Skip to main content

Cholinergic Imaging and Dementia

  • Chapter
  • First Online:
Molecular Imaging of Neurodegenerative Disorders

Abstract

There is evidence of early pathological changes in cholinergic neurons of patients with Alzheimer’s disease and Lewy body disease. This makes cholinergic molecular imaging one of the most important tools for studying prodromal and preclinical disease states of dementia. Various tracers have been developed for visualizing the cholinergic system. They have demonstrated profound cholinergic dysfunction in the cholinergic system of manifest dementia. Cholinergic dysfunction is also evident in prodromal stages of dementia. Evidence points to pathology first arising in the cholinergic axons and cell bodies of the basal forebrain in Alzheimer’s disease dementia and some cases of Parkinson’s disease dementia and dementia with Lewy bodies. In another group of patients with Lewy body disease, the early pathology involves peripheral cholinergic neurons of the parasympathetic nervous system. Cholinergic molecular imaging is an important tool contributing to the search of where and when the pathological processes leading to dementia begins.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Picciotto MR, Higley MJ, Mineur YS. Acetylcholine as a neuromodulator: cholinergic signaling shapes nervous system function and behavior. Neuron. 2012;76(1):116–29. https://doi.org/10.1016/j.neuron.2012.08.036.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Sarter M, Bruno JP. Cognitive functions of cortical acetylcholine: toward a unifying hypothesis. Brain Res Rev. 1997;23(1–2):28–46.

    Article  CAS  PubMed  Google Scholar 

  3. Roy R, Niccolini F, Pagano G, Politis M. Cholinergic imaging in dementia spectrum disorders. Eur J Nucl Med Mol Imaging. 2016;43(7):1376–86. https://doi.org/10.1007/s00259-016-3349-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Bohnen NI, Grothe MJ, Ray NJ, Müller ML, Teipel SJ. Recent advances in cholinergic imaging and cognitive decline—revisiting the cholinergic hypothesis of dementia. Curr Geriatr Rep. 2018;7(1):1–11.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Hampel H, Mesulam MM, Cuello AC, Farlow MR, Giacobini E, Grossberg GT, et al. The cholinergic system in the pathophysiology and treatment of Alzheimer's disease. Brain. 2018;141(7):1917–33. https://doi.org/10.1093/brain/awy132.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Hampel H, Mesulam MM, Cuello AC, Khachaturian AS, Vergallo A, Farlow MR, et al. Revisiting the cholinergic hypothesis in Alzheimer's disease: emerging evidence from translational and clinical research. J Prev Alzheimers Dis. 2019;6(1):2–15. https://doi.org/10.14283/jpad.2018.43.

    Article  CAS  PubMed  Google Scholar 

  7. Pasquini J, Brooks DJ, Pavese N. The cholinergic brain in Parkinson's disease. Mov Disord Clin Pract. 2021;8(7):1012–26. https://doi.org/10.1002/mdc3.13319.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Bohnen NI, Yarnall AJ, Weil RS, Moro E, Moehle MS, Borghammer P, et al. Cholinergic system changes in Parkinson's disease: emerging therapeutic approaches. Lancet Neurol. 2022;21:381. https://doi.org/10.1016/s1474-4422(21)00377-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Richter N, Beckers N, Onur OA, Dietlein M, Tittgemeyer M, Kracht L, et al. Effect of cholinergic treatment depends on cholinergic integrity in early Alzheimer's disease. Brain. 2018;141(3):903–15. https://doi.org/10.1093/brain/awx356.

    Article  PubMed  Google Scholar 

  10. Kuhl DE, Minoshima S, Fessler JA, Ficaro EP, Wieland DM, Koeppe RA, et al. In vivo mapping of cholinergic terminals in normal aging, Alzheimer's disease, and Parkinson's disease. Ann Neurol. 1996;40(3):399–410.

    Article  CAS  PubMed  Google Scholar 

  11. Staer K, Iranzo A, Stokholm MG, Ostergaard K, Serradell M, Otto M, et al. Cortical cholinergic dysfunction correlates with microglial activation in the substantia innominata in REM sleep behavior disorder. Parkinsonism Relat Disord. 2020;81:89–93. https://doi.org/10.1016/j.parkreldis.2020.10.014.

    Article  PubMed  Google Scholar 

  12. Aghourian M, Legault-Denis C, Soucy JP, Rosa-Neto P, Gauthier S, Kostikov A, et al. Quantification of brain cholinergic denervation in Alzheimer's disease using PET imaging with [(18)F]-FEOBV. Mol Psychiatry. 2017;22(11):1531–8. https://doi.org/10.1038/mp.2017.183.

