期刊
BRAIN COMMUNICATIONS
卷 3, 期 1, 页码 -出版社
OXFORD UNIV PRESS
DOI: 10.1093/braincomms/fcaa198
关键词
Down syndrome; Alzheimer's disease; positron emission tomography; neurodegeneration; perfusion
资金
- Medical Research Council [98480]
- Alzheimer's Research, UK
- Alzheimer's Society Junior Research Fellowship [RG9611, 443 JF-18017]
- National Institute for Health Research, Cambridge Biomedical Research Centre
- National Institute for Health Research Collaborations in Leadership for Applied Health Research and Care for the East of England
- National Institute for Health Research Cambridge Dementia Biomedical Research Unit
- Down Syndrome Association
- Health Foundation
The study found significant and widespread reductions of cerebral perfusion in individuals with elevated amyloid burden in Down syndrome, independent of age, gender, cognitive function, and cortical thickness. Additionally, cerebral perfusion was associated with cognitive impairment in individuals with elevated amyloid burden, highlighting the promising utility of relative tracer delivery of [C-11]-Pittsburgh Compound B as a surrogate index in clinical trials.
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 [C-11]-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 [C-11]-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 [C-11]-Pittsburgh Compound B as a surrogate index in clinical trials for monitoring disease progression or tracking physiologic changes over time in Down syndrome.
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