Effects of Rivastigmine Combined with Reinhartdt and Sea Cucumber Capsule in Patients with Mild-to-Moderate Parkinson’s Disease Dementia: A Pilot Study


Many patients with Parkinson’s disease suffer cognitive impairment or dementia. Cholinesterase inhibitors (ChEIs) have positive effects on patients with Parkinson’s Disease Dementia (PDD). But it is only improve symptoms. There is no etiological cure for PDD. So, In order to achieve the best outcomes, the combination of ChEIs and other therapeutic strategies is needed to study. In the present study, we investigate the efficacy and safety of rivastigmine combined with Reinhartdt and Sea Cucumber Capsule (RSC) in patients with mild-to-moderate PDD, and its effect on thyroid function. There were 52 patients were randomly assigned to receive either rivastigmine (3 mg/ day) or rivastigmine plus RSC (2.7 g/day) treatment for 24 weeks. Efficacy was investigated by the change of the scores of Alzheimer’s Disease Assessment Scale cognitive subscale (ADAS-Cog), Activities of Daily Life (ADL) and Unified Parkinson’s Disease Rating Scale (UPDRS) part III (motor scale). Meanwhile, thyroid hormone levels were detected before and after 12 weeks, 24 weeks treatment in all patients. Results showed that the patients treated with rivastigmine plus RSC showed more improvement in the cognition and the daily life activities compared to those treated with rivastigmine alone. Significant difference was present after being treated for 12 weeks or more. However, no group difference was found on UPDRS part III, thyroid hormone level change and the incidence of adverse events (11.1% vs 16.0%) between the two groups of treatment. Adverse effects were nausea and vomiting which were the main reasons for the dropout. The finding suggests that Rivastigmine plus RSC may improves the treatment effects in cognition and the ADL of the patients with mild-to-moderate PDD, compared with the rivastigmine treatment alone. However, no effect was observed on the motor symptoms and thyroid hormone levels. In addition, this joint treatment is safe.

Share and Cite:

Yan, Y. , Liang, L. , Xie, T. , Shen, Y. and Cao, Y. (2014) Effects of Rivastigmine Combined with Reinhartdt and Sea Cucumber Capsule in Patients with Mild-to-Moderate Parkinson’s Disease Dementia: A Pilot Study. Chinese Medicine, 5, 94-103. doi: 10.4236/cm.2014.52011.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Jankovic, J. (2008) Parkinson’s Disease: Clinical Features and Diagnosis. Journal of Neurology, Neurosurgery & Psychiatry, 79, 368-376.
[2] Hirtz, D., Thurman, D.J., Gwinn-Hardy, K., Mohamed, M., Chaudhuri, A.R. and Zalutsky, R. (2007) How Common Are the “Common” Neurologic Disorders? Neurology, 68, 326-337.
[3] Zhang, Z.X., Roman, G.C., Hong, Z., Wu, C.B., Qu, Q.M., Huang, J.B., Zhou, B., Geng, Z.P., Wu, J.X., Wen, H.B., Zhao, H. and Zahner, G.E. (2005) Parkinson’s Disease in China: Prevalence in Beijing, Xian, and Shanghai. Lancet, 365, 595-597.
[4] Galvin, J.E., Pollack, J. and Morris, J.C. (2006) Clinical Phenotype of Parkinson Disease Dementia. Neurology, 67, 1605-1611.
[5] Aarsland, D., Zaccai, J. and Brayne, C. (2005) A Systematic Review of Prevalence Studies of Dementia in Parkinson’s Disease. Movement Disorders, 20, 1255-1263.
[6] Riedel, O., Klotsche, J., Spottke, A., Deuschl, G., Forstl, H., Henn, F., Heuser, I., Oertel, W., Reichmann, H., Riederer, P., Trenkwalder, C., Dodel, R. and Wittchen, H.U. (2010) Frequency of Dementia, Depression, and Other Neuropsychiatric Symptoms in 1449 Outpatients with Parkinson’s Disease. Journal of Neurology, 257, 1073-1082.
[7] Winter, Y., von Campenhausen, S., Arend, M., Longo, K., Boetzel, K., Eggert, K., Oertel, W.H., Dodel, R. and Barone, P. (2011) Health-Related Quality of Life and Its Determinants in Parkinson’s Disease: Results of an Italian Cohort study. Parkinsonism & Related Disorders, 17, 265-269.
[8] Vossius, C., Larsen, J.P., Janvin, C. and Aarsland, D. (2011) The Economic Impact of Cognitive Impairment in Parkinson’s Disease. Movement Disorders, 26, 1541-1544.
[9] Fletcher, P., Leake, A. and Marion, M.H. (2011) Patients with Parkinson’s Disease Dementia Stay in the Hospital Twice as Long as Those without Dementia. Movement Disorders, 26, 919.
