A team of researchers at Sweden’s Karolinska Institutet says that a ten-year study has shown the potential benefits of drugs called cholinesterase inhibitors (ChEIs) as treatment for patients suffering from dementia with Lewy bodies.
Lewy body disease includes both dementia with Lewy bodies (DLB) and Parkinson’s disease with and without dementia. Similar to Alzheimer’s disease, Lewy body disease is the second most common neurodegenerative disorder, with DLB accounting for between 10% and 15% of dementia cases. It is characterized by changes in sleep, behavior, cognition movement, and regulation of autonomic body functions.
“There are currently no approved treatments for DLB, so doctors often use drugs for Alzheimer’s disease, such as cholinesterase inhibitors and memantine, for symptom relief,” said Hong Xu, PhD, assistant professor at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and first author of the paper, published in Alzheimer’s & Dementia. “However, the effectiveness of these treatments remains uncertain due to inconsistent trial results and limited long-term data.”
The purpose of the study was to better understand the use of off-label treatments for patients with DLB over the long term. The investigators noted that there is a lack of data on the clinical benefits of treatments for the condition.
“It is noteworthy that most clinical trials for DLB have been limited to a maximum duration of six months to one year, leaving a paucity of knowledge regarding the long-term effects of these treatments on cognition,” the researchers wrote.
The Karolinska investigators had two goals for their study investigating the use of ChEIs or memantine for up to 10 years. The first was to evaluate how long-term use of these drugs affected patient scores on the Mini-Mental State Examination (MMSE), a widely used 30-point questionnaire that measures cognitive impairment. The second was to investigate the potential use of ChEIs and memantine with the risk of major adverse cardiovascular events (MACE) and all-cause mortality. In addition, the researchers assessed the effects of different dosages on their potential effects on cognition.
For their study, Xu and team examined the long-term effects of ChEIs and memantine and compared these with no treatment for up to 10 years in a cohort of 1,095 patients with DLB. Their findings showed that ChEIs may slow down cognitive decline over five years compared with memantine or no treatment, and that ChEIs were also associated with reduced risk of death in the first year after diagnosis.
Of the three ChEIs in the study—donepezil, galantamine, and rivastigmine—the data showed significantly improved MMSE scores of patients prescribed donepezil and galantamine, but not rivastigmine. A dose-response relationship was also found suggesting higher doses of ChEIs provided greater cognitive benefits. The researchers said these findings were consistent with other clinical trials and meta-analyses found in the literature.
“Our results highlight the potential benefits of ChEIs for patients with DLB and support updating treatment guidelines,” said senior author Maria Eriksdotter, PhD, professor at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet.
The team suggests that future clinical trials for the treatment effects should be conducted for longer than two years to assess long-term outcomes such as cardiovascular events and mortality and that follow-up should be conducted in future studies for three to five years starting in patients with mild cognitive impairment with Lewy bodies.