    Article  CAS  PubMed  Google Scholar 

  13. Bohnen N, Mueller ML, Kuwabara H, Constantine G, Studenski S. Age-associated leukoaraiosis and cortical cholinergic deafferentation. Neurology. 2009;72(16):1411–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kanel P, Bedard MA, Aghourian M, Rosa-Neto P, Soucy JP, Albin RL, et al. Molecular imaging of the cholinergic system in Alzheimer and Lewy body dementias: expanding views. Curr Neurol Neurosci Rep. 2021;21(10):52. https://doi.org/10.1007/s11910-021-01140-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Berg D, Borghammer P, Fereshtehnejad S-M, Heinzel S, Horsager J, Schaeffer E, et al. Prodromal Parkinson disease subtypes—key to understanding heterogeneity. Nat Rev Neurol. 2021;17(6):349–61.

    Article  PubMed  Google Scholar 

  16. Prado VF, Roy A, Kolisnyk B, Gros R, Prado MA. Regulation of cholinergic activity by the vesicular acetylcholine transporter. Biochem J. 2013;450(2):265–74.

    Article  CAS  PubMed  Google Scholar 

  17. Nejad-Davarani S, Koeppe RA, Albin RL, Frey KA, Müller ML, Bohnen NI. Quantification of brain cholinergic denervation in dementia with Lewy bodies using PET imaging with [18 F]-FEOBV. Mol Psychiatry. 2018;1:322.

    Google Scholar 

  18. van der Zee S, García DV, Elsinga PH, Willemsen AT, Boersma HH, Gerritsen MJ, et al. [18 F] Fluoroethoxybenzovesamicol in Parkinson’s disease patients: quantification of a novel cholinergic positron emission tomography tracer. Mov Disord. 2019;34(6):924–6.

    Article  PubMed  Google Scholar 

  19. Kikuchi T, Okamura T, Zhang MR, Irie T. PET probes for imaging brain acetylcholinesterase. J Labelled Comp Radiopharm. 2013;56(3–4):172–9. https://doi.org/10.1002/jlcr.3002.

    Article  CAS  PubMed  Google Scholar 

  20. Nathanson NM. Synthesis, trafficking, and localization of muscarinic acetylcholine receptors. Pharmacol Ther. 2008;119(1):33–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Dani JA, Bertrand D. Nicotinic acetylcholine receptors and nicotinic cholinergic mechanisms of the central nervous system. Annu Rev Pharmacol Toxicol. 2007;47:699–729.

    Article  CAS  PubMed  Google Scholar 

  22. Tiepolt S, Becker G-A, Wilke S, Cecchin D, Rullmann M, Meyer PM, et al. (+)-[18F] Flubatine as a novel α4β2 nicotinic acetylcholine receptor PET ligand—results of the first-in-human brain imaging application in patients with β-amyloid PET-confirmed Alzheimer’s disease and healthy controls. Eur J Nucl Med Mol Imaging. 2021;48(3):731–46.

    Article  CAS  PubMed  Google Scholar 

  23. Sultzer DL, Lim AC, Gordon HL, Yarns BC, Melrose RJ. Cholinergic receptor binding in unimpaired older adults, mild cognitive impairment, and Alzheimer’s disease dementia. Alzheimers Res Ther. 2022;14(1):25. https://doi.org/10.1186/s13195-021-00954-w.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kadir A, Darreh-Shori T, Almkvist O, Wall A, Grut M, Strandberg B, et al. PET imaging of the in vivo brain acetylcholinesterase activity and nicotine binding in galantamine-treated patients with AD. Neurobiol Aging. 2008;29(8):1204–17.

    Article  CAS  PubMed  Google Scholar 

  25. Zubieta JK, Koeppe RA, Frey KA, Kilbourn MR, Mangner TJ, Foster NL, et al. Assessment of muscarinic receptor concentrations in aging and Alzheimer disease with [11C] NMPB and PET. Synapse. 2001;39(4):275–87.

    Article  CAS  PubMed  Google Scholar 

  26. Liu AKL, Chang RC-C, Pearce RK, Gentleman SM. Nucleus basalis of meynert revisited: anatomy, history and differential involvement in Alzheimer’s and Parkinson’s disease. Acta Neuropathol. 2015;129(4):527–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Mesulam MM. Cholinergic circuitry of the human nucleus basalis and its fate in Alzheimer’s disease. J Comp Neurol. 2013;521(18):4124–44. https://doi.org/10.1002/cne.23415.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Selden NR, Gitelman DR, Salamon-Murayama N, Parrish TB, Mesulam M-M. Trajectories of cholinergic pathways within the cerebral hemispheres of the human brain. Brain J Neurol. 1998;121(12):2249–57.

