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Clinical Trials in Parkinson's Disease Dementia and Dementia with Lewy Bodies

Published online by Cambridge University Press:  02 December 2014

Richard Camicioli  and
Serge Gauthier
Richard Camicioli*
Affiliation:
The Glenrose Rehabilitation Hospital, Edmonton, AB
Serge Gauthier
Affiliation:
Alzheimer Disease Research Unit, McGill Centre for Studies in Aging, Verdun, QC, Canada
*
E223, Glenrose Rehabilitation Hospital, 10230 - 111th Avenue, Edmonton, Alberta, T5G 0B7, Canada.
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Abstract

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Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) are pathological overlapping and important causes of dementia for which clinical trials are in their infancy. Cholinesterase inhibitors may be of benefit in DLB and PDD, as suggested by placebo-controlled clinical trials of rivastigmine and donepezil. The anti-psychotic agent clozapine has been of benefit in PD and PDD, but other agents, such as quetiapine, require adequate assessment. Barriers to trials include pathological overlap that can lead to inaccuracies in clinical diagnosis, unavailability of a consensus definition for PDD, unanswered questions regarding natural history and the paucity of validated outcome measures. Motor impairment must be considered in patients with PDD and DLB; conversely, cognitive impairment should be assessed in trials targeting motor impairment in advanced PD. Potential targets for treatment include onset of dementia, cognitive impairment, behavioral impairment, functional decline, falls, nursing home placement, mortality, quality of life and economic impact. Biomarkers including neuroimaging and cerebrospinal fluid markers are not currently established. At present PDD and DLB are distinct entities by definition. Future studies, including clinical trials and biomarker studies, will help to further define the clinical and therapeutic implications of this distinction.

Résumé:

RÉSUMÉ:

La maladie de Parkinson avec démence (MPD) et la démence à corps de Lewy (DCL) sont des causes importantes de démence qui se chevauchent au point de vue pathologique. Les essais cliniques sur ces deux types de démence en sont au tout début. Selon des essais cliniques contrôlés par placebo portant sur la rivastigmine et le donépézil, les inhibiteurs de la cholinestérase pourraient être bénéfiques dans la DCL et la MPD. Les patients atteints de MP et de MPD ont tiré un bénéfice du traitement par la clozapine, un anti-psychotique, mais d'autres agents tels la quétiapine n'ont pas été évalués adéquatement. Plusieurs obstacles devront être surmontés, notamment le chevauchement des pathologies qui peut entraîner des erreurs diagnostiques, le manque de consensus sur la définition de la MPD, des questions non résolues concernant leur évolution naturelle et le manque de critères d'évaluation validés. Chez les patients atteints de MPD et de DCL, on doit tenir compte de l'atteinte motrice et dans la MPD en phase avancée, l'atteinte cognitive devrait être évaluée au cours d'essais cliniques ciblant l'atteinte motrice. Le début de la démence, l'atteinte cognitive, l'atteinte comportementale, le déclin fonctionnel, les chutes, le placement en établissement de soins prolongés, la mortalité, la qualité de vie et l'impact économique sont des cibles pour l'évaluation du traitement. Les biomarqueurs tels les marqueurs de neuro-imagerie et ceux du liquide céphalorachidien ne sont pas validés. Pour l'instant, la MPD et la DCL sont des entités distinctes par définition. D'autres études, en particulier des essais cliniques et des études de biomarqueurs aideront à mieux définir les implications cliniques et thérapeutiques de cette distinction.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 34 , Issue S1 , March 2007 , pp. S109 - S117
