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01-03-2021 | Parkinson's Disease | Original Article

Frontal lobe metabolic alterations characterizing Parkinson’s disease cognitive impairment

Authors: Shefali Chaudhary, S. Senthil Kumaran, Vinay Goyal, M. Kalaivani, Gauri Shanker Kaloiya, Rajesh Sagar, Nalin Mehta, Achal Kumar Srivastava, N. R. Jagannathan

Published in: Neurological Sciences | Issue 3/2021

Abstract

Background and purpose

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 (¹H-MRSI).

Method

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) ¹H-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.

Result

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.

Conclusion

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.

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Lopiano L, Modugno N, Marano P, Sensi M, Meco G, Cannas A, Gusmaroli G, Tamma F, Mancini F, Quatrale R, Costanzo AM, Gualberti G, Melzi G, di Luzio Paparatti U, Antonini A (2016) Motor outcomes in patients with advanced Parkinson’s disease treated with levodopa/carbidopa intestinal gel in Italy: an interim analysis from the GREENFIELD observational study. Neurol Sci 37:1785–1792. https://doi.org/10.1007/s10072-016-2664-0CrossRefPubMedPubMedCentral

Goldman JG, Vernaleo BA, Camicioli R et al (2018) Cognitive impairment in Parkinson’s disease: a report from a multidisciplinary symposium on unmet needs and future directions to maintain cognitive health. NPJ Parkinsons Dis 4:19. https://doi.org/10.1038/s41531-018-0055-3CrossRefPubMedPubMedCentral

Aarsland D, Kvaløy JT, Andersen K, Larsen JP, Tang MX, Lolk A, Kragh-Sørensen P, Marder K (2007) The effect of age of onset of PD on risk of dementia. J Neurol 254:38–45. https://doi.org/10.1007/s00415-006-0234-8CrossRefPubMed

Lucetti C, Del Dotto P, Gambaccini G et al (2001) Proton magnetic resonance spectroscopy (1H-MRS) of motor cortex and basal ganglia in de novo Parkinson’s disease patients. Neurol Sci 22:69–70. https://doi.org/10.1007/s100720170051CrossRefPubMed

Prell T (2018) Structural and functional brain patterns of non-motor syndromes in Parkinson’s disease. Front Neurol 9:138. https://doi.org/10.3389/fneur.2018.00138CrossRefPubMedPubMedCentral

Pagonabarraga J, Gómez-Ansón B, Rotger R, Llebaria G, García-Sánchez C, Pascual-Sedano B, Gironell A, Delfino M, Ruscalleda J, Kulisevsky J (2012) Spectroscopic changes associated with mild cognitive impairment and dementia in Parkinson’s disease. Dement Geriatr Cogn Disord 34:312–318. https://doi.org/10.1159/000345537CrossRefPubMed

Almuqbel M, Melzer TR, Myall DJ, MacAskill MR, Pitcher TL, Livingston L, Wood KL, Keenan RJ, Dalrymple-Alford JC, Anderson TJ (2016) Metabolite ratios in the posterior cingulate cortex do not track cognitive decline in Parkinson’s disease in a clinical setting. Parkinsonism Relat Disord 22:54–61. https://doi.org/10.1016/j.parkreldis.2015.11.008CrossRefPubMed

Gratwicke J, Jahanshahi M, Foltynie T (2015) Parkinson’s disease dementia: a neural networks perspective. Brain. 138:1454–1476. https://doi.org/10.1093/brain/awv104CrossRefPubMedPubMedCentral

Tal A, Kirov II, Grossman RI, Gonen O (2012) The role of gray and white matter segmentation in quantitative proton MR spectroscopic imaging. NMR Biomed 25:1392–1400. https://doi.org/10.1002/nbm.2812CrossRefPubMedPubMedCentral

10.

