Insulin Resistance and Alzheimer-like Reductions in Regional Cerebral Glucose Metabolism for Cognitively Normal Adults With Prediabetes or Early Type 2 Diabetes

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Abstract
Insulin modulates numerous physiological actions in the periphery and central nervous system that are related to late-life neurodegenerative disease, including glucose metabolism, vascular function, synaptic maintenance, β-amyloid (Aβ) regulation, and tau phosphorylation.1 Insulin resistance, a condition characterized by an insufficient response to insulin in target tissues, is a causal factor in prediabetes (PD) and type 2 diabetes (T2D) and also increases the risk of developing Alzheimer disease (AD).1 Reductions in regional cerebral glucose metabolic rate (CMRglu) as measured by fludeoxyglucose F 18–positron emission tomography (FDG-PET) are also associated with increased AD risk and can be observed years before dementia onset.2,3 A recent large study comparing FDG-PET patterns in cognitively normal adults and adults with prodromal AD (amnestic mild cognitive impairment [MCI]) demonstrated lower CMRglu in posterior cingulate, precuneus, parietotemporal, and frontal cortices.4 Similar patterns have been reported in cognitively normal carriers of the apolipoprotein E ε4 allele (APOE ε4) AD risk factor.5