Top

Alzheimer's Research & Therapy

Published in:

Open Access 01-12-2015 | Research

Long-term donepezil use for dementia with Lewy bodies: results from an open-label extension of Phase III trial

Authors: Etsuro Mori, Manabu Ikeda, Reiko Nagai, Kazutaka Matsuo, Masaki Nakagawa, Kenji Kosaka

Published in: Alzheimer's Research & Therapy | Issue 1/2015

Abstract

Introduction

The long-term efficacy and safety of donepezil 10 mg in patients with dementia with Lewy bodies (DLB) were investigated in a 52-week Phase 3 trial.

Methods

This 52-week study consisted of 16-week randomized placebo-controlled (RCT) and 36-week open-label extension phases. Of 142 DLB patients enrolled in the RCT phase (three arms: placebo, 5 mg, and 10 mg), 110 entered the extension phase. The placebo group of the RCT phase initiated active treatment at week 16, and the active groups maintained allocated treatment and dosages until week 24. After week 24, all patients received 10 mg. Dose reduction to 5 mg for safety concerns was allowed. Efficacy measures included Mini-Mental State Examination (MMSE) for cognitive function and Neuropsychiatric Inventory (NPI) for behavioral symptoms. Safety evaluations included adverse events (AEs) and the unified Parkinson disease rating scale.

Results

In total, 100 subjects completed the study. Cognitive function improvement was sustained for 52 weeks (MMSE at week 52 in 10 mg: 2.8 ± 3.5 (mean ± standard deviation); P <0.001, Student paired t test)). Those who received placebo in the RCT phase showed an improvement after starting active treatment. NPI improved in all the groups throughout the study, including the placebo period. In the subgroup of the 5 mg group without remarkable cognitive or behavioral improvement at week 24, further improvement was observed after a dose increase to 10 mg. After week 24, 21 patients experienced dose reduction. The incidence of any AEs did not increase over time.

Conclusions

The long-term administration of donepezil at 10 mg/day improved cognitive function for up to 52 weeks in patients with DLB without increasing the risk of clinically significant safety events.

Trial registration

NCT01278407. Trial registration date: January 14, 2011.

Available only for authorised users

McKeith I, Mintzer J, Aarsland D, Burn D, Chiu H, Cohen-Mansfield J, et al. International Psychogeriatric Association Expert Meeting on DLB: Dementia with Lewy bodies. Lancet Neurol. 2004;3:19–28.CrossRefPubMed

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;47:1113–24.CrossRefPubMed

Ballard C, O’Brien J, Morris CM, Barber R, Swann A, Neill D, et al. The progression of cognitive impairment in dementia with Lewy bodies, vascular dementia and Alzheimer’s disease. Int J Geriatr Psychiatry. 2001;16:499–503.CrossRefPubMed

Ballard C, Patel A, Oyebode F, Wilcock G. Cognitive decline in patients with Alzheimer’s disease, vascular dementia and senile dementia of Lewy body type. Age Ageing. 1996;25:209–13.CrossRefPubMed

Olichney JM, Galasko D, Salmon DP, Hofstetter CR, Hansen LA, Katzman R, et al. Cognitive decline is faster in Lewy body variant than in Alzheimer’s disease. Neurology. 1998;51:351–7.CrossRefPubMed

Walker Z, McKeith I, Rodda J, Qassem T, Tatsch K, Booij J, et al. Comparison of cognitive decline between dementia with Lewy bodies and Alzheimer’s disease: a cohort study. BMJ Open. 2012;2:e000380.CrossRefPubMedCentralPubMed

Imamura T, Hirono N, Hashimoto M, Kazui H, Tanimukai S, Hanihara T, et al. Fall-related injuries in dementia with Lewy bodies (DLB) and Alzheimer’s disease. Eur J Neurol. 2000;7:77–9.CrossRefPubMed

Kudo Y, Imamura T, Sato A, Endo N. Risk factors for falls in community-dwelling patients with Alzheimer’s disease and dementia with Lewy bodies: walking with visuocognitive impairment may cause a fall. Dement Geriatr Cogn Disord. 2009;27:139–46.CrossRefPubMed

Hanyu H, Sato T, Hirao K, Kanetaka H, Sakurai H, Iwamoto T. Differences in clinical course between dementia with Lewy bodies and Alzheimer’s disease. Eur J Neurol. 2009;16:212–7.CrossRefPubMed

10.

Ballard C, Walker M, O’Brien J, Rowan E, McKeith I. The characterisation and impact of ‘fluctuating’ cognition in dementia with Lewy bodies and Alzheimer’s disease. Int J Geriatr Psychiatry. 2001;16:494–8.CrossRefPubMed

11.

Boström F, Jönsson L, Minthon L, Londos E. Patients with dementia with lewy bodies have more impaired quality of life than patients with Alzheimer disease. Alzheimer Dis Assoc Disord. 2007;21:150–4.CrossRefPubMed

12.

Lee DR, McKeith I, Mosimann U, Ghosh-Nodyal A, Thomas AJ. Examining carer stress in dementia: the role of subtype diagnosis and neuropsychiatric symptoms. Int J Geriatr Psychiatry. 2013;28:135–41.CrossRefPubMed

13.

McKeith IG, Rowan E, Askew K, Naidu A, Allan L, Barnett N, et al. More severe functional impairment in dementia with lewy bodies than Alzheimer disease is related to extrapyramidal motor dysfunction. Am J Geriatr Psychiatry. 2006;14:582–8.CrossRefPubMed

14.

