Systemic metabolism in frontotemporal dementia

Objective: To document the metabolic changes in frontotemporal dementia, including serum cholesterol and insulin levels, and compare and contrast these changes to motor neuron disease, where metabolism is proposed to affect disease progression. Methods: A cohort of 90 patients with dementia (31 behavioral-variant frontotemporal dementia [bvFTD], 30 semantic dementia [SD], and 29 Alzheimer disease [AD]) underwent fasting blood cholesterol, glucose, and peripheral insulin level analysis. Insulin resistance was calculated using the homeostasis model assessment of insulin resistance (HOMA-IR). These results were compared with a cohort of 19 control subjects. Results: The bvFTD cohort had lower high-density lipoprotein (HDL) cholesterol levels compared with control and AD groups, and increased total cholesterol/HDL ratio and triglyceride levels compared with the control group. The SD cohort had increased triglyceride levels compared with control subjects. Both FTD groups had increased fasting insulin levels and HOMA-IR index compared with the control group, and this remained increased in the subjects with bvFTD compared to subjects with AD. Conclusion: Both patients with bvFTD and those with SD have increased triglyceride and insulin levels and lower HDL cholesterol levels compared with controls, suggesting a state of peripheral insulin resistance. These factors have been found to affect prognosis in motor neuron disease favorably, although insulin resistance has been proposed as a mechanism promoting neurodegeneration. We discuss the potential role of metabolism in FTD pathophysiology and progression.