Review finds no proof Alzheimer’s drugs help Huntington’s cognition
Researchers call for more studies as data on repurposing are limited
Available evidence does not indicate that treatments approved for people with Alzheimer’s disease can improve cognitive function in people with Huntington’s disease, according to a review study.
“The existing literature does not provide sufficient evidence to support the use of cholinesterase inhibitors or memantine for managing cognitive symptoms in HD [Huntington’s disease] patients,” the researchers wrote.
Cholinesterase inhibitors, a therapy class that works by increasing the levels of the brain-signaling molecule acetylcholine, include donepezil (sold as Aricept, with generics available) and rivastigmine (sold as Exelon, with generics available). Memantine, sold as Namenda (with generics available), is designed to block the effects of another brain-signaling molecule called glutamate.
The study, “Efficacy and safety of cholinesterase inhibitors and memantine for cognitive symptoms in patients with Huntington’s disease: A systematic review,” was published in the Journal of Huntington’s Disease by a team led by scientists in Portugal.
Huntington’s and Alzheimer’s share many similarities. They are both neurogenerative disorders characterized by problems with memory, thinking, and regulating mood. Alzheimer’s is the most common cause of dementia, which refers to a decline in mental skills severe enough to interfere with daily life. About 50% to 80% of people with Huntington’s is reported to have mild cognitive impairment at diagnosis, which can progress to dementia in more advanced disease stages.
Repurposing seen as option amid lack of treatment for cognition in Huntington’s
There are no approved treatments to improve cognitive function in Huntington’s, but a few studies have tested whether approved Alzheimer’s treatments may help. Those include donepezil, rivastigmine, and memantine.
“Since there are currently no approved medications for either symptomatic or disease-modifying treatment of cognitive symptoms in patient with [Huntington’s], repurposing medications approved for the symptomatic treatment of dementia in other neurodegenerative disorders might emerge as a potential option for these patients,” the scientists wrote.
The team conducted a review of the scientific literature published up to February 2024 to assess what’s currently known about the effects of these treatments in Huntington’s patients.
From more than 300 studies initially identified, only five — covering 137 patients and 18 healthy controls — met inclusion criteria and were included in the final analysis. Three studies reported results of rivastigmine, one of donepezil, and one of memantine.
Three studies were appropriately controlled clinical trials, one was an extension study of an appropriately controlled trial, and another was a retrospective comparison of patients on or off the therapy.
“Previous cognitive functioning was not specified in three out of five studies,” the researchers wrote, adding that only two studies followed participants for longer than eight months. Most of the studies were fairly small, “likely lacking sufficient power to detect meaningful effects,” the scientists wrote.
Results from all of the studies showed that none of the Alzheimer’s treatments led to statistically significant improvements in cognitive function for people with Huntington’s.
“None of the five studies included in this review identified a significant effect of either cholinesterase inhibitors or memantine on the natural progression of cognitive symptoms in HD,” the scientists wrote.
Adverse events, reported in two studies, were common, affecting up to half of patients. Most reported adverse events were judged to be mild in severity.
“There is insufficient evidence in the literature to support the use of cholinesterase inhibitors or memantine for cognitive symptoms in patients with HD,” the researchers concluded.
They stressed, however, that available data are limited, and emphasized a need for additional studies to better understand the biological mechanisms of cognitive impairment in Huntington’s and develop new treatment strategies.
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