Chaudhary S, Kumaran SS, Kaloiya GS, Goyal V, Sagar R, Kalaivani M, Jaganathan NR, Mehta N, Srivastava A (2020) Domain specific cognitive impairment in Parkinson’s patients with mild cognitive impairment. J Clin Neurosci 75:99–105. https://doi.org/10.1016/j.jocn.2020.03.015CrossRefPubMed

11.

Calabresi P, Galletti F, Saggese E, Ghiglieri V, Picconi B (2007) Neuronal networks and synaptic plasticity in Parkinson’s disease: beyond motor deficits. Parkinsonism Relat Disord 13:S259–S262. https://doi.org/10.1016/S1353-8020(08)70013-0CrossRefPubMed

12.

Provencher SW (1993) Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med 30:672–679. https://doi.org/10.1002/mrm.1910300604CrossRefPubMed

13.

Griffith HR, den Hollander JA, Okonkwo OC, O’Brien T, Watts RL, Marson DC (2008) Brain metabolism differs in Alzheimer’s disease and Parkinson’s disease dementia. Alzheimers Dement 4:421–427. https://doi.org/10.1016/j.jalz.2008.04.008CrossRefPubMedPubMedCentral

14.

Provencher SW (2019) LCModel & LCMgui User’s Manual

15.

Penny W, Friston K, Ashburner J, Kiebel S, Nichols T (2007) Statistical parametric mapping. Elsevier. https://doi.org/10.1016/B978-0-12-372560-8.X5000-1

16.

Asman AJ, Chambless LB, Thompson RC, Landman BA (2013) Out-of-atlas likelihood estimation using multi-atlas segmentation. Med Phys 40:043702. https://doi.org/10.1118/1.4794478CrossRefPubMedPubMedCentral

17.

Doelken MT, Mennecke A, Stadlbauer A, Kecskeméti L, Kasper BS, Struffert T, Doerfler A, Stefan H, Hammen T (2010) Multi-voxel magnetic resonance spectroscopy at 3T in patients with idiopathic generalised epilepsy. Seizure. 19:485–492. https://doi.org/10.1016/j.seizure.2010.07.005CrossRefPubMed

18.

Robbins TW, Cools R (2014) Cognitive deficits in Parkinson’s disease: a cognitive neuroscience perspective. Mov Disord 29:597–607. https://doi.org/10.1002/mds.25853CrossRefPubMed

19.

Williams-Gray CH, Evans JR, Goris A, Foltynie T, Ban M, Robbins TW, Brayne C, Kolachana BS, Weinberger DR, Sawcer SJ, Barker RA (2009) The distinct cognitive syndromes of Parkinson’s disease: 5 year follow-up of the CamPaIGN cohort. Brain. 132:2958–2969. https://doi.org/10.1093/brain/awp245CrossRefPubMed

20.

Trojano L, Papagno C (2018) Cognitive and behavioral disorders in Parkinson’s disease: an update. II: behavioral disorders. Neurol Sci 39:53–61. https://doi.org/10.1007/s10072-017-3155-7CrossRefPubMed

21.

Bohnen NI, Albin RL (2011) The cholinergic system and Parkinson disease. Behav Brain Res 221:564–573. https://doi.org/10.1016/j.bbr.2009.12.048CrossRefPubMed

22.

Japee S, Holiday K, Satyshur MD, Mukai I, Ungerleider LG (2015) A role of right middle frontal gyrus in reorienting of attention: a case study. Front Syst Neurosci 9:23. https://doi.org/10.3389/fnsys.2015.00023CrossRefPubMedPubMedCentral

23.

Li W, Qin W, Liu H, Fan L, Wang J, Jiang T, Yu C (2013) Subregions of the human superior frontal gyrus and their connections. Neuroimage. 78:46–58. https://doi.org/10.1016/j.neuroimage.2013.04.011CrossRefPubMed

24.

Su L, Blamire AM, Watson R, He J, Hayes L, O’Brien JT (2016) Whole-brain patterns of 1H-magnetic resonance spectroscopy imaging in Alzheimer’s disease and dementia with Lewy bodies. Transl Psychiatry 6:e877–e877. https://doi.org/10.1038/tp.2016.140CrossRefPubMedPubMedCentral

25.