[10] Klein, J.C., Eggers, C., Kalbe, E., Weisenbach, S., Hohmann, C., Vollmar, S., Baudrexel, S., Diederich, N.J., Heiss, W.D. and Hilker, R. (2010) Neurotransmitter Changes in Dementia with Lewy Bodies and Parkinson Disease Dementia in Vivo. Neurology, 74, 885-892.
[11] Bohnen, N.I., Kaufer, D.I., Ivanco, L.S., Lopresti, B., Koeppe, R.A., Davis, J.G., Mathis, C.A., Moore, R.Y. and DeKosky, S.T. (2003) Cortical Cholinergic Function Is More Severely Affected in Parkinsonian Dementia Than in Alzheimer Disease: An in Vivo Positron Emission Tomographic Study. Arch Neurol, 60, 1745-1748.
[12] Rolinski, M., Fox, C., Maidment, I. and McShane, R. (2012) Cholinesterase Inhibitors for Dementia with Lewy Bodies, Parkinson’s Disease Dementia and Cognitive Impairment in Parkinson’s Disease. Cochrane Database of Systematic Reviews, 3, CD006504.
[13] Wu, T.Y., Chen, C.P. and Jinn, T.R. (2011) Traditional Chinese Medicines and Alzheimer’s Disease. Taiwanese Journal of Obstetrics and Gynecology, 50, 131-135.
[14] Lin, H.Q., Ho, M.T., Lau, L.S., Wong, K.K., Shaw, P.C. and Wan, D.C. (2008) Anti-Acetylcholinesterase Activities of Traditional Chinese Medicine for Treating Alzheimer’s Disease. Chemico-Biological Interactions, 175, 352-354.
[15] Kim, H.G. and Oh, M.S. (2012) Herbal Medicines for the Prevention and Treatment of Alzheimer’s Disease. Current Pharmaceutical Design, 18, 57-75.
[16] Li, D.Q., Zhou, Y.P. and Yang, H. (2012) Donepezil Combined with Natural Hirudin Improves the Clinical Symptoms of Patients with Mild-to-Moderate Alzheimer’s Disease: A 20-Week Open-Label Pilot Study. International Journal of Medical Sciences, 9, 248-255.
[17] Yan, Y.X., Liang, L.Z. and Zhou, Z.L. (2007) Clinical Study of Combined Treatment with Compound Reinhartdt and Sea Cumber Capsule and Donepezil for Vascular Dementia. Chinese Journal of Integrated Traditional and Western Medicine, 27, 887-890.
[18] Wang, C.F., Ma, Y.X., Gu, Y.D., Xie, S.Z., Yu, Z.Y. and Yang, J.Y. (2000) A Double-Blind Clinical Study on the Reinhardt and Sea Cucumber Capsule in Treating Dementia in the Aged. Geriatrics & Health Care, 6, 11-15.
[19] Kang, J. (2009) Research of Compound Reinhartdt and Sea Cumber Capsule Treating Encephalopathy. World Chinese Medicine, 4, 58-59.
[20] Gibb, W.R. and Lees, A.J. (1988) The Relevance of the Lewy Body to the Pathogenesis of Idiopathic Parkinson’s Disease. Journal of Neurology, Neurosurgery & Psychiatry, 51, 745-752.
[21] Emre, M., Aarsland, D., Brown, R., Burn, D.J., Duyckaerts, C., Mizuno, Y., Broe, G.A., Cummings, J., Dickson, D.W., Gauthier, S., Goldman, J., Goetz, C., Korczyn, A., Lees, A., Levy, R., Litvan, I., McKeith, I., Olanow, W., Poewe, W., Quinn, N., Sampaio, C., Tolosa, E. and Dubois, B. (2007) Clinical Diagnostic Criteria for Dementia Associated with Parkinson’s Disease. Movement Disorders, 22, 1689-1707.
[22] Hurtig, H.I., Trojanowski, J.Q., Galvin, J., Ewbank, D., Schmidt, M.L., Lee, V.M., Clark, C.M., Glosser, G., Stern, M.B., Gollomp, S.M. and Arnold, S.E. (2000) Alpha-Synuclein Cortical Lewy Bodies Correlate with Dementia in Parkinson’s Disease. Neurology, 54, 1916-1921.
[23] Aarsland, D., Perry, R., Brown, A., Larsen, J.P. and Ballard, C. (2005) Neuropathology of Dementia in Parkinson’s Disease: A Prospective, Community-Based Study. Annals of Neurology, 58, 773-776.
[24] Braak, H., Rüb, U., Jansen Steur, E.N., Del Tredici, K. and de Vos, R.A. (2005) Cognitive Status Correlates with Neuropathologic Stage in Parkinson Disease. Neurology, 64, 1404-1410.
[25] Hutchinson, M. and Fazzini, E. (1996) Cholinesterase Inhibition in Parkinson’s Disease. Journal of Neurology, Neurosurgery & Psychiatry, 61, 324-325.
