It is increasingly evident that ‘peripheral’ diseases, including various metabolic diseases and chronic inflammation, can adversely affect the brain, either causing or exacerbating neurodegeneration. For example, chronic metabolic/inflammatory disease states have been associated with increased risk of conditions such as Alzheimer’s and Parkinson’s diseases (AD and PD, respectively), as well as greater severity of deficits. For example, three major studies suggest that mid-life adiposity is associated with increased risk of developing PD. In the first of these, Abbott et al. showed that, amongst 7990 men in the Honolulu Heart Project, those with the lowest triceps skinfold thickness, subscapular skinfold thickness and BMI at baseline had an increased risk of developing PD during a 30-year follow up.1 In the second, greater waist circumference and waist-to-hip ratio were associated with increased risk of PD among never smokers in the combined follow-up to the Health-Professionals study, and the Nurses’ Health Study.2 Finally, amongst nearly 50,000 Finnish men and women, the risk of developing PD was higher in those patients with baseline BMI >23 during an 18.8 year follow-up.3
This link…show more content… Chronic over nutrition produces oxidative stress and inflammatory responses, which can lead to damage in the central nervous system, affecting neurons and neural stem cells (NSCs). Dysregulation of the various pathways shown here can generate feedback loops, which amplify these adverse effects. Schematic adapted from6.
Besides these possible direct causes of neural damage, evidence suggests that chronic metabolic/inflammatory conditions can affect the major immune component of the CNS, the microglia, thereby causing adverse events to other neural cell types. The mechanisms, by which these peripheral diseases affect microglia, and the specific subsequent microglial responses, are not understood.
3 PERIPHERAL METABOLIC DISORDERS MAY AFFECT THE BRAIN’S IMMUNE CELLS: