Do refined carbohydrates, glycemic index, subclinical hypothyroidism, and insulin resistance contribute to the brain senescence of subjective cognitive decline in aging in man and animals? Here is what the lab rats are saying

Abstract

The onset and progression of subjective cognitive decline (SCD) in aging typically occurs gradually over an extended duration, often escaping recognition by friends and family during the early stages of the disorder. The incidence of SCD in developed counties, where the abundant consumption of refined carbohydrate sources is also commonplace, is virtually staggering, currently approaching over 10% of the population over age 45 with no definitive end in sight.1 The development of SCD has been associated with factors of socioeconomic, educational, metabolic and pathophysiological comorbidities, including diet and impaired insulin sensitivity common to obesity, Type 2 and 3 diabetes (T2DM; T3DM). While early intervention is preferable for the treatment of many illnesses and disorders, effective remedies for the senescence of aging and SCD remain a challenge for the practicing clinician, in part because the metabolic and nutritional factors which initiate the process remain largely unclear. The development of symptoms consistent with subclinical hypothyroidism (SCHT) are also commonplace among the aged. The independent contributions of thyroidal dysregulation and insulin resistance to dysregulation of energy balance, although strongly linked, some aspects remain unclear and incompletely known. Several
recent studies have now associated obesity and insulin resistance (IR) to brain senescence in aging congenic obese rats. Several studies also support a link between chronic hyperinsulinemia, epigenetic expression of obesity, brain shrinkage and decreased brain protein and cellular deoxyribose nucleic acid (DNA) content in a congenic rodent model of early onset obesity.

Aging congenic obese LA/Ntul//-cp rats develop obesity and hyperinsulinemia soon after weaning regardless of diet and which pathophysiologic stigmata persist throughout their lifespan. The stigmata of insulin resistance may become further aggravated when fed a high glycemic index diet. Groups of lean and obese rats were fed USDA-formulated nutritionally complete isoenergetic diets continuing cornstarch (ST) or sucrose (SUC) asthe only carbohydrate source from weaning until 10.5 months of age. Longevity of obese << lean in both sexes. Obese rats were found to exhibit SCHT and decreased brain mass associated with IR, and accompanied with proportionate decreases in brain lipid, protein and DNA content in the obese but not the lean phenotype. In addition, the decreases in brain mass, protein and DNA composition were of greater magnitude when fed the SUC vs the ST diets in both phenotypes. These observations are suggestive of an increased potential for a contribution of the metabolic sequelae of insulin resistance as a pathophysiologic factor in the progression of brain shrinkage and presumed cognitive decline in the aging obese, hyper insulinemic rat, analogous to clinical observations which may occur in senescence, dementia and Alzheimer’s disease in aging populations and implicate the glycemic index of the refined carbohydrate source as a contributory factor.