Klietz M, Bronzlik P, Nösel P, Wegner F, Dressler DW, Dadak M, Maudsley AA, Sheriff S, Lanfermann H, Ding XQ (2019) Altered neurometabolic profile in early Parkinson’s disease: a study with short echo-time whole brain MR spectroscopic imaging. Front Neurol 10:777. https://doi.org/10.3389/fneur.2019.00777CrossRefPubMedPubMedCentral

26.

Riese F, Gietl A, Zölch N, Henning A, O’Gorman R, Kälin AM, Leh SE, Buck A, Warnock G, Edden RAE, Luechinger R, Hock C, Kollias S, Michels L (2015) Posterior cingulate γ-aminobutyric acid and glutamate/glutamine are reduced in amnestic mild cognitive impairment and are unrelated to amyloid deposition and apolipoprotein E genotype. Neurobiol Aging 36:53–59. https://doi.org/10.1016/j.neurobiolaging.2014.07.030CrossRefPubMed

27.

Xu H, Zhang H, Zhang J, Huang Q, Shen Z, Wu R (2016) Evaluation of neuron-glia integrity by in vivo proton magnetic resonance spectroscopy: implications for psychiatric disorders. Neurosci Biobehav Rev 71:563–577. https://doi.org/10.1016/j.neubiorev.2016.09.027CrossRefPubMed

28.

Gómez-Ansón B, Alegret M, Muñoz E, Sainz A, Monte GC, Tolosa E (2007) Decreased frontal choline and neuropsychological performance in preclinical Huntington disease. Neurology. 68:906–910. https://doi.org/10.1212/01.wnl.0000257090.01107.2fCrossRefPubMed

29.

Lindner M, Bell T, Iqbal S, Mullins PG, Christakou A (2017) In vivo functional neurochemistry of human cortical cholinergic function during visuospatial attention. PLoS One 12:e0171338. https://doi.org/10.1371/journal.pone.0171338CrossRefPubMedPubMedCentral

30.

Müller MLTM, Bohnen NI (2013) Cholinergic dysfunction in Parkinson’s disease. Curr Neurol Neurosci Rep 13:377. https://doi.org/10.1007/s11910-013-0377-9CrossRefPubMedPubMedCentral

31.

Chung W-S, Welsh CA, Barres BA, Stevens B (2015) Do glia drive synaptic and cognitive impairment in disease? Nat Neurosci 18:1539–1545. https://doi.org/10.1038/nn.4142CrossRefPubMedPubMedCentral

32.

Heinrichs-Graham E, Santamaria PM, Gendelman HE, Wilson TW (2017) The cortical signature of symptom laterality in Parkinson’s disease. NeuroImage Clin 14:433–440. https://doi.org/10.1016/j.nicl.2017.02.010CrossRefPubMedPubMedCentral

33.

Boecker H, Ceballos-Baumann AO, Volk D, Conrad B, Forstl H, Haussermann P (2007) Metabolic alterations in patients with Parkinson disease and visual hallucinations. Arch Neurol 64(7):984–988. https://doi.org/10.1001/archneur.64.7.984CrossRefPubMed

Title: Frontal lobe metabolic alterations characterizing Parkinson’s disease cognitive impairment
Authors: Shefali Chaudhary
S. Senthil Kumaran
Vinay Goyal
M. Kalaivani
Gauri Shanker Kaloiya
Rajesh Sagar
Nalin Mehta
Achal Kumar Srivastava
N. R. Jagannathan
Publication date: 01-03-2021
Publisher: Springer International Publishing
Keywords: Parkinson's Disease
Biomarkers
Published in: Neurological Sciences / Issue 3/2021
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-020-04626-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Frontal lobe metabolic alterations characterizing Parkinson’s disease cognitive impairment

Abstract

Background and purpose

Method

Result

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background and purpose

Method

Result

Conclusion

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