[26] Emre, M., Aarsland, D., Albanese, A., Byrne, E.J., Deuschl, G., De Deyn, P.P., Durif, F., Kulisevsky, J., van Laar, T., Lees, A., Poewe, W., Robillard, A., Rosa, M.M., Wolters, E., Quarg, P., Tekin, S. and Lane, R. (2004) Rivastigmine for Dementia Associated with Parkinson’s Disease. The New England Journal of Medicine, 351, 2509-2518.
[27] Poewe, W., Wolters, E., Emre, M., Onofrj, M., Hsu, C., Tekin, S. and Lane, R., EXPRESS Investigators (2006) Long-Term Benefits of Rivastigmine in Dementia Associated with Parkinson’s Disease: An Active Treatment Extension Study. Movement Disorders, 21, 456-461.
[28] Ceravolo, R., Volterrani, D., Frosini, D., Bernardini, S., Rossi, C., Logi, C., Manca, G., Kiferle, L., Mariani, G., Murri, L. and Bonuccelli, U. (2006) Brain Perfusion Effects of Cholinesterase Inhibitors in Parkinson’s Disease with Dementia. Journal of Neural Transmission, 113, 1787-1790.
[29] Fogelson, N., Kogan, E., Korczyn, A.D., Giladi, N., Shabtai, H. and Neufeld, M.Y. (2003) Effects of Rivastigmine on the Quantitative EEG in Demented Parkinsonian Patients. Acta Neurologica Scandinavica, 107, 252-255.
[30] van Laar, T., De Deyn, P.P., Aarsland, D., Barone, P. and Galvin, J.E. (2011) Effects of Cholinesterase Inhibitors in Parkinson’s Disease Dementia: A Review of Clinical Data. CNS Neuroscience & Therapeutics, 17, 428-441.
[31] Wang, C.F., Ma, Y.X., Xie, S.Z., Li, W.B., Zhang, B.L. and Tao, G.S. (1999) The Study of Reinhartdt and Sea Cucumber Capsule on the Efficacy and Mechanism of Action in the Dementia Model. In: Ma, Y.X., Wang, C.F. and Shi, F,Y., Eds., New Progress of Aging and Geriatrics, 1st Edition, FU Dan University Press, Shanghai, 477-487.
[32] Lv, J., Jia, H., Jiang, Y., Ruan, Y., Liu, Z., Yue, W., Beyreuther, K., Tu, P. and Zhang, D. (2009) Tenuifolin, an Extract Derived from Tenuigenin, Inhibits Amyloid-Beta Secretion in Vitro. Acta Physiologica, 196, 419-425.
[33] Jia, H., Jiang, Y., Ruan, Y., Zhang, Y., Ma, X., Zhang, J., Beyreuther, K., Tu, P. and Zhang, D. (2004) Tenuigenin Treatment Decreases Secretion of the Alzheimer’s Disease Amyloid Betaprotein in Cultured Cells. Neuroscience Letters, 367, 123-128.
[34] Zhou, Z.L., Liang, L.Z. and Yan, Y.X. (2007) Clinical Study of Reinhartdt and Sea Cucumber Capsule Combined with Donepezil in Treating Alzheimer’s Disease. Chinese Journal of Integrated Traditional and Western Medicine, 27, 110-113.
[35] Jahagirdar, V. and McNay, E.C. (2012) Thyroid Hormone’s Role in Regulating Brain Glucose Metabolism and Potentially Modulating Hippocampal Cognitive Processes. Metabolic Brain Disease, 27, 101-111.
[36] Carreón-Rodríguez, A. and Pérez-Martínez, L. (2012) Clinical Implications of Thyroid Hormones Effects on Nervous System Development. Pediatric Endocrinology Reviews, 9, 644-649.
[37] Bauer, M., Goetz, T., Glenn, T. and Whybrow, P.C. (2008) The Thyroid-Brain Interaction in Thyroid Disorders and Mood Disorders. Journal of Neuroendocrinology, 20, 1101-1114.
[38] Bunevicius, R. (2009) Thyroid Disorders in Mental Patients. Current Opinion in Psychiatry, 22, 391-395.
[39] Schaefer, S., Vogt, T., Nowak, T. and Kann, P.H., German KIMS board (2008) Pituitary Function and the Somatotmphie System in Patients with Idiopathic Parkinson’s Disease under Chronic Dopaminersic Therapy. Journal of Neuroendocrinology, 20, 104-109.
[40] Bonuccelli, U., D’Avino, C., Caraccio, N., Del Guerra, P., Casolaro, A., Pavese, N., Del Dotto, P. and Monzani, F. (1999) Thyroid Function and Autoimmunity in Parkinson’s Disease: A Study of 101 Patients. Parkinsonism & Related Disorders, 5, 49-53.
[41] Oertel, W., Poewe, W., Wolters, E., De Deyn, P.P., Emre, M., Kirsch, C., Hsu, C., Tekin, S. and Lane, R. (2008) Effects of Rivastigmine on Tremor and Other Motor Symptoms in Patients with Parkinson’s Disease Dementia: A Retrospective Analysis of a Double-Blind Trial and an Open-Label Extension. Drug Safety, 31, 79-94.

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.