Dementia with Lewy bodies (DLB) is a common form of dementia in the elderly. It accounts for 10-15% of patients with dementia and constitutes the second largest group after Alzheimer's disease. Recent studies have shown that cholinesterase inhibitors like donepezil (Brand name: Aricept®) can help in the short term. This study is the first to show how it can help over the long run.
Long-Term Results are Positive
The 108 patients with DLB who participated in this "extension study" were continuing on from an earlier, shorter 12-week clinical trial testing donepezil for DLB.
The latest results demonstrate that cognitive function and dementia-related behavioral symptoms, including cognitive fluctuations, were improved after the start of donepezil treatment, and maintained for 52 weeks. That is to say, an entire year of benefit was seen in this trial, and if the preceding 12-week period is included, an impressive 64 weeks of treatment efficacy was demonstrated.
The findings suggest that treatment efficacy of donepezil for these symptoms may be maintained for even longer than the 64 weeks of this trial. This is because no linear decrease in evaluation scores was observed.
DLB versus Alzheimer's
Donepezil was originally FDA-approved for Alzheimer's, for which there have been extensive trials. Therefore, a comparison of this DLB trial to similat Alzheimer's trials reveals important insights.
The results indicate that cognitive decline in DLB may be faster than or at least similar to that in Alzheimer's Disease (AD) patients. This implies that patients with DLB might be even more likely to benefit from donepezil treatment compared to Alzheimer's patients.
As for caregivers, the donepezil treatment seemed to help them avoid the typical increase in burden that typically occurs with an untreated patient over such a long period of time. In other words, the medicine did not improve the situation for the caregiver; notwithstanding, it succeeded in keeping the situation from getting any worse.
Unsurprisingly, a relationship between the washout period and attenuation in the treatment effect was suggested. Among patients who were assigned to the donepezil treatment groups in the preceding RCT, cognitive function and behavioral/psychiatric symptoms deteriorated more in patients with a longer washout period. This could indicate that the treatment effect might eventually diminish if donepezil administration was stopped for a long period of time.
Since there was no significant imbalance in the AE incidence analyzed by onset time, it is therefore suggested that delayed onset of AE induced by long-term donepezil administration is unlikely to appear in these patients. Patients with DLB may be at increased risk of bradyarrhythmia resulting from treatment with ChEIs though . In this long-term study, however, only 2 patients experienced abnormal changes in pulse rate (1 bradycardia and 1 sinus bradycardia), and neither of these were serious. Also, long-term administration of donepezil is unlikely to worsen parkinsonian symptoms since UPDRS scores did not worsen over 52 weeks. Furthermore, only 3 patients received dose reductions to 3 mg/day due to AEs. Two of them completed this study with the reduced dose, thereby enabling the patients to continue treatment with donepezil by reducing the dosage to 3 mg/day. In comparison to a study of donepezil in patients with AD, AEs reported in this study were similar to those reported in the study of AD patients, except for parkinsonism .
The results appear to reliably indicate the efficacy of donepezil as a worthwhile treatment for DLB.
In conclusion, the long-term administration of donepezil at 5 mg/day was safe in patients with DLB, and is expected to exhibit lasting effects on improving impaired cognitive function and psychiatric symptoms.
Long-Term Safety and Efficacy of Donepezil in Patients with Dementia with Lewy Bodies: Results from a 52-Week, Open-Label, Multicenter Extension Study, Dementia and Geriatric Cognitive Disorders