Copyright
Copyright © The Canadian Journal of Neurological 2007

References

1. Camicioli, R, Fisher, N. Progress in clinical neurosciences: Parkinson’s disease with dementia and dementia with Lewy bodies. Can J Neurol Sci. 2004; 31 (1):7–21.CrossRefGoogle ScholarPubMed
2. McKeith, IG, Galasko, D, Kosaka, K, Perry, EK, Dickson, DW, Hansen, LA, et al. Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology. 1996; 47 (5):1113–24.Google Scholar
3. McKeith, IG, Dickson, DW, Lowe, J, Emre, M, O’Brien, JT, Feldman, H, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology. 2005; 65 (12):1863–72.Google Scholar
4. Tiraboschi, P, Salmon, DP, Hansen, LA, Hofstetter, RC, Thal, LJ, Corey-Bloom, J. What best differentiates Lewy body from Alzheimer’s disease in early-stage dementia? Brain. 2006; 129 (Pt 3):729–35.CrossRefGoogle ScholarPubMed
5. American Psychiatric Association; Diagnostic and statistical manual of mental disorders: DSM-IV. 4th ed. Washington, DC: American Psychiatric Association; 1994.Google Scholar
6. Burn, DJ, Rowan, EN, Minett, T, Sanders, J, Myint, P, Richardson, J, et al. Extrapyramidal features in Parkinson’s disease with and without dementia and dementia with Lewy bodies: a crosssectional comparative study. Mov Disord. 2003; 18 (8):884–9.Google Scholar
7. Boeve, BF, Silber, MH, Parisi, JE, Dickson, DW, Ferman, TJ, Benarroch, EE, et al. Synucleinopathy pathology and REM sleep behavior disorder plus dementia or parkinsonism. Neurology. 2003; 61 (1):40–5.Google Scholar
8. Miyasaki, JM, Shannon, K, Voon, V, Ravina, B, Kleiner-Fisman, G, Anderson, K, et al. Practice parameter: evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006; 66 (7):996–1002.CrossRefGoogle Scholar
9. Stern, Y, Tang, MX, Jacobs, DM, Sano, M, Marder, K, Bell, K, et al. Prospective comparative study of the evolution of probable Alzheimer’s disease and Parkinson’s disease dementia. J Int Neuropsychol Soc. 1998; 4 (3):279–84.Google Scholar
10. Noe, E, Marder, K, Bell, KL, Jacobs, DM, Manly, JJ, Stern, Y. Comparison of dementia with Lewy bodies to Alzheimer’s disease and Parkinson’s disease with dementia. Mov Disord. 2004; 19 (1):60–7.Google Scholar
11. Hamilton, JM, Salmon, DP, Galasko, D, Delis, DC, Hansen, LA, Masliah, E, et al. A comparison of episodic memory deficits in neuropathologically-confirmed Dementia with Lewy bodies and Alzheimer’s disease. J Int Neuropsychol Soc. 2004; 10 (5):689–97.Google Scholar
12. Simard, M, van Reekum, R, Myran, D, Panisset, M, Cohen, T, Freedman, M, et al. Differential memory impairment in dementia with Lewy bodies and Alzheimer’s disease. Brain Cogn. 2002; 49 (2):244–9.Google ScholarPubMed
13. Collerton, D, Burn, D, McKeith, I, O’Brien, J. Systematic review and meta-analysis show that dementia with Lewy bodies is a visualperceptual and attentional-executive dementia. Dement Geriatr Cogn Disord. 2003; 16 (4):229–37.Google Scholar
14. Lambon, RMA, Powell, J, Howard, D, Whitworth, AB, Garrard, P, Hodges, JR. Semantic memory is impaired in both dementia with Lewy bodies and dementia of Alzheimer’s type: a comparative neuropsychological study and literature review. J Neurol Neurosurg Psychiatry. 2001; 70 (2):149–56.Google Scholar
15. Davis, HS, Rockwood, K. Conceptualization of mild cognitive impairment: a review. Int J Geriatr Psychiatry. 2004; 19 (4): 313–9.CrossRefGoogle ScholarPubMed
16. Cormack, F, Aarsland, D, Ballard, C, Tovee, MJ. Pentagon drawing and neuropsychological performance in Dementia with Lewy bodies, Alzheimer’s disease, Parkinson’s disease and Parkinson’s disease with dementia. Int J Geriatr Psychiatry. 2004; 19 (4): 371–7.Google Scholar
17. Ballard, CG, Aarsland, D, McKeith, I, O’Brien, J, Gray, A, Cormack, F, et al. Fluctuations in attention: PD dementia vs DLB with parkinsonism. Neurology. 2002; 59 (11):1714–20.Google Scholar
