An Effective Treatment for Dementia with Lewy Bodies
Donepezil improved cognition and behavior.
Dementia with Lewy bodies is characterized by parkinsonism and by deficits of visual perception, executive function, and attention. Because of presynaptic cholinergic loss in the brainstem and forebrain, acetylcholinesterase inhibitors such as rivastigmine have been studied, with some demonstration of efficacy. This multicenter, placebo-controlled, manufacturer-funded study of donepezil was conducted to investigate its safety and efficacy in this patient population.
The 140 patients were randomized to receive placebo or donepezil at 3, 5, or 10 mg for 12 weeks. Researchers assessed cognition (Mini-Mental State Examination [MMSE] and other specific tests), behavior, caregiver burden, and global function. Rate of cognitive response (MMSE change, ¥3 points) was higher in all donepezil groups compared with the placebo group (donepezil 3 mg, 42.9%; 5 mg, 65.6%; 10 mg, 44.4%; vs. placebo, 12.9%). All doses improved measures of attention/concentration and processing speed. Delusions, hallucinations, and cognitive fluctuation significantly improved at the 5- and 10-mg doses compared with placebo, which was associated with worsening. Improvement in global function with all donepezil doses was superior to placebo. Donepezil was well tolerated, with an increase in reported parkinsonian motor symptoms, but adverse events in the drug groups were, overall, no different from those in the placebo group.
Comment: In contrast to donepezil’s isolated cognitive effect in Alzheimer disease, neuropsychiatric improvement, not just cognitive stabilization, appears to result with donepezil treatment for dementia with Lewy bodies. Considering the difficulty in treating both the cognitive and behavioral problems in patients with this disease, donepezil should be a strongly considered therapeutic option. As the authors mention, longer-term studies are needed.
Jonathan Silver, MD
Published in Journal Watch Psychiatry March 5, 2012