Tuesday, February 5, 2013

Donepezil Improves Dementia With Lewy Bodies

Dementia with Lewy bodies (DLB) is a type of dementia less common than Alzheimer's disease.  However, Lewy bodies (brain neuron deposits of the proteins alpha-synuclean and ubiquitin) are found in up to 10 to 15% of individuals dying of dementia.

DLB is known to deplete brain acetylcholine and dopamine neurotransmitter levels in the brain.  This leads to a clinical syndrome characterized by both cognitive decline and motor symptoms similar to Parkinson's disease.

DLB may be difficult to distinguish from Alzheimer's disease but typically exhibits fluctuations in cognitive function, visual hallucinations, visuoperceptual impairment and concurrent motor symptoms.

Few clinical trials have targeted DLB due to it's relative infrequency and diagnostic classification.  A Japanese study of 148 subjects with DLB recent found support for the effectiveness of the Alzheimer's drug donepezil.

Mori and colleagues conducted a randomized clinical trial with the following key elements in the research design:

  • Subjects: Met probable DLB diagnosis using structured criteria, no Parkinson's disease diagnosis more than one year before onset of dementia, no evidence of focal vascular disease on CT or MRI
  • Drug administration: Double-blind randomization of donepezil 3 mg, 5 mg, 10 mg or placebo for 12 weeks
  • Outcome measures: Minimental state exam (MMSE) scores, attention, executive function and visuoperceptual cognitive function from the Wechsler Memory Scale-Revised (WMS-R), tests for verbal fluency and agnosia.  Ten behavioral domains were also assessed.  Clinicians blind to treatment rated global clinical status.  Caregivers rated burden of care.  Motor symptoms were assessed using the Unified Parkinson's Disease Rating Scale.
  • Statistical analysis: Last observation carried forward analysis on all subjects with at least one valid post-treatment measurement

This trial found significant therapeutic effects for donepezil across a variety of DLB disease domains (doses statistically associated with improvement compared to placebo)

  • Minimental status exam: 5 and 10 mg
  • Clinician global improvement scores: 3, 5 and 10 mg
  • Behavioral scores for hallucinations, cognitive fluctuation, delusions, apathy and depression: 5 and 10 mg
  • Caregiver burden scores: 10 mg

Photo of two brain Lewy Bodies 
Donepezil was fairly well tolerated in this study sample with 3 to 8% of the active drug groups discontinued due to adverse effects.  This rate was not different than placebo withdrawals.

The authors conclude that their study provides support for the effectiveness of donepezil across a variety of clinical domains.  They note the study supports using a 10 mg dose if tolerated.  

Recruiting clinical sample sizes sufficient to study treatment options in DLB is not easy.  This makes the current study an important one.  Additional clinical trials have also found support for rivastigmine, galantamine and memantine for DLB.  However, there is likely to be a paucity of clinical trials for DLB in the future relative to the number of trials in Alzheimer's dementia. 

Individuals with additional interest in this clinical trial can access the free full-text of the study by clicking on the PMID link below.

Photo of cinnamon teal duck is from the author's files.

Photo of Lewy bodies from the Wikipedia Commons file authored by Dr. Andreas Becker

Mori E, Ikeda M, Kosaka K, & Donepezil-DLB Study Investigators (2012). Donepezil for dementia with Lewy bodies: a randomized, placebo-controlled trial. Annals of neurology, 72 (1), 41-52 PMID: 22829268

No comments:

Post a Comment