18. Downes, JJ, Priestley, NM, Doran, M, Ferran, J, Ghadiali, E, Cooper, P. Intellectual, mnemonic, and frontal functions in dementia with Lewy bodies: a comparison with early and advanced Parkinson’s disease. Behav Neurol. 1998; 11 (3):173–83.Google Scholar
19. Boeve, BF, Silber, MH, Ferman, TJ, Lucas, JA, Parisi, JE. Association of REM sleep behavior disorder and neurodegenerative disease may reflect an underlying synucleinopathy. Mov Disord. 2001; 16 (4):622–30.Google Scholar
20. Boeve, BF, Silber, MH, Ferman, TJ. REM sleep behavior disorder in Parkinson’s disease and dementia with Lewy bodies. J Geriatr Psychiatry Neurol. 2004; 17 (3):146–57.CrossRefGoogle ScholarPubMed
21. Merdes, AR, Hansen, LA, Jeste, DV, Galasko, D, Hofstetter, CR, Ho, GJ, et al. Influence of Alzheimer pathology on clinical diagnostic accuracy in dementia with Lewy bodies. Neurology. 2003; 60 (10):1586–90.Google Scholar
22. Delis, DC, Kramer, JH, Kaplan, E, Holdnack, J. Reliability and validity of the Delis-Kaplan executive function system: an update. J Int Neuropsychol Soc. 2004; 10 (2):301–3.CrossRefGoogle ScholarPubMed
23. Beatty, WW, Ryder, KA, Gontkovsky, ST, Scott, JG, McSwan, KL, Bharucha, KJ. Analyzing the subcortical dementia syndrome of Parkinson’s disease using the RBANS. Arch Clin Neuropsychol. 2003; 18 (5):509–20.Google Scholar
24. Brown, GG, Rahill, AA, Gorell, JM, McDonald, C, Brown, SJ, Sillanpaa, M, et al. Validity of the Dementia rating scale in assessing cognitive function in Parkinson’s disease. J Geriatr Psychiatry Neurol. 1999; 12 (4):180–8.Google Scholar
25. Peavy, GM, Salmon, D, Bear, PI, Paulsen, JS, Cahn, DA, Hofstetter, CR, et al. Detection of mild cognitive deficits in Parkinson’s disease patients with the WAIS-R NI. J Int Neuropsychol Soc. 2001; 7 (5):535–43.Google Scholar
26. Marinus, J, Visser, M, Verwey, NA, Verhey, FR, Middelkoop, HA, Stiggelbout, AM, et al. Assessment of cognition in Parkinson’s disease. Neurology. 2003; 61 (9):1222–8.Google Scholar
27. Royall, DR, Lauterbach, EC, Cummings, JL, Reeve, A, Rummans, TA, Kaufer, DI, et al. Executive control function: a review of its promise and challenges for clinical research. A report from the Committee on Research of the American Neuropsychiatric Association. J Neuropsychiatry Clin Neurosci. 2002; 14 (4): 377–405.Google Scholar
28. Wesnes, KA, McKeith, IG, Ferrara, R, Emre, M, Del Ser, T, Spano, PF, et al. Effects of rivastigmine on cognitive function in dementia with Lewy bodies: a randomized placebo-controlled international study using the cognitive drug research computerised assessment system. Dement Geriatr Cogn Disord. 2002; 13 (3):183–92.Google Scholar
29. Pate, DS, Margolin, DI. Cognitive slowing in Parkinson’s and Alzheimer’s patients: distinguishing bradyphrenia from dementia. Neurology. 1994; 44 (4):669–74.Google Scholar
30. Bradshaw, J, Saling, M, Hopwood, M, Anderson, V, Brodtmann, A. Fluctuating cognition in dementia with Lewy bodies and Alzheimer’s disease is qualitatively distinct. J Neurol Neurosurg Psychiatry. 2004; 75 (3):382–7.Google Scholar
31. Ferman, TJ, Smith, GE, Boeve, BF, Ivnik, RJ, Petersen, RC, Knopman, D, et al. DLB fluctuations: specific features that reliably differentiate DLB from AD and normal aging. Neurology. 2004; 62 (2):181–7.CrossRefGoogle ScholarPubMed
32. Gelinas, I, Gauthier, L, McIntyre, M, Gauthier, S. Development of a functional measure for persons with Alzheimer’s disease: the disability assessment for dementia. Am J Occup Ther. 1999; 53 (5):471–81.Google Scholar
33. Galasko, D, Bennett, D, Sano, M, Ernesto, C, Thomas, R, Grundman, M, et al. An inventory to assess activities of daily living for clinical trials in Alzheimer’s disease. The Alzheimer’s Disease Cooperative Study. Alzheimer Dis Assoc Disord. 1997; 11 Suppl 2:S33–9.Google Scholar
