P1‐379: Changes in cerebral glucose metabolism in early symptomatic frontotemporal dementia linked to chromosome 3 (FTD‐3)

Background: Frontotemporal dementia linked to chromosome 3 (FTD-3) is a rare autosomal dominantly inherited neurodegenerative disease first described in a Danish family where it is caused by a truncating mutation in CHMP2B (1). The disease is characterized by insidious and progressive changes in personality, behavior and cognition (2). The CHMP2B protein is a part of the ESCRTIII complex necessary for endosomal trafficking and protein degradation (1,3). The study assesses regional cerebral glucose metabolism in early symptomatic CHMP2B-mutation carriers using 18Fflourodeoxyglucose (FDG) and positron emission tomography (PET). Methods: Three CHMP2B mutation carriers were FDG-PET scanned for 10 minutes on a Siemens Biograph 40 PET/CT scanner, 40 minutes after injection of 200 MBq of FDG. Images were transformed into a standard stereotactic space and compared to a database of healthy age matched subjects (Neurostat (4)). Results: Three early symptomatic mutation carriers all showed abnormal cerebral glucose metabolism. Patient A (58 years, male): Showed moderately reduced activity bilaterally in the inferior parietal and posterior temporal lobes as well as around fissura interhemispherica. Frontal lobes, subcortical structures and cerebellum were unaffected. The pattern resembles an Alzheimer’s profile more than FTD. Patient B (69 years, male): Showed extensive metabolic reductions on frontal, temporal and parietal cortices resembling both FTD and AD. Basal ganglia and cerebellum were unaffected. Patient C (59 years, male): Showed mild to moderate metabolic reductions bilateral in the entire frontal cortex, anterior parts of the temporal and parietal cortex as well as basal ganglia resembling FTD. Conclusions: Decreased cerebral glucose metabolism is present in early symptomatic FTD-3. The pattern of reduced metabolism is very variable ranging from a pattern resembling classical FTD to a more Alzheimer like pattern. Though the genetic background is identical, functional changes differ considerably, presumably due to other genetic and environmental factors. Atypical metabolic patterns do not exclude FTD. References: [1] Nature Genetics 2005;37:806-8. [2] Neurology 2002;59:1585-94. [3] Biochem Soc Trans. 2009;37:208-12. [4] J Nucl Med 1995;36:1238.