Perry EK, Haroutunian V, Davis KL, Levy R, Lantos P, Eagger S, et al. Neocortical cholinergic activities differentiate Lewy body dementia from classical Alzheimer’s disease. Neuroreport. 1994;5:747–9.CrossRefPubMed

15.

Perry EK, Irving D, Kerwin JM, McKeith IG, Thompson P, Collerton D, et al. Cholinergic transmitter and neurotrophic activities in Lewy body dementia: similarity to Parkinson’s and distinction from Alzheimer disease. Alzheimer Dis Assoc Disord. 1993;7:69–79.CrossRefPubMed

16.

Edwards K, Royall D, Hershey L, Lichter D, Hake A, Farlow M, et al. Efficacy and safety of galantamine in patients with dementia with Lewy bodies: a 24-week open-label study. Dement Geriatr Cogn Disord. 2007;23:401–5.CrossRefPubMed

17.

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;13:199–205.CrossRefPubMed

18.

Mori S, Mori E, Iseki E, Kosaka K. Efficacy and safety of donepezil in patients with dementia with Lewy bodies: preliminary findings from an open-label study. Psychiatry Clin Neurosci. 2006;60:190–5.CrossRefPubMed

19.

Rowan E, McKeith IG, Saxby BK, O’Brien JT, Burn D, Mosimann U, et al. Effects of donepezil on central processing speed and attentional measures in Parkinson’s disease with dementia and dementia with Lewy bodies. Dement Geriatr Cogn Disord. 2007;23:161–7.CrossRefPubMed

20.

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;20:938–44.CrossRefPubMed

21.

McKeith I, Del Ser T, Spano P, Emre M, Wesnes K, Anand R, et al. Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study. Lancet. 2000;356:2031–6.CrossRefPubMed

22.

Mori E, Ikeda M, Kosaka K. Donepezil-DLB Study Investigators: Donepezil for dementia with Lewy bodies: a randomized, placebo-controlled trial. Ann Neurol. 2012;72:41–52.CrossRefPubMed

23.

Ikeda M, Mori E, Kosaka K, Iseki E, Hashimoto M, Matsukawa N, et al. Donepezil-DLB Study Investigators: Long-term safety and efficacy of donepezil in patients with dementia with Lewy bodies: results from a 52-week, open-label, multicenter extension study. Dement Geriatr Cogn Disord. 2013;36:229–41.CrossRefPubMed

24.

Ikeda M, Mori E, Matsuo K, Nakagawa M, Kosaka K. Donepezil for dementia with Lewy bodies: a randomized placebo-controlled, confirmatory phase III trial. Alzheimers Res Ther. in press.

25.

Cummings JL. The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology. 1997;48:S10–6.CrossRefPubMed

26.

Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology. 1994;44:2308–14.CrossRefPubMed

27.

Hashimoto M, Manabe Y, Mori E, Hirono N, Kosaka K, Ikeda M. Content validity and inter-rater reliability of the Cognitive Fluctuation Inventory. Brain Nerve [in Japanese]. 2014;66:175–83.

28.

Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology. 1967;17:427–42.CrossRefPubMed

29.

Folstein MF, Folstein SE, McHugh PR. “Mini-mental state. a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189–98.CrossRefPubMed

30.

Zarit SH, Reever KE, Bach-Peterson J. Relatives of the impaired elderly: correlates of feelings of burden. Gerontologist. 1980;20:649–55.CrossRefPubMed

31.

Fahn SER: UPDRS Development Committee. Unified Parkinson’s disease rating scale. In: Fahn SMC, Calne D, Goldstein M, editors. Recent developments in Parkinson’s disease, vol. 2. New York: Macmillan Healthcare Information; 1987. p. 153–63. 293–304.

32.

Tohgi H, Homma A, Imai Y, Udaka F, Takeda M, Nishimura T, et al. Long-term safety and efficacy of acetylcholinesterase inhibitor E2020 in patients with Alzheimer-type dementia: 52-week open label study. Clin Eval. 2000;28:97–126.

33.

Homma A, Imai Y, Tago H, Asada T, Shigeta M, Iwamoto T, et al. Long-term safety and efficacy of donepezil in patients with severe Alzheimer’s disease: results from a 52-week, open-label, multicenter, extension study in Japan. Dement Geriatr Cogn Disord. 2009;27:232–9.CrossRefPubMed

Title: Long-term donepezil use for dementia with Lewy bodies: results from an open-label extension of Phase III trial
Authors: Etsuro Mori
Manabu Ikeda
Reiko Nagai
Kazutaka Matsuo
Masaki Nakagawa
Kenji Kosaka
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Alzheimer's Research & Therapy / Issue 1/2015
Electronic ISSN: 1758-9193
DOI: https://doi.org/10.1186/s13195-014-0081-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Long-term donepezil use for dementia with Lewy bodies: results from an open-label extension of Phase III trial

Abstract

Introduction

Methods

Results

Conclusions

Trial registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusions

Trial registration

Please log in to get access to this content

Other articles of this Issue 1/2015

Follow-up plasma apolipoprotein E levels in the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing (AIBL) cohort

Total testosterone and neuropsychiatric symptoms in elderly men with Alzheimer’s disease

Post-mortem analysis of neuroinflammatory changes in human Alzheimer’s disease

Cerebrospinal fluid levels of IL-6 are decreased and correlate with cognitive status in DLB patients

The need for thorough phase II studies in medicines development for Alzheimer’s disease

In vivo molecular neuroimaging of glucose utilization and its association with fibrillar amyloid-β load in aged APPPS1-21 mice