34. Emre, M, Aarsland, D, Albanese, A, Byrne, EJ, Deuschl, G, De Deyn, PP, et al. Rivastigmine for dementia associated with Parkinson’s disease. N Engl J Med. 2004; 351 (24):2509–18.Google Scholar
35. Aarsland, D, Ballard, C, Larsen, JP, McKeith, I. A comparative study of psychiatric symptoms in dementia with Lewy bodies and Parkinson’s disease with and without dementia. Int J Geriatr Psychiatry. 2001; 16 (5):528–36.Google Scholar
36. Weintraub, D, Moberg, PJ, Duda, JE, Katz, IR, Stern, MB. Effect of psychiatric and other nonmotor symptoms on disability in Parkinson’s disease. J Am Geriatr Soc. 2004; 52 (5):784–8.Google Scholar
37. Norman, S, Troster, AI, Fields, JA, Brooks, R. Effects of depression and Parkinson’s disease on cognitive functioning. J Neuropsychiatry Clin Neurosci. 2002; 14 (1):31–6.Google Scholar
38. Cubo, E, Bernard, B, Leurgans, S, Raman, R. Cognitive and motor function in patients with Parkinson’s disease with and without depression. Clin Neuropharmacol. 2000; 23 (6):331–4.CrossRefGoogle ScholarPubMed
39. Pluck, GC, Brown, RG. Apathy in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2002; 73 (6):636–42.CrossRefGoogle ScholarPubMed
40. Isella, V, Melzi, P, Grimaldi, M, Iurlaro, S, Piolti, R, Ferrarese, C, et al. Clinical, neuropsychological, and morphometric correlates of apathy in Parkinson’s disease. Mov Disord. 2002; 17 (2):366–71.CrossRefGoogle ScholarPubMed
41. Cummings, JL, Mega, M, Gray, K, Rosenberg-Thompson, S, Carusi, DA, Gornbein, J. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology. 1994; 44 (12):2308–14.Google Scholar
42. Del Ser, T, McKeith, I, Anand, R, Cicin-Sain, A, Ferrara, R, Spiegel, R. Dementia with Lewy bodies: findings from an international multicentre study. Int J Geriatr Psychiatry. 2000; 15 (11):1034–45.Google Scholar
43. McKeith, I, Del Ser, T, Spano, P, Emre, M, Wesnes, K, Anand, R, et al. Efficacy of rivastigmine in dementia with Lewy bodies: a randomized, double-blind, placebo-controlled international study. Lancet. 2000; 356 (9247):2031–6.Google Scholar
44. Alexopoulos, GS, Abrams, RC, Young, RC, Shamoian, CA. Cornell scale for depression in Dementia. Biol Psychiatry. 1988; 23 (3):271–84.Google Scholar
45. Robert, PH, Clairet, S, Benoit, M, Koutaich, J, Bertogliati, C, Tible, O, et al. The apathy inventory: assessment of apathy and awareness in Alzheimer’s disease, Parkinson’s disease and mild cognitive impairment. Int J Geriatr Psychiatry. 2002; 17 (12):1099–105.Google Scholar
46. Lee, VM, Giasson, BI, Trojanowski, JQ. More than just two peas in a pod: common amyloidogenic properties of tau and alphasynuclein in neurodegenerative diseases. Trends Neurosci. 2004; 27 (3):129–34.Google Scholar
47. Perry, EK, McKeith, I, Thompson, P, Marshall, E, Kerwin, J, Jabeen, S, et al. Topography, extent, and clinical relevance of neurochemical deficits in dementia of Lewy body type, Parkinson’s disease, and Alzheimer’s disease. Ann N Y Acad Sci. 1991; 640:197–202.Google Scholar
48. Burton, EJ, McKeith, IG, Burn, DJ, Williams, ED, O’Brien, JT. ?Cerebral atrophy in Parkinson’s disease with and without dementia: a comparison with Alzheimer’s disease, dementia with Lewy bodies and controls. Brain. 2004; 127 (Pt 4):791–800.Google Scholar
49. Camicioli, R, Moore, MM, Kinney, A, Corbridge, E, Glassberg, K, Kaye, JA. Parkinson’s disease is associated with hippocampal atrophy. Mov Disord. 2003; 18 (7):784–90.Google Scholar
50. Cousins, DA, Burton, EJ, Burn, D, Gholkar, A, McKeith, IG, O’Brien, JT. Atrophy of the putamen in dementia with Lewy bodies but not Alzheimer’s disease: an MRI study. Neurology. 2003; 61 (9):1191–5.Google Scholar
51. Almeida, OP, Burton, EJ, McKeith, I, Gholkar, A, Burn, D, O’Brien, JT. MRI study of caudate nucleus volume in Parkinson’s disease with and without dementia with Lewy bodies and Alzheimer’s disease. Dement Geriatr Cogn Disord. 2003; 16 (2):57–63.Google Scholar
