Woodward Matthew R, Amrutkar Chaitanya V, Shah Harshit C, Benedict Ralph H B, Rajakrishnan Sanjanaa, Doody Rachelle S, Yan Li, Szigeti Kinga
Alzheimer's Disease and Memory Disorders Center, Department of Neurology (MRW, CVA, HCS, RHBB, SR, KS), and Department of Bioinformatics (LY), University at Buffalo, SUNY, NY; and Alzheimer's Disease and Memory Disorders Center (RSD), Department of Neurology, Baylor College of Medicine, Houston, TX.
Neurol Clin Pract. 2017 Feb;7(1):5-14. doi: 10.1212/CPJ.0000000000000293.
We evaluated smell identification as a biomarker for Alzheimer disease (AD) by assessing its utility in differentiating normal aging from an amnestic disorder and determining its predictive value for conversion from amnestic mild cognitive impairment (aMCI) to AD.
Cross-sectional study (AD = 262, aMCI = 110, controls = 194) measuring smell identification (University of Pennsylvania Smell Identification Test [UPSIT]) and cognitive status was performed, as well as longitudinal analysis of aMCI participants (n = 96) with at least 1 year follow-up (mean 477.6 ± 223.3 days), to determine conversion by National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria.
Odor identification and disease status were highly correlated after correcting for age, sex, and ( < 0.001). Receiver operating characteristic (ROC)/area under the curve (AUC) was similar for the 40-item UPSIT, the top 10 smells in our study, and the 10-item subset previously proposed. Smeller/nonsmeller based on the 10-item subset with a cutoff of 7 (≤7, nonsmeller; >7, smeller) had a sensitivity and specificity of 88% and 71% for identifying AD and 74% sensitivity and 71% specificity for identifying an amnestic disorder. A total of 36.4% of participants with impaired olfaction and 17.3% with intact olfaction converted to AD ( = 0.03). The ROC/AUC for prediction of conversion to AD was 0.62.
Olfactory identification deficit is a useful screening tool for AD-related amnestic disorder, with sensitivity and specificity comparable to other established biomarkers, with benefits such as ease of administration and low cost. Olfactory identification deficit can be utilized to stratify risk of conversion from aMCI to AD and enrich clinical trials of disease-modifying therapy.
This study provides Class III evidence that smell identification (10-item UPSIT subset) accurately identifies patients with amnestic disorders.
我们通过评估嗅觉识别在区分正常衰老与遗忘症中的作用以及确定其对遗忘型轻度认知障碍（aMCI）转化为阿尔茨海默病（AD）的预测价值，来评价嗅觉识别作为AD生物标志物的意义。
进行了一项横断面研究（AD = 262例，aMCI = 110例，对照 = 194例），测量嗅觉识别（宾夕法尼亚大学嗅觉识别测试[UPSIT]）和认知状态，并对aMCI参与者（n = 96例）进行了至少1年的随访（平均477.6 ± 223.3天）的纵向分析，以根据美国国立神经疾病与中风研究所 - 阿尔茨海默病及相关疾病协会标准确定是否转化。
在校正年龄、性别和[此处原文缺失内容]后，气味识别与疾病状态高度相关（<0.001）。40项UPSIT、我们研究中的前10种气味以及先前提出的10项子集的受试者工作特征（ROC）/曲线下面积（AUC）相似。基于10项子集，以7分为界值（≤7为嗅觉减退者；>7为嗅觉正常者），识别AD的敏感性和特异性分别为88%和71%，识别遗忘症的敏感性和特异性分别为74%和71%。嗅觉受损的参与者中有36.4%转化为AD，嗅觉正常的参与者中有17.3%转化为AD（P = 0.03）。预测转化为AD的ROC/AUC为0.62。
嗅觉识别缺陷是一种用于AD相关遗忘症的有用筛查工具，其敏感性和特异性与其他既定生物标志物相当，具有易于实施和成本低等优点。嗅觉识别缺陷可用于分层aMCI转化为AD的风险，并丰富疾病修饰疗法的临床试验。
本研究提供了III类证据，表明嗅觉识别（10项UPSIT子集）能准确识别遗忘症患者。
