Cognitive functioning in relation to brain amyloid-β in healthy adults with Down syndrome
Cognitive functioning in relation to brain amyloid-β in healthy adults with Down syndrome
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DOI：
10.1093/brain/awu173
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发表时间：
2014-09-01
期刊：
影响因子：
14.5
通讯作者：
Christian, Bradley T.
中科院分区：
文献类型：
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作者：
Hartley, Sigan L.;Handen, Benjamin L.;Christian, Bradley T.
几乎所有患有唐氏综合症的成年人在五岁时都表现出阿尔茨海默病的神经病理学特征，包括淀粉样蛋白沉积。在当前的研究中，我们检查了 63 名年龄在 30-53 岁、没有表现出痴呆症状的唐氏综合症成人（31 名男性、32 名女性）的大脑淀粉样蛋白沉积之间的关联，通过新皮质匹兹堡化合物 B 的体内评估进行评估，并通过一系列广泛的神经心理学认知功能测量得分进行评估。 22 名患有唐氏综合症的成年人被确定为新皮质匹兹堡化合物 B 保留水平升高。年龄与新皮质匹兹堡化合物 B 保留量之间存在显着正相关（r = 0.62，P < 0.0001）。这种强有力的关联使得很难将与年龄相关的认知功能正常下降与β-淀粉样蛋白沉积的任何潜在影响区分开来。当控制心理年龄和实际年龄时，新皮质匹兹堡化合物 B 保留水平升高的唐氏综合症成人与未进行任何神经心理学测量的成人之间没有显着差异。同样，当将匹兹堡化合物 B 作为连续变量进行检查时，在控制心理年龄和实际年龄后，只有 Rivermead 图片识别评分与新皮层匹兹堡化合物 B 保留呈显着负相关。我们的研究结果表明，许多患有唐氏综合症的成年人可以耐受淀粉样蛋白沉积，而不会对认知功能产生有害影响。然而，通过在分析中控制实际年龄，我们可能掩盖了β淀粉样蛋白沉积的真实影响。此外，我们的样本包括对淀粉样蛋白沉积的影响最具“抵抗力”的唐氏综合症成年人，因为已经表现出痴呆症状临床症状的成年人被排除在研究之外。
Nearly all adults with Down syndrome show neuropathology of Alzheimer's disease, including amyloid-beta deposition, by their fifth decade of life. In the current study, we examined the association between brain amyloid-beta deposition, assessed via in vivo assessments of neocortical Pittsburgh compound B, and scores on an extensive neuropsychological battery of measures of cognitive functioning in 63 adults (31 male, 32 female) with Down syndrome aged 30-53 years who did not exhibit symptoms of dementia. Twenty-two of the adults with Down syndrome were identified as having elevated neocortical Pittsburgh compound B retention levels. There was a significant positive correlation (r = 0.62, P < 0.0001) between age and neocortical Pittsburgh compound B retention. This robust association makes it difficult to discriminate normative age-related decline in cognitive functioning from any potential effects of amyloid-beta deposition. When controlling for chronological age in addition to mental age, there were no significant differences between the adults with Down syndrome who had elevated neocortical Pittsburgh compound B retention levels and those who did not on any of the neuropsychological measures. Similarly, when examining Pittsburgh compound B as a continuous variable, after controlling for mental age and chronological age, only the Rivermead Picture Recognition score was significantly negatively associated with neocortical Pittsburgh compound B retention. Our findings indicate that many adults with Down syndrome can tolerate amyloid-beta deposition without deleterious effects on cognitive functioning. However, we may have obscured true effects of amyloid-beta deposition by controlling for chronological age in our analyses. Moreover, our sample included adults with Down syndrome who were most 'resistant' to the effects of amyloid-beta deposition, as adults already exhibiting clinical symptoms of dementia symptoms were excluded from the study.