1Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China 2Beijing Neurosurgical Institute, Capital Medical University, Beijing, China 3Beijing Key Laboratory of Neurostimulation, Beijing, China 4Department of Neurosurgery, Beijing Children’s hospital, Capital Medical University, Beijing, China
Positron emission tomography (PET) scan with tracer [18F]-fluorodeoxy-glucose (18F-FDG) is widely used to measure the glucose metabolism in neurodegenerative disease such as Idiopathic Parkinson’s disease (IPD). Previous studies using 18F-FDG PET mainly focused on the motor or non-motor symptoms but not the severity of IPD. In this study, we aimed to determine the metabolic patterns of 18F-FDG in different stages of IPD defined by Hoehn and Yahr rating scale (H-Y rating scale) and to identify regions in the brain that play critical roles in disease progression. Fifty IPD patients were included in this study. They were 29 men and 21 women (mean±SD, age 57.7±11.1 years, disease duration 4.0±3.8 years, H-Y 2.2±1.1). Twenty healthy individuals were included as normal controls. Following 18F-FDG PET scan, image analysis was performed using Statistical Parametric Mapping (SPM) and Resting-State fMRI Data Analysis Toolkit (REST). The metabolic feature of IPD and regions-of-interests (ROIs) were determined. Correlation analysis between ROIs and H-Y stage was performed. SPM analysis demonstrated a significant hypometabolic activity in bilateral putamen, caudate and anterior cingulate as well as left parietal lobe, prefrontal cortex in IPD patients. In contrast, hypermetabolism was observed in the cerebellum and vermis. There was a negative correlation (p=0.007, r=-0.412) between H-Y stage and caudate metabolic activity. Moreover, the prefrontal area also showed a negative correlation with H-Y (P=0.033, r=-0.334). Thus, the uptake of FDG in caudate and prefrontal cortex can potentially be used as a surrogate marker to evaluate the severity of IPD.
Jun-Sheng Chu,Ting-Hong Liu,Kai-Liang Wang, et al. The Metabolic Activity of Caudate and Prefrontal Cortex Negatively Correlates with the Severity of Idiopathic Parkinson’s Disease[J]. Aging and disease,
2019, 10(4): 847-853.
Table 1 Clinical and Demographic characteristics of 50 patients (29 men; 21 women) and 20 health control (13 men; 7 women).
Fig 1. The metabolism of FDG in IPD patients compared to healthy controls. Brain areas with increased/decreased glucose metabolism are superimposed on the Montreal Neurological Institute template (Top row) (p < 0.001, uncorrected) and the 3D render (Bottom row). A) Significant hypometabolism in bilateral putamen, caudate, anterior cingulate, parietal lobe and prefrontal cortex was identified. B) The relative hypermetabolism was identified in the cerebellum and vermis.
Figure 2. The relationship between the metabolic activity of ROIs and H-Y stages
A) In caudate, the metabolic activity decreased as H-Y stages increased (p=0.004 r=-0.441). B) Similar to caudate, prefrontal metabolic activity also decreased as H-Y stages increased (p=0.004 r=-0.441). C, D, E and F, show no correlation in vermis (C), angular (D), occipital (E) and temporal lobes (F). The Pearson correlation analysis was performed using SPSS software.
Table 2 MNI coordinate of significant clusters.
Jankovic J (2008). Parkinson's disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry, 79: 368-376.
Ma SY, Roytta M, Rinne JO, Collan Y, Rinne UK (1995). Single section and disector counts in evaluating neuronal loss from the substantia nigra in patients with Parkinson's disease. Neuropathol Appl Neurobiol, 21: 341-343.
Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F (1973). Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. J Neurol Sci, 20: 415-455.
Delval A, Tard C, Defebvre L (2014). Why we should study gait initiation in Parkinson's disease. Neurophysiol Clin, 44: 69-76.
Poston KL, Eidelberg D (2010). FDG PET in the Evaluation of Parkinson's Disease. PET Clin, 5: 55-64.
Huang C, Mattis P, Perrine K, Brown N, Dhawan V, Eidelberg D (2008). Metabolic abnormalities associated with mild cognitive impairment in Parkinson disease. Neurology, 70: 1470-1477.
Hellwig S, Frings L, Amtage F, Buchert R, Spehl TS, Rijntjes M, et al. (2015). 18F-FDG PET Is an Early Predictor of Overall Survival in Suspected Atypical Parkinsonism. J Nucl Med, 56: 1541-1546.
Wang R, Xu B, Guo Z, Chen T, Zhang J, Chen Y, et al. (2017). Suite PET/CT neuroimaging for the diagnosis of Parkinson's disease: statistical parametric mapping analysis. Nucl Med Commun, 38: 164-169.
Wang X, Zhang J, Yuan Y, Li T, Zhang L, Ding J, et al. (2017). Cerebral metabolic change in Parkinson's disease patients with anxiety: A FDG-PET study. Neurosci Lett, 653: 202-207.
Tomse P, Jensterle L, Grmek M, Zaletel K, Pirtosek Z, Dhawan V, et al. (2017). Abnormal metabolic brain network associated with Parkinson's disease: replication on a new European sample. Neuroradiology, 59: 507-515.
Cho SS, Aminian K, Li C, Lang AE, Houle S, Strafella AP (2017). Fatigue in Parkinson's disease: The contribution of cerebral metabolic changes. Hum Brain Mapp, 38: 283-292.
Huang C, Ravdin LD, Nirenberg MJ, Piboolnurak P, Severt L, Maniscalco JS, et al. (2013). Neuroimaging markers of motor and nonmotor features of Parkinson's disease: an 18f fluorodeoxyglucose positron emission computed tomography study. Dement Geriatr Cogn Disord, 35: 183-196.
