Frontotemporal Dementia and Glucose Metabolism

Abstract

Frontotemporal dementia (FTD), hallmarked by antero-temporal degeneration in the human brain, is the second most common early onset dementia. FTD is a diverse disease with three main clinical presentations, four different identified proteinopathies and many disease-associated genes. The exact pathophysiology of FTD remains to be elucidated. One common characteristic all forms of FTD share is the dysregulation of glucose metabolism in patients’ brains. The brain consumes around 20% of the body’s energy supply and predominantly utilizes glucose as a fuel. Glucose metabolism dysregulation could therefore be extremely detrimental for neuronal health. Research into the association between glucose metabolism and dementias has recently gained interest in Alzheimer’s disease. FTD also presents with glucose metabolism dysregulation, however, this remains largely an unexplored area. A better understanding of the link between FTD and glucose metabolism may yield further insight into FTD pathophysiology and aid the development of novel therapeutics. Here we review our current understanding of FTD and glucose metabolism in the brain and discuss the evidence of impaired glucose metabolism in FTD. Lastly, we review research potentially suggesting a causal relationship between FTD proteinopathies and impaired glucose metabolism in FTD.

Disease specific and nonspecific metabolic brain networks in behavioral variant of frontotemporal dementia

“…As expected, the atrophy pattern corresponded well to the metabolic network, despite that expression of the atrophy pattern was significantly less expressed in the same patients on a standardized z ‐scale. These findings are consistent with previous univariate results proving that metabolic changes are more pronounced and precede atrophy (Garrett & Niccoli, 2022 ), a finding that was well documented also in other neurodegenerative disorders (Jack et al, 2013 ). Cortical atrophy needs to be considered in the interpretation of metabolic patterns associated with neurodegenerative disorders such as bvFTD.…”

Effects of age and dietary methionine restriction on cognitive and behavioural phenotypes in the rTg4510 model of frontotemporal dementia

“…Further investigating MR effects in the hippocampus, we observed elevated expression of plasticity and homeostasis mediators such as RELN, encoding for the extracellular matrix glycoprotein reelin (F (1, 26) = 5.641, p<0.05) and stem cell marker SOX2 (F (1, 24) = 30.97, p<0.0001, Fig. 4E & F), but low expression of nerve growth factor BDNF (F (1, 26) = 17.24, p<0.001) and mitochondrial regulator Pgc1α (F (1, 26) = 6.328, p<0.05) in rTg4510 vs. WT animals (overall genotype effects, Fig.…”

“…4A). (24). We therefore investigated effects of diet and genotype on the glycolytic pathway in the hippocampus by determining gene expression of key regulatory markers of glycolysis (Fig.…”

“…Given the benefits of MR on metabolic and cognitive health and disturbances in brain glucose homeostasis seen in dementia patients (9,24,25), this study investigated behavioural, molecular, and metabolic effects in a mouse model of FTD. We carried out a longitudinal MR study in the well-characterised rTg4510 tauopathy model at 6– and 12 months of age.…”

An Indonesian elderly with primary progressive aphasia and behavioral variant of frontotemporal dementia: A case report and review article

“…Memantine (NMDA antagonist) and cholinesterase inhibitors have no clinically significant efficacy in treating FTD, and they potentially hasten cognitive decline or worsen behavioral symptoms [ 9 , 10 ]. This is likely because cholinergic deficit may not contribute toFTDe pathophysiology [ 10 , 14 ]. Antipsychotics and mood stabilizers are occasionally used to treat psychosis and agitation of patients with FTD, but they are not FDA-approved and could be detrimental in dementia-associated agitation due to increased risk of mortality and unwanted side effects 3 .…”