Measuring cerebral perfusion with [11C]-PiB R1 in Down syndrome: associations with amyloid burden and longitudinal cognitive decline. Issue 1 (18th November 2020)

• Record Type: Journal Article
• Authors: Mak, Elijah; Grigorova, Monika; Beresford-Webb, Jessica; Malpetti, Maura; Walpert, Madeline; Brown, Stephanie; Jones, Elizabeth; Clare, Isabel; Hong, Young T; Fryer, Tim D; Coles, Jonathan P; Aigbirhio, Franklin I; Menon, David K; Nestor, Peter J; Holland, Anthony J; Zaman, Shahid H
• Is Part Of: Brain communications. Volume 3:Issue 1(2021)
• Publication Date: 2020-11-18
• Subjects: Down syndrome -- Alzheimer's disease -- positron emission tomography -- neurodegeneration -- perfusion; 616
• DOI: 10.1093/braincomms/fcaa198
• Languages: English
• ISSNs: 2632-1297

Abstract

Abstract: Positron emission tomography imaging of glucose hypometabolism and amyloid deposition are two well-established methods to evaluate preclinical changes in Alzheimer's disease and people with Down syndrome. However, the use of both imaging modalities may overburden participants, particularly those with intellectual disabilities and cognitive impairment. The relative tracer delivery of the [ 11 C]-Pittsburgh Compound B has been proposed as a viable surrogate for cerebral perfusion. Here, we studied the impact of amyloid pathology on perfusion changes in Down syndrome and evaluated its associations with cognitive impairment. In total, 47 adults with Down syndrome underwent the [ 11 C]-Pittsburgh Compound B imaging and structural imaging. The structural data were processed with Freesurfer to obtain anatomical segmentations and cortical thickness. The relative tracer delivery from [ 11 C]-Pittsburgh Compound B was derived using a simplified reference tissue model. The sample was stratified into those with minimal amyloid burden ( n = 25) and those with elevated amyloid ( n = 22). We found significant and widespread reductions of cerebral perfusion in those with elevated amyloid burden, independent of age, gender, cognitive function and cortical thickness. In addition, cerebral perfusion was associated with the cognitive impairment among the Down syndrome group with elevated amyloid burden. These findings highlight the promising utility of the relative tracer delivery of the [ 11 C]-Pittsburgh Compound B as a surrogate index in clinical trials for monitoring disease progression or tracking physiologic changes over time in Down syndrome. Abstract : Mak et al. showed that elevated amyloid burden among people with Down syndrome is associated with reduced cerebral perfusion. Perfusion deficits were independent of grey-matter atrophy and also correlated with worse cognitive performance. These findings demonstrate the potential utility of perfusion imaging as a surrogate marker of disease progression. Graphical Abstract: