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

Posted Sep 12 2008 12:05pm
Posted on 11 April 2008

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.


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

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