Skip to main content
PMC home page
Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 2002 Dec;73(6):665–671. doi: 10.1136/jnnp.73.6.665

Alterations in brain activation during cholinergic enhancement with rivastigmine in Alzheimer's disease

S Rombouts 1, F Barkhof 1, C S van Meel 1, P Scheltens 1
PMCID: PMC1757335  PMID: 12438467

Abstract

Background: Rivastigmine enhances cholinergic activity and has been shown in clinical trials to decrease the rate of deterioration in Alzheimer's disease. It remains unclear where in the brain it exerts its effect. Functional magnetic resonance imaging (fMRI) can be used to measure changes in brain function and relate these to cognition.

Objectives: To use fMRI to study brain activation with rivastigmine treatment.

Methods: The effect on brain activation of a single dose of rivastigmine was tested in seven patients with mild Alzheimer's disease using fMRI during face encoding, and in five patients during a parametric working memory task.

Results: During face encoding, rivastigmine increased bilateral activation in the fusiform gyrus. Brain activation was also enhanced in the prefrontal cortex in a simple working memory task. When working memory load was further increased, not only was increased activation seen, but in certain areas there was also decreased activation.

Conclusions: These findings link the previously observed increase in cognitive performance in Alzheimer's disease after treatment with a cholinesterase inhibitor to altered brain activation. Although the results cannot be generalised to the Alzheimer's disease population at large, they provide evidence that in mild Alzheimer's disease, rivastigmine enhances brain activation in the fusiform and frontal cortices. This is compatible with the concept of cholinergic circuitry.

Full Text

The Full Text of this article is available as a PDF (226.5 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baron J. C., Chételat G., Desgranges B., Perchey G., Landeau B., de la Sayette V., Eustache F. In vivo mapping of gray matter loss with voxel-based morphometry in mild Alzheimer's disease. Neuroimage. 2001 Aug;14(2):298–309. doi: 10.1006/nimg.2001.0848. [DOI] [PubMed] [Google Scholar]
  2. Braver T. S., Cohen J. D., Nystrom L. E., Jonides J., Smith E. E., Noll D. C. A parametric study of prefrontal cortex involvement in human working memory. Neuroimage. 1997 Jan;5(1):49–62. doi: 10.1006/nimg.1996.0247. [DOI] [PubMed] [Google Scholar]
  3. D'Esposito M., Aguirre G. K., Zarahn E., Ballard D., Shin R. K., Lease J. Functional MRI studies of spatial and nonspatial working memory. Brain Res Cogn Brain Res. 1998 Jul;7(1):1–13. doi: 10.1016/s0926-6410(98)00004-4. [DOI] [PubMed] [Google Scholar]
  4. Folstein M. F., Folstein S. E., McHugh P. R. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975 Nov;12(3):189–198. doi: 10.1016/0022-3956(75)90026-6. [DOI] [PubMed] [Google Scholar]
  5. Forette F., Anand R., Gharabawi G. A phase II study in patients with Alzheimer's disease to assess the preliminary efficacy and maximum tolerated dose of rivastigmine (Exelon). Eur J Neurol. 1999 Jul;6(4):423–429. doi: 10.1046/j.1468-1331.1999.640423.x. [DOI] [PubMed] [Google Scholar]
  6. Furey M. L., Pietrini P., Haxby J. V. Cholinergic enhancement and increased selectivity of perceptual processing during working memory. Science. 2000 Dec 22;290(5500):2315–2319. doi: 10.1126/science.290.5500.2315. [DOI] [PubMed] [Google Scholar]
  7. Genovese Christopher R., Lazar Nicole A., Nichols Thomas. Thresholding of statistical maps in functional neuroimaging using the false discovery rate. Neuroimage. 2002 Apr;15(4):870–878. doi: 10.1006/nimg.2001.1037. [DOI] [PubMed] [Google Scholar]
  8. Haxby J. V., Ungerleider L. G., Horwitz B., Maisog J. M., Rapoport S. I., Grady C. L. Face encoding and recognition in the human brain. Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):922–927. doi: 10.1073/pnas.93.2.922. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Jack C. R., Jr, Petersen R. C., Xu Y. C., Waring S. C., O'Brien P. C., Tangalos E. G., Smith G. E., Ivnik R. J., Kokmen E. Medial temporal atrophy on MRI in normal aging and very mild Alzheimer's disease. Neurology. 1997 Sep;49(3):786–794. doi: 10.1212/wnl.49.3.786. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Jann M. W. Rivastigmine, a new-generation cholinesterase inhibitor for the treatment of Alzheimer's disease. Pharmacotherapy. 2000 Jan;20(1):1–12. doi: 10.1592/phco.20.1.1.34664. [DOI] [PubMed] [Google Scholar]
  11. Julien J. P., Beaulieu J. M. Cytoskeletal abnormalities in amyotrophic lateral sclerosis: beneficial or detrimental effects? J Neurol Sci. 2000 Nov 1;180(1-2):7–14. doi: 10.1016/s0022-510x(00)00422-6. [DOI] [PubMed] [Google Scholar]
  12. Kanwisher N., McDermott J., Chun M. M. The fusiform face area: a module in human extrastriate cortex specialized for face perception. J Neurosci. 1997 Jun 1;17(11):4302–4311. doi: 10.1523/JNEUROSCI.17-11-04302.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. McKhann G., Drachman D., Folstein M., Katzman R., Price D., Stadlan E. M. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984 Jul;34(7):939–944. doi: 10.1212/wnl.34.7.939. [DOI] [PubMed] [Google Scholar]
  14. Morris J. C. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology. 1993 Nov;43(11):2412–2414. doi: 10.1212/wnl.43.11.2412-a. [DOI] [PubMed] [Google Scholar]
  15. Rombouts S. A., Barkhof F., Witter M. P., Scheltens P. Unbiased whole-brain analysis of gray matter loss in Alzheimer's disease. Neurosci Lett. 2000 May 19;285(3):231–233. doi: 10.1016/s0304-3940(00)01067-3. [DOI] [PubMed] [Google Scholar]
  16. Small S. A., Perera G. M., DeLaPaz R., Mayeux R., Stern Y. Differential regional dysfunction of the hippocampal formation among elderly with memory decline and Alzheimer's disease. Ann Neurol. 1999 Apr;45(4):466–472. doi: 10.1002/1531-8249(199904)45:4<466::aid-ana8>3.0.co;2-q. [DOI] [PubMed] [Google Scholar]
  17. Spencer C. M., Noble S. Rivastigmine. A review of its use in Alzheimer's disease. Drugs Aging. 1998 Nov;13(5):391–411. doi: 10.2165/00002512-199813050-00005. [DOI] [PubMed] [Google Scholar]
  18. Sperling Reisa, Greve Douglas, Dale Anders, Killiany Ronald, Holmes Jennifer, Rosas H. Diana, Cocchiarella Andrew, Firth Paul, Rosen Bruce, Lake Stephen. Functional MRI detection of pharmacologically induced memory impairment. Proc Natl Acad Sci U S A. 2001 Dec 26;99(1):455–460. doi: 10.1073/pnas.012467899. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Publishing Group

RESOURCES