Glucose metabolism and serotonin receptors in the frontotemporal lobe degeneration

In patients with the frontal variant of frontotemporal lobar degeneration (fv-FTLD), behavioral abnormalities may vary from apathy with motor slowness (apathetic form) to disinhibition with agitation (disinhibited form). These clinical presentations may be related to specific regional cerebral dysfunction and to deficit in the serotoninergic system. We studied cerebral glucose uptake using F-18-fluorodeoxyglucose and positron emission tomography in 18 patients fulfilling clinical criteria for fv-FTLD and showing, respectively, an apathetic or disinhibited behavioral syndrome. In eight of these patients, we also evaluated the 5-hydroxytryptamine-2A receptor cerebral receptor distribution with [C-11]MDL and positron emission tomography. We found a reduction of frontal glucose metabolism in the whole group of fv-FTLD patients. Apathetic syndrome was associated with a prevalent dorsolateral and frontal media] hypometabolism, whereas the disinhibited syndrome demonstrated a selective hypometabolism in interconnected limbic structures (the cingulate cortex, hippocampus/amygdala, and accumbens nucleus). The in vivo measurements of [C-11]MDL indicated a significant reduction of 5-hydroxytryptamine-2A receptors in orbitofrontal, frontal medial, and cingulate cortices. These F-18-fluorodeoxyglucose positron emission tomography changes can be considered as specific functional markers of the different behavioral presentations in fv-FTLD. The serotoninergic system dysfunction provides a rationale for therapeutic trials with selective serotonin reuptake inhibitors.