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IMAGING SYNAPTIC DENSITY IN AGING AND FRONTOTEMPORAL DEMENTIA
Abstract
Aims
Tissue loss happens in aging and neurodegenerative conditions, such as frontotemporal dementia (FTD), with specific patterns related to the symptomatology. Tissue degeneration is hypothesized to be a consequence of synaptic loss. Our goal is to assess synaptic density in vivo using novel radiotracer [18F]SDM8 in aging and FTD.
Methods
Cognitively unimpaired young (CUY) [21-22yoa], cognitively unimpaired elderlies (CUE) [60-81yoa] and FTD [47-72yoa] participants from TRIAD cohort underwent an MRI, neuropsychological evaluation, and 90-minutes dynamic [18F]SDM8 PET-scan (synaptic density). We calculated the standardized uptake value ratio from 40-90 minutes and used the centrum semiovale as reference region. Voxel-wise analyses were conducted to assess synaptic density differences between CUY, CUE and FTD. Analyses were corrected for sex; when including only CUE and FTD, we also corrected for age.
Results
CUY present high [18F]SDM8 binding as compared to CUE, in the precuneus, and frontal and temporal lobes (Figure1A). Moreover, when comparing CUE and FTD, we observed greater [18F]SDM8 binding in the medial frontal lobe and the frontal pole (Figure1B).
Conclusions
Synaptic loss seems to increase with age, and with dementia onset. CUE show less synaptic density as compared to CUY, in regions vulnerable to neurodegenerative conditions’ development. Moreover, we observed a strong difference between CUE and FTD, in brain regions related to the disease symptomatology, i.e. frontal lobe. Frontal synaptic loss seems to appear in aging around the orbitofrontal cortex. Conversely, in FTD, it is located towards the dorsomedial prefrontal cortex. We hypothesize that synaptic loss is a process appearing in aging, possibly potentiated in FTD.