    Article  Google Scholar 

  29. Richter N, Michel A, Onur OA, Kracht L, Dietlein M, Tittgemeyer M, et al. White matter lesions and the cholinergic deficit in aging and mild cognitive impairment. Neurobiol Aging. 2017;53:27–35. https://doi.org/10.1016/j.neurobiolaging.2017.01.012.

    Article  PubMed  Google Scholar 

  30. Iranzo A, Fernández-Arcos A, Tolosa E, Serradell M, Molinuevo JL, Valldeoriola F, et al. Neurodegenerative disorder risk in idiopathic REM sleep behavior disorder: study in 174 patients. PLoS One. 2014;9(2):e89741.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Aarsland D, Andersen K, Larsen JP, Lolk A. Prevalence and characteristics of dementia in Parkinson disease: an 8-year prospective study. Arch Neurol. 2003;60(3):387–92.

    Article  PubMed  Google Scholar 

  32. Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):270–9. https://doi.org/10.1016/j.jalz.2011.03.008.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Mazère J, Lamare F, Allard M, Fernandez P, Mayo W. 123I-Iodobenzovesamicol SPECT imaging of cholinergic systems in dementia with Lewy bodies. J Nucl Med. 2017;58(1):123–8.

    Article  PubMed  Google Scholar 

  34. Shimada H, Hirano S, Shinotoh H, Aotsuka A, Sato K, Tanaka N, et al. Mapping of brain acetylcholinesterase alterations in Lewy body disease by PET. Neurology. 2009;73(4):273–8.

    Article  CAS  PubMed  Google Scholar 

  35. Bohnen NI, Kaufer DI, Ivanco LS, Lopresti B, Koeppe RA, Davis JG, et al. Cortical cholinergic function is more severely affected in parkinsonian dementia than in Alzheimer disease: an in vivo positron emission tomographic study. Arch Neurol. 2003;60(12):1745–8.

    Article  PubMed  Google Scholar 

  36. Shimada H, Hirano S, Sinotoh H, Ota T, Tanaka N, Sato K, et al. Dementia with Lewy bodies can be well-differentiated from Alzheimer’s disease by measurement of brain acetylcholinesterase activity-a [11C]MP4A PET study. Int J Geriatr Psychiatry. 2015;30(11):1105–13. https://doi.org/10.1002/gps.4338.

    Article  CAS  PubMed  Google Scholar 

  37. Haense C, Kalbe E, Herholz K, Hohmann C, Neumaier B, Krais R, et al. Cholinergic system function and cognition in mild cognitive impairment. Neurobiol Aging. 2012;33(5):867–77. https://doi.org/10.1016/j.neurobiolaging.2010.08.015.

    Article  CAS  PubMed  Google Scholar 

  38. Rinne JO, Kaasinen V, Järvenpää T, Någren K, Roivainen A, Yu M, et al. Brain acetylcholinesterase activity in mild cognitive impairment and early Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2003;74(1):113–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Marcone A, Garibotto V, Moresco RM, Florea I, Panzacchi A, Carpinelli A, et al. [11C]-MP4A PET cholinergic measurements in amnestic mild cognitive impairment, probable Alzheimer’s disease, and dementia with Lewy bodies: a Bayesian method and voxel-based analysis. J Alzheimers Dis. 2012;31(2):387–99. https://doi.org/10.3233/JAD-2012-111748.

    Article  CAS  PubMed  Google Scholar 

  40. Kendziorra K, Wolf H, Meyer PM, Barthel H, Hesse S, Becker GA, et al. Decreased cerebral α4β2* nicotinic acetylcholine receptor availability in patients with mild cognitive impairment and Alzheimer’s disease assessed with positron emission tomography. Eur J Nucl Med Mol Imaging. 2011;38(3):515–25.

    Article  CAS  PubMed  Google Scholar 

  41. Sabri O, Kendziorra K, Wolf H, Gertz H-J, Brust P. Acetylcholine receptors in dementia and mild cognitive impairment. Eur J Nucl Med Mol Imaging. 2008;35(1):30–45.

