Insulin resistance in the brain: an old-age or new-age problem?

Life expectancy is rising however with more people living longer there is a concomitant rise in the incidence of dementia. In addition to age-related cognitive decline there is a higher risk of going on to develop vascular dementia and Alzheimer's disease associated with aspects of modern lifestyle. Most worryingly, recent data reports accelerated cognitive decline in adolescents associated with poor diet (high fat and calorie intake). Thus the increase in dementia in 'old-age' may have as much to do with 'new-age' lifestyle as it does with normal ageing. It would seem wise therefore to investigate the molecular connections between lifestyle and cognitive decline in more detail. Epidemiological evidence suggests an increased risk of developing dementia (including Alzheimer's disease) in individuals with obesity and type 2 diabetes but also in those with poor insulin sensitivity without diabetes, implicating a mechanistic link between adiposity, insulin sensitivity and dementia. Insulin receptors are expressed in the brain and physiological roles for insulin in the CNS are starting to be delineated. Indeed disrupted neuronal insulin action may underlie the link between diabetes and neurodegenerative disorders. This review discusses the difficulties in quantifying insulin sensitivity of the brain and why it is vital that we develop technology for this purpose so that we can establish its role in this 'new-age' dementia. This has particular relevance to the design and interpretation of clinical trials in progress to assess potential benefits of insulin and insulin sensitisers on prevention of cognitive decline.