Skip to main content

Advertisement

SpringerLink
Log in

Frontal lobe metabolic alterations characterizing Parkinson’s disease cognitive impairment

  • Original Article
  • Published:
Neurological Sciences Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

Data are available as supplementary material.

References

  1. 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/s10072-016-2664-0

    Article  PubMed  PubMed Central  Google Scholar 

  2. 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/s41531-018-0055-3

    Article  PubMed  PubMed Central  Google Scholar 

  3. 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/s00415-006-0234-8

    Article  CAS  PubMed  Google Scholar 

  4. 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/s100720170051

    Article  CAS  PubMed  Google Scholar 

  5. 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.2018.00138

    Article  PubMed  PubMed Central  Google Scholar 

  6. 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/10.1159/000345537

    Article  PubMed  Google Scholar 

  7. 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.2015.11.008

    Article  PubMed  Google Scholar 

  8. 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/awv104

    Article  PubMed  PubMed Central  Google Scholar 

  9. 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.2812

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.2020.03.015

    Article  PubMed  Google Scholar 

  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)70013-0

    Article  PubMed  Google Scholar 

  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.1910300604

    Article  CAS  PubMed  Google Scholar 

  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.2008.04.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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/10.1118/1.4794478

    Article  PubMed  PubMed Central  Google Scholar 

  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.2010.07.005

    Article  CAS  PubMed  Google Scholar 

  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.25853

    Article  PubMed  Google Scholar 

  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/awp245

    Article  PubMed  Google Scholar 

  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/s10072-017-3155-7

    Article  PubMed  Google Scholar 

  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.2009.12.048

    Article  CAS  PubMed  Google Scholar 

  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.2015.00023

    Article  PubMed  PubMed Central  Google Scholar 

  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.2013.04.011

    Article  PubMed  Google Scholar 

  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.2016.140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.2019.00777

    Article  PubMed  PubMed Central  Google Scholar 

  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.2014.07.030

    Article  CAS  PubMed  Google Scholar 

  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.2016.09.027

    Article  PubMed  Google Scholar 

  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.0000257090.01107.2f

    Article  CAS  PubMed  Google Scholar 

  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.0171338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.4142

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.2017.02.010

    Article  PubMed  PubMed Central  Google Scholar 

  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.64.7.984

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

SC acknowledges Fellowship from SERB (SB/CT/046/2013) and AIIMS. JC Bose fellowship from SERB is acknowledged by NRJ.

Funding

This research work did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Department of NMR & MRI Facility, All India Institute of Medical Sciences, New Delhi, 110029, India

    Shefali Chaudhary, S. Senthil Kumaran & N. R. Jagannathan

  2. Department of Neurology, All India Institute of Medical Sciences, New Delhi, 110029, India

    Vinay Goyal & Achal Kumar Srivastava

  3. Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, 110029, India

    M. Kalaivani

  4. National Drug Dependence Treatment Centre, All India Institute of Medical Sciences, New Delhi, 110029, India

    Gauri Shanker Kaloiya

  5. Department of Psychiatry, All India Institute of Medical Sciences, New Delhi, 110029, India

    Rajesh Sagar

  6. Department of Physiology, All India Institute of Medical Sciences, New Delhi, 110029, India

    Nalin Mehta

Authors
  1. Shefali Chaudhary
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Senthil Kumaran
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vinay Goyal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Kalaivani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gauri Shanker Kaloiya
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rajesh Sagar
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nalin Mehta
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Achal Kumar Srivastava
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. N. R. Jagannathan
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SC participated in data acquisition, processing, analysis, and manuscript preparation. SSK participated in MRI protocol designing, execution, analysis, and manuscript preparation. VG helped in diagnosing patients with Parkinson’s disease and patient recruitment. GSK helped in cognitive evaluation of subjects. MK helped in statistical analysis. NRJ helped in concept development and discussion. RS helped in cognitive evaluation of subjects; NM helped in concept and discussion. AS helped in participant recruitment.

Corresponding author

Correspondence to S. Senthil Kumaran.

Ethics declarations

Conflict of interest

Authors declare no conflict of interest regarding the publication of the work.

Ethics approval

The study is approved by the institutional ethics committee (approval number IECPG-503/21.09.2016).

Consent to participate

A written informed consent has been obtained from the participants prior to the commencement of study.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOCX 99.8 kb)

ESM 2

(XLSX 63.4 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chaudhary, S., Kumaran, S.S., Goyal, V. et al. Frontal lobe metabolic alterations characterizing Parkinson’s disease cognitive impairment. Neurol Sci 42, 1053–1064 (2021). https://doi.org/10.1007/s10072-020-04626-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10072-020-04626-9

Keywords

Search

Navigation