Quantitative EEG Changes in Patients with Parkinson’s Disease during Therapy with Rasagiline


It has been suggested that in patients with Parkinson’s disease (PD) metabolism of the MAO-B inhibitor selegiline to methamphetamine may contribute and/or exacerbate sleep problems, possibly leading to deficits of cognition. This open-label exploratory study included 30 PD patients currently being treated with selegiline (7.5 mg/day) and complaining of sleep disturbances. The aim of the study was to determine whether switching from selegiline to another MAO-B inhibitor without amphetamine-like metabolites, namely rasagiline, would improve sleep behaviour and cognitive function in PD patients. Pathologic aberrations as determined by comparison of the frequency pattern of patients to a database consisting of healthy subjects revealed an approximation of electric brain activity to normality. For verification of efficacy, a combination of questionnaires, quantitative source density EEG recording with CATEEMò and performance of two psychometric tasks (d2-test of attention and reading) during the EEG recording were done on the last day of selegiline treatment (7.5 mg/day) as well as 2 and 4 months later, during which the patients were treated with rasagiline (1 mg/day). In addition, performance of the mental tasks revealed a statistically significant (p < 0.05) increase of theta power (4.75 - 6.75 Hz) indicative of improved cognitive abilities at the end of the treatment period. At the same time evaluation of the psychometric test results indicated a statistical improvement with respect to the score of the d2-test (increase from 6.54 to 7.37; p < 0.05). Serum levels of methamphetamine were measured before and after intake of selegiline or rasagiline. They were correlated to alpha2 power, which is under dopaminergic control, within the temporal lobe. From these results it is concluded that the switch from selegiline to rasagiline not only improved sleep behaviour as reported separately but also had a positive effect on electric brain activity and on cognition in these patients.

Share and Cite:

