Title: Glucose metabolism measured with FDG PET distinguishes cases of mild cognitive impairment and Alzheimer’s disease from cognitively stable adults with Down syndrome
Legend: Interregional fluorodeoxyglucose (FDG) metabolic connectivity matrices for healthy, non-DS sibling controls, cognitively stable DS adults (CS-DS) and DS adults with mild cognitive impairment or Alzheimer’s disease (MCI-DS/AD). The number and strength of interregional connecti ons distinguish DS from healthy controls, as well as distinguish cases of MCI-DS/AD from CS-DS. Bottom – Representative PET images of β-amyloid (measured with [11C]PiB) and FDG for cases of CS-DS and MCI-DS/AD. Voxel regressions revealed a negative association between β-amyloid and FDG in the parietal cortex, precuneus and the poster cingulate (p < .05 adjusted for family-wise error correction). A positive association was observed between Aβ and FDG in the putamen, which is susceptible to early accumulation of diffuse Aβ plaques in DS.
Citation: Zammit, M., Laymon, C., Tudorascu, D., Hartley, S., … & Christian, B. (2020). Patterns of glucose hypometabolism in Down syndrome resemble sporadic Alzheimer’s disease except for the putamen. Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring. Under Review.
Zammit, M., Laymon, C., Tudorascu, D., DiFilippo, A., Tullis, T., McVea, A., Hartley, S., … & Christian, B. (2020). Regional associations between amyloid and glucose metabolism during the progression of Alzheimer’s disease in Down syndrome. Journal of Nuclear Medicine, 61 (supplement 1), 21-21.
Abstract: Adults with Down syndrome (DS) are predisposed to Alzheimer’s disease (AD) and a characterization of glucose metabolism change throughout AD progression has yet to be performed in this population. Using FDG PET, regional glucose metabolism was evaluated across groups of cognitively stable DS (CS-DS), DS with mild cognitive impairment or Alzheimer’s disease (MCI-DS/AD), and healthy non-DS sibling controls. Utilizing an individual metabolic brain network analysis, interregional FDG metabolic connectivity was assessed for each participant. Compared to healthy controls, CS-DS showed lower baseline metabolic connectivity and MCI-DS/AD showed significant reductions in metabolic connectivity when compared to CS-DS (p < .05 adjusted for Bonferroni correction). When compared against global Aβ burden, a negative association was observed between Aβ and glucose metabolism in the parietal cortex, precuneus and posterior cingulate in DS, similar to the regional pattern of glucose hypometabolism observed in late-onset AD. A positive association was observed between Aβ and glucose metabolism in the putamen, which is subject to early and aggressive accumulation of diffuse Aβ plaques rather than the more neurotoxic cored plaques observed in the cortex, suggesting this region may be spared from AD-related neurodegeneration.
About the Lab: Christian’s research focuses on the use of positron emission tomography (PET) to interrogate molecular pathways involved in various brain processes. [11C]PiB imaging is used to detect Aβ plaques in elderly participants with and without Alzheimer’s disease, as well as young adults with Down syndrome. A variety of radiolabelled tracers such as [18F]THK5351, [18F]nifene, [18F]mefway, [11C]PBR28, and [11C]clozapine are also used to understand tauopathies, addiction, and neuroinflammation.