    Article  Google Scholar 

  42. Vogels O, Broere C, Ter Laak H, Ten Donkelaar H, Nieuwenhuys R, Schulte B. Cell loss and shrinkage in the nucleus basalis Meynert complex in Alzheimer’s disease. Neurobiol Aging. 1990;11(1):3–13.

    Article  CAS  PubMed  Google Scholar 

  43. Herholz K, Weisenbach S, Kalbe E, Diederich NJ, Heiss W-D. Cerebral acetylcholine esterase activity in mild cognitive impairment. Neuroreport. 2005;16(13):1431–4.

    Article  CAS  PubMed  Google Scholar 

  44. Wilson RS, Leurgans SE, Boyle PA, Bennett DA. Cognitive decline in prodromal Alzheimer disease and mild cognitive impairment. Arch Neurol. 2011;68(3):351–6.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Grothe M, Heinsen H, Teipel SJ. Atrophy of the cholinergic basal forebrain over the adult age range and in early stages of Alzheimer’s disease. Biol Psychiatry. 2012;71(9):805–13. https://doi.org/10.1016/j.biopsych.2011.06.019.

    Article  CAS  PubMed  Google Scholar 

  46. Grothe MJ, Ewers M, Krause B, Heinsen H, Teipel SJ, Alzheimer’s disease neuroimaging Initiative. Basal forebrain atrophy and cortical amyloid deposition in nondemented elderly subjects. Alzheimers Dement. 2014;10(5 Suppl):S344–53. https://doi.org/10.1016/j.jalz.2013.09.011.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Grothe MJ, Heinsen H, Amaro E Jr, Grinberg LT, Teipel SJ. Cognitive correlates of basal forebrain atrophy and associated cortical hypometabolism in mild cognitive impairment. Cereb Cortex. 2016;26(6):2411–26. https://doi.org/10.1093/cercor/bhv062.

    Article  PubMed  Google Scholar 

  48. Schmitz TW, Nathan Spreng R, Alzheimer’s Disease Neuroimaging Initiative. Basal forebrain degeneration precedes and predicts the cortical spread of Alzheimer’s pathology. Nat Commun. 2016;7:13249. https://doi.org/10.1038/ncomms13249.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Gersel Stokholm M, Iranzo A, Ostergaard K, Serradell M, Otto M, Bacher Svendsen K, et al. Cholinergic denervation in patients with idiopathic rapid eye movement sleep behaviour disorder. Eur J Neurol. 2020;27(4):644–52. https://doi.org/10.1111/ene.14127.

    Article  CAS  PubMed  Google Scholar 

  50. Stokholm MG, Iranzo A, Østergaard K, Serradell M, Otto M, Svendsen KB, et al. Assessment of neuroinflammation in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a case-control study. Lancet Neurol. 2017;16(10):789–96. https://doi.org/10.1016/s1474-4422(17)30173-4.

    Article  PubMed  Google Scholar 

  51. Braak H, Del Tredici K, Rüb U, De Vos RA, Steur ENJ, Braak E. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging. 2003;24(2):197–211.

    Article  PubMed  Google Scholar 

  52. Knudsen K, Fedorova TD, Hansen AK, Sommerauer M, Otto M, Svendsen KB, et al. In-vivo staging of pathology in REM sleep behaviour disorder: a multimodality imaging case-control study. Lancet Neurol. 2018;17:618.

    Article  PubMed  Google Scholar 

  53. Horsager J, Andersen KB, Knudsen K, Skjærbæk C, Fedorova TD, Okkels N, et al. Brain-first versus body-first Parkinson’s disease: a multimodal imaging case-control study. Brain. 2020;143(10):3077–88.

    Article  PubMed  Google Scholar 

  54. Giannini G, Calandra-Buonaura G, Asioli GM, Cecere A, Barletta G, Mignani F, et al. The natural history of idiopathic autonomic failure: the IAF-BO cohort study. Neurology. 2018;91(13):e1245–e54. https://doi.org/10.1212/WNL.0000000000006243.

    Article  PubMed  Google Scholar 

  55. van de Beek M, van Steenoven I, van der Zande J, Porcelijn I, Barkhof F, Stam C, et al. Characterization of symptoms and determinants of disease burden in dementia with Lewy bodies: DEvELOP design and baseline results. Alzheimers Res Ther. 2021;13(1):1–13.