Dimpfel, W. , Oehlwein, C. , Hoffmann, J. and Müller, T. (2014) Quantitative EEG Changes in Patients with Parkinson’s Disease during Therapy with Rasagiline. Advances in Parkinson's Disease, 3, 22-34. doi: 10.4236/apd.2014.33005.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Chaudhuri, K.R. (2002) The Basis for Day- and Night-Time Control of Symptoms of Parkinson’s Disease. European Journal of Neurology, 3, 40-43. http://dx.doi.org/10.1046/j.1468-1331.9.s3.5.x
[2] Kumar, S., Bhatia, M. and Behari, M. (2002) Sleep Disorders in Parkinson’s Disease. Movement Disorders, 17, 775- 781. http://dx.doi.org/10.1002/mds.10167
[3] Young, A., Home, M., Churchward, T., Freezer, N., Holmes, P. and Ho, M. (2002) Comparison of Sleep Disturbance in Mild versus Severe Parkinson’s Disease. Sleep, 25, 573-577.
[4] Wiegmann, D.A., Stanny, R.R., McKay, D.L., Neri, D.F. and McCardie, A.H. (1996) Methamphetamine Effects on Cognitive Processing during Extended Wakefulness. The International Journal of Aviation Psychology, 6, 379-397. http://dx.doi.org/10.1207/s15327108ijap0604_5
[5] Thébault, J.J., Guillaume, M. and Levy, R. (2004) Tolerability, Safety, Pharmacodynamics, and Pharmacokinetics of Rasagiline: A Potent, Selective, and Irreversible Monoamine Oxydase Type B Inhibitor. Pharmacotherapy, 24, 1295- 1305. http://dx.doi.org/10.1592/phco.24.14.1295.43156
[6] Finberg, J.P., Lamensdorf, I., Commissiong, W. and Youdim, M.B. (1996) Pharmacology and Neuroprotective Proper- ties of Rasagiline. Journal of Neural Transmission. Supplementa, 48, 95-101.
[7] Stern, M.B., Marek, K.L., Friedmann, J., Hauser, R.A., LeWitt, P.A., Tarsy, D. and Olanow, C.W. (2001) Double Blind, Randomized, Controlled Trial of Rasagiline as Monotherapy in Early Parkinson’s Disease Patients. Movement Disorders, 19, 916-923. http://dx.doi.org/10.1002/mds.20145
[8] Rabey, J.M., Sagi, L., Huberman, M., Melamed, E., Korczyn, A., Giladi, N., Inzelberg, R., Djaldetti, R., Klein, C. and Berecz, G. (2000) Rasagiline Mesylate: A New MAO B Inhibitor for the Treatment of Parkinson’s Disease: A Double Blind Study as Adjunctive Therapy to Levodopa. Clinical Neuropharmacology, 23, 324-330. http://dx.doi.org/10.1097/00002826-200011000-00005
[9] Reichmann, H. and Jost, W.H. (2010) Efficacy and Tolerability of Rasagiline in Daily Clinical Use—A Post-Marketing Observational Study in Patients with Parkinson’s Disease. European Journal of Neurology, 17, 1164-1171. http://dx.doi.org/10.1111/j.1468-1331.2010.02986.x
[10] Dimpfel, W. and Hoffmann, J.A. (2010) Electropharmacograms of Rasagiline, Its Metabolite Aminoindan and Se- legiline in the Freely Moving Rat. Neuropsychobiology, 62, 213-220. http://dx.doi.org/10.1159/000319947
[11] Müller, T., Hoffmann, J.A., Dimpfel, W. and Oehlwein, C. (2013) Switch from Selegiline to Rasagiline Is Beneficial in Patients with Parkinson’s Disease. Journal of Neural Transmission, 120, 315-318. http://dx.doi.org/10.1007/s00702-012-0927-3
[12] Ziegler, E. and Rambach, H. (1978) Development of Standard Psychological Values for Measuring Brain Performance at Different Ages under Normal and Pathological Aspects. Zentralstelle für das Auslandsschulwesen, 33, 413-419.
[13] Dimpfel, W., Kler, A., Kriesl, E., Lehnfeld, R. and Keplinger-Dimpfel, I.K. (2006) Neurophysiological Characterization of a Functionally Active Drink Containing Extracts of Ginkgo and Ginseng by Source Density Analysis of the Hu- man EEG. Nutritional Neuroscience, 9, 213-224. http://dx.doi.org/10.1080/10284150601043713
[14] Dimpfel, W., Koch, K. and Weiss, G. (2011) Early Effect of NEURAPAS? Balance on Current Source Density (CSD) of Human EEG. BMC Psychiatry, 11, 123. http://dx.doi.org/10.1186/1471-244X-11-123
[15] Vonderheid-Guth, B., Todorova, A., Wedekind, W. and Dimpfel, W. (2000) Evidence for Neuronal Dysfunction in Mi- graine: Concurrence between Specific qEEG Findings and Clinical Drug Response—A Retrospective Analysis. European Journal of Medical Research, 5, 473-483.
[16] Dimpfel, W. (2008) Pharmacological Modulation of Dopaminergic Brain Activity and Its Reflection in Spectral Frequencies of the Rat Electropharmacogram. Neuropsychobiology, 58, 178-186.
[17] Johnson, A.L., Brown, K. and Weaver, M.T. (2010) Sleep Deprivation and Psychomotor Performance among Night- Shift Nurses. AAOHN Journal, 58, 147-154.
[18] Marshall, J.F., Belcher, A.M., Feinstein, E.M. and O’Dell, S.J. (2007) Methamphetamine-Induced Neural and Cognitive Changes in Rodents. Addiction, 102, 61-69. http://dx.doi.org/10.1111/j.1360-0443.2006.01780.x
[19] Schober, F., Schellenberg, R. and Dimpfel, W. (1995) Reflection of Mental Exercise in the Dynamic Quantitative Topographical EEG. Neuropsychobiology, 31, 98-112. http://dx.doi.org/10.1159/000119179
[20] Jelic, V., Johansson, S.E., Almkvist, O., Shigeta, M., Julin, P., Nordberg, A., Winblad, B. and Wahlund, L.O. (2000) Quantitative Electroencephalography in Mild Cognitive Impairment: Longitudinal Changes and Possible Prediction of Alzheimer’s Disease. Neurobiology of Aging, 21, 533-540. http://dx.doi.org/10.1016/S0197-4580(00)00153-6
[21] Alexander, D.M., Arns, M.W., Paul, R.H., Rowe, D.L., Cooper, N., Esser, A.H. and Fallahpour, K. (2006) EEG Markers for Cognitive Decline in Elderly Subjects with Subjective Memory Complaints. Journal of Integrative Neurosci- ence, 5, 49-74. http://dx.doi.org/10.1142/S0219635206001021
[22] Prichep, L.S., John, E.R., Ferris, S.H., Rausch, L., Fang, Z., Cancro, R., Torossian, C. and Reisberg, B. (2006) Prediction of Longitudinal Cognitive Decline in Normal Elderly with Subjective Complaints Using Electrophysiological Imaging. Neurobiology of Aging, 27, 471-481. http://dx.doi.org/10.1002/mds.23738
[23] Hanagasi, H.A., Gurvit, H., Unsalan, P., Horozoglu, H., Tuncer, N., Feyzioglu, A., Gunal, D.I., Yener, G.G., Cakmur, R., Sahin, H.A. and Emre, M. (2011) The Effects of Rasagiline on Cognitive Deficits in Parkinson’s Disease Patients without Dementia: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study. Movement Disorders, 26, 1851-1858. http://dx.doi.org/10.1002/mds.23738
[24] Naoi, M. and Maruyama, W. (2009) Functional Mechanism of Neuroprotection by Inhibitors of Type B Monoamine Oxidase in Parkinson’s Disease. Movement Disorders, 9, 1233-1250. http://dx.doi.org/10.1586/ern.09.68
[25] Bar-Am, O., Weinreb, O., Amit, T. and Youdim, M.B. (2010) The Neuroprotective Mechanism of 1-(R)-Aminoindan, the Major Metabolite of the Anti-Parkinsonian Drug Rasagiline. Journal of Neurochemistry, 112, 1131-1137. http://dx.doi.org/10.1111/j.1471-4159.2009.06542.x
[26] Jenner, P. and Langston, J.W. (2011) Explaining ADAGIO: A Critical Review of the Biological Basis for the Clinical Effects of Rasagiline. Movement Disorders, 26, 2316-2323. http://dx.doi.org/10.1002/mds.23926

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.