- Parkinson’s disease dementia develops in people who have a Parkinson’s disease diagnosis.
- Experts are interested in finding the best ways to address and prevent Parkinson’s disease dementia.
- A randomized clinical trial found that the drug Ambroxol may help stabilize the neuropsychiatric symptoms of Parkinson’s disease dementia, and confirmed the safety of the drug’s use among participants.
Dementia is a common problem that remains a critical focus of clinical research. One subtype of dementia is Parkinson’s disease dementia, which has to do with the mental changes that occur in some people who already have Parkinson’s disease.
A study published in
While primary and secondary outcomes were similar, participants on the placebo experienced worsening neuropsychiatric symptoms compared to symptoms remaining the same in the intervention group.
The results also showed a possible improvement in cognitive symptoms for people with variants of a particular gene.
The authors of the current study note the need for disease-modifying interventions for Parkinson’s disease dementia. They note that focusing on a particular enzyme, beta-glucocerebrosidase, has potential, with an increase in this enzyme possibly making things better. They also note that the medication Ambroxol affects this enzyme.
This study involved examining the safety of Ambroxol, how well participants tolerated the medication, and how it affected cognitive symptoms.
There were 55 participants in total. All participants were over 50 years old and had confirmed Parkinson’s disease for 1 year or more before developing dementia. All participants also had a study partner, someone who was in contact with them “at least 4 days per week.”
Participants took either Ambroxol or the placebo for 1 year. Researchers had trouble with recruitment for a low-dose Ambroxol group, so this group was not included in the statistical analyses of primary and secondary outcomes. Overall, there were 22 participants in the high-dose Ambroxol group and 24 participants in the placebo group.
As a primary outcome, researchers evaluated participants’ conditions using two evaluations: the Clinician’s Global Impression of Change and the Alzheimer Disease Assessment Scale-cognitive subscale version 13.
They also used other evaluation tools for secondary outcomes, including the Parkinson’s Disease Cognitive Rating Scale, the Clinical Dementia Rating Scale, and the neuropsychiatric inventory. Researchers were able to look at cerebral spinal fluid and plasma biomarkers in some participants as well.
Throughout the study, some participants withdrew due to adverse events. Eight participants in the Ambroxol group withdrew, and three in the placebo group withdrew.
Participants in the Ambroxol group saw more gastrointestinal adverse events. The placebo group experienced more psychiatric adverse events and falls than the intervention group.
In the statistical analyses, the primary and secondary outcomes between the two groups were about the same. Thus, Ambroxol did not appear to have a significant impact on cognition.
However, researchers did observe that the neuropsychiatric inventory stayed the same for the Ambroxol group, but the placebo group got worse in this area, indicating the placebo group experienced worsening behavioral functioning.
The authors of the study note that GBA1 gene variants can increase the risk for cognitive decline in people who have Parkinson’s disease, and that “homozygous disease-causing variants in GBA1” can increase the risk for Parkinson’s disease.
In participants with GBA1 gene variants, those taking the high-dose Ambroxol had decreases in neuropsychiatric inventory scores, three to a level of “clinically meaningful improvement,” and three also had clinically important improved cognitive scores.
Researchers also observed increased beta-glucocerebrosidase levels among Ambroxol participants at the 26-week mark.
Study author Stephen H. Pasternak, MD, PhD, FRCPC, a specialist in neurology, explained the following about the study to Medical News Today:
“Our goal was to test the safety and tolerability of Ambroxol and to assess its effect on cognition. We randomized 55 patients to Ambroxol 1,050 mg/day [milligrams per day] or placebo for 1 year. Ambroxol was well tolerated; we only saw stomach upset as a side effect, and it was mostly mild. Patients on Ambroxol had fewer psychiatric symptoms. Patients on placebo had a worsening of plasma GFAP, a marker of neurodegeneration. A subgroup of patients (with GBA1 mutations) appeared to have improved cognition.”
Pasternak told MNT that: “We hope that Ambroxol, or drugs like Ambroxol, will be able to prevent the onset of Parkinson’s disease and dementia if it is given early enough.”
While more research is needed, this study sets up the possibility of using Ambroxol in the future to help people with Parkinson’s disease dementia.
Daniel Truong, MD, a neurologist, medical director of the Truong Neuroscience Institute at MemorialCare Orange Coast Medical Center in Fountain Valley, CA, and editor-in-chief of the Journal of Clinical Parkinsonism and Related Disorders, who was not involved in this research, explained that with future research this could lead to “a new class of disease-modifying therapy for [Parkinson’s disease dementia].
Hypothesising on the potential mechanisms of action, Truong explained that:
“Ambroxol, by enhancing lysosomal function via GCase [beta-glucocerebrosidase], may slow underlying neurodegeneration, especially in GBA1-related PDD [Parkinson’s disease dementia] — marking a shift toward targeted disease modification rather than purely symptomatic treatment.”
He also noted that this could lead to “repurposing an established drug” as “Ambroxol is already widely used as a mucolytic agent with a known safety profile.”
“This reduces development time, regulatory barriers, and cost, making it more feasible for rapid clinical adoption — especially in resource-limited settings,” Truong added.
However, while it is commonly used in medical settings in many European countries, the expectorant drug is currently
Still, should the current study findings be confirmed by further research, Pasternak hopes experts may see the drug in a new light.
“Current therapies for Parkinson’s disease and dementia address symptoms but do not stop the underlying disease. These [new] findings suggest Ambroxol may protect brain function, especially in those genetically at risk. It offers a promising new treatment avenue where few currently exist,” he noted in a press release.
The study does have a few limitations. It was a fairly small study with mostly white male participants that only went on for one year. It is possible that 1 year was not long enough to evaluate changes in cognitive symptoms since the placebo group did not see declines in cognitive symptoms.
Researchers also note that the study was limited since it was a phase 2 trial out of a single center.
They also acknowledge difficulties in recruitment and retention, and note that participants had “limited ability to tolerate the long cognitive assessments.”
The researchers did not get to conduct statistical analyses to look at differences between high and low doses of Ambroxol. They also note that the low-dose group appeared to have worse cognition. They suggest that future studies should possibly stratify participants by cognitive severity.
They also acknowledge that it is possible that the Alzheimer Disease Assessment Scale-cognitive subscale version 13 might not have been sensitive enough to detect changes in 1 year in participants who had mild Parkinson’s disease dementia. All participants in this study only had mild to moderate dementia.
Finally, only eight participants total had GBA1 gene variants, so more research is needed to see if people in this group could experience distinct benefits from Ambroxol. Only three participants with GBA1 gene variants had the minimal clinically important difference in cognitive scores, and researchers acknowledge that “this sample is too small to support any conclusion.”
Pasternak and his colleagues are planning to conduct a follow-up clinical trial later in 2025. The current research received funding from the Garfield Weston Foundation, a grant-giving nongovernmental organisation in the United Kingdom.