    Google Scholar 

  56. McKeith IG, Ferman TJ, Thomas AJ, Blanc F, Boeve BF, Fujishiro H, et al. Research criteria for the diagnosis of prodromal dementia with Lewy bodies. Neurology. 2020;94(17):743–55.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Kantarci K, Nedelska Z, Chen Q, Senjem ML, Schwarz CG, Gunter JL, et al. Longitudinal atrophy in prodromal dementia with Lewy bodies points to cholinergic degeneration. Brain Commun. 2022;4:fcac013.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Grothe MJ, Labrador-Espinosa MA, Jesus S, Macias-Garcia D, Adarmes-Gomez A, Carrillo F, et al. In vivo cholinergic basal forebrain degeneration and cognition in Parkinson’s disease: imaging results from the COPPADIS study. Parkinsonism Relat Disord. 2021;88:68–75. https://doi.org/10.1016/j.parkreldis.2021.05.027.

    Article  CAS  PubMed  Google Scholar 

  59. Pereira JB, Hall S, Jalakas M, Grothe MJ, Strandberg O, Stomrud E, et al. Longitudinal degeneration of the basal forebrain predicts subsequent dementia in Parkinson’s disease. Neurobiol Dis. 2020;139:104831. https://doi.org/10.1016/j.nbd.2020.104831.

    Article  CAS  PubMed  Google Scholar 

  60. Ray NJ, Bradburn S, Murgatroyd C, Toseeb U, Mir P, Kountouriotis GK, et al. In vivo cholinergic basal forebrain atrophy predicts cognitive decline in de novo Parkinson’s disease. Brain. 2018;141(1):165–76.

    Article  PubMed  Google Scholar 

  61. Schumacher J, Taylor JP, Hamilton CA, Firbank M, Cromarty RA, Donaghy PC, et al. In vivo nucleus basalis of Meynert degeneration in mild cognitive impairment with Lewy bodies. Neuroimage Clin. 2021;30:102604. https://doi.org/10.1016/j.nicl.2021.102604.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Craig CE, Ray NJ, Muller M, Bohnen NI. New developments in cholinergic imaging in Alzheimer and Lewy body disorders. Curr Behav Neurosci Rep. 2020;7(4):278–86. https://doi.org/10.1007/s40473-020-00221-6.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Schumacher J, Ray NJ, Hamilton CA, Donaghy PC, Firbank M, Roberts G, et al. Cholinergic white matter pathways in dementia with Lewy bodies and Alzheimer’s disease. Brain. 2021;145:1773. https://doi.org/10.1093/brain/awab372.

    Article  PubMed Central  Google Scholar 

  64. Schmitz TW, Mur M, Aghourian M, Bedard MA, Spreng RN, Alzheimer’s disease Neuroimaging Initiative. Longitudinal Alzheimer’s degeneration reflects the spatial topography of cholinergic basal forebrain projections. Cell Rep. 2018;24(1):38–46. https://doi.org/10.1016/j.celrep.2018.06.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Geula C, Nagykery N, Nicholas A, Wu C-K. Cholinergic neuronal and axonal abnormalities are present early in aging and in Alzheimer disease. J Neuropathol Exp Neurol. 2008;67(4):309–18.

    Article  PubMed  Google Scholar 

  66. Legault-Denis C, Aghourian M, Soucy J-P, Rosa-Neto P, Dagher A, Wickens R, et al. Normal cognition in Parkinson’s disease may involve hippocampal cholinergic compensation: a PET imaging study with [18F]-FEOBV. Parkinsonism Relat Disord. 2021;91:162. https://doi.org/10.1016/j.parkreldis.2021.09.018.

    Article  CAS  PubMed  Google Scholar 

  67. Sanchez-Catasus C, Bohnen NI, D’Cruz N, Muller M. Striatal acetylcholine-dopamine imbalance in Parkinson’s disease: in vivo neuroimaging study with dual-tracer PET and dopaminergic PET-informed correlational tractography. J Nucl Med. 2021;62:545. https://doi.org/10.2967/jnumed.121.261939.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Ikonomovic MD, Abrahamson EE, Isanski BA, Wuu J, Mufson EJ, DeKosky ST. Superior frontal cortex cholinergic axon density in mild cognitive impairment and early Alzheimer disease. Arch Neurol. 2007;64(9):1312–7.

    Article  PubMed  Google Scholar 

  69. Davis KL, Mohs RC, Marin D, Purohit DP, Perl DP, Lantz M, et al. Cholinergic markers in elderly patients with early signs of Alzheimer disease. JAMA. 1999;281(15):1401–6.

    Article  CAS  PubMed  Google Scholar 

  70. DeKosky ST, Ikonomovic MD, Styren SD, Beckett L, Wisniewski S, Bennett DA, et al. Upregulation of choline acetyltransferase activity in hippocampus and frontal cortex of elderly subjects with mild cognitive impairment. Ann Neurol. 2002;51(2):145–55.

