Translational Research Center for Medical Innovation, Foundation for Biomedical Research and Innovation, Kobe, Japan.
Department of Biostatistics, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Behav Neurol. 2020 Oct 29;2020:7029642. doi: 10.1155/2020/7029642. eCollection 2020.
To identify the factors protecting Abeta-positive subjects with normal cognition (NC) or mild cognitive impairment (MCI) from conversion to Alzheimer's disease (AD).
Subjects with MCI in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, with baseline data for neuropsychological tests, brain beta amyloid (Abeta), magnetic resonance imaging (MRI), APOE genotyping, and 18F-FDG-PET (FDG), were included for analysis.
Elevated brain amyloid was associated with a higher risk of conversion from MCI to AD (41.5%) relative to Abeta levels of <1.231 (5.5%) but was not associated with conversion from NC to AD (0.0 vs. 1.4%). In the multivariate Cox regression analyses, elevated Abeta increased the risk of AD, while higher whole-brain cerebral glucose metabolism (CGM) assessed by FDG decreased the risk of AD in subjects with the same amount of Abeta. Even in the patients with heavily elevated brain amyloid, those with FDG > 5.946 had a lower risk of AD. ApoE4 carrier status did not influence the protective effect.
Higher average CGM based on FDG modified the progression to AD, indicating a protective function. The results suggest that the inclusion of this CGM measured by FDG would enrich clinical trial design and that increasing CGM along with the use of anti-Abeta agents might be a potential prevention strategy for AD.
确定哪些因素能够保护认知正常（NC）或轻度认知障碍（MCI）的 Abeta 阳性患者不向阿尔茨海默病（AD）转化。
从阿尔茨海默病神经影像学倡议（ADNI）数据库中纳入 MCI 患者，这些患者有基线神经心理学测试、脑β淀粉样蛋白（Abeta）、磁共振成像（MRI）、载脂蛋白 E （APOE）基因分型和 18F-FDG-PET（FDG）等数据。
与 Abeta 水平<1.231（5.5%）相比，大脑淀粉样蛋白水平升高与 MCI 向 AD 转化的风险更高（41.5%），但与 NC 向 AD 转化无关（0.0%比 1.4%）。在多变量 Cox 回归分析中，Abeta 升高会增加 AD 的风险，而 FDG 评估的全脑葡萄糖代谢（CGM）升高则降低了具有相同 Abeta 水平的 AD 风险。即使在大脑淀粉样蛋白大量升高的患者中，FDG>5.946 的患者 AD 风险也较低。APOE4 载脂蛋白状态并不影响这种保护作用。
基于 FDG 的更高平均 CGM 改变了向 AD 的进展，表明具有保护作用。结果表明，纳入 FDG 测量的这种 CGM 将丰富临床试验设计，增加 CGM 并与使用抗 Abeta 药物结合可能是 AD 的一种潜在预防策略。
