Department of Psychology University of Oslo Oslo Norway.
Department of Neurology Akershus University Hospital Lørenskog Norway.
Brain Behav. 2017 Jul 28;7(9):e00776. doi: 10.1002/brb3.776. eCollection 2017 Sep.
Preclinical Alzheimers disease (AD) patients may or may not show cognitive impairment on testing. AD biomarkers are central to the identification of those at low, intermediate, or high risk of later dementia due to AD. We investigated biomarker distribution in those identified as subjective cognitive decline (SCD), amnestic (aMCI), and nonamnestic (naMCI) mild cognitive impairment (MCI) subtypes. In addition, the clinical groups were compared with controls on downstream neuroimaging markers.
Cerebrospinal fluid (CSF) amyloid-β42 (A β42) and total tau (t-tau), phosphorylated tau (p-tau), fluorodeoxyglucose (FDG), positron-emission tomography (PET), and MRI neuroimaging measures were collected from 116 memory clinic patients. They were characterized as SCD, aMCI, and naMCI according to comprehensive neuropsychological criteria. ANOVAs were used to assess differences when biomarkers were treated as continuous variables and chi square analyses were used to assess group differences in distribution of biomarkers.
We did not find any between group differences in Aβ42, nor in p-tau, but we observed elevated t-tau in aMCI and SCD relative to the naMCI group. Significantly lower cortical glucose metabolism (as measured by FDG PET) was found in aMCI relative to SCD and controls, and there was a trend for lower metabolism in naMCI. Significant thinner entorhinal cortex (ERC) was found in aMCI and SCD. As expected biomarkers were significantly more frequently pathological in aMCI than in naMCI and SCD, whereas the naMCI and SCD groups displayed similar pathological biomarker burden.
aMCI cases show the most pathologic biomarker burden. Interestingly naMCI and SCD subjects show similar levels of pathological biomarkers albeit the former displayed neuropsychological deficits. That the latter group may represent a risk group is supported by our observation of both elevated CSF tau and thinner ERC relative to controls.
临床前阿尔茨海默病（AD）患者在测试中可能表现出认知障碍，也可能没有表现出认知障碍。AD 生物标志物是识别 AD 导致的低、中、高痴呆风险人群的核心。我们研究了被诊断为主观认知下降（SCD）、遗忘型（aMCI）和非遗忘型（naMCI）轻度认知障碍（MCI）亚型的患者的生物标志物分布情况。此外，我们还将临床组与对照组的下游神经影像学标志物进行了比较。
从 116 名记忆诊所患者中收集了脑脊液（CSF）β淀粉样蛋白 42（Aβ42）和总 tau（t-tau）、磷酸化 tau（p-tau）、氟脱氧葡萄糖（FDG）、正电子发射断层扫描（PET）和 MRI 神经影像学测量值。根据全面的神经心理学标准，将他们分为 SCD、aMCI 和 naMCI。当生物标志物被视为连续变量时，我们使用方差分析来评估差异，当生物标志物的分布时，我们使用卡方分析来评估组间差异。
我们没有发现 Aβ42 或 p-tau 在组间存在差异，但我们观察到 aMCI 和 SCD 组的 t-tau 水平升高。与 SCD 和对照组相比，aMCI 组的皮质葡萄糖代谢（FDG PET 测量）显著降低，naMCI 组也有代谢降低的趋势。在 aMCI 和 SCD 中，发现内嗅皮层（ERC）明显变薄。正如预期的那样，aMCI 中生物标志物的病理频率显著高于 naMCI 和 SCD，而 naMCI 和 SCD 组显示出相似的病理生物标志物负担。
aMCI 病例显示出最严重的病理生物标志物负担。有趣的是，尽管 naMCI 和 SCD 患者表现出神经心理学缺陷，但他们显示出相似水平的病理性生物标志物。后者可能代表一个风险群体，这一点得到了我们的观察结果的支持，即与对照组相比，后者组的 CSF tau 水平升高和 ERC 变薄。
