纵向多巴胺 D2 受体变化与衰老中的脑血管健康。
Longitudinal Dopamine D2 Receptor Changes and Cerebrovascular Health in Aging.
机构信息
From the Departments of Radiation Sciences, Diagnostic Radiology (N.K., J.J., K.R., L.N.) and Radiation Physics (A.W., J.A.), Department of Applied Physics and Electronics (A.W.), and Umeå Center for Functional Brain Imaging (UFBI) (N.K., J.J., A.W., A.S., M.A., J.A., K.R., L.N.), Umeå University; Aging Research Center (G.P., A.S., L.B.), Karolinska Institutet & Stockholm University; Department of Integrative Medical Biology (A.S., M.A., L.N.), and Wallenberg Center for Molecular Medicine (A.S., L.N.), Umeå University, Sweden; Center for Lifespan Psychology (Y.K., A.M.B., U.L.), Max Planck Institute for Human Development; Max Planck UCL Centre for Computational Psychiatry and Ageing Research (A.M.B., U.L.), Berlin, Germany and London, UK; and Department of Psychology (M.L.), University of Gothenburg, Sweden.
出版信息
Neurology. 2022 Sep 20;99(12):e1278-e1289. doi: 10.1212/WNL.0000000000200891. Epub 2022 Jul 5.
BACKGROUND AND OBJECTIVES
Cross-sectional studies suggest marked dopamine (DA) decline in aging, but longitudinal evidence is lacking. The aim of this study was to estimate within-person decline rates for DA D2-like receptors (DRD2) in aging and examine factors that may contribute to individual differences in DRD2 decline rates.
METHODS
We investigated 5-year within-person changes in DRD2 availability in a sample of older adults. At both occasions, PET with C-raclopride and MRI were used to measure DRD2 availability in conjunction with structural and vascular brain integrity.
RESULTS
Longitudinal analyses of the sample (baseline: n = 181, ages: 64-68 years, 100 men and 81 women; 5-year follow-up: n = 129, 69 men and 60 women) revealed aging-related striatal and extrastriatal DRD2 decline, along with marked individual differences in rates of change. Notably, the magnitude of striatal DRD2 decline was ∼50% of past cross-sectional estimates, suggesting that the DRD2 decline rate has been overestimated in past cross-sectional studies. Significant DRD2 reductions were also observed in select extrastriatal regions, including hippocampus, orbitofrontal cortex (OFC), and anterior cingulate cortex (ACC). Distinct profiles of correlated DRD2 changes were found across several associative regions (ACC, dorsal striatum, and hippocampus) and in the reward circuit (nucleus accumbens and OFC). DRD2 losses in associative regions were associated with white matter lesion progression, whereas DRD2 losses in limbic regions were related to reduced cortical perfusion.
DISCUSSION
These findings provide the first longitudinal evidence for individual and region-specific differences of DRD2 decline in older age and support the hypothesis that cerebrovascular factors are linked to age-related dopaminergic decline.
背景和目的
横断面研究表明，多巴胺（DA）在衰老过程中明显下降，但缺乏纵向证据。本研究旨在估计衰老过程中 DA D2 样受体（DRD2）的个体内下降率，并探讨可能导致 DRD2 下降率个体差异的因素。
方法
我们在一组老年人样本中研究了 5 年内 DRD2 丰度的个体内变化。在两次就诊时，均使用 C-racopride 的 PET 和 MRI 来测量 DRD2 丰度，同时还测量了结构和血管脑完整性。
结果
对样本的纵向分析（基线：n = 181，年龄：64-68 岁，100 名男性和 81 名女性；5 年随访：n = 129，69 名男性和 60 名女性）显示，与衰老相关的纹状体和纹状体外 DRD2 下降，以及变化率的显著个体差异。值得注意的是，纹状体 DRD2 下降的幅度约为过去横断面研究估计值的 50%，这表明过去的横断面研究中对 DRD2 下降率的估计过高。还观察到包括海马体、眶额皮质（OFC）和前扣带回皮质（ACC）在内的一些纹状体外区域的显著 DRD2 减少。在几个关联区域（ACC、背侧纹状体和海马体）和奖励回路（伏隔核和 OFC）中发现了不同的 DRD2 相关变化模式。关联区域的 DRD2 损失与白质病变进展相关，而边缘区域的 DRD2 损失与皮质灌注减少有关。
讨论
这些发现为老年人中 DRD2 下降的个体和区域特异性差异提供了首个纵向证据，并支持了脑血管因素与年龄相关的多巴胺能下降相关的假说。
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