, if anything, found that LOW insulin levels were associated with an increased Alzheimer’s disease risk.

Reading in the paper in search of an explanation I discovered that the authors reference previous work that has found a U-shaped association between insulin levels and Alzheimer’s disease risk [2]. In other words, both relatively high and low levels of insulin are linked with an increased risk of this condition.

Risk of Alzheimer’s disease is believed to be partly genetically determined. One risk factor appears to be the presence of something known as APOE E-4 in an individual’s genetic makeup.

The relationship between lowered insulin response and enhanced Alzheimer’s disease risk was only found in individuals without APOE E-4 (i.e. those at generally low risk). On the other hand, in individuals WITH APOE E-4 (generally high risk individuals), HIGHER insulin levels were associated with INCREASED risk.

Making sense of this is not easy, as it seems that the relationship between insulin and risk of Alzheimer’s disease is partly dictated by genetic factors and quite complex.

Nevertheless, whatever one’s genetic make-up, it seems that optimising insulin levels (not too high, not too low) makes sense for those seeking to reduce the risk of Alzheimer’s disease and dementia. One strategy here (again) is to ensure the diet is low in foods which disrupt blood sugar. This should help, for obvious reasons, to keep insulin levels from rising too high. Such a diet may also, as it happens, reduce the risk of ‘exhaustion’ of the cells in the pancreas that make insulin (known as the ‘beta’ cells). So this diet should reduce the risk of insulin levels getting too low too.

References:

1. Ronnemaa E, et al. Impaired insulin secretion increased the risk of Alzheimer disease. Neurology. 9th April 2008 [epub ahead of print]

2. Peila U, et al. Fasting insulin and incident dementia in an elderly population of Japanese-American men. Neurology 2004;63:228-233

10 Responses to More evidence that insulin plays a role in the development of dementia

  1. Jenny Ruhl 11 April 2008 at 11:54 pm #

    I just blogged about this on my blog, too. I was confused as to whether they had measured insulin output or just estimated it based on the results of the intraventous glucose tolerance test.

    I don’t have access to the full text of the article. Did you see it? And if so, did they measure the actual insulin output to see if people were truly insulin deficient?

  2. Dr John Briffa 12 April 2008 at 6:10 am #

    Jenny
    Insulin was directly measured in this study.

  3. Jenny Ruhl 12 April 2008 at 1:01 pm #

    Thanks. Do you think that the damage is actually caused by low insulin, or by the very high blood sugars that result when people are insulin deficient.

    This was a population who were diabetic for decades BEFORE DCCT suggested there were benefits to lowering blood sugar even to the relatively high 7% A1c level. So it is safe to assume their blood sugars were at toxic levels for 30+ years.

    Even now, most doctors consider 7% to be a safe blood sugar and won’t start treating patients until the A1c is over 8%, though both these blood sugar levels are high enough to cause major organ damage all over the brain.

    I do wish these studies would map these possible diabetic complications to actual blood sugar levels rather than a diagnosis.

  4. rm 12 April 2008 at 4:46 pm #

    Dr. in the introduction to the article above and in other advice on diet you make remarks suggesting a “diet low in ‘disruptive’ carbs including many forms of bread, potato, rice, pasta and breakfast cereal. I am left wondering about the rice. Are all forms of rice (processed, whole, organic, varietals) included? Of course I am hoping you will say only “white” rice. Also as many pastas are now made from soy, rice and other sources does this mitigate your advice. rm

  5. Peter Deadman 13 April 2008 at 6:41 am #

    The problem with low carb diets is that carbohydrates have formed – and still form – the foundation of most human diets. Common sense would suggest that we have adapted to them. And the implications of suggesting low carb diets to that large proportion of humans who have limited alternative food sources are profound.

  6. Dr John Briffa 13 April 2008 at 8:09 am #

    Jenny
    “Do you think that the damage is actually caused by low insulin, or by the very high blood sugars that result when people are insulin deficient.”
    Of these options, I reckon the later is more likely.
    RM
    There are variations in the GI across varieties of rice and pasta (see 6. Foster-Powell K, et al. International tables of glycemic index. Am J Clin Nutr 1995;62(suppl);871S—93S for details). However, generally speaking, bearing in mind the quantity such foods tend to be eaten in, they are disruptive to blood sugar and insulin. Also, though this is somewhat off-topic, just because a food has a lower/low GI, that doesn’t mean it’s a ‘healthy’ food.
    Peter
    Can you be a bit more specific about what you mean by “carbohydrates have formed – and still form – the foundation of most human diets.” In particular, can you detail your understanding of our diet throughout evolution (assuming you believe in evolution), and what appears to have made up our diet and the evidence for this?

    Could you also perhaps tell us your understanding of the timing of the introduction of grains into the diet, and the potential consequences of that bearing in mind the generally slow, creeping nature of evolutionary adaptation.

