German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany; Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany.
German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany.
Neuroimage Clin. 2020;28:102495. doi: 10.1016/j.nicl.2020.102495. Epub 2020 Nov 11.
Dysfunction of the cholinergic basal forebrain (cBF) is associated with cognitive decline in Alzheimer's disease (AD). Multimodal MRI allows for the investigation of cBF changes in-vivo. In this study we assessed alterations in cBF functional connectivity (FC), mean diffusivity (MD), and volume across the spectrum of AD. We further assessed effects of amyloid pathology on these changes.
Participants included healthy controls, and subjects with subjective cognitive decline (SCD), mild cognitive impairment (MCI), or AD dementia (ADD) from the multicenter DELCODE study. Resting-state functional MRI (rs-fMRI) and structural MRI data was available for 477 subjects, and a subset of 243 subjects also had DTI data available. Differences between diagnostic groups were investigated using seed-based FC, volumetric, and MD analyses of functionally defined anterior (a-cBF) and posterior (p-cBF) subdivisions of a cytoarchitectonic cBF region-of-interest. In complementary analyses groups were stratified according to amyloid status based on CSF Aβ42/40 biomarker data, which was available in a subset of participants.
a-cBF and p-cBF subdivisions showed regional FC profiles that were highly consistent with previously reported patterns, but there were only minimal differences between diagnostic groups. Compared to controls, cBF volumes and MD were significantly different in MCI and ADD but not in SCD. The Aβ42/40 stratified analyses largely matched these results.
We reproduced subregion-specific FC profiles of the cBF in a clinical sample spanning the AD spectrum. At least in this multicentric cohort study, cBF-FC did not show marked changes along the AD spectrum, and multimodal MRI did not provide more sensitive measures of AD-related cBF changes compared to volumetry.
胆碱能基底前脑（cBF）功能障碍与阿尔茨海默病（AD）的认知能力下降有关。多模态 MRI 可用于研究 cBF 的变化。在这项研究中，我们评估了 AD 谱中 cBF 功能连接（FC）、平均扩散系数（MD）和体积的变化。我们进一步评估了淀粉样蛋白病理学对这些变化的影响。
参与者包括来自多中心 DELCODE 研究的健康对照组以及有主观认知下降（SCD）、轻度认知障碍（MCI）或 AD 痴呆（ADD）的患者。477 名患者有静息状态功能磁共振成像（rs-fMRI）和结构 MRI 数据，243 名患者有弥散张量成像（DTI）数据。使用基于种子的 FC、功能定义的前（a-cBF）和后（p-cBF）cBF 亚区的容积和 MD 分析，研究了诊断组之间的差异。在补充分析中，根据 CSF Aβ42/40 生物标志物数据将组根据淀粉样蛋白状态分层，该数据在部分参与者中可用。
a-cBF 和 p-cBF 亚区显示出与先前报道的模式高度一致的区域 FC 图谱，但诊断组之间只有微小差异。与对照组相比，MCI 和 ADD 患者的 cBF 体积和 MD 明显不同，但 SCD 患者则不同。Aβ42/40 分层分析基本符合这些结果。
我们在一个涵盖 AD 谱的临床样本中重现了 cBF 的亚区特异性 FC 图谱。至少在这项多中心队列研究中，cBF-FC 在 AD 谱中没有明显变化，与容积相比，多模态 MRI 并未提供更敏感的 AD 相关 cBF 变化测量指标。
