Journal of Neurology

, Volume 253, Issue 2, pp 242–247 | Cite as

Cognitive correlates of cortical cholinergic denervation in Parkinson’s disease and parkinsonian dementia

  • N. I. BohnenEmail author
  • D. I. Kaufer
  • R. Hendrickson
  • L. S. Ivanco
  • B. J. Lopresti
  • G. M. Constantine
  • Ch. A. Mathis
  • J. G. Davis
  • R. Y. Moore
  • S. T. DeKosky


We recently reported findings that loss of cortical acetylcholinesterase (AChE) activity is greater in parkinsonian dementia than in Alzheimer’s disease (AD). In this study we determined cognitive correlates of in vivo cortical AChE activity in patients with parkinsonian dementia (PDem, n = 11), Parkinson’s disease without dementia (PD, n = 13), and in normal controls (NC, n = 14) using N–[11C]methyl–piperidin–4–yl propionate ([11C]PMP) AChE positron emission tomography (PET). Cortical AChE activity was significantly reduced in the PDem (–20.9%) and PD (–12.7 %) subjects (P < 0.001) when compared with the control subjects. Analysis of the cognitive data within the patient groups demonstrated that scores on the WAIS-III Digit Span, a test of working memory and attention, had most robust correlation with cortical AChE activity (R = 0.61, p < 0.005). There were also significant correlations between cortical AChE activity and other tests of attentional and executive functions, such as the Trail Making and Stroop Color Word tests. There was no significant correlation between cortical AChE activity and duration of motor disease (R = –0.01, ns) or severity of parkinsonian motor symptoms (R = 0.14, ns). We conclude that cortical cholinergic denervation in PD and parkinsonian dementia is associated with decreased performance on tests of attentional and executive functioning.

