

The recent FDA approvals for donanemab (Kinsunla®) and lecanemab (Leqembi®) for the treatment of Alzheimer’s mark a major step forward for dementia research. While these treatments focus on Alzheimer’s, they offer hope for Parkinson’s disease as well.
In May 2024, the APDA (American Parkinson Disease Association) hosted a presentation by neuroscientist Claire Sexton, DPhil, from the Alzheimer’s Association. This webinar was part of the APDA’s “Dr. Gilbert Hosts” series by neurologist and movement disorder specialist Rebecca Gilbert, MD, PhD. While Dr. Sexton’s main presentation was focused on the latest in Alzheimer’s disease and dementia research, the question- and-answer portion of the presentation addressed the connection between Alzheimer’s disease and Parkinson’s disease.
Both Alzheimer’s and Parkinson’s involve abnormal brain proteins and neurodegeneration, but they affect different brain areas and cause distinct symptoms. Over time, symptoms can overlap. People with Parkinson’s can develop dementia and people with Alzheimer’s can develop language and motor symptoms. To make things more complex, mixed dementia is also common. Between a third to a half of clinically diagnosed cases of Alzheimer’s show at least some degree of Lewy body pathology at autopsy and studies also show that between 20-60% of people with Parkinson’s disease dementia also have Alzheimer pathology (meaning they have amyloid protein or tau protein in the brain).
While the new Alzheimer’s drugs show promise, they also have potential side effects, including brain swelling. Regular monitoring is essential. Other advances in the Alzheimer’s community include the use of biomarkers in the clinical setting such as amyloid PET, CSF tests, and blood tests. In the Parkinson’s disease field, there are tests currently in development for biomarkers to measure alpha synuclein. Once biomarkers are available clinically in the Parkinson’s field, they could potentially be used to aid in early diagnosis of Parkinson’s disease.
Ultimately, the progress made in Alzheimer’s research brings optimism to the Parkinson’s community. The Alzheimer’s field seems to be a little ahead of the Parkinson’s field in certain specific clinical and research areas but, the recent advances provide a window of what is to come and paves the way for similar progress in the Parkinson’s disease field.
A recording of the webinar is available on the American Parkinson Disease Association’s YouTube Channel.
You can find relevant resources about dementia on the Stanford Parkinson’s website:
Cognition and PD
And now for my notes,
Elizabeth
“Dr. Gilbert Hosts: The Connection Between Parkinson’s and Alzheimer’s”
Speaker: Dr. Claire Sexton, Senior Director of Scientific Programs and Outreach, Alzheimer’s Association
Webinar Host: Rebecca Gilbert, MD, PhD, Chief Mission Officer, American Parkinson Disease Association
Webinar Date: May 23, 2024
Summary by: Elizabeth Wong, Stanford Parkinson’s Community Outreach
Dementia is an umbrella term for a range of symptoms that affect memory, thinking, and behavior. Memory changes can be forgetting material that was just read and difficulty remembering newly learned information. Changes in thinking can be challenges in planning or solving problems, or difficulties in concentrating. An example of affected behavior can be changes in mood, apathy, personality changes, and inappropriate social behavior. For diagnoses of dementia to be made, the symptoms must be severe enough to be interfering with daily life.
There are different types of dementia, and each type of dementia is unique and has its own unique set of symptoms and progression and underlying brain changes. Types of dementia include:
Alzheimer’s disease
Vascular dementia
Frontotemporal dementia
Dementia with Lewy bodies
Mixed dementia (where the symptoms have more than one underlying cause).
Alzheimer’s disease is the most common cause of dementia. Alzheimer’s disease is characterized by three main hallmark features which are:
1. The buildup of amyloid plaques made of beta amyloid.
2. Tau tangles made up of protein tau.
3. Cell death, there is shrinkage of the brain and neurodegeneration.
There is no cure for Alzheimer’s disease, but there have been recent advances that have been in the headlines and the past two years in anti-amyloid therapies, therapeutic landscape, biomarkers, and modifiable factors.
Anti-Amyloid Therapies
Anti-amyloid therapies aim to reduce the presence of amyloid plaque in the brain. Leqembi® /llecanemab (approved by FDA) and donanemab (pending review by FDA) are examples of recent treatments in anti-amyloid therapy that reduce the presence of amyloid in the brain. (Editor’s note: donanemab was approved by the FDA in July 2024.) These therapies do not represent a cure for Alzheimer’s, and they do not reverse the decline in cognition or functioning that occurs with Alzheimer’s.
Therapeutic Landscape
There are currently 164 clinical trials going on assessing 127 drugs for the treatment of Alzheimer’s disease. There are different targets such as amyloid, tau, cellular communication, neurotransmitters, vascular stress, etc. This is exciting because there are drugs being developed that are combinations of therapies that are targeting both amyloid and tau. Future treatment can be therapies looking at combinations of targets, personalization of treatments for everyone, and early intervention of treatments/therapies before the emergence of symptoms.
Biomarkers
Biomarkers offer a window into the brain and can help with diagnosis and treatment of Alzheimer’s disease. Amyloid PET scans are a type of biomarker that can be used to visualize amyloid in the brain. Blood tests are a promising area of research for the development of Alzheimer’s disease biomarkers. There has been rapid progress over the past 5-10 years in terms of how blood tests are being used to ensure that the right people are enrolled in clinical trials and evaluate the success of treatments and gain understanding on how the treatments work along the course of the clinical trial.
Modifiable Factors
In addition to pharmacological approaches, there are also non-pharmacological approaches to reducing the risk of dementia. Modifiable factors cannot give us insight on an individual basis as to whether an individual will develop dementia, but it can provide information at population level about what factors in general may slightly increase or decrease the risk of dementia. In 2020, the Lancet Commission released a report on dementia prevention and intervention that reported that modifying 12 risk factors may prevent or delay up to 40% of dementia. Those factors include: traumatic brain injury, depression, diabetes, hypertension, obesity, smoking, hearing loss, air pollution, education levels, alcohol, physical activity, and social contact. In general, things that are good for the heart are good for the head.
In March 2023, a 2-year clinical trial started to evaluate whether lifestyle interventions that target many risk factors can protect cognitive function in older adults who are at increased risk for