Pilotto A, Premi E, Paola Caminiti S, Presotto L, Turrone R, Alberici A, et al. (2018). Single-subject SPM FDG-PET patterns predict risk of dementia progression in Parkinson disease. Neurology, 90: e1029-e1037.
Teune LK, Renken RJ, de Jong BM, Willemsen AT, van Osch MJ, Roerdink JB, et al. (2014). Parkinson's disease-related perfusion and glucose metabolic brain patterns identified with PCASL-MRI and FDG-PET imaging. Neuroimage Clin, 5: 240-244.
Wang K, Liu T, Zhao X, Xia X, Zhang K, Qiao H, et al. (2016). Comparative Study of Voxel-Based Epileptic Foci Localization Accuracy between Statistical Parametric Mapping and Three-dimensional Stereotactic Surface Projection. Front Neurol, 7: 164.
Eidelberg D (2009). Metabolic brain networks in neurodegenerative disorders: a functional imaging approach. Trends Neurosci, 32: 548-557.
Lozza C, Baron JC, Eidelberg D, Mentis MJ, Carbon M, Marie RM (2004). Executive processes in Parkinson's disease: FDG-PET and network analysis. Hum Brain Mapp, 22: 236-245.
Eckert T, Van Laere K, Tang C, Lewis DE, Edwards C, Santens P, et al. (2007). Quantification of Parkinson's disease-related network expression with ECD SPECT. Eur J Nucl Med Mol Imaging, 34: 496-501.
Asanuma K, Tang C, Ma Y, Dhawan V, Mattis P, Edwards C, et al. (2006). Network modulation in the treatment of Parkinson's disease. Brain, 129: 2667-2678.
Huang C, Mattis P, Tang C, Perrine K, Carbon M, Eidelberg D (2007). Metabolic brain networks associated with cognitive function in Parkinson's disease. Neuroimage, 34: 714-723.
Juh R, Pae CU, Lee CU, Yang D, Chung Y, Suh T, et al. (2005). Voxel based comparison of glucose metabolism in the differential diagnosis of the multiple system atrophy using statistical parametric mapping. Neurosci Res, 52: 211-219.
Juh R, Kim J, Moon D, Choe B, Suh T (2004). Different metabolic patterns analysis of Parkinsonism on the 18F-FDG PET. Eur J Radiol, 51: 223-233.
Strafella AP, Bohnen NI, Perlmutter JS, Eidelberg D, Pavese N, Van Eimeren T, et al. (2017). Molecular imaging to track Parkinson's disease and atypical parkinsonisms: New imaging frontiers. Mov Disord, 32: 181-192.
Apostolova LG, Beyer M, Green AE, Hwang KS, Morra JH, Chou YY, et al. (2010). Hippocampal, caudate, and ventricular changes in Parkinson's disease with and without dementia. Mov Disord, 25: 687-695.
Dagher A, Owen AM, Boecker H, Brooks DJ (2001). The role of the striatum and hippocampus in planning: a PET activation study in Parkinson's disease. Brain, 124: 1020-1032.
Polito C, Berti V, Ramat S, Vanzi E, De Cristofaro MT, Pellicano G, et al. (2012). Interaction of caudate dopamine depletion and brain metabolic changes with cognitive dysfunction in early Parkinson's disease. Neurobiol Aging, 33: 206 e229-239.
Broussolle E, Dentresangle C, Landais P, Garcia-Larrea L, Pollak P, Croisile B, et al. (1999). The relation of putamen and caudate nucleus 18F-Dopa uptake to motor and cognitive performances in Parkinson's disease. J Neurol Sci, 166: 141-151.
Kish SJ, Shannak K, Hornykiewicz O (1988). Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson's disease. Pathophysiologic and clinical implications. N Engl J Med, 318: 876-880.
Bruck A, Portin R, Lindell A, Laihinen A, Bergman J, Haaparanta M, et al. (2001). Positron emission tomography shows that impaired frontal lobe functioning in Parkinson's disease is related to dopaminergic hypofunction in the caudate nucleus. Neurosci Lett, 311: 81-84.
Ko JH, Katako A, Aljuaid M, Goertzen AL, Borys A, Hobson DE, et al. (2017). Distinct brain metabolic patterns separately associated with cognition, motor function, and aging in Parkinson's disease dementia. Neurobiol Aging, 60: 81-91.
Son HJ, Jeong YJ, Yoon HJ, Kim JW, Choi GE, Park JH, et al. (2017). Parkinson disease-related cortical and striatal cognitive patterns in dual time F-18 FP CIT: evidence for neural correlates between the caudate and the frontal lobe. Q J Nucl Med Mol Imaging.
Collins P, Wilkinson LS, Everitt BJ, Robbins TW, Roberts AC (2000). The effect of dopamine depletion from the caudate nucleus of the common marmoset (Callithrix jacchus) on tests of prefrontal cognitive function. Behav Neurosci, 114: 3-17.
Argyelan M, Carbon M, Ghilardi MF, Feigin A, Mattis P, Tang C, et al. (2008). Dopaminergic suppression of brain deactivation responses during sequence learning. J Neurosci, 28: 10687-10695.
Kalbe E, Voges J, Weber T, Haarer M, Baudrexel S, Klein JC, et al. (2009). Frontal FDG-PET activity correlates with cognitive outcome after STN-DBS in Parkinson disease. Neurology, 72: 42-49.
Marie RM, Barre L, Dupuy B, Viader F, Defer G, Baron JC (1999). Relationships between striatal dopamine denervation and frontal executive tests in Parkinson's disease. Neurosci Lett, 260: 77-80.