52. Middelkoop, HA, van der Flier, WM, Burton, EJ, Lloyd, AJ, Paling, S, Barber, R, et al. Dementia with Lewy bodies and AD are not associated with occipital lobe atrophy on MRI. Neurology. 2001; 57 (11):2117–20.Google Scholar
53. Barber, R, McKeith, I, Ballard, C, O’Brien, J. Volumetric MRI study of the caudate nucleus in patients with dementia with Lewy bodies, Alzheimer’s disease, and vascular dementia. J Neurol Neurosurg Psychiatry. 2002; 72 (3):406–7.Google Scholar
54. O’Brien, JT, Paling, S, Barber, R, Williams, ED, Ballard, C, McKeith, IG, et al. Progressive brain atrophy on serial MRI in dementia with Lewy bodies, AD, and vascular dementia. Neurology. 2001; 56 (10):1386–8.Google Scholar
55. Molina, JA, Garcia-Segura, JM, Benito-Leon, J, Gomez-Escalonilla, C, del Ser, T, Martinez, V, et al. Proton magnetic resonance spectroscopy in dementia with Lewy bodies. Eur Neurol. 2002; 48 (3):158–63.Google Scholar
56. Summerfield, C, Gomez-Anson, B, Tolosa, E, Mercader, JM, Marti, MJ, Pastor, P, et al. Dementia in Parkinson disease: a proton magnetic resonance spectroscopy study. Arch Neurol. 2002; 59 (9):1415–20.Google Scholar
57. Camicioli, RM, Korzan, JR, Foster, SL, Fisher, NJ, Emery, DJ, Bastos, AC, et al. Posterior cingulate metabolic changes occur in Parkinson’s disease patients without dementia. Neurosci Lett. 2004; 354 (3):177–80.Google Scholar
58. Firbank, MJ, Colloby, SJ, Burn, DJ, McKeith, IG, O’Brien, JT. Regional cerebral blood flow in Parkinson’s disease with and without dementia. Neuroimage. 2003; 20 (2):1309–19.Google Scholar
59. Colloby, S, O’Brien, J. Functional imaging in Parkinson’s disease and dementia with Lewy bodies. J Geriatr Psychiatry Neurol. 2004; 17 (3):158–63.Google Scholar
60. Gilman, S, Koeppe, RA, Little, R, An, H, Junck, L, Giordani, B, et al. Striatal monoamine terminals in Lewy body dementia and Alzheimer’s disease. Ann Neurol. 2004; 55 (6):774–80.Google Scholar
61. Plotkin, M, Amthauer, H, Klaffke, S, Kuhn, A, Ludemann, L, Arnold, G, et al. Combined (123)I-FP-CIT and (123)I-IBZM SPECT for the diagnosis of parkinsonian syndromes: study on 72 patients. J Neural Transm. 2005;112(5):677–92.Google Scholar
62. O’Brien, JT, Colloby, S, Fenwick, J, Williams, ED, Firbank, M, Burn, D, et al. Dopamine transporter loss visualized with FP-CIT SPECT in the differential diagnosis of dementia with Lewy bodies. Arch Neurol. 2004; 61 (6):919–25.Google Scholar
63. Walker, Z, Costa, DC, Walker, RW, Lee, L, Livingston, G, Jaros, E, et al. Striatal dopamine transporter in dementia with Lewy bodies and Parkinson disease: a comparison. Neurology. 2004; 62 (9):1568–72.Google Scholar
64. Bohnen, NI, Kaufer, DI, Ivanco, LS, Lopresti, B, Koeppe, RA, Davis, JG, et al. Cortical cholinergic function is more severely affected in parkinsonian dementia than in Alzheimer disease: an in vivo positron emission tomographic study. Arch Neurol. 2003; 60 (12):1745–8.Google Scholar
65. Gomez-Tortosa, E, Gonzalo, I, Fanjul, S, Sainz, MJ, Cantarero, S, Cemillan, C, et al. Cerebrospinal fluid markers in dementia with Lewy bodies compared with Alzheimer disease. Arch Neurol. 2003; 60 (9):1218–22.Google Scholar
66. Hanyu, H, Shimizu, S, Hirao, K, Kanetaka, H, Iwamoto, T, Chikamori, T, et al. Comparative value of brain perfusion SPECT and [(123)I]MIBG myocardial scintigraphy in distinguishing between dementia with Lewy bodies and Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2006; 33 (3):248–53.Google Scholar
67. Kaufer, DI, Catt, KE, Lopez, OL, DeKosky, ST. Dementia with Lewy bodies: response of delirium-like features to donepezil. Neurology. 1998; 51 (5):1512.Google Scholar
68. Shea, C, MacKnight, C, Rockwood, K. Donepezil for treatment of dementia with Lewy bodies: a case series of nine patients. Int Psychogeriatr. 1998; 10 (3):229–38.Google Scholar
69. Aarsland, D, Bronnick, K, Karlsen, K. Donepezil for dementia with Lewy bodies: a case study. Int J Geriatr Psychiatry. 1999; 14 (1):69–72.Google Scholar
70. Samuel, W, Caligiuri, M, Galasko, D, Lacro, J, Marini, M, McClure, FS, et al. Better cognitive and psychopathologic response to donepezil in patients prospectively diagnosed as dementia with Lewy bodies: a preliminary study. Int J Geriatr Psychiatry. 2000; 15 (9):794–802.Google Scholar
71. Querfurth, HW, Allam, GJ, Geffroy, MA, Schiff, HB, Kaplan, RF. Acetylcholinesterase inhibition in dementia with Lewy bodies: results of a prospective pilot trial. Dement Geriatr Cogn Disord. 2000; 11 (6):314–21.Google Scholar
72. McKeith, IG, Grace, JB, Walker, Z, Byrne, EJ, Wilkinson, D, Stevens, T, et al. Rivastigmine in the treatment of dementia with Lewy bodies: preliminary findings from an open trial. Int J Geriatr Psychiatry. 2000; 15 (5):387–92.Google Scholar
73. Grace, J, Daniel, S, Stevens, T, Shankar, KK, Walker, Z, Byrne, EJ, et al. Long-term use of rivastigmine in patients with dementia with Lewy bodies: an open-label trial. Int Psychogeriatr. 2001; 13 (2):199–205.Google Scholar
74. Maclean, LE, Collins, CC, Byrne, EJ. Dementia with Lewy bodies treated with rivastigmine: effects on cognition, neuropsychiatric symptoms, and sleep. Int Psychogeriatr. 2001; 13 (3):277–88.Google Scholar
75. Edwards, KR, Hershey, L, Wray, L, Bednarczyk, EM, Lichter, D, Farlow, M, et al. Efficacy and safety of galantamine in patients with dementia with Lewy bodies: a 12-week interim analysis. Dement Geriatr Cogn Disord. 2004; 17 Suppl 1:S40–8.Google Scholar
76. Holm, AC. Alleviation of multiple abnormalities by galantamine treatment in two patients with dementia with Lewy bodies. Am J Alzheimers Dis Other Demen. 2004; 19 (4):215–8.Google Scholar
77. Wild, R, Pettit, T, Burns, A. Cholinesterase inhibitors for dementia with Lewy bodies. Cochrane Database Syst Rev 2003; (3):CD003672.Google Scholar
78. McKeith, IG, Wesnes, KA, Perry, E, Ferrara, R. Hallucinations predict attentional improvements with rivastigmine in dementia with Lewy bodies. Dement Geriatr Cogn Disord. 2004; 18 (1):94–100.Google Scholar
79. Pakrasi, S, Mukaetova-Ladinska, EB, McKeith, IG, O’Brien, JT. Clinical predictors of response to Acetyl Cholinesterase Inhibitors: experience from routine clinical use in Newcastle. Int J Geriatr Psychiatry. 2003; 18 (10):879–86.Google Scholar
80. Werber, EA, Rabey, JM. The beneficial effect of cholinesterase inhibitors on patients suffering from Parkinson’s disease and dementia. J Neural Transm. 2001; 108 (11):1319–25.Google Scholar
81. Hutchinson, M, Fazzini, E. Cholinesterase inhibition in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 1996; 61 (3):324–5.Google Scholar
82. Aarsland, D, Litvan, I, Salmon, D, Galasko, D, Wentzel-Larsen, T, Larsen, JP. Performance on the dementia rating scale in Parkinson’s disease with dementia and dementia with Lewy bodies: comparison with progressive supranuclear palsy and Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2003; 74 (9):1215–20.Google Scholar
83. Leroi, I, Brandt, J, Reich, SG, Lyketsos, CG, Grill, S, Thompson, R, et al. Randomized placebo-controlled trial of donepezil in cognitive impairment in Parkinson’s disease. Int J Geriatr Psychiatry. 2004; 19 (1):1–8.Google Scholar
84. Ravina, B, Putt, M, Siderowf, A, Farrar, JT, Gillespie, M, Crawley, A, et al. Donepezil for dementia in Parkinson’s disease: a randomized, double blind, placebo controlled, crossover study. J Neurol Neurosurg Psychiatry. 2005; 76 (7):934–9.Google Scholar
85. Minett, TS, Thomas, A, Wilkinson, LM, Daniel, SL, Sanders, J, Richardson, J, et al. What happens when donepezil is suddenly withdrawn? An open label trial in dementia with Lewy bodies and Parkinson’s disease with dementia. Int J Geriatr Psychiatry. 2003; 18 (11):988–93.Google Scholar
