Hippocampal damage and memory impairments as possible early brain complications of type 2 diabetes

Abstract

Aims/hypothesis There is evidence that type 2 diabetes mellitus is associated with cognitive impairment. Most studies investigating this association have evaluated elderly individuals, after many years of diabetes, who generally have poor glycaemic control and significant vascular disease. The aim of the current study was to investigate the early cognitive consequences and associated brain correlates of type 2 diabetes. Materials and methods With regard to cognition and brain measures, we compared 23 age-, sex-and educationmatched control subjects with 23 mostly middle-aged individuals with relatively well-controlled diabetes of less than 10 years from the time of diagnosis. Results We found deficits in hippocampal-based memory performance and preservation of other cognitive domains. Relative to control subjects, individuals with diabetes had reductions in brain volumes that were restricted to the hippocampus. There was an inverse relationship between glycaemic control and hippocampal volume; in multivariate regression analysis, HbA 1c was the only significant predictor of hippocampal volume, accounting for 33% of the observed variance. Other variables commonly associated with type 2 diabetes, such as elevated BMI, hypertension or dyslipidaemia, did not independently contribute to the variance in hippocampal volume. Conclusions/interpretation These results suggest that the medial temporal lobe may be the first brain site affected by type 2 diabetes and that individuals in poorer metabolic control may be affected to a greater extent.

Region-Specific Cerebral Metabolic Alterations in Streptozotocin-Induced Type 1 Diabetic Rats: An in vivo Proton Magnetic Resonance Spectroscopy Study

“…All these clinical findings suggested that the basal ganglia and temporal lobe are more vulnerable to hyperglycemia-related injuries, while occipital lesions may occur only as a secondary effect of microangiopathy or DR. 34 There are results in the literature suggesting this may also be true for T2DM. 35 The regional-specific metabolic alterations in the brain of STZ-treated animals found in this study are consistent with this notion.…”

Short-Term High-Fat-and-Fructose Feeding Produces Insulin Signaling Alterations Accompanied by Neurite and Synaptic Reduction and Astroglial Activation in the Rat Hippocampus

“…In a previous study, a reduction of hippocampal volume in patients with type-2 diabetes mellitus was reported, while total brain weight remains unaffected, suggesting that the hippocampus High-fat diet decreases hippocampal insulin signaling E Calvo-Ochoa et al presents a particular sensitivity to metabolic diseases. 32 The decrease that we observed in hippocampal weight was not accompanied by evident changes in the area or the general appearance of the hippocampal layers, as showed by the conventional Nissl staining. At this point, it is unclear whether all the hippocampal morphologic changes due to HFFD that we observed are the sole responsible for the reduction of weight in the hippocampus, or other mechanisms such as tissue dehydration, a modification in the composition of the membrane lipids and cholesterol levels, etc.…”

Diet‐induced insulin resistance impairs hippocampal synaptic plasticity and cognition in middle‐aged rats

“…Diets high in refined sugars and saturated fats increase the risk of type 2 diabetes (Everitt et al, 2006), and individuals with poorly controlled diabetes frequently exhibit impaired cognitive function (Gold et al, 2007). We recently demonstrated that some aspects of diabetesinduced hippocampal dysfunction are mediated by adrenal corticosteroids (Stranahan et al, 2008).…”