    And could you also perhaps share some of your knowledge of the impact grain foods have on blood sugar balance and insulin secretion, and what implications you feel this has for health (whatever evolutionary theory states)?

  7. helen 13 April 2008 at 10:53 pm #

    well they don’t call sugar “the white death” for nothing. It’s main function in cooking (I bet you think it is to make things sweet) well it is a binder it makes things nice and sticky. Think of toffee, jam, cakes caramel, fairyfloss (cotten candy) etc try making these things without sugar the results are less than average, oh you can make a reasonable replication of these things but there is always something lacking in the texture. Just think about the clogging sticky mess sugar produces when added to liquids & heated a little & you can get the picture. Where as fat only clogs if it is cold & even then it has a nice slippery texture not so sugar. Is it any wonder sugar disrupts the production of hormone insulin in your body when you eat too much of the sticky sweet stuff. Your body only needs a teaspoon of sugar in the blood at any one time, in fact sugar is a toxin to the body that causes damage to the cells and allows them to mutate (they actually grow cancer cells in sugar cultures, doesn’t that tell you anything? It has been well known in medical circles for decades that sugar feeds cancer.) & insulin’s job is to regulate sugar in the blood so that it doesn’t get to dangerous levels. So over many years of injesting copious amounts of sugar making your pancreas work overtime continuously to get rid of the sugar in your blood is it any little wonder that things break down. Sugar we can all live without it and as for the other “white” carbohydrates that turn into sugar when you eat them we can do without those in our diets too. They only make profits for the big agri groups & pharmaceuticals because they make us sick which gives them a market to flog their so called “cures” to.
    So too much insulin is the direct cause of too much sugar in the diet guess what we should cut out of our diets to combat this the so called experts tell us – saturated fat. Now doesn’t that make a lot of sense? NOT !!

  8. Peter Deadman 18 April 2008 at 9:18 am #

    Hi John

    Food riots at the moment seem to be about bread or rice – staple foods for much of the world, plus maize in South America, and – traditionally – oats and potatoes in Northern Europe. I would imagine that the move to these foods more or less coinicided with the development of settled communities and agriculture.
    I believe that dietary recommendations need to be ethical & practical, so, for example, I would deem something like the Atkins diet to be neither since it is unfeasible for more than a small proportion of the world to follow. I don’t see how the world can be fed without maintaining the primacy of these staples.
    You are the nutritionist and I would not like to engage in debate on that aspect, although my understanding is that whole grain foods tend to have slow release effects on blood sugars.

    best

    Peter

  9. John Briffa 21 April 2008 at 1:11 pm #

    Peter

    “I would imagine that the move to these foods more or less coinicided with the development of settled communities and agriculture.”

    I think that’s true, but this was about 10,000 years ago — which is very recent from an evolutionary perspective (I’m assuming that you’re not a Creationist, Peter).

    “I believe that dietary recommendations need to be ethical & practical, so, for example, I would deem something like the Atkins diet to be neither since it is unfeasible for more than a small proportion of the world to follow.”

    Lower/low/controlled carb does not necessarily mean eating a la Atkins (this is a common misconception and is often used to discredit the approach).

    And I’m aware of how ‘politically incorrect’ some of the nutritional notions put forward on this site are. But I’m not in the business of political correctness, but of giving people the best health advice and information I can. I don’t see me condoning and even recommending quite crappy food for the sake of political correctness helps anyone in particular. Though for some people I accept that it’s better to eat, say, rice or corn, than nothing at all.

    “You are the nutritionist and I would not like to engage in debate on that aspect, although my understanding is that whole grain foods tend to have slow release effects on blood sugars.”

    Many grains are highly disruptive to blood sugar and insulin levels, including some wholegrain ones (e.g. most wholemeal breads). Plus, they’re really not as ‘nutritious’ as many claim them to be.

    The reality is there are plenty of good reasons not to ram the diet full of these foods. To do so jeopardises health, I reckon. Whatever another’s World view may be, I couldn’t recommend such foods and live with myself.

  10. John A. LeRoy 4 November 2012 at 12:54 am #

    insulin controls the access of sugar to the cells.Within the cell the molecule of sugar is chemically reduced in a controlled process, releasing energy pulses. The pulses activate the DNA by switching on the appropriate gene(s) via the responsive RM nucleotides. Without a controlled function the cell is inefficient. The protein injected into the connecting synapses between cells to allow incoming messages (energy pulses) to be downloaded to action cells (Neurons) is normally demolished and recycled by supporting cells, allowing the cognitive cells to be once again freed up for further action. On lose of efficiency of these cells due to several reasons i.e. low levels of potassium, low insulin resulting in reduced energy availability, with ageing of these involved cells also playing a part the protein builds up in an uncontrolled manner, chocking and damaging the cognitivelly involved cells. Hence loss of cognitive function, but retention of long term memories, i.e. Alzheimers etc.

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