Imaging of brain glucose uptake by PET in obesity and cognitive dysfunction: life-course perspective

Abstract

The prevalence of obesity has reached epidemic proportions and keeps growing. Obesity seems implicated in the pathogenesis of cognitive dysfunction, Alzheimer’s disease and dementia, and vice versa. Growing scientific efforts are being devoted to the identification of central mechanisms underlying the frequent association between obesity and cognitive dysfunction. Glucose brain handling undergoes dynamic changes during the life-course, suggesting that its alterations might precede and contribute to degenerative changes or signaling abnormalities. Imaging of the glucose analog 18F-labeled fluorodeoxyglucose (18FDG) by positron emission tomography (PET) is the gold-standard for the assessment of cerebral glucose metabolism in vivo. This review summarizes the current literature addressing brain glucose uptake measured by PET imaging, and the effect of insulin on brain metabolism, trying to embrace a life-course vision in the identification of patterns that may explain (and contribute to) the frequent association between obesity and cognitive dysfunction. The current evidence supports that brain hypermetabolism and brain insulin resistance occur in selected high-risk conditions as a transient phenomenon, eventually evolving toward normal or low values during life or disease progression. Associative studies suggest that brain hypermetabolism predicts low BDNF levels, hepatic and whole body insulin resistance, food desire and an unfavorable balance between anticipated reward from food and cognitive inhibitory control. Emerging mechanistic links involve the microbiota and the metabolome, which correlate with brain metabolism and cognition, deserving attention as potential future prevention targets.

Insulin Resistance Is Associated With Enhanced Brain Glucose Uptake During Euglycemic Hyperinsulinemia: A Large-Scale PET Cohort

“…Regarding the insulin effect, seminal work by Talbot et al ( 12 ) showed normal activation of the insulin-signaling pathway in ex vivo studies in cognitively normal brains and brains with MCI under normal and supraphysiologic insulin levels, and of insulin resistance in AD brain slices. Accumulating evidence supports the notion that AD may be considered a metabolic disease of the brain, in which brain glucose use is impaired and, whereas early brain glucose hypermetabolism (i.e., MCI) may be considered a compensatory phase to the initial neurodegenerative insult, this compensation may eventually accelerate the degenerative process and ultimately lead to brain hypometabolism ( 33 ). Similar temporal paradoxical patterns have been described in other neuroimaging studies, in which memory-related functional MRI showed hyperactivation in less-impaired patients with MCI and hypoactivation in more-impaired patients with MCI ( 34 ).…”

Obesity and Brain Function: The Brain–Body Crosstalk

“…Imaging of brain glucose by positron emission tomography is a standard method for assessing brain metabolism in vivo. Lozzo et al’s (2019) review [ 43 ] assessed studies that employed this technique in attempts to reveal the underlying mechanisms that link obesity and cognitive dysfunction. They concluded that brain hypermetabolism is associated with cognitive control for food rewards, low BDNF levels, and insulin resistance.…”

Glucose-level dependent brain hypometabolism in type 2 diabetes mellitus and obesity

“…In addition, frontotemporal brain regions were registered to show decreased brain glucose uptake in type 2 diabetic individuals, even after controlling for different vascular risk factors [27]. While some studies indicated higher fasting cerebral metabolism in obese patients compared to lean people, others pointed out no associations between obesity and brain glucose uptake [17,28]. The underlying mechanism behind cerebral metabolic changes related to metabolic diseases is not exactly known.…”