Key words

acetylcholinesterase cognitive dementia Parkinson’s disease positron emission tomography 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Aarsland D, Mosimann UP, McKeith IG (2004) Role of cholinesterase inhibitors in Parkinson’s disease and dementia with Lewy bodies. J Geriatr Psychiatry Neurol 17:164–171PubMedGoogle Scholar
  2. 2.
    Arendt T, Bigl V, Arendt A, Tennstedt A (1983) Loss of neurons in the nucleus basalis of Meynert in Alzheimer’s disease, paralysis agitans and Korsakoff ’s Disease. Acta Neuropathol (Berl) 61:101–108CrossRefPubMedGoogle Scholar
  3. 3.
    Bedard MA, Lemay S, Gagnon JF, Masson H, Paquet F (1998) Induction of a transient dysexecutive syndrome in Parkinson’s disease using a subclinical dose of scopolamine. Behav Neurol 11:187–195PubMedGoogle Scholar
  4. 4.
    Bedard MA, Pillon B, Dubois B, Duchesne N, Masson H, Agid Y (1999) Acute and long-term administration of anticholinergics in Parkinson’s disease: specific effects on the subcorticofrontal syndrome. Brain Cogn 40:289–313PubMedGoogle Scholar
  5. 5.
    Benton AL, Hamsher K (1976) Multilingual aphasia examination. AJA Associates, Iowa CityGoogle Scholar
  6. 6.
    Bohnen NI, Kaufer DI, Ivanco L, Lopresti B, Koeppe RA, Davis J, Mathis CA, Moore RY, DeKosky ST (2003) Cortical cholinergic function is more severely affected in Parkinsonian dementia than in Alzheimer’s Disease: an in vivo PET study. Arch Neurol 60:1745–1748CrossRefPubMedGoogle Scholar
  7. 7.
    Bohnen NI, Kaufer DI, Hendrickson R, Ivanco LS, Lopresti B, Koeppe RA, Meltzer CC, Constantine G, Davis JG, Mathis CA, DeKosky ST, Moore RY (2005) Degree of inhibition of cortical acetylcholinesterase activity and cognitive effects by donepezil treatment in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 76:315–319CrossRefPubMedGoogle Scholar
  8. 8.
    Boller F, Mizutani T, Roessmann U, Gambetti P (1980) Parkinson’s disease, dementia and Alzheimer’s disease: clinicopathologic correlations. Ann Neurol 7:329–335CrossRefPubMedGoogle Scholar
  9. 9.
    Candy JM, Perry RH, Perry EK, Irving D, Blessed G, Fairbairn AF, Tomlinson BE (1983) Pathological changes in the nucleus of Meynert in Alzheimer’s and Parkinson’s diseases. J Neurol Sci 59:277–289CrossRefPubMedGoogle Scholar
  10. 10.
    Cooper JA, Sagar HJ, Doherty SM, Jordan N, Tidswell P, Sullivan EV (1992) Different effects of dopaminergic and anticholinergic therapies on cognitive and motor function in Parkinson’s disease. A follow-up study of untreated patients. Brain 115:1701–1725PubMedGoogle Scholar
  11. 11.
    Delis DC, Kramer JH, Kaplan E, Ober BA (1987) California Verbal Learning Test: Adult Version. The Psychological Corporation, San Antonio, TXGoogle Scholar
  12. 12.
    DSM-IV (1994) Diagnostic and Statistical Manual of Mental Disorders. 4th ed., American Psychiatric Association, Washington, DCGoogle Scholar
  13. 13.
    Dubois B, Pillon B, Lhermitte F, Agid Y (1990) Cholinergic deficiency and frontal dysfunction in Parkinson’s disease. Ann Neurol 28:117–121CrossRefPubMedGoogle Scholar
  14. 14.
    Dubois B, Danze F, Pillon B, Cusimano G, Lhermitte F, Agid Y (1987) Cholinergic- dependent cognitive deficits in Parkinson’s disease. Ann Neurol 22:26–30CrossRefPubMedGoogle Scholar
  15. 15.
    Fahn S, Elton R. Members of the UPDRS development committee (1987) Unified Parkinson’s disease rating scale. In: Fahn S, Marsden C, Calne D, Goldstein M (eds) Recent developments in Parkinson’s disease. Macmillan Healthcare Information, Florham Park, NJ, pp 153–164Google Scholar
  16. 16.
    Folstein MF, Folstein SE, McHugh PR (1975) Mini-mental state: a practical method for grading the cognitive state of patients for the clinician. J Psychiatry Res 12:189–198Google Scholar
  17. 17.
    Gibb W (1989) Dementia and Parkinson’s disease. Br J Psychiatry 154:596–614PubMedGoogle Scholar
  18. 18.
    Gotham AM, Brown RG, Marsden CD (1988) ‘Frontal’ cognitive function in patients with Parkinson’s disease ‘on’ and ‘off ’ levodopa. Brain 111:299–321PubMedGoogle Scholar
  19. 19.
    Irie T, Fukushi K, Akimoto Y, Tamagami H, Nozaki T (1994) Design and evaluation of radioactive acetylcholine analogs for mapping brain acetylcholinesterase (AChE) in vivo. Nucl Med Biol 21:801–808PubMedGoogle Scholar
  20. 20.
    Koeppe RA, Frey KA, Snyder SE, Meyer P, Kilbourn MR, Kuhl DE (1999) Kinetic modeling of N-[11C]methylpiperidin-4-yl propionate: alternatives for analysis of an irreversible positron emission tomography tracer for measurement of acetylcholinesterase activity in human brain. J Cereb Blood Flow Metab 19:1150–1163PubMedGoogle Scholar
  21. 21.
    Korczyn AD (2001) Dementia in Parkinson’s disease. J Neurol 248(Suppl 3):III/1–III/4Google Scholar
  22. 22.
    Kuhl DE, Koeppe RA, Minoshima S, Snyder SE, Ficaro EP, Foster NL, Frey KA, Kilbourn MR (1999) In vivo mapping of cerebral acetylcholinesterase activity in aging and Alzheimer’s disease. Neurology 52:691–699PubMedGoogle Scholar
  23. 23.
