and Sutherland, C., Insulin resistance in the brain: an old-age or new-age problem

Biomedical Research Institute, University of Dundee, UK.
Biochemical pharmacology (Impact Factor: 5.01). 05/2012; 84(6):737-45. DOI: 10.1016/j.bcp.2012.05.007
Source: PubMed


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.

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    Aging and Disease 08/2015; 6(4):282-99. DOI:10.14336/AD.2014.002 · 3.07 Impact Factor
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    • "High fat and calorie intakes not only lead to metabolic disorders but could also accelerate age-related cognitive decline (Williamson et al., 2012; Fadel et al., 2013). Epidemiological studies suggest that type 2 diabetes and obesity increase the risk of dementias (Williamson et al., 2012). Stress exposure over the lifespan may also accelerate cellular aging and promote cognitive dysfunction (Lupien et al., 2009; O'Donovan et al., 2013). "
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    Frontiers in Aging Neuroscience 04/2014; 6(81). DOI:10.3389/fnagi.2014.00081 · 4.00 Impact Factor
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    • "Insulin resistance also occurs in the brain and there are insulin receptors in the hippocampus, where, similar to leptin, insulin is also involved in signaling pathways that modulate synaptic plasticity (Messier & Teutenberg, 2005). This is consistent with the reductions in learning and memory and hippocampal atrophy that have been observed in insulin-resistant diabetic patients (Craft, 2009; Williamson, McNeilly, & Sutherland, 2012; Xu et al., 2010). "
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