Abstract：
BACKGROUND: Spatial extent-based measures of how far amyloid beta (Aβ) has spread throughout the neocortex may be more sensitive than traditional Aβ-positron emission tomography (PET) measures of Aβ level for detecting early Aβ deposits in preclinical Alzheimer\'s disease (AD) and improve understanding of Aβ\'s association with tau proliferation and cognitive decline.
METHODS: Pittsburgh Compound-B (PIB)-PET scans from 261 cognitively unimpaired older adults from the Harvard Aging Brain Study were used to measure Aβ level (LVL; neocortical PIB DVR) and spatial extent (EXT), calculated as the proportion of the neocortex that is PIB+.
RESULTS: EXT enabled earlier detection of Aβ deposits longitudinally confirmed to reach a traditional LVL-based threshold for Aβ+ within 5 years. EXT improved prediction of cognitive decline (Preclinical Alzheimer Cognitive Composite) and tau proliferation (flortaucipir-PET) over LVL.
CONCLUSIONS: These findings indicate EXT may be more sensitive to Aβ\'s role in preclinical AD than level and improve targeting of individuals for AD prevention trials.
CONCLUSIONS: Aβ spatial extent (EXT) was measured as the percentage of the neocortex with elevated Pittsburgh Compound-B. Aβ EXT improved detection of Aβ below traditional PET thresholds. Early regional Aβ deposits were spatially heterogeneous. Cognition and tau were more closely tied to Aβ EXT than Aβ level. Neocortical tau onset aligned with reaching widespread neocortical Aβ.
METHODS: Pittsburgh Compound-B (PIB)-PET scans from 261 cognitively unimpaired older adults from the Harvard Aging Brain Study were used to measure Aβ level (LVL; neocortical PIB DVR) and spatial extent (EXT), calculated as the proportion of the neocortex that is PIB+.
RESULTS: EXT enabled earlier detection of Aβ deposits longitudinally confirmed to reach a traditional LVL-based threshold for Aβ+ within 5 years. EXT improved prediction of cognitive decline (Preclinical Alzheimer Cognitive Composite) and tau proliferation (flortaucipir-PET) over LVL.
CONCLUSIONS: These findings indicate EXT may be more sensitive to Aβ\'s role in preclinical AD than level and improve targeting of individuals for AD prevention trials.
CONCLUSIONS: Aβ spatial extent (EXT) was measured as the percentage of the neocortex with elevated Pittsburgh Compound-B. Aβ EXT improved detection of Aβ below traditional PET thresholds. Early regional Aβ deposits were spatially heterogeneous. Cognition and tau were more closely tied to Aβ EXT than Aβ level. Neocortical tau onset aligned with reaching widespread neocortical Aβ.
摘要：
背景：基于空间范围的淀粉样β（Aβ）在整个新皮质中扩散的程度的测量可能比传统的Aβ-正电子发射断层扫描（PET）测量的Aβ水平更敏感，以检测早期Aβ沉积在临床前阿尔茨海默病（AD）中，并提高对Aβ与tau增殖和认知能力下降的相关性的理解。
方法：使用来自哈佛衰老大脑研究的261名认知未受损的老年人的匹兹堡复合B（PIB）-PET扫描来测量Aβ水平（LVL；新皮质PIBDVR）和空间范围（EXT），计算为PIB+的新皮层的比例。
结果：EXT能够较早地检测Aβ沉积物，纵向证实在5年内达到传统的基于LVL的Aβ+阈值。与LVL相比，EXT改善了认知下降（临床前阿尔茨海默认知组合）和tau增殖（flortaucipir-PET）的预测。
结论：这些发现表明，EXT可能对Aβ在临床前AD中的作用比对水平更敏感，并改善了个体在AD预防试验中的靶向性。
结论：Aβ空间范围（EXT）以匹兹堡化合物B升高的新皮层的百分比进行测量。AβEXT将Aβ的检测提高到低于传统的PET阈值。早期区域Aβ矿床具有空间异质性。认知和tau与AβEXT的关系比Aβ水平更紧密。新皮质tau发作与达到广泛的新皮质Aβ一致。
方法：使用来自哈佛衰老大脑研究的261名认知未受损的老年人的匹兹堡复合B（PIB）-PET扫描来测量Aβ水平（LVL；新皮质PIBDVR）和空间范围（EXT），计算为PIB+的新皮层的比例。
结果：EXT能够较早地检测Aβ沉积物，纵向证实在5年内达到传统的基于LVL的Aβ+阈值。与LVL相比，EXT改善了认知下降（临床前阿尔茨海默认知组合）和tau增殖（flortaucipir-PET）的预测。
结论：这些发现表明，EXT可能对Aβ在临床前AD中的作用比对水平更敏感，并改善了个体在AD预防试验中的靶向性。
结论：Aβ空间范围（EXT）以匹兹堡化合物B升高的新皮层的百分比进行测量。AβEXT将Aβ的检测提高到低于传统的PET阈值。早期区域Aβ矿床具有空间异质性。认知和tau与AβEXT的关系比Aβ水平更紧密。新皮质tau发作与达到广泛的新皮质Aβ一致。
