From the Center for Vital Longevity (M.E.F., X.C., M.M.R., M.Y.C., G.S.W., D.C.P.), School of Behavioral and Brain Sciences, University of Texas at Dallas; and Department of Psychiatry (G.S.W., D.C.P.), University of Texas Southwestern Medical Center, Dallas.
Neurology. 2018 Nov 6;91(19):e1809-e1821. doi: 10.1212/WNL.0000000000006469. Epub 2018 Oct 10.
To assess whether global or regional changes in amyloid burden over 4 years predict early declines in episodic memory in initially amyloid-negative adults.
One hundred twenty-six initially amyloid-negative, cognitively normal participants (age 30-89 years) were included from the Dallas Lifespan Brain Study who completed florbetapir PET and a cognitive battery at baseline and 4-year follow-up. Standardized uptake value ratio (SUVR) change was computed across 8 bilateral regions of interest. Using general linear models, we examined the relationship between change in global and regional SUVR and change in episodic memory, controlling for baseline SUVR, baseline memory, age, sex, education, and status.
In initially amyloid-negative adults, we detected a regionally specific relationship between declining episodic memory and increasing amyloid accumulation across multiple posterior cortical regions. In addition, these amyloid-related changes in memory persisted when we focused on middle-aged adults only and after controlling for atrophy in global cortical, hippocampal, and Alzheimer disease signature cortical volume.
Our results indicate that assessing regional changes in amyloid, particularly in posterior cortical regions, can aid in the early detection of subclinical amyloid-related decline in episodic memory as early as middle age. Future research incorporating tau and other markers of neurodegeneration is needed to clarify the sequence of events that lead to this early, subclinical memory decline.
评估 4 年内淀粉样蛋白负荷的全球或区域性变化是否可预测最初淀粉样蛋白阴性的成年人早期出现情景记忆衰退。
本研究纳入了来自达拉斯寿命大脑研究的 126 名最初淀粉样蛋白阴性、认知正常的参与者（年龄 30-89 岁），他们在基线和 4 年随访时完成了 florbetapir PET 和认知测试。计算了 8 个双侧感兴趣区的标准化摄取值比值（SUVR）变化。采用一般线性模型，我们在控制基线 SUVR、基线记忆、年龄、性别、教育和 状况的情况下，检验了全局和区域 SUVR 变化与情景记忆变化之间的关系。
在最初淀粉样蛋白阴性的成年人中，我们在多个后皮质区域发现了情景记忆下降与淀粉样蛋白积累增加之间的区域特异性关系。此外，当我们仅关注中年成年人并在控制了全局皮质、海马和阿尔茨海默病特征性皮质体积的萎缩后，这些与记忆相关的淀粉样蛋白变化仍然存在。
我们的研究结果表明，评估淀粉样蛋白的区域性变化，特别是在后皮质区域，可以帮助早期发现亚临床淀粉样蛋白相关的情景记忆衰退，甚至在中年时期就可以发现。未来的研究需要结合 tau 和其他神经退行性变的标志物，以阐明导致这种早期亚临床记忆衰退的事件序列。