    Article  CAS  PubMed  Google Scholar 

  71. Woolf NJ. Cholinergic systems in mammalian brain and spinal cord. Prog Neurobiol. 1991;37(6):475–524.

    Article  CAS  PubMed  Google Scholar 

  72. Bedard M-A, Aghourian M, Legault-Denis C, Postuma RB, Soucy J-P, Gagnon J-F, et al. Brain cholinergic alterations in idiopathic REM sleep behaviour disorder: a PET imaging study with 18F-FEOBV. Sleep Med. 2019;58:35–41.

    Article  PubMed  Google Scholar 

  73. Liu S-Y, Wile DJ, Fu JF, Valerio J, Shahinfard E, McCormick S, et al. The effect of LRRK2 mutations on the cholinergic system in manifest and premanifest stages of Parkinson’s disease: a cross-sectional PET study. Lancet Neurol. 2018;17(4):309–16. https://doi.org/10.1016/s1474-4422(18)30032-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Coughlin JM, Rubin LH, Du Y, Rowe SP, Crawford JL, Rosenthal HB, et al. High availability of the alpha7-nicotinic acetylcholine receptor in brains of individuals with mild cognitive impairment: a pilot study using (18)F-ASEM PET. J Nucl Med. 2020;61(3):423–6. https://doi.org/10.2967/jnumed.119.230979.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Ellis J, Villemagne VL, Nathan PJ, Mulligan RS, Gong SJ, Chan JG, et al. Relationship between nicotinic receptors and cognitive function in early Alzheimer’s disease: a 2-[18F] fluoro-A-85380 PET study. Neurobiol Learn Mem. 2008;90(2):404–12.

    Article  CAS  PubMed  Google Scholar 

  76. Colloby SJ, Nathan PJ, Bakker G, Lawson RA, Yarnall AJ, Burn DJ, et al. Spatial covariance of cholinergic muscarinic M1/M4 receptors in Parkinson’s disease. Mov Disord. 2021;36(8):1879–88. https://doi.org/10.1002/mds.28564.

    Article  CAS  PubMed  Google Scholar 

  77. Stokin GB, Lillo C, Falzone TL, Brusch RG, Rockenstein E, Mount SL, et al. Axonopathy and transport deficits early in the pathogenesis of Alzheimer’s disease. Science. 2005;307:1282.

    Article  CAS  PubMed  Google Scholar 

  78. Kolisnyk B, Al-Onaizi M, Soreq L, Barbash S, Bekenstein U, Haberman N, et al. Cholinergic surveillance over hippocampal RNA metabolism and Alzheimer’s-like pathology. Cereb Cortex. 2017;27(7):3553–67. https://doi.org/10.1093/cercor/bhw177.

    Article  PubMed  Google Scholar 

  79. Terrière E, Dempsey MF, Herrmann LL, Tierney KM, Lonie JA, O’Carroll RE, et al. 5-123I-A-85380 binding to the α4β2-nicotinic receptor in mild cognitive impairment. Neurobiol Aging. 2010;31(11):1885–93.

    Article  PubMed  Google Scholar 

  80. Richter N, Nellessen N, Dronse J, Dillen K, Jacobs HIL, Langen KJ, et al. Spatial distributions of cholinergic impairment and neuronal hypometabolism differ in MCI due to AD. Neuroimage Clin. 2019;24:101978. https://doi.org/10.1016/j.nicl.2019.101978.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Xia Y, Eeles E, Fripp J, Pinsker D, Thomas P, Latter M, et al. Reduced cortical cholinergic innervation measured using [(18)F]-FEOBV PET imaging correlates with cognitive decline in mild cognitive impairment. Neuroimage Clin. 2022;34:102992. https://doi.org/10.1016/j.nicl.2022.102992.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgement

To Michel J. Grothe, PhD., Movement Disorders Group, Instituto de Biomedicina de Sevilla (iBiS), for commenting on the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Niels Okkels .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Okkels, N., Horsager, J., Pavese, N., Brooks, D.J., Borghammer, P. (2023). Cholinergic Imaging and Dementia. In: Cross, D.J., Mosci, K., Minoshima, S. (eds) Molecular Imaging of Neurodegenerative Disorders. Springer, Cham. https://doi.org/10.1007/978-3-031-35098-6_8

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-35098-6_8

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-35097-9

  • Online ISBN: 978-3-031-35098-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics