A Novel Treatment and Other Parkinson's Updates From AAN 2022

Kathrin LaFaver, MD; Indu Subramanian, MD


August 17, 2022

This transcript has been edited for clarity.

Kathrin LaFaver, MD: Welcome back, everyone. This is part two of our highlights from the American Academy of Neurology annual meeting abstracts in the movement disorders sphere, specifically in Parkinson's disease, which were selected by Dr Indu Subramanian. Thanks again for joining us, Indu.

Indu Subramanian, MD: Thank you. It's a pleasure to talk to you about the cool things of the meeting and some of the abstracts that caught my eye.

LaFaver: Wonderful. So, what were your highlights in the therapeutic sphere? What's new in the treatment of Parkinson's disease?

A Promising Novel Treatment

Subramanian: One of the things that caught my eye was a study of the GLP-1 agonist liraglutide, which is a novel treatment in Parkinson's disease. It's something that's been approved, I believe, in diabetes and obesity treatment. There's been a lot of interest in the GLP-1, which are the glucagon-like peptide 1 drugs, the agonists of those receptors.

Basically, Dr Michele Tagliati, who's a colleague of mine just up the street at Cedars-Sinai, has put a lot of passion, interest, and focus into studying liraglutide. This was a single-center, randomized, double-blind, placebo-controlled trial. In addition to regular medicines, they gave once-daily, self-administered injections of liraglutide at 1.2 or 1.8 mg as tolerated, vs placebo, for 52 weeks after titration. They looked at some outcome measures that included the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part three, which is the motor measure. They also looked at the nonmotor symptoms scale, as well as the Mattis Dementia Rating Scale at week 54. There were 63 patients randomized, 43 to liraglutide and 21 to placebo.

The bottom line was interesting. There was improvement in the clinical features of Parkinson's disease, including nonmotor symptoms and activities of daily living. But it didn't look like there were improvements in terms of the MDS-UPDRS or the Mattis Dementia Rating Scale.

I think this is an exciting taste of what this sort of medication possibly may offer, and I think there are further studies that need to be done. But it was exciting that they did look at the nonmotor subscale, because historically we spent a lot of time focusing on motor subscales of the UPDRS. Many of these studies have been negative in the past in terms of disease modification or other things, because perhaps we've been missing out on looking at nonmotor subscales better.

So this is exciting initial data with this medication specifically, and additional data to support possible use of this medication and this class of the GLP-1 drugs. They've been out on the market and used in these other disease states.

Kathrin, what's your take on this as a sort of somebody who may be taking care of patients on a day-to-day basis in more of a private practice setting?

LaFaver: Thanks so much for that nice summary. One other thing I'd highlight is when you think about this as a possibly disease-modifying medication, as we know some of the nonmotor symptoms, including depression and cognitive issues, are among the main drivers of disability. So, as you said, I think it's a very interesting point to really specifically look at the nonmotor features.

My thought was, what would you say to a patient who wants to start this medication? It's obviously not approved for this indication currently. What's your take on that? Have you had any patients inquire about it yet?

Subramanian: We've had some patients inquire about it. Some patients also sometimes lose weight as well, which I think is an attractive thing them. I live in Southern California, and so patients are always wondering how they can get their appearance to look better.

But, I would say these are relatively expensive medications and these are relatively early data. It's good that it's safe and tolerated in our patient population. But I'll probably stand by and wait for further data before I start my patients on it. We'll have to see what the future holds. Is that what you think too, Kathrin?

LaFaver: I agree. It's just too soon. We always want to encourage patients to participate in trials. And of course, if people have a different indication, to be on it. If this is a diabetic patient, there might be other reasons. But as you said, we definitely need more data, but it's exciting to see drug study with a new mechanism. 

Survival in Parkinson's Disease Psychosis

LaFaver: Let's switch gears a little bit with our next abstract here, which is titled, "Survival Differences Among Patients with Parkinson's Disease and Parkinson's Disease Psychosis: a Population-based Study (2006-2015)." This comes from Dr Rodolfo Savica, who is at the Mayo Clinic and is a friend of mine, and his colleagues. They've done amazing epidemiologic studies based on the Rochester Epidemiology Project.

I found this study very interesting, because it's something that hasn't been looked at specifically. Patients will always ask, how does Parkinson's disease affect my long-term prognosis and so on. We know that in general, there's not a large difference in life expectancy. But this study looked at how patients who experience psychosis do using this amazing database. They looked at 69 patients out of 225 with Parkinson's disease over a 10-year time span.

They found that patients who had met criteria for Parkinson's disease psychosis showed higher rates of cognitive impairment (40% vs 25%, respectively). That's probably not too surprising. They also had higher rates of orthostatic hypotension (26% vs only 14%) and a significantly higher rate of all-cause mortality.

These are the main takeaway findings. The practical takeaway for someone like me as a clinician, a movement disorder specialist in practice, is that we really need to really pay attention to those things. Questioning about these nonmotor symptoms, including psychosis, should be a standard of care at follow-up visits and knowing about the implications this can have. We also know that patients with psychosis have a higher rate of hospitalization, postsurgical delirium, and associated infection. So, I think these are good data to have.

We know that Parkinson's disease is not one disease, but it's really a spectrum. Knowing which patients we really need to pay a lot of attention to and who might be frailer and higher-risk is important.

Subramanian: Absolutely. It's a very high-risk population with high morbidity and mortality. From a caregiver burden perspective, this is hugely problematic. When people start to hallucinate, they can't be left alone. The caregiver really has to be around 24/7 almost.

What struck me about the data in this abstract was the high incidence of orthostasis as well. You have a population that may be psychotic, who are seeing things that aren't there, sometimes to the point of acting upon them. For example, they may see a burglar and want to jump up and save their wife, and can drop their blood pressure as soon as they stand up and pass out. It's a really, really tough patient population to get activities of daily living and quality-of-life scores up in.

We need to find ways to support the caregiver, keep patients in their homes but with help. Because I if you're dealing with orthostasis on top of psychosis, often in a frail patient with advanced Parkinson's disease, it can be a lot for the caregivers. This gives us additional data to try to support the caregiver.

Also, from a therapeutic standpoint, if there's that high an incidence of orthostasis at baseline, some of the medications that we sometimes treat psychosis with can also drop blood pressure as well. It's useful data to find out about those blood pressures, which I may not have been as good about checking in some of these patients.

Much-Needed Data on Bent Spines

LaFaver: Absolutely. It should be a standard of care to check orthostasis in our in our patients, especially with more complicated Parkinson's.

We're tying back into this theme of interdisciplinary care, possibly palliative care services for patients to really address their needs.

Let's finish with a study on camptocormia that caught your eye from the Wake Forest group.

Subramanian: For those of you who don't know, camptocormia is a Greek word for bent spine. Patients with advancing Parkinson's disease, Parkinson's-plus disorders, and sometimes other neuromuscular disorders can get this issue where their spine bends forward. It's often not responsive to changing dopaminergic medications.

It's really the bane of my existence when it happens, because patients are often otherwise doing relatively well. Cosmetically, it can be really devastating for our patients because it's just so obvious that they have this bent spine and many of them don't want to go out because the stigma of looking very different from others. It really changes their quality of life and activities of daily living when this happens.

So, I was fascinated to look at the array of treatments that they offered their patients. And I know you have the details, if you want to just mention some of the treatments.

LaFaver: I'd be happy to. They looked at 19 consecutive patients with camptocormia and parkinsonism. They did a retrospective review of how they did with different treatments. Those include a dopamine replacement therapies, physical therapy, steroids, deep brain stimulation of both the subthalamic nucleus or globus pallidus interna, and spinal fixation surgery.

As I often say, if there's 10 different treatments for a single condition, it might already be a hint that there's not one standard of care. That's exactly what they found, that the treatment outcome of patients to these different modalities varied quite a bit. In their conclusion, they highlighted that treatment outcomes were highly variable and unpredictable.

I think it's a good starting point to remind us of what options do we have. I've personally seen some patients benefit from spinal surgery, which is not something people would automatically think of. They think this is more of a muscle tone issue, so to speak. But I think it can be helpful for these patients to benefit from multidisciplinary expertise, and hopefully there will be more treatment options or refined treatment options in the future.

Subramanian: It almost makes you think that a registry might be helpful for something like this. We all have 10 patients in our careers whom we see and or maybe more, but it's not something we see every day. It's sort of piecemeal. We might have an odd patient that does well with this type of phenomenology or that type of phenomenology. If we gather that information across the board, we can help our patients with this problem that can be very devastating.

Dr Siddiqui and his team were being very systematic about how categorizing these 19 patients. This is a nice starting place, and hopefully there will be more to come.

LaFaver: It was a pleasure talking to you. It was hard to pick among the many, many abstracts.

For those who want to hear more, there's still the virtual meeting, and you can still buy access to all these amazing scientific and educational updates. Hopefully, we'll see each other again and in person at the meeting next year. Thank you so much for talking to me today.

Subramanian: Thank you. Take care.

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