    Lees AJ, Smith E (1983) Cognitive deficits in the early stages of Parkinson’s disease. Brain 106:257–270PubMedGoogle Scholar
  24. 24.
    Lezak M (1995) Neuropsychological Assessment. Oxford University Press, New York, NYGoogle Scholar
  25. 25.
    Mahler ME, Cummings JL (1990) Alzheimer disease and the dementia of Parkinson disease: Comparative investigations. Alz Dis Ass Dis 4:133–149Google Scholar
  26. 26.
    Mattila PM, Roytta M, Lonnberg P, Marjamaki P, Helenius H, Rinne JO (2001) Choline acetyltransferase activity and striatal dopamine receptors in Parkinson’s disease in relation to cognitive impairment. Acta Neuropathol (Berl) 102:160–166PubMedGoogle Scholar
  27. 27.
    McKeith IG, Perry EK, Perry RH (1999) Report of the second dementia with Lewy body international workshop. Diagnosis and treatment. Neurology 53:902–905PubMedGoogle Scholar
  28. 28.
    Nakano I, Hirano A (1984) Parkinson’s disease: neuron loss in the nucleus basalis without concomitant Alzheimer’s disease. Ann Neurol 5:415–418Google Scholar
  29. 29.
    Namba H, Iyo M, Fukushi K, Shinotoh H, Nagatsuka S, Suhara T, Sudo Y, Suzuki K, Irie T (1999) Human cerebral acetylcholinesterase activity measured with positron emission tomography: procedure, normal values and effect of age. Eur J Nucl Med 26:135–143CrossRefPubMedGoogle Scholar
  30. 30.
    Perry EK, Curtis M, Dick DJ, Candy JM, Atack JR, Bloxham CA, Blessed G, Fairbairn A, Tomlinson BE, Perry RH (1985) Cholinergic correlates of cognitive impairment in Parkinson’s disease: comparisons with Alzheimer’s disease. J Neurol Neurosurg Psychiatry 48:413–421PubMedGoogle Scholar
  31. 31.
    Reitan R (1958) Validity of the Trailmaking Tests as an indication of organic brain damage. Mot Skills 8:271–276Google Scholar
  32. 32.
    Rogers JD, Brogan D, Mirra SS (1985) The nucleus basalis of Meynert in neurological disease: a quantitative morphological study. Ann Neurol 17:163–170CrossRefPubMedGoogle Scholar
  33. 33.
    Ruberg M, Rieger F, Villageois A, Bonnet AM, Agid Y (1986) Acetylcholinesterase and butyrylcholinesterase in frontal cortex and cerebrospinal fluid of demented and non-demented patients with Parkinson’s disease. Brain Res 362:83–91CrossRefPubMedGoogle Scholar
  34. 34.
    Snyder SE, Tluczek L, Jewett DM, Nguyen TB, Kuhl DE, Kilbourn MR (1998) Synthesis of 1-[11C]methylpiperidin- 4-yl propionate ([11C]PMP) for in vivo measurements of acetylcholinesterase activity. Nucl Med Biol 25:751–754PubMedGoogle Scholar
  35. 35.
    Stern Y, Mayeux R, Rosen J, Ilson J (1983) Perceptual motor dysfunction in Parkinson’s disease: a deficit in sequential and predictive voluntary movement. J Neurol Neurosurg Psychiatry 46:145–151PubMedGoogle Scholar
  36. 36.
    Tagliavini F, Pilleri G, Bouras C, Constantinidis J (1984) The basal nucleus of Meynert in idiopathic Parkinson’s disease. Acta Neurol Scand 70:20–28PubMedGoogle Scholar
  37. 37.
    Talairach J, Tournoux P (1988) Coplanar stereotaxic atlas of the human brain. Thieme, New YorkGoogle Scholar
  38. 38.
    Tanaka N, Fukushi K, Shinotoh H, Nagatsuka S, Namba H, Iyo M, Aotsuka A, Ota T, Tanada S, Irie T (2001) Positron emission tomographic measurement of brain acetylcholinesterase activity using N-[11C]methylpiperidin-4-yl acetate without arterial blood sampling: methodology of shape analysis and its diagnostic power for Alzheimer’s disease. J Cereb Blood Flow Metab 21:295–306PubMedGoogle Scholar
  39. 39.
    Wechsler D (1997) Wechsler Adult Intelligence Scale-Third Edition. Psychological Corporation, San Antonio, TXGoogle Scholar
  40. 40.
    Weinhard K (1998) Applications of 3D PET. In: Bendriem B, Townsend DW (eds) The theory and practice of 3D PET. Kluwer Academic Publishers, Boston, pp 133–167Google Scholar
  41. 41.
    Whitehouse PJ, Hedreen JC, White CL, Price DL (1983) Basal forebrain neurons in the dementia of Parkinson disease. Ann Neurol 13:243–248CrossRefPubMedGoogle Scholar
  42. 42.
    Wiseman MB, Nichols TE, Woods RP, Sweeney JA, Mintun MA (1996) Stereotaxic techniques comparing foci intensity and location of activation areas in the brain as obtained using positron emission tomography (PET). J Nucl Med 36(Suppl):93PGoogle Scholar
  43. 43.
    Woods RP, Mazziota JC, Cherry SR (1993) MRI-PET registration with automated algorithm. J Comput Assist Tomogr 17:536–546PubMedGoogle Scholar

Copyright information

© Steinkopff-Verlag 2005

Authors and Affiliations

  • N. I. Bohnen
    • 1
    • 2
    • 4
    Email author
  • D. I. Kaufer
    • 4
  • R. Hendrickson
    • 4
  • L. S. Ivanco
    • 4
  • B. J. Lopresti
    • 1
  • G. M. Constantine
    • 3
  • Ch. A. Mathis
    • 1
  • J. G. Davis
    • 1
  • R. Y. Moore
    • 4
  • S. T. DeKosky
    • 4
  1. 1.Department of RadiologyUniversity of Pittsburgh Medical SchoolPittsburghUSA
  2. 2.VA Pittsburgh Healthcare systemPittsburghUSA
  3. 3.Department of Mathematics and StatisticsUniversity of PittsburghPittsburghUSA
  4. 4.Department of NeurologyUniversity of Pittsburgh Liliane S.Kaufmann Building, Suite 811PittsburghUSA

Personalised recommendations