Chaudhary Shefali, Kumaran S Senthil, Goyal Vinay, Kalaivani M, Kaloiya Gauri Shanker, Sagar Rajesh, Mehta Nalin, Srivastava Achal Kumar, Jagannathan N R
Department of NMR & MRI Facility, All India Institute of Medical Sciences, New Delhi, 110029, India.
Department of Neurology, All India Institute of Medical Sciences, New Delhi, 110029, India.
Neurol Sci. 2021 Mar;42(3):1053-1064. doi: 10.1007/s10072-020-04626-9. Epub 2020 Jul 29.
Diagnosis of Parkinson's disease (PD) cognitive impairment at early stages is challenging compared to the stage of PD dementia where functional impairment is apparent and easily diagnosed. Hence, to evaluate potential early stage cognitive biomarkers, we assessed frontal lobe metabolic alterations using in vivo multi-voxel proton magnetic resonance spectroscopic imaging (H-MRSI).
Frontal metabolism was studied in patients with PD with normal cognition (PD-CN) (n = 26), with cognitive impairment (PD-CI) (n = 27), and healthy controls (HC) (n = 30) using a single slice (two-dimensional) H-MRSI at 3 T. The acquired spectra were post-processed distinctly for voxels corresponding to the bilateral middle/superior frontal gray matter (GM) and frontal white matter (WM) regions (delineated employing neuromorphometrics atlas) using the LC-Model software.
Significant (post hoc p < 0.016) reduction in the concentration of N-acetyl aspartate (NAA) in the middle and superior frontal GMs and total choline (tCho) and total creatine (tCr) in the frontal WM was observed in PD-CI compared to PD-CN and HC, while that in HC and PD-CN groups were comparable. The NAA and tCr/tCho metabolite concentrations showed significant (p < 0.05) positive correlations with cognitive test scores in the frontal GM and WM, respectively. The receiver operating curve (ROC) analysis revealed significant (p < 0.05) "area under curve" for NAA/tNAA in the frontal GM and tCho in the frontal WM.
The frontal metabolic profile is altered in cognitively impaired PD compared with cognitively normal PD. Neuronal function loss (NAA), altered energy metabolism (Cr), and cholinergic (Cho) neural transmission are implicated in PD cognitive pathology. Frontal neuro-metabolism may promisingly serve as PD cognitive biomarker.
与帕金森病痴呆阶段（此时功能障碍明显且易于诊断）相比，帕金森病（PD）认知障碍的早期诊断具有挑战性。因此，为了评估潜在的早期认知生物标志物，我们使用活体多体素质子磁共振波谱成像（H-MRSI）评估额叶代谢改变。
使用3T的单层（二维）H-MRSI对认知正常的PD患者（PD-CN，n = 26）、有认知障碍的PD患者（PD-CI，n = 27）和健康对照者（HC，n = 30）的额叶代谢进行研究。使用LC-Model软件对与双侧中/上额叶灰质（GM）和额叶白质（WM）区域（采用神经形态计量学图谱划定）相对应的体素所获取的波谱进行不同的后处理。
与PD-CN和HC相比，PD-CI患者中额叶中/上GM的N-乙酰天门冬氨酸（NAA）浓度以及额叶WM中的总胆碱（tCho）和总肌酸（tCr）显著降低（事后检验p < 0.016），而HC组和PD-CN组的上述指标相当。NAA和tCr/tCho代谢物浓度分别与额叶GM和WM中的认知测试分数呈显著正相关（p < 0.05）。受试者工作特征曲线（ROC）分析显示，额叶GM中的NAA/tNAA和额叶WM中的tCho的“曲线下面积”具有显著性（p < 0.05）。
与认知正常的PD相比，认知受损的PD患者额叶代谢特征发生改变。神经元功能丧失（NAA）、能量代谢改变（Cr）和胆碱能（Cho）神经传递与PD认知病理学有关。额叶神经代谢有望作为PD认知生物标志物。