86. Thomas, AJ, Burn, DJ, Rowan, EN, Littlewood, E, Newby, J, Cousins, D, et al. A comparison of the efficacy of donepezil in Parkinson’s disease with dementia and dementia with Lewy bodies. Int J Geriatr Psychiatry. 2005; 20 (10):938–44.Google Scholar
87. Richard, IH, Justus, AW, Greig, NH, Marshall, F, Kurlan, R. Worsening of motor function and mood in a patient with Parkinson’s disease after pharmacologic challenge with oral rivastigmine. Clin Neuropharmacol. 2002; 25 (6):296–9.CrossRefGoogle Scholar
88. Onofrj, M, Thomas, A. Severe worsening of parkinsonism in Lewy body dementia due to donepezil. Neurology 2003; 61 (10):1452.Google Scholar
89. Giladi, N, Shabtai, H, Gurevich, T, Benbunan, B, Anca, M, Korczyn, AD. Rivastigmine (Exelon) for dementia in patients with Parkinson’s disease. Acta Neurol Scand. 2003; 108 (5):368–73.Google Scholar
90. Fogelson, N, Kogan, E, Korczyn, AD, Giladi, N, Shabtai, H, Neufeld, MY. Effects of rivastigmine on the quantitative EEG in demented Parkinsonian patients. Acta Neurol Scand. 2003; 107 (4):252–5.Google Scholar
91. Bullock, R, Cameron, A. Rivastigmine for the treatment of dementia and visual hallucinations associated with Parkinson’s disease: a case series. Curr Med Res Opin. 2002; 18 (5):258–64.Google Scholar
92. Bergman, J, Lerner, V. Successful use of donepezil for the treatment of psychotic symptoms in patients with Parkinson’s disease. Clin Neuropharmacol. 2002; 25 (2):107–10.Google Scholar
93. Wesnes, KA, McKeith, I, Edgar, C, Emre, M, Lane, R. Benefits of rivastigmine on attention in dementia associated with Parkinson disease. Neurology. 2005; 65 (10):165–6.Google Scholar
94. Poewe, W, Wolters, E, Emre, M, Onofrj, M, Hsu, C, Tekin, S, et al. Long-term benefits of rivastigmine in dementia associated with Parkinson’s disease: an active treatment extension study. Mov Disord. 2006; 21 (4):456–61.Google Scholar
95. Aarsland, D, Hutchinson, M, Larsen, JP. Cognitive, psychiatric and motor response to galantamine in Parkinson’s disease with dementia. Int J Geriatr Psychiatry. 2003; 18 (10):937–41.Google Scholar
96. Maidment, I, Fox, C, Boustani, M. Cholinesterase inhibitors for Parkinson’s disease dementia. Cochrane Database Syst Rev. 2006; (1):CD004747.Google Scholar
97. Ballard, C, Grace, J, McKeith, I, Holmes, C. Neuroleptic sensitivity in dementia with Lewy bodies and Alzheimer’s disease. Lancet. 1998; 351 (9108):1032–3.Google Scholar
98. The French Clozapine Parkinson Study Group. Clozapine in druginduced psychosis in Parkinson’s disease. Lancet. 1999; 353 (9169):2041–2.CrossRefGoogle Scholar
99. Pollak, P, Tison, F, Rascol, O, Destee, A, Pere, JJ, Senard, JM, et al. Clozapine in drug induced psychosis in Parkinson’s disease: a randomised, placebo controlled study with open follow up. J Neurol Neurosurg Psychiatry. 2004; 75 (5):689–95.Google Scholar
100. The Parkinson Study Group. Low-dose clozapine for the treatment of drug-induced psychosis in Parkinson’s disease. N Engl J Med. 1999; 340 (10):757–63.Google Scholar
101. Factor, SA, Friedman, JH, Lannon, MC, Oakes, D, Bourgeois, K. Clozapine for the treatment of drug-induced psychosis in Parkinson’s disease: results of the 12 week open label extension in the PSYCLOPS trial. Mov Disord. 2001; 16 (1):135–9.Google Scholar
102. Ondo, WG, Levy, JK, Vuong, KD, Hunter, C, Jankovic, J. Olanzapine treatment for dopaminergic-induced hallucinations. Mov Disord. 2002; 17 (5):1031–5.Google Scholar
103. Breier, A, Sutton, VK, Feldman, PD, Kadam, DL, Ferchland, I, Wright, P, et al. Olanzapine in the treatment of dopamimetic-induced psychosis in patients with Parkinson’s disease. Biol Psychiatry. 2002; 52 (5):438–45.Google Scholar
104. Goetz, CG, Blasucci, LM, Leurgans, S, Pappert, EJ. Olanzapine and clozapine: comparative effects on motor function in hallucinating PD patients. Neurology. 2000; 55 (6):789–94.CrossRefGoogle ScholarPubMed
