Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany;
German Center for Neurodegenerative Diseases, Bonn, Germany.
J Nucl Med. 2024 Jan 2;65(1):147-155. doi: 10.2967/jnumed.123.265931.
Deviations of brain age from chronologic age, known as the brain age gap (BAG), have been linked to neurodegenerative diseases such as Alzheimer disease (AD). Here, we compare the associations of MRI-derived (atrophy) or F-FDG PET-derived (brain metabolism) BAG with cognitive performance, neuropathologic burden, and disease progression in cognitively normal individuals (CNs) and individuals with subjective cognitive decline (SCD) or mild cognitive impairment (MCI). Machine learning pipelines were trained to estimate brain age from 185 matched T1-weighted MRI or F-FDG PET scans of CN from the Alzheimer's Disease Neuroimaging Initiative and validated in external test sets from the Open Access of Imaging and German Center for Neurodegenerative Diseases-Longitudinal Cognitive Impairment and Dementia studies. BAG was correlated with measures of cognitive performance and AD neuropathology in CNs, SCD subjects, and MCI subjects. Finally, BAG was compared between cognitively stable and declining individuals and subsequently used to predict disease progression. MRI (mean absolute error, 2.49 y) and F-FDG PET (mean absolute error, 2.60 y) both estimated chronologic age well. At the SCD stage, MRI-based BAG correlated significantly with beta-amyloid (Aβ) in cerebrospinal fluid, whereas F-FDG PET BAG correlated with memory performance. At the MCI stage, both BAGs were associated with memory and executive function performance and cerebrospinal fluid Aβ, but only MRI-derived BAG correlated with phosphorylated-tau/Aβ Lastly, MRI-estimated BAG predicted MCI-to-AD progression better than F-FDG PET-estimated BAG (areas under the curve, 0.73 and 0.60, respectively). Age was reliably estimated from MRI or F-FDG PET. MRI BAG reflected cognitive and pathologic markers of AD in SCD and MCI, whereas F-FDG PET BAG was sensitive mainly to early cognitive impairment, possibly constituting an independent biomarker of brain age-related changes.
大脑年龄与实际年龄的偏差,即脑龄差距(BAG),与阿尔茨海默病(AD)等神经退行性疾病有关。在这里,我们比较了 MRI 衍生(萎缩)或 F-FDG PET 衍生(脑代谢)BAG 与认知表现、神经病理学负担和认知正常个体(CNs)及有主观认知下降(SCD)或轻度认知障碍(MCI)个体的疾病进展的相关性。机器学习管道从阿尔茨海默病神经影像学倡议中 185 个匹配的 T1 加权 MRI 或 F-FDG PET 扫描中训练了估计脑龄,并在来自成像和德国神经退行性疾病中心的开放访问的外部测试集中进行了验证——纵向认知障碍和痴呆研究。BAG 与 CNs、SCD 受试者和 MCI 受试者的认知表现和 AD 神经病理学测量值相关。最后,比较了认知稳定和下降个体之间的 BAG,并随后用于预测疾病进展。MRI(平均绝对误差,2.49 岁)和 F-FDG PET(平均绝对误差,2.60 岁)都很好地估计了实际年龄。在 SCD 阶段,MRI 衍生的 BAG 与脑脊液中的β-淀粉样蛋白(Aβ)显著相关,而 F-FDG PET BAG 与记忆表现相关。在 MCI 阶段,两个 BAG 都与记忆和执行功能表现和脑脊液 Aβ相关,但只有 MRI 衍生的 BAG与磷酸化 tau/Aβ相关。最后,MRI 估计的 BAG 比 F-FDG PET 估计的 BAG 更好地预测了 MCI 到 AD 的进展(曲线下面积分别为 0.73 和 0.60)。从 MRI 或 F-FDG PET 可以可靠地估计年龄。MRI BAG 反映了 SCD 和 MCI 中 AD 的认知和病理标志物,而 F-FDG PET BAG 主要对早期认知障碍敏感,可能构成脑年龄相关变化的独立生物标志物。