Brain Glucose Hypometabolism and Iron Accumulation in Different Brain Regions in Alzheimer’s and Parkinson’s Diseases

Abstract

The aim of this study was to examine the relationship between the presence of glucose hypometabolism (GHM) and brain iron accumulation (BIA), two potential pathological mechanisms in neurodegenerative disease, in different regions of the brain in people with late-onset Alzheimer’s disease (AD) or Parkinson’s disease (PD). Studies that conducted fluorodeoxyglucose positron emission tomography (FDG-PET) to map GHM or quantitative susceptibility mapping—magnetic resonance imaging (QSM–MRI) to map BIA in the brains of patients with AD or PD were reviewed. Regions of the brain where GHM or BIA were reported in each disease were compared. In AD, both GHM and BIA were reported in the hippocampus, temporal, and parietal lobes. GHM alone was reported in the cingulate gyrus, precuneus and occipital lobe. BIA alone was reported in the caudate nucleus, putamen and globus pallidus. In PD, both GHM and BIA were reported in thalamus, globus pallidus, putamen, hippocampus, and temporal and frontal lobes. GHM alone was reported in cingulate gyrus, caudate nucleus, cerebellum, and parietal and occipital lobes. BIA alone was reported in the substantia nigra and red nucleus. GHM and BIA are observed independent of one another in various brain regions in both AD and PD. This suggests that GHM is not always necessary or sufficient to cause BIA and vice versa. Hypothesis-driven FDG-PET and QSM–MRI imaging studies, where both are conducted on individuals with AD or PD, are needed to confirm or disprove the observations presented here about the potential relationship or lack thereof between GHM and BIA in AD and PD.

Quantitative susceptibility mapping as an imaging biomarker for Alzheimer’s disease: The expectations and limitations

“…Additionally, a longitudinal study of cognitively normal adults showed that accumulation of iron in the putamen could predict its shrinkage (Daugherty and Raz, 2016). Although less investigated for associations between QSM and the other biomarkers of neurodegeneration, a combined 18 F-FDG-PET and QSM study in different AD cohorts revealed glucose hypometabolism and brain iron accumulation in the hippocampus, temporal, and parietal lobes (Rao et al, 2022).…”

Regional high iron deposition on quantitative susceptibility mapping correlates with cognitive decline in type 2 diabetes mellitus

“…Another study found that excessive iron accumulation was associated with region-specific advanced atrophy ( Lee et al, 2013 , 2015 ). Brain iron abnormally accumulates in a number of neurological disorders such as AD, PD leads to the neurotoxicity of oxidative stress which can promote neuron loss and degeneration, and may manifest as brain atrophy ( Dixon et al, 2012 ; Ward et al, 2014 ; Rao et al, 2022 ; Yang et al, 2022 ). Lots of people believe that insulin resistance and diminished insulin signaling in the brain play a role in glucose hypometabolism ( Freiherr et al, 2013 ; Ferreira et al, 2018 ).…”

Nano-Theranostics Approaches and Mitochondrial Targeted Drug Delivery: Alzheimer ’s Disease Therapeutic Interventions

“…Before AD pathogenesis, changes in glucose metabolism happen when oxidative damage builds up. Early-stage AD patients have significantly reduced glucose absorption, which suggests that the condition is preceded by altered glucose metabolism and elevated steady-state glucose concentrations [57]. In addition to facilitating glucose metabolism and influencing tau protein and Aβ processing, insulin in the brain is essential for learning, memory, neurite growth, and development.…”

“…Additionally, increased GSK3/ activity encourages Tau phosphorylation and Aβ accumulation [56]. When set side by side to age-matched controls, AD patients show drastical and insignificant brain levels of insulin, insulin-like growth factor I (IGF-I), insulin-like growth factor II, and IGF-I receptor [57].…”

“…It is not very much evident that abnormality in glucose metabolism can have a cascade of poisonous effects since glucose utilization underpins essential brain functions like energy supply and antioxidant defense [58,59]. As such, disturbances in glucose metabolism likely represent a major underlying cause of disease initiation and progression [57]. However, the precise origins and effects of AD-associated glucose hypometabolism have remained unknown up to this point, impeding the search for a cure.…”