105. Morgante, L, Epifanio, A, Spina, E, Zappia, M, Di Rosa, AE, Marconi, R, et al. Quetiapine and clozapine in parkinsonian patients with dopaminergic psychosis. Clin Neuropharmacol. 2004; 27 (4):153–6.Google Scholar
106. Carson, S, McDonagh, MS, Peterson, K. A systematic review of the efficacy and safety of atypical antipsychotics in patients with psychological and behavioral symptoms of dementia. J Am Geriatr Soc. 2006; 54 (2):354–61.Google Scholar
107. Schneider, LS, Dagerman, KS, Insel, P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA. 2005; 294 (15):1934–43.Google Scholar
108. Juncos, JL, Roberts, VJ, Evatt, ML, Jewart, RD, Wood, CD, Potter, LS, et al. Quetiapine improves psychotic symptoms and cognition in Parkinson’s disease. Mov Disord. 2004; 19 (1):29–35.CrossRefGoogle ScholarPubMed
109. Targum, SD, Abbott, JL. Efficacy of quetiapine in Parkinson’s patients with psychosis. J Clin Psychopharmacol. 2000; 20 (1):54–60.Google Scholar
110. Fernandez, HH, Trieschmann, ME, Burke, MA, Jacques, C, Friedman, JH. Long-term outcome of quetiapine use for psychosis among Parkinsonian patients. Mov Disord. 2003; 18 (5):510–4.Google Scholar
111. Fernandez, HH, Trieschmann, ME, Friedman, JH. Aripiprazole for drug-induced psychosis in Parkinson disease: preliminary experience. Clin Neuropharmacol. 2004; 27 (1):4–5.Google Scholar
112. Ondo, WG, Tintner, R, Dat Voung, K, Lai, D, Ringholz, G. Doubleblind, placebo-controlled, unforced titration parallel trial of quetiapine for dopaminergic-induced hallucinations in Parkinson’s disease. Mov Disord. 2005; 20(8):958–63.Google Scholar
113. Fernandez, HH, Trieschmann, ME, Burke, MA, Friedman, JH. Quetiapine for psychosis in Parkinson’s disease versus dementia with Lewy bodies. J Clin Psychiatry. 2002; 63 (6):513–5.Google Scholar
114. Bonelli, SB, Ransmayr, G, Steffelbauer, M, Lukas, T, Lampl, C, Deibl, M. L-dopa responsiveness in dementia with Lewy bodies, Parkinson disease with and without dementia. Neurology. 2004; 63 (2):376–8.Google Scholar
115. Molloy, S, McKeith, IG, O’Brien, JT, Burn, DJ. The role of levodopa in the management of dementia with Lewy bodies. J Neurol Neurosurg Psychiatry. 2005; 76 (9):1200–3.Google Scholar
116. Reisberg, B, Doody, R, Stoffler, A, Schmitt, F, Ferris, S, Mobius, HJ. Memantine in moderate-to-severe Alzheimer’s disease. N Engl J Med. 2003; 348 (14):1333–41.Google Scholar
117. Tariot, PN, Farlow, MR, Grossberg, GT, Graham, SM, McDonald, S, Gergel I. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA. 2004; 291 (3):317–24.Google Scholar
118. Ridha, BH, Josephs, KA, Rossor, MN. Delusions and hallucinations in dementia with Lewy bodies: worsening with memantine. Neurology. 2005; 65 (3):481–2.Google Scholar
119. Sabbagh, MN, Hake, AM, Ahmed, S, Farlow, MR. The use of memantine in dementia with Lewy bodies. J Alzheimers Dis. 2005; 7 (4):285–9.Google Scholar
120. Schapira, AH. Disease modification in Parkinson’s disease. Lancet. Neurol 2004; 3 (6):362–8.Google Scholar
121. Citron, M. Strategies for disease modification in Alzheimer’s disease. Nat Rev Neurosci. 2004; 5 (9):677–85.Google Scholar
122. Mani, RB. The evaluation of disease modifying therapies in Alzheimer’s disease: a regulatory viewpoint. Stat Med. 2004; 23 (2):305–14.Google Scholar
123. Parkinson Study Group. A controlled, randomized, delayed-start study of rasagiline in early Parkinson disease. Arch Neurol. 2004; 61 (4):561–6.Google Scholar
124. Schneider, LS, Olin, JT, Lyness, SA, Chui, HC. Eligibility of Alzheimer’s disease clinic patients for clinical trials. J Am Geriatr Soc. 1997; 45 (8):923–8.Google Scholar
125. Mitchell, SL, Sullivan, EA, Lipsitz, LA. Exclusion of elderly subjects from clinical trials for Parkinson disease. Arch Neurol. 1997; 54 (11):1393–8.Google Scholar
126. Dymek, MP, Atchison, P, Harrell, L, Marson, DC. Competency to consent to medical treatment in cognitively impaired patients with Parkinson’s disease. Neurology. 2001; 56 (1):17–24.Google Scholar