Glucose metabolism and serotonin receptors in the frontotemporal lobe degeneration

Abstract

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 (18)F-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 [(11)C]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 medial 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 [(11)C]MDL indicated a significant reduction of 5-hydroxytryptamine-2A receptors in orbitofrontal, frontal medial, and cingulate cortices. These (18)F-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.

Mutation withinTARDBPleads to Frontotemporal Dementia without motor neuron disease

“…Functional brain imaging study was consistent with dorsolateral and frontal medial hypoperfusion, in accordance with previous work on apathetic presentation of bvFTD [Franceschi et al, 2005].…”

A tensor based morphometry study of longitudinal gray matter contraction in FTD

“…Previous cross-sectional neuroimaging studies have consistently shown that FTD is associated with atrophy or decreased metabolism in this region compared to controls or other dementias (Ishii et al, 1998;Garraux et al, 1999;Rosen et al, 2002;Varrone et al, 2002;Salmon et al, 2003;Boccardi et al, 2005;Franceschi et al, 2005;Jeong et al, 2005;Williams et al, 2005). The other regions that showed longitudinal loss of gray matter (the medial temporal, medial frontal, and insular cortices) are heavily anatomically interconnected with the anterior cingulate and with each other.…”

Effectiveness and Safety of 18F-FDG PET in the Evaluation of Dementia: A Review of the Recent Literature

“…However, this finding remains controversial, because assessment of the magnitude of hippocampal hypometabolism on 18 F-FDG PET is less reliable and as such is less recognized on visual inspection. Furthermore, hippocampal and medial temporal glucose hypometabolism can be prominent in some subtypes of FTD (68,69). Cerebral glucose metabolic activity is an index of synaptic function and density (19,20), but hypometabolism is not specific for AD and is observed in other neurodegenerative disorders.…”