Olfactory impairment is a potential marker for prodromal dementia, but the underlying mechanisms are poorly understood. This population-based study included 4214 dementia-free participants (age ≥65 years). Olfaction was assessed using the 16-item Sniffin’ Sticks identification test. In the subsamples, we measured plasma amyloid beta (Aβ)40, Aβ42, total tau, and neurofilament light chain (NfL; n = 1054); and quantified hippocampal, entorhinal cortex, and white matter hyperintensity (WMH) volumes, and Alzheimer's disease (AD)-signature cortical thickness (n = 917). Data were analyzed with logistic and linear regression models. In the total sample, mild cognitive impairment (MCI) was diagnosed in 1102 persons (26.2%; amnestic MCI, n = 931; non-amnestic MCI, n = 171). Olfactory impairment was significantly associated with increased likelihoods of MCI, amnestic MCI, and non-amnestic MCI. In the subsamples, anosmia was significantly associated with higher plasma total tau and NfL concentrations, smaller hippocampal and entorhinal cortex volumes, and greater WMH volume, and marginally with lower AD-signature cortical thickness. These results suggest that cerebral neurodegenerative and microvascular lesions are common neuropathologies linking anosmia with MCI in older adults.

中文翻译：

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老年人的嗅觉缺失、轻度认知障碍和脑老化的生物标志物

嗅觉障碍是前驱性痴呆的潜在标志，但其潜在机制知之甚少。这项基于人群的研究包括 4214 名无痴呆症的参与者（年龄≥65 岁）。使用 16 项 Sniffin' Sticks 识别测试评估嗅觉。在子样本中，我们测量了血浆淀粉样蛋白 β (Aβ)40、Aβ42、总 tau 蛋白和神经丝轻链 (NfL；n = 1054)；并量化了海马体、内嗅皮质和白质高信号 (WMH) 体积，以及阿尔茨海默病 (AD) 特征皮质厚度 ( n = 917)。用逻辑和线性回归模型分析数据。在总样本中，轻度认知障碍 (MCI) 被诊断为 1102 人（26.2%；遗忘性 MCI，n = 931；非遗忘性 MCI，n = 171）。嗅觉障碍与 MCI、遗忘性 MCI 和非遗忘性 MCI 的可能性增加显着相关。在子样本中，嗅觉缺失与较高的血浆总 tau 和 NfL 浓度、较小的海马和内嗅皮质体积以及较大的 WMH 体积显着相关，并且与较低的 AD 特征皮质厚度略有相关。这些结果表明，大脑神经退行性和微血管病变是常见的神经病理学，将老年人的嗅觉丧失与 MCI 联系起来。