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
Department of Psychiatry, University of Cambridge, School of Clinical Medicine, Cambridge Biomedical Campus, CB2 0QQ, UK.
Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0SZ, UK.
Brain Commun. 2020 Nov 18;3(1):fcaa198. doi: 10.1093/braincomms/fcaa198. eCollection 2021.
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]-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]-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 [C]-Pittsburgh Compound B was derived using a simplified reference tissue model. The sample was stratified into those with minimal amyloid burden ( = 25) and those with elevated amyloid ( = 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]-Pittsburgh Compound B as a surrogate index in clinical trials for monitoring disease progression or tracking physiologic changes over time in Down syndrome.
正电子发射断层扫描成像检测葡萄糖代谢减退和淀粉样蛋白沉积是评估阿尔茨海默病和唐氏综合征患者临床前变化的两种成熟方法。然而，同时使用这两种成像方式可能会给参与者带来负担，尤其是那些有智力障碍和认知障碍的人。[C] -匹兹堡化合物B的相对示踪剂输送已被提议作为脑灌注的可行替代指标。在此，我们研究了淀粉样蛋白病理对唐氏综合征患者灌注变化的影响，并评估了其与认知障碍的关联。共有47名成年唐氏综合征患者接受了[C] -匹兹堡化合物B成像和结构成像。使用Freesurfer处理结构数据以获得解剖分割和皮质厚度。使用简化参考组织模型得出[C] -匹兹堡化合物B的相对示踪剂输送量。将样本分为淀粉样蛋白负荷最小的患者（n = 25）和淀粉样蛋白升高的患者（n = 22）。我们发现，淀粉样蛋白负荷升高的患者脑灌注显著且广泛降低，与年龄、性别、认知功能和皮质厚度无关。此外，在淀粉样蛋白负荷升高的唐氏综合征组中，脑灌注与认知障碍有关。这些发现突出了[C] -匹兹堡化合物B的相对示踪剂输送作为替代指标在监测唐氏综合征疾病进展或随时间追踪生理变化的临床试验中的潜在效用。
