Professor Velandai Srikanth
There is very good evidence from longitudinal or long term large studies - more than ten such studies have been performed until now - confirming that type two diabetes is associated with a twofold increase in the risk of dementia. More recently, there have been large studies performed in the United States confirming that type one diabetes is also associated with an increased risk of dementia, in a similar twofold increase in the risk of dementia.
So type one diabetes is an important disease, affecting mainly younger people, and in such people, there is difficulty in controlling their blood sugar within a good range of blood sugar, with the treatments that we have. They are more prone to have very low blood sugar, and those people who have more than one episode of low blood sugar can have damage to brain cells or the white matter, which is the wiring connecting brain cells. Annually, about 30% of people with type one diabetes have low blood sugar episodes or hypoglycemia. Any more than four such episodes in a year can be associated with a very high risk of cognitive impairment, or slowing of brain function, and, as such people get older, it is possible that this reduction in cognitive function lowers their brain capacity to withstand other insults to the brain. So, as they get older, they become more prone to the risk of dementia.
Type two diabetes can increase the risk of dementia by affecting health of blood vessels in the brain and the health of neurons, which are the brain cells. In type two diabetes, the cells of the brain are resistant to the action of insulin, and insulin is quite an important chemical in the brain to allow other chemicals to talk between cells. So this might be one way in which type two diabetes affects cognitive function. Another way insulin can be important is to affect the transport of a substance called beta amyloid, which is known to be important for the development of Alzheimer’s Disease. So insulin resistance in cells of the brain can, theoretically, be involved in the deposition of plaques in the brain due to beta amyloid.
In people with type two diabetes, we found that the levels of a protein called tau is increased in the spinal fluid of patients. Tau is an important protein for neuronal health and, if we find increased levels in spinal fluid, it means that nerve cells are being damaged. It is possible that diabetes causes a low grade chronic inflammation in nerve cells, and this might provoke their death.
So, in summary, the effects of type two diabetes on the brain can be a combination of causes. It can be due to the effects of vascular disease and also due to the effect of neuronal death, or what we call neurodegeneration. Although Alzheimer’s Disease is associated with the development of amyloid plaques, it is not clear whether diabetes is a provocative factor in the development of plaque definitely, and further research or investigations are currently happening to try and work this problem out. While type two diabetes increases the risk of dementia overall, it is not clear whether everyone with type two diabetes will develop dementia, and we’re trying to work out in our research who might be more prone to do so.
Pre-diabetes is an important condition that’s been recognised in the last 10 years or so. When we diagnose diabetes, we require a plasma or blood glucose level of 7 millimoles or greater. It has now been recognised that people with blood levels of glucose of about six millimoles are also at risk of complications of diabetes, and will be developing diabetes within the next 10 years. The important thing about pre-diabetes is that it is a preventable condition. Now more recently, studies from the United States have shown that those with pre-diabetes can be at fourfold risk of dementia in the future. Mechanisms by which this might occur are not quite clear, but it is important to realise that, if we treat and prevent diabetes - exercise and diet are important interventions that can help people with pre-diabetes and stop them from developing diabetes in the future - it is possible that such lifestyle interventions can also reduce the risk of dementia in such people.
In people who have pre-diabetes or diabetes, attending your practitioner or specialist on a regular basis, having your medications regularly, making sure that your blood sugar is well controlled but not too aggressively controlled, making sure that your blood pressure is treated effectively and your cholesterol levels are watched carefully; all these things could have an impact on your future health and the risk of dementia, possibly by reducing the risk of vascular disease going into the future.