Brain perfusion effects of cholinesterase inhibitors in Parkinson’s disease with dementia Short Communication First Online: 14 June 2006 Received: 13 January 2005 Accepted: 15 February 2006 DOI:
Cite this article as: Ceravolo, R., Volterrani, D., Frosini, D. et al. J Neural Transm (2006) 113: 1787. doi:10.1007/s00702-006-0478-6 Summary.
Several evidences suggest that cholinergic deficits may significantly contribute to dementia in Parkinson’s disease (PDD) and acetylcholinesterase inhibitors (ChEIs) have been reported to improve cognitive symptoms in PDD, without worsening parkinsonism. Nineteen PDD patients underwent brain perfusion SPECT with
99mTc-ethyl cysteinate dimer after 6 months ChEIs treatment in order to evaluate the functional correlates of clinical improvement. A clear-cut cognitive improvement was reported in PDD patients with a significant improvement of ADAS-cog total score as well as of subscores exploring executive functions ( p < 0.01). MMSE total score did not significantly change after ChEIs but the subscore of attention significantly improved after therapy ( p < 0.01). No difference in motor performance as evaluated by UPDRS was reported. SPM analysis showed a significant increase of perfusion ( p < 0.0001) in bilateral cingulate, and frontal regions after ChEIs. Our data confirm the efficacy of ChEIs in the treatment of dementia associated with PD mainly on attention and executive functions, and the functional findings indicate that this cognitive improvement could be associated with a sort of pharmacological frontal “re-afferentation”. Keywords: Parkinson’s disease, dementia, SPECT, acetylcholinesterase inhibitors References Aarsland, D, Hutchinson, M, Larsen, JP 2003 Cognitive, psychiatric and motor response to galantamine in Parkinson’s disease with dementia Int J Geriatr Psychiatry 18 937 941 PubMed CrossRef Google Scholar Aarsland, D, Laake, K, Larsen, JP, Janvin, C 2002 Donepezil for cognitive impairment in Parkinson’s disease: a randomised controlled study J Neurol Neurosurg Psychiatry 72 708 712 PubMed CrossRef Google Scholar
American Psychiatric Association (APA) (1994) Diagnostic and Statistical Manual of Mental Disorders, IV edn (DSM IV). American Psychiatric Association, Washington. DC
Bohnen, NI, Kaufer, DI, Ivanco, LS, et al. 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 PubMed CrossRef Google Scholar Bosboom, JLW, Stoffers, D, Wolters, Ech 2004 Cognitive dysfunction and dementia in Parkinson’s disease J Neural Transm 111 1303 1315 PubMed CrossRef Google Scholar Ceravolo, R, Volterrani, D, Tognoni, G, et al. 2004 Cerebral perfusion effects of Cholinesterase inhibitors in Alzheimer disease Clin Neuropharmacol 27 166 170 PubMed CrossRef Google Scholar Emre, M, Aarsland, D, Albanese, A, et al. 2004 Rivastigmine for dementia associated with Parkinson’s disease N Engl J Med 351 2509 2518 PubMed CrossRef Google Scholar Fournet, N, Moreaud, O, Roulin, J, Naegele, B, Pellat, J 2000 Working memory functioning in medicated Parkinson’s disease patients and the effect of withdrawal of dopaminergic medication Neuropsychology 38 252 271 CrossRef Google Scholar Giladi, N, Shabtai, H, Gurevich, T, Benbunan, B, Anca, M, Korczyn, AD 2003 Rivastigmine for dementia in patients with Parkinson’s disease Acta Neurol Scand 108 368 373 PubMed CrossRef Google Scholar Glowinski, J 1990 Recent finding on dopaminergic transmission in the basal ganglia Adv Neurol 53 67 73 PubMed Google Scholar Hughes, AJ, Daniel, SE, Kilford, L, Less, AJ 1992 Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases J Neurol Neurosurg Psychiatry 55 181 184 PubMed CrossRef Google Scholar Leroi, I, Brandt, J, Reich, SG, Lyketsos, CG, Grill, S, Thompson, R, Marsh, L 2004 Randomized placebo-controlled trial of donepezil in cognitive impairment in Parkinson’s disease Int J Geriatr Psychiatry 19 1 8 PubMed CrossRef Google Scholar Levy, G, Tang, MX, Louis, ED, et al. 2002 The association of incident dementia with mortality in PD Neurology 59 1708 1713 PubMed Google Scholar Linazasoro, G, Lasa, A, Van Blercom, N 2005 Efficacy and safety of donepezil in the treatment of exectuive dysfunction in Parkinson disease: a pilot study Clin Neuropharmacol 28 176 178 PubMed CrossRef Google Scholar McKeith, IG, Del Ser, T, Spano, P, et al. 2000 Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study Lancet 356 2031 2036 PubMed CrossRef Google Scholar Nakano, I, Hirano, A 1984 Parkinson’s disease: neuron loss in the nucleus basalis without concomitant Alzheimer’s disease Ann Neurol 15 415 418 PubMed CrossRef Google Scholar Nakano, S, Asada, T, Matsuda, H, Uno, M, Takasaki, M 2001 Donepezil hydrochloride preserves regional cerebral blood flow in patients with Alzheimer’s disease J Nucl Med 42 1441 1445 PubMed Google Scholar Nobili, F, Vitali, P, Canfora, M, et al. 2002 Effects of long-term Donepezil therapy on rCBF of Alzheimer’s patients Clin Neurophysiol 113 1241 1248 PubMed CrossRef Google Scholar Pakrasi, S, Mukaetova-Ladinska, EB, McKeith, IG, O’Brien, JT 2003 Clinical predictors of response to Acetyl Cholinesterase Inhibitors: experience from routine clinical use in Newcastle Int J Geriatr Psychiatry 18 879 886 PubMed CrossRef Google Scholar Perry, EK, Kilford, L, Lees, AJ, Burn, DJ, Perry, RH 2003 Increased Alzheimer pathology in Parkinson’s disease related to antimuscarinic drugs Ann Neurol 54 235 238 PubMed CrossRef Google Scholar Ravina, B, Putt, M, Siderowf, A, et al. 2005 Donepezil for dementia in Parkinson’s disease: a randomised, double-blind, placebo controlled, crossover study J Neurol Neurosurg Psychiatr 76 903 904 CrossRef Google Scholar Tiraboschi, P, Hansen, LA, Alford, M, et al. 2000 Cholinergic dysfunction in diseases with Lewy bodies Neurology 54 407 411 PubMed Google Scholar Venneri, A, Shanks, MF, Staff, RT, et al. 2002 Cerebral blood flow and cognitive responses to rivastigmine treatment in Alzheimer’s disease Neuroreport 13 83 87 CrossRef Google Scholar Werber, EA, Rabey, JM 2001 The beneficial effect of cholinesterase inhibitors on patients suffering from Parkinson’s disease and dementia J Neural Transm 108 1319 1325 PubMed CrossRef Google Scholar Wesnes, KA, McKeith, I, Edgar, C, Emre, M, Lane, R 2005 Benefits of rivastigmine on attention in dementia associated with Parkinson disease Neurology 65 1654 1656 PubMed CrossRef Google Scholar Zhou, FM, Wilson, C, Dani, JA 2003 Muscarinic and nicotinic cholinergic mechanisms in the mesostriatal dopamine systems Neuroscientist 9 23 36 PubMed CrossRef Google Scholar