A 10-year study looked at cholinesterase inhibitors and memantine as potential treatments for LBD symptoms. Here's what the scientists found.
For years, a commonly prescribed treatment for managing the symptoms of Alzheimer’s disease has been a type of drug called a cholinesterase inhibitor (ChEI). These drugs target a neurotransmitter in the body called acetylcholine — an essential part of the brain’s cholinergic system, which helps control learning and memory. Under brand names like Aricept, Razadyne and Exelon, ChEI drugs are designed to keep acetylcholine from breaking down, and while this can’t slow down, stop, or reverse Alzheimer’s itself, it can help ease cognitive decline symptoms. So, do cholinesterase inhibitors have potential for treating these symptoms in other types of dementias, too? A new study from the Karolinska Institutet in Sweden looked into the potential of ChEIs in treating another type of dementia, Lewy body dementia.
Alzheimer’s Drugs 101: How Do Cholinesterase Inhibitors Work?
LBD has long been one of the most challenging types to diagnose, let alone effectively treat. Scientists at the Karolinska Institutet conducted a meta-analysis of data from 1,095 people living with dementia who had been treated with different ChEIs, as well as memantine – another drug which is believed to slow the neurotoxicity in the brains of people living with dementia. They hoped to assess whether these drugs proved effective in managing symptoms of LBD and slowing cognitive decline.
The study examined data several online health registries between 2007 and 2018. The data chosen for closer examination included those who had begun treatment using ChEIs and memantine within three months of being diagnosed.
Donepezil (brand name Aricept) and galantamine (Razadyne), both cholinesterase inhibitors, showed the most promise in reducing the effects of cognitive decline after a five-year period.
Researchers found that rivastigmine (Exelon), another ChEI, didn’t work as well as others, but did show the most “significant beneficial effect” in reducing mortality risk after a one-year follow-up — a noteworthy finding because the disease is often difficult to diagnose and is sometimes only discovered after the patient has died.
The study found that higher ChEI doses provided greater cognitive benefits, and that memantine showed no significant cognitive effect.”
What Is the Difference Between Lewy Body Dementia and Alzheimer’s?
Dosage matters
There are caveats to the study’s findings. The meta analysis relied on a number of different studies into ChEIs and focused on patients with LBD — specifically individuals who began ChEI treatment within three months of diagnosis and followed a “defined daily dosage” rule outlined by the World Health Organization.
This meant that the reason one ChEI in the study, rivastigmine, had no impact on improved cognition, could have been because the majority of people taking it did not reach the adequate dose needed for efficacy. To make matters more complicated, the study’s co-author Dr. Maria Eriksdotter, noted that “individuals who were older, living alone, and had prescriptions of hypnotics, antipsychotics, and antidepressants were less likely to be treated with higher doses of ChEIs,” indicating that some patients were undergoing different treatments for the disease and possibly other medical conditions.
What’s next for ChEIs and LBD symptoms?
To monitor the long-term effects of ChEIs on LBD, Eriksdotter noted that patients underwent regular follow-ups and cognitive assessments using the Mini-Mental State Examination.
But, as neurologist Dr. Andrew Larner pointed out to Being Patient, there is no universal benchmark for what constitutes a clinically meaningful reduction in cognitive decline. “ChEIs are purely symptomatic treatments,” Larner said. “There is no evidence that they modify the disease course of [LBD] — or Alzheimer’s disease.”
The study itself notes that “to our knowledge, [LBD] lacks an approved treatment worldwide except in Japan, and clinical trials have proven unsuccessful in all disease-modifying therapies.” It adds that most symptom-modifying treatments are prescribed off-label.
Larner also noted that studies into viable drugs can be influenced by the drug approval process and should be taken with a grain of salt. “Criteria for assessing a reduced rate of cognitive decline are likely to be bureaucratic,” he said, or “whatever needs to be fulfilled to gain regulatory approval.”
“However, whether [a given study] represents a meaningful change for patients and relatives,” such as a patient’s ability to dress themselves, use the toilet, or handle money without assistance, “is a different question,” he said, “and may not follow from the claim of a ‘reduced rate of cognitive decline.’”
Lisa Power is a recent graduate of the Columbia University Graduate School of Journalism.
