Olfactory Function and Markers of Brain Pathology in Non-Demented Individuals with Autosomal Dominant Alzheimer's Disease.
Olfactory Function and Markers of Brain Pathology in Non-Demented Individuals with Autosomal Dominant Alzheimer's Disease.
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常染色体显性阿尔茨海默氏病的非痴呆个体中脑病理学的嗅觉功能和标志物。
DOI：
10.3233/jad-220075
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发表时间：
2022
影响因子：
4
通讯作者：
Quiroz, Yakeel T.
中科院分区：
文献类型：
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作者：
Ramirez-Gomez, Liliana;Albers, Mark W.;Baena, Ana;Vila-Castelar, Clara;Fox-Fuller, Joshua T.;Sanchez, Justin;Jain, Felipe;Albers, Alefiya D.;Lopera, Francisco;Quiroz, Yakeel T.
关键词：
嗅觉功能障碍是阿尔茨海默病（AD）的早期症状之一，突出了其作为早期检测生物标志物的潜在用途。它还与从轻度认知障碍（MCI）到痴呆症的进展有关。研究常染色体显性阿尔茨海默病（ADAD）非痴呆突变携带者和非携带者家族成员的嗅觉功能及其与阿尔茨海默病脑病理标志物的关系。我们分析了来自哥伦比亚的16名Presenilin1 E280A ADAD突变非痴呆携带者（平均年龄[SD]: 40.1[5.3]）和19名非携带者家庭成员（平均年龄[SD]: 36.0[5.5]）的横断数据，他们完成了嗅觉和认知测试，并接受了淀粉样蛋白和tau正电子发射断层扫描（PET）成像。嗅觉识别能力差的突变携带者年龄越大（r= - 0.52 p=0.037）。在携带者中，较差的嗅觉识别能力与较差的MMSE评分（r=0.55, p=0.024）、CERAD延迟回忆（r= 0.63, p=0.007）、较大的皮质淀粉样蛋白-β (r= - 0.53, p=0.042)和tau病理负担（内嗅：r= - 0.59, p= 0.016；下颞：r= - 0.52, p= 0.038）有关。嗅觉识别任务中较差的表现与较大的年龄相关，这是该遗传易感的ADAD队列中疾病进展的一个代理。此外，本研究首次报道了诊断为MCI的ADAD突变携带者的嗅觉功能障碍及其与内嗅区tau病理异常积累的相关性。综上所述，我们的研究结果表明嗅觉功能障碍有望作为脑病理和未来痴呆风险的早期标志。
Olfactory dysfunction is one of the earliest signs of Alzheimer’s Disease (AD), highlighting its potential use as a biomarker for early detection. It has also been linked to progression from mild cognitive impairment (MCI) to dementia. To study olfactory function and its associations with markers of AD brain pathology in non-demented mutation carriers of an autosomal dominant AD (ADAD) mutation and non-carrier family members. We analyzed cross-sectional data from 16 non-demented carriers of the Presenilin1 E280A ADAD mutation (mean age [SD]: 40.1 [5.3], and 19 non-carrier family members (mean age [SD]: 36.0 [5.5]) from Colombia, who completed olfactory and cognitive testing and underwent amyloid and tau positron emission tomography (PET) imaging. Worse olfactory identification performance was associated with greater age in mutation carriers (r=−0.52 p=0.037). In carriers, worse olfactory identification performance was related to worse MMSE scores (r=0.55, p=0.024), CERAD delayed recall (r= 0.63, p=0.007) and greater cortical amyloid-β (r= −0.53, p=0.042) and tau pathology burden (entorhinal: r= −0.59, p= 0.016; inferior temporal: r= −0.52, p= 0.038). Worse performance on olfactory identification tasks was associated with greater age, a proxy for disease progression in this genetically vulnerable ADAD cohort. In addition, this is the first study to report olfactory dysfunction in ADAD mutation carriers with diagnosis of MCI and its correlation with abnormal accumulation of tau pathology in the entorhinal region. Taken together, our findings suggest that olfactory dysfunction has promise as an early marker of brain pathology and future risk for dementia.