The Australian e-Health Research Centre, CSIRO Health and Biosecurity, Brisbane, QLD, Australia.
Internal Medicine Service, The Prince Charles Hospital, Brisbane, QLD, Australia; School of Medicine, Northside Clinical School, The Prince Charles Hospital, Brisbane, QLD, Australia; Dementia & Neuro Mental Health Research Unit, UQCCR, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
Neuroimage Clin. 2022;34:102992. doi: 10.1016/j.nicl.2022.102992. Epub 2022 Mar 24.
Dysfunction of the cholinergic basal forebrain (BF) neurotransmitter system, including cholinergic axon denervation of the cortex, plays an important role in cognitive decline and dementia. A validated method to directly quantify cortical cholinergic terminal integrity enables exploration of the involvement of this system in diverse cognitive profiles associated with dementia, particularly at a prodromal stage. In this study, we used the radiotracer [F]-fluoroethoxybenzovesamicol (FEOBV) as a direct measure of cholinergic terminal integrity and investigated its value for the assessment of cholinergic denervation in the cortex and associated cognitive deficits. Eighteen participants (8 with mild cognitive impairment (MCI) and 10 cognitively unimpaired controls) underwent neuropsychological assessment and brain imaging using FEOBV and [F]-florbetaben for amyloid-β imaging. The MCI group showed a significant global reduction of FEOBV retention in the cortex and in the parietal and occipital cortices specifically compared to the control group. The global cortical FEOBV retention of all participants positively correlated with the BF, hippocampus and grey matter volumes, but no association was found between the global FEOBV retention and amyloid-β status. Topographic profiles from voxel-wise analysis of FEOBV images revealed significant positive correlations with the cognitive domains associated with the underlying cortical areas. Overlapping profiles of decreased FEOBV were identified in correlation with impairment in executive function, attention and language, which covered the anterior cingulate gyrus, olfactory cortex, calcarine cortex, middle temporal gyrus and caudate nucleus. However, the absence of cortical atrophy in these areas suggested that reduced cholinergic terminal integrity in the cortex is an important factor underlying the observed cognitive decline in early dementia. Our results provide support for the utility and validity of FEOBV PET for quantitative assessment of region-specific cholinergic terminal integrity that could potentially be used for early detection of cholinergic dysfunction in dementia following further validation in larger cohorts.
胆碱能基底前脑（BF）神经递质系统的功能障碍，包括皮质胆碱能轴突去神经支配，在认知能力下降和痴呆中起着重要作用。一种经过验证的方法可以直接量化皮质胆碱能末梢的完整性，从而可以探索该系统在与痴呆相关的不同认知特征中的参与，尤其是在前期阶段。在这项研究中，我们使用放射性示踪剂[F]-氟乙氧基苯并维司莫尔（FEOBV）作为胆碱能末梢完整性的直接测量指标，研究了其在评估皮质胆碱能去神经支配和相关认知缺陷中的价值。18 名参与者（8 名轻度认知障碍（MCI）和 10 名认知正常对照）接受了神经心理学评估和脑成像，使用 FEOBV 和[F]-氟比他滨进行淀粉样β成像。与对照组相比，MCI 组的皮质 FEOBV 保留量整体显著降低，特别是在顶叶和枕叶皮质。所有参与者的皮质整体 FEOBV 保留量与 BF、海马体和灰质体积呈正相关，但与淀粉样蛋白-β状态之间没有关联。FEOBV 图像的体素分析的拓扑分布与与皮质下区域相关的认知域呈显著正相关。与执行功能、注意力和语言相关的认知域相关的 FEOBV 减少的重叠分布与损伤相关，这些分布涵盖了前扣带回、嗅觉皮层、距状裂皮质、中颞回和尾状核。然而，这些区域没有皮质萎缩，这表明皮质中胆碱能末梢完整性的降低是早期痴呆中观察到的认知下降的一个重要因素。我们的研究结果为 FEOBV PET 用于定量评估区域特异性胆碱能末梢完整性提供了支持，这可能有助于在更大的队列中进一步验证后，用于早期发现痴呆中的胆碱能功能障碍。
