Odor identification as a biomarker of preclinical AD in older adults at risk.
Odor identification as a biomarker of preclinical AD in older adults at risk.
复制标题
在处于危险中的老年人中，气味鉴定为临床前广告的生物标志物。
DOI：
10.1212/wnl.0000000000004159
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发表时间：
2017-07-25
期刊：
影响因子：
9.9
通讯作者：
PREVENT-AD Research Group
中科院分区：
文献类型：
--
作者：
Lafaille-Magnan ME;Poirier J;Etienne P;Tremblay-Mercier J;Frenette J;Rosa-Neto P;Breitner JCS;PREVENT-AD Research Group
评估气味识别 (OI) 作为阿尔茨海默病 (AD) 症状前发病机制的指标，适用于认知正常、阿尔茨海默病 (AD) 痴呆风险增加的老年人。在 PREVENT-AD 队列的 274 名健康老年人中，有父母或多兄弟姐妹患有 AD 痴呆病史，我们评估了 OI 与症状前 AD 潜在指标的横断面关联。约 101 名参与者捐赠了脑脊液，从而能够利用生物标志物总 tau (t-tau)、磷酸化 tau (P181-tau) 及其与 β-淀粉样蛋白 (Aβ1-42) 的比率来评估 AD 病理学。调整后的分析将年龄、认知、APOE ε4 状态、教育程度和性别视为协变量。我们使用宾夕法尼亚大学气味识别测试测量 OI，并使用可重复电池评估神经心理状态测量认知表现。标准试剂盒提供 AD 生物标志物的检测。分析使用稳健拟合线性回归模型。 OI 降低与较低的认知评分和年龄较大以及 CSF t-tau 和 P181-tau 与 Aβ1-42 的比率增加相关（所有 p < 0.02）。然而，在调整后的模型中，观察到的成骨不全与年龄和认知的关联并不明显，这些模型将观察限制在脑脊液捐赠者身上，并包括 AD 生物标志物。除了具有最低四分位数 Aβ1-42 水平的 APOE ε4 携带者外，OI 与单独的 CSF Aβ1-42 几乎没有相关性。这些来自健康高危老年人的研究结果表明，成骨不全反映了临床前 AD 病理的程度，而其与年龄和认知的关系则源于后者变量与此类病理的关联。 OI 减少可能是 AD 病理学的一种实用且负担得起的生物标志物。
To assess odor identification (OI) as an indicator of presymptomatic Alzheimer disease (AD) pathogenesis in cognitively normal aging individuals at increased risk of AD dementia. In 274 members of the PREVENT-AD cohort of healthy aging persons with a parental or multiple-sibling history of AD dementia, we assessed the cross-sectional association of OI with potential indicators of presymptomatic AD. Some 101 participants donated CSF, thus enabling assessment of AD pathology with the biomarkers total tau (t-tau), phospho-tau (P181-tau), and their ratios with β-amyloid (Aβ1-42). Adjusted analyses considered age, cognition, APOE ε4 status, education, and sex as covariates. We measured OI using the University of Pennsylvania Smell Identification Test and cognitive performance using the Repeatable Battery for Assessment of Neuropsychological Status. Standard kits provided assays of the AD biomarkers. Analyses used robust-fit linear regression models. Reduced OI was associated with lower cognitive score and older age, as well as increased ratios of CSF t-tau and P181-tau to Aβ1-42 (all p < 0.02). However, the observed associations of OI with age and cognition were unapparent in adjusted models that restricted observations to CSF donors and included AD biomarkers. OI showed little association with CSF Aβ1-42 alone except in APOE ε4 carriers having lowest-quartile Aβ1-42 levels. These findings from healthy high-risk older individuals suggest that OI reflects degree of preclinical AD pathology, while its relationships with age and cognition result from the association of these latter variables with such pathology. Diminished OI may be a practical and affordable biomarker of AD pathology.