- Parkinson’s disease dementia can develop in people who have been diagnosed with Parkinson’s disease.
- The best ways to treat and prevent Parkinson’s disease-associated dementia are of particular concern to experts.
- Ambroxol may help ameliorate neuropsychiatric symptoms of Parkinson’s disease dementia, randomized clinical trial that also found the drug safe for the participants to take, researchers said.
One common problem that remains a major area of clinical research is dementia. The mental changes some people who have Parkinson’s disease already experience are part of the topic of Parkinson ‘s disease dementia, a subtype of dementia.
This was inferred from a study that involved people with Parkinson’s disease / dementia taking either a placebo or the anti-depressant Ambroxol published in JAMA Neurology(Trusted Source).
The primary and secondary outcomes were similar, but the neuropsychiatric symptoms of the placebo group worsened compared with those of the intervention group.
Those with variations of one gene also seemed to suffer fewer symptoms of cognitive decline, research also showed.
Ambroxol potential and limitations for brain health
Newly published study authors stress that there needs to be disease-modifying therapy for dementia in patients with Parkinson’s disease, but there is scope for specific targeting of one enzyme, beta-glucocerebrosidase, and that increased levels of this enzyme could help treat the condition. They note that this enzyme is inhibited by drug Ambroxol.
Ambroxol safety, participant tolerance, and its effect on cognitive symptoms were investigated in this study.
All the people participating (the whole group of participants was 55 ) had Parkinson’s disease for at least a year before they had dementia, all were over the age of 50. All had a research partner who communicated with them ” at least 4 days per week “.
For a year the participants were given either Ambroxol or placebo. The statistical analyses of primary and secondary outcome were not done for the low-dose Ambroxol group due to recruitment problems In total 24 people were in the placebo group and 22 people were in the high-dose Ambroxol group.
The Clinician’s Global Impression of Change and the Alzheimer Disease Assessment Scale-cognitive subscale (version 13) were the two tests researchers used to measure the conditions of the participants as a major outcome.
One of the additional measurement instruments their researchers used for secondary outcomes was the Parkinson’s Disease Cognitive Rating Scale, Clinical Dementia Rating Scale and neuropsychiatric inventory. Some participants also had plasma biomarkers and cerebral spinal fluid drawn by researchers.
Consequences of withdrawal Some participants in the trial discontinued it due to adverse events, of which three were in the placebo group and eight in the Ambroxol group.
Among the Ambroxol group, there were greatergastrointestinal adverse effects. At the same time as the intervention group there were more falls and mental adverse events in the placebo group.
The two groups’ primary and secondary outcomes in the statistical analyses were roughly equal. Ambroxol did not seem to significantly affect cognition as a result.
Overall the neuropsychiatric inventory of Ambroxol group was unchanged, but in this domain of performance of placebo group dropped, indicate that behavioral functioning of placebo group worsened.
The more likely it will work in people who are at risk for Parkinson’s dementia
“Homozygous disease-causing variants in GBA1 may also increase risk of Parkinson’s disease, and variation in the GBA1 gene may increase risk of cognitive decline in Parkinson’s disease patients, ” the study’s authors write.
The high-dose Ambroxol group also exhibited reduced neuropsychiatric inventory scores in people with GBA1 gene variations, 3 percent at a level of “clinically relevant improvement”, and 3 percent at a clinically significant improvement in cognition scores.
At 26 weeks the researchers also found high beta-glucocerebrosidase levels in people taking Ambroxol.
In what ways might a cough medicine support cognitive function?
“If Ambroxol or other medicines like it are administered early enough they will probably be able to stop the development of Parkinson’s disease and dementia, ” Pasternak told MNU.
Although further study is needed to see if the treatment Ambroxol might have potential in PD dementia treatment this latest study suggests that there may be hope.
Future research “may lead to the development of an entirely new class of disease-modifying therapy for [Parkinson’s disease dementia]. ” said 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. Truong was not involved in this study.
Additional investigation is required to validate the results.
There are some limitations to the study. It was only a year study and the participants were mostly white male. Also because the placebo group did not experience a decrease in cognitive symptoms, it is most likely that it was not a long study that could adequately assess the effects of cognitive symptoms.
Because the study was a phase 2 trial at one specific institution, the researchers also say, it had flaws.
Another significant problem they note is the “limited capacity of the subjects to undergo long cognitive examinations”, as well as recruitment and retention problems.
No statistical analysis was performed to examine differences in high and low Ambroxol doses, the researchers report. They also note that the low-dose group seems to have weaker cognitive function. In future studies, participants should be allocated to study groups based on cognitive disability, they advise.
The Alzheimer Disease Assessment Scale-cognitive subscale (version 13) may not have been sensitive enough to detect changes in patients with mild Parkinson’s disease dementia within a year, they admit. All participants involved in this study were subject to mild to moderate dementia.
Thirdly, the total number of patients with GBA1 gene mutations was only eight (we’ve just discovered this), so further study is needed to find out whether Ambroxol can have particular benefits for such people. The researchers admit “this sample is too small to justify any conclusion”, since – aside from three participants with GBA1 gene mutations – only three of them showed the least clinically significant difference in intelligence scores.
Pasternak and his associates
