Metabolism in frontotemporal dementia

Abstract

AbstractBackgroundMetabolic changes incorporating changes in weight, insulin resistance and cholesterol levels have been identified across a number of neurodegenerative conditions. It remains unknown whether these changes represent the result of the process of neurodegeneration affecting critical brain regions involved in metabolic regulation, or are causative, driving the process. Changes in eating behaviour affecting metabolism have been incorporated into the diagnostic criteria for frontotemporal dementia (FTD), and have been shown to potentially effect disease progression, with the potential to aid in clinical phenotyping and early diagnoses.MethodsA number of studies will be reviewed examining changes in eating behaviour in FTD using ecological valid assessments including a test meal approach. The effect that these eating changes have on metabolism will be examined, including changes in cholesterol, and insulin levels and metabolic rate. The role of key brain regions including the hypothalamus will be explored through a number of studies incorporating brain imaging, neuropeptide examination and pathological analyses.ResultsPatients with FTD exhibit a strong fat and sucrose preference, that is not present in normal or Alzheimer’s disease controls. These changes result in increased cholesterol levels and a state of insulin resistance which has been associated with changes in disease progression. Patients with FTD have been found to be hypermetabolic, with increased cholesterol levels, from changes in eating behaviour, likely resulting in improved energy stores in a hypermetabolic state and potentially slowing disease progression. Changes in eating behaviour and metabolism have been linked to changes in key neural networks involving fronto‐insular‐ striatal networks, with connections to the hypothalamus. Changes in key hypothalamic peptides including agouti‐related peptide and leptin have also been implicated in mediating metabolic changes and changes in disease progression.ConclusionsGiven the spectrum of metabolic and eating changes observed in FTD, with emerging evidence that these changes may effect disease progression and prognoses, an understanding of metabolism in FTD may provide a model to better understand the pathophysiology of metabolic change and its complex interaction with the process of neurodegeneration.