Kjelvik Grete, Evensmoen Hallvard R, Hummel Thomas, Engedal Knut, Selbæk Geir, Saltvedt Ingvild, Håberg Asta K
Norwegian National Advisory Unit on Ageing and Health (Ageing and Health), Tønsberg, Norway.
Department of Radiology and Nuclear Medicine, St. Olavs Hospital (Norwegian National Advisory Unit for Functional Magnetic Resonance Imaging), University Hospital of Trondheim, Trondheim, Norway.
Front Neurol. 2021 Jan 13;11:607566. doi: 10.3389/fneur.2020.607566. eCollection 2020.
Odor identification (OI) ability is a suggested early biomarker of Alzheimer's disease. In this study, we investigated brain activity within the brain's olfactory network associated with OI in patients with amnestic mild cognitive impairment (aMCI) and mild Alzheimer's dementia (mAD) to uncover the neuronal basis of this impairment. Patients with aMCI ( = 11) or mAD ( = 6) and 28 healthy older adults underwent OI functional MRI (fMRI) at 3T, OI, odor discrimination, and cognitive tests and apolipoprotein-e4 (APOE4) genotyping. Eleven patients had cerebrospinal fluid (CSF) analyzed. Those with aMCI were followed for 2 years to examine conversion to dementia. The aMCI/mAD group performed significantly worse on all OI tests and the odor discrimination test compared to controls. The aMCI/mAD group had reduced activation in the right anterior piriform cortex compared to the controls during OI fMRI [Gaussian random field (GRF) corrected cluster threshold, < 0.05]. This group difference remained after correcting for age, sex education, and brain parenchymal fraction. This difference in piriform activity was driven primarily by differences in odor discrimination ability and to a lesser extent by OI ability. There was no group by odor discrimination/identification score interaction on brain activity. Across both groups, only odor discrimination score was significantly associated with brain activity located to the right piriform cortex. Brain activity during OI was not associated with Mini Mental Status Examination scores. At the group level, the aMCI/mAD group activated only the anterior insula, while the control group had significant activation within all regions of the olfactory network during OI fMRI. There was no association between brain activity during OI fMRI and total beta-amyloid levels in the CSF in the aMCI/mAD group. The OI impairment in aMCI/mAD patients is associated with significantly reduced activity in the piriform cortex compared to controls. Activation of downstream regions within the olfactory network is also significantly affected in the aMCI/mAD group, except the anterior insula, which is impinged late in the course of Alzheimer's disease. OI tests thus reflect Alzheimer's disease pathology in olfactory brain structures.
气味识别（OI）能力被认为是阿尔茨海默病的一种早期生物标志物。在本研究中，我们调查了遗忘型轻度认知障碍（aMCI）和轻度阿尔茨海默病痴呆（mAD）患者大脑嗅觉网络中与OI相关的脑活动，以揭示这种损伤的神经基础。aMCI患者（n = 11）或mAD患者（n = 6）以及28名健康老年人接受了3T的OI功能磁共振成像（fMRI）、OI、气味辨别和认知测试以及载脂蛋白E4（APOE4）基因分型。对11名患者的脑脊液（CSF）进行了分析。对aMCI患者进行了2年的随访，以检查其是否转化为痴呆。与对照组相比，aMCI/mAD组在所有OI测试和气味辨别测试中的表现明显更差。在OI fMRI期间，与对照组相比，aMCI/mAD组右侧前梨状皮质的激活减少[高斯随机场（GRF）校正簇阈值，p < 0.05]。在校正年龄、性别、教育程度和脑实质分数后，这种组间差异仍然存在。梨状皮质活动的这种差异主要由气味辨别能力的差异驱动，在较小程度上由OI能力驱动。在脑活动方面，不存在按气味辨别/识别分数分组的交互作用。在两组中，只有气味辨别分数与右侧梨状皮质的脑活动显著相关。OI期间的脑活动与简易精神状态检查表得分无关。在组水平上，aMCI/mAD组在OI fMRI期间仅激活了前岛叶，而对照组在嗅觉网络的所有区域均有显著激活。在aMCI/mAD组中，OI fMRI期间的脑活动与CSF中总β-淀粉样蛋白水平之间没有关联。与对照组相比，aMCI/mAD患者的OI损伤与梨状皮质活动显著减少有关。在aMCI/mAD组中，嗅觉网络下游区域的激活也受到显著影响，但前岛叶除外，前岛叶在阿尔茨海默病病程后期才受到影响。因此，OI测试反映了嗅觉脑结构中的阿尔茨海默病病理。
