Department of Neurology, UMC Ljubljana, Ljubljana, Slovenia.
Medical Faculty, University of Ljubljana, Ljubljana, Slovenia.
Mov Disord. 2022 Nov;37(11):2247-2256. doi: 10.1002/mds.29188. Epub 2022 Aug 23.
Idiopathic Parkinson's disease (iPD) is associated with two distinct brain networks, PD-related pattern (PDRP) and PD-related cognitive pattern (PDCP), which correlate respectively with motor and cognitive symptoms. The relationship between the two networks in individual patients is unclear.
To determine whether a consistent relationship exists between these networks, we measured the difference between PDRP and PDCP expression, termed delta, on an individual basis in independent populations of patients with iPD (n = 356), patients with idiopathic REM sleep behavioral disorder (iRBD) (n = 21), patients with genotypic PD (gPD) carrying GBA1 variants (n = 12) or the LRRK2-G2019S mutation (n = 14), patients with atypical parkinsonian syndromes (n = 238), and healthy control subjects (n = 95) from the United States, Slovenia, India, and South Korea.
We used [ F]-fluorodeoxyglucose positron emission tomography and resting-state fMRI to quantify delta and to compare the measure across samples; changes in delta over time were likewise assessed in longitudinal patient samples. Lastly, we evaluated delta in prodromal individuals with iRBD and subjects with gPD.
Delta was abnormally elevated in each of the four iPD samples (P < 0.05), as well as in the at-risk iRBD group (P < 0.05), with increasing values over time (P < 0.001). PDRP predominance was also present in gPD, with higher values in patients with GBA1 variants compared with the less aggressive LRRK2-G2019S mutation (P = 0.005). This trend was not observed in patients with atypical parkinsonian syndromes, who were accurately discriminated from iPD based on PDRP expression and delta (area under the curve = 0.85; P < 0.0001).
PDRP predominance, quantified by delta, assays the spread of dysfunction from motor to cognitive networks in patients with PD. Delta may therefore aid in differential diagnosis and in tracking disease progression in individual patients. © 2022 International Parkinson and Movement Disorder Society.
特发性帕金森病（iPD）与两个不同的大脑网络相关，即与帕金森病相关的模式（PDRP）和与帕金森病相关的认知模式（PDCP），它们分别与运动和认知症状相关。个体患者中这两个网络之间的关系尚不清楚。
为了确定这两个网络之间是否存在一致的关系，我们在独立的 iPD 患者群体（n=356）、特发性 REM 睡眠行为障碍（iRBD）患者（n=21）、携带 GBA1 变体的基因型 PD（gPD）患者（n=12）或 LRRK2-G2019S 突变患者（n=14）、非典型帕金森综合征患者（n=238）和来自美国、斯洛文尼亚、印度和韩国的健康对照者（n=95）中，基于个体分别测量 PDRP 和 PDCP 表达之间的差异，称为 delta，并在样本间比较该测量值；同样，在纵向患者样本中评估 delta 的随时间变化。最后，我们评估了 iRBD 前驱期个体和 gPD 患者的 delta。
我们使用[ F]-氟脱氧葡萄糖正电子发射断层扫描和静息状态 fMRI 来量化 delta，并比较不同样本中的测量值；同样，在纵向患者样本中评估 delta 的随时间变化。最后，我们评估了 iRBD 前驱期个体和 gPD 患者的 delta。
四个 iPD 样本中的每个样本（P<0.05）以及高危 iRBD 组（P<0.05）的 delta 均异常升高，且随时间增加而升高（P<0.001）。gPD 中也存在 PDRP 优势，与侵袭性较小的 LRRK2-G2019S 突变相比，GBA1 变体患者的 delta 值更高（P=0.005）。在非典型帕金森综合征患者中未观察到这种趋势，他们基于 PDRP 表达和 delta 可以准确地区分与 iPD（曲线下面积=0.85；P<0.0001）。
由 delta 定量的 PDRP 优势检测到 PD 患者的功能障碍从运动网络向认知网络的扩散。因此，delta 可能有助于鉴别诊断和跟踪个体患者的疾病进展。
