Mark R. Cobain a, John P. Foreyt b, a Unilever Corporate Research, Colworth House, Sharnbrook, Bedfordshire MK46 4AA, UK
The central hypothesis examined in this issue is that insulin resistance promotes maladaptive brain function and contributes to reduced neuronal plasticity, potentially accelerating brain aging. Therefore, if we were to prevent or treat insulin resistance, through weight loss and exercise, cognitive function would be improved. In this article, we argue that successful interventions influencing these outcomes depend upon overriding maladaptive neurobiology. This maladaptation may have developed over the course of the lifespan through interaction with modern environments. Furthermore, we emphasize the need to take this emergent neurobiology into account when designing interventions.
The need for lifestyle interventions
Whilst debate continues about the role of insulin sensitivity in age-related cognitive impairment, it is of note that the benefits of intervening in insulin resistant individuals have already been demonstrated in terms of reduced diabetes risk. A program of 150 min of physical activity per week and 7% body weight loss resulted in a 58% reduction in the incidence of new cases of type 2 diabetes in “at risk” individuals . Therefore, physical activity, dietary change and weight loss are already deemed important for successful aging and avoidance of disease. However, large scale interventions, such as the diabetes prevention program (DPP), are not easily translated into everyday life. The impressive results were in part due to the intensive coaching and social support administered throughout the trial enabling compliance with appropriate health behaviors. So why is it so difficult to change health behavior at the individual level? Are neurobiological mechanisms responsible? How do we try to overcome these difficulties in interventions and how might these be translated at the community level? The brain as a mediator of successful behavior change? There is evidence to suggest that those who most need to make these changes for health reasons may actually have lower cognitive resources to cope with the demand. A number of studies have shown that people under chronic stress gain weight over time  and psychological distress and impaired mental performance can result from restricting dietary intake of calories and preferred foods . A number of studies provide evidence that maladaptive neural systems may underpin these phenomena. Unhealthy food choices in stressful situations have been shown to be accompanied by a hyper-responsive HPA axis . Furthermore, PET studies have demonstrated that although obese individuals can successfully lose weight, abnormal neural responses to food intake still persist in structures responsible for autonomic control of digestion and emotional centers  and after a prolonged fast, obese subjects display heightened neural activity in the gustatory cortex when given a liquid meal . These persistent brain changes may be the result of a cumulative life history of overweight or obesity, making voluntary changes in diet and exercise extremely difficult. In combination with environments that are rich in energy dense foods these biological drives become hard to resist, potentially creating a vicious cycle. Obesity, hypertension , and impaired glucose tolerance  have been associated with poor cognitive performance. The unifying feature to all of these conditions may be insulin resistance, which through a variety of mechanisms (reviewed in this issue) may influence cognitive performance. The question remains as to whether obesity and insulin resistance are states that compromise cognitive performance or that reduced cognitive ability predisposes an individual to obesity and insulin resistance. Nevertheless, we should still consider psychological factors as important in interventions. Without this, our interventions will not succeed, as many high profile “information” campaigns have not had the desired effect. Investigation of the baseline psychological profile of DPP participants highlighted a need to teach “dietary restraint skills”, strategies to “reduce binge eating” and prevent the participant from “fantasizing about favorite foods” . These are factors that clearly go beyond peripheral satiety and highlight the fact that lifestyle change is stressful, demanding, and likely influenced by the integration of multiple signals in the brain associated with reward, satiety, and habit. So, how do studies like the DPP  and the Look AHEAD study , which is an ongoing, long-term multi-site weight loss trial, manage individuals to maintain health behaviors?