CSF Biomarker and PIB-PET-Derived Beta-Amyloid Signature Predicts Metabolic, Gray Matter, and Cognitive Changes in Nondemented Subjects
CSF Biomarker and PIB-PET-Derived Beta-Amyloid Signature Predicts Metabolic, Gray Matter, and Cognitive Changes in Nondemented Subjects
复制标题
DOI：
10.1093/cercor/bhr271
复制
发表时间：
2012-09-01
期刊：
影响因子：
3.7
通讯作者：
Weiner, Michael W.
中科院分区：
文献类型：
--
作者：
Ewers, Michael;Insel, Philip;Weiner, Michael W.
β-淀粉样蛋白（A β）是阿尔茨海默病痴呆的组织病理学标志，但在相当大比例的非痴呆受试者中也可以发现大脑中高水平的A β。在这里，我们研究了高和低A β水平的非痴呆受试者的2年脑和认知变化率，通过脑脊液和基于分子正电子发射断层扫描（PET）的A β生物标志物进行评估。在轻度认知功能障碍受试者中，脑A β水平升高与认知功能下降显著加快、颞叶和顶叶脑区灰质萎缩进展以及顶叶氟脱氧葡萄糖（FDG）-PET代谢下降加快的趋势相关。灰质和FDG-PET的变化介导了A β和认知能力下降之间的关联。与此相反，老年认知健康对照组（HC）与高A β水平相比，仅表现出更快的内侧颞叶和楔前叶体积下降与HC与低A β。总之，目前的结果表明，不仅功能和体积的脑变化与痴呆发作前的高A β相关，而且具有大量A β水平的HC显示出较高的A β病理学抗性，缺乏其他病理学条件的神经毒性作用的A β，或积累A β较短的时间段。
Beta-amyloid (A beta) is a histopathological hallmark of Alzheimer's disease dementia, but high levels of A beta in the brain can also be found in a substantial proportion of nondemented subjects. Here we investigated which 2-year rate of brain and cognitive changes are present in nondemented subjects with high and low A beta levels, as assessed with cerebrospinal fluid and molecular positron emission tomography (PET)-based biomarkers of A beta. In subjects with mild cognitive impairment, increased brain A beta levels were associated with significantly faster cognitive decline, progression of gray matter atrophy within temporal and parietal brain regions, and a trend for a faster decline in parietal Fludeoxyglucose (FDG)-PET metabolism. Changes in gray matter and FDG-PET mediated the association between A beta and cognitive decline. In contrast, elderly cognitively healthy controls (HC) with high A beta levels showed only a faster medial temporal lobe and precuneus volume decline compared with HC with low A beta. In conclusion, the current results suggest not only that both functional and volumetric brain changes are associated with high A beta years before the onset of dementia but also that HC with substantial A beta levels show higher A beta pathology resistance, lack other pathologies that condition neurotoxic effects of A beta, or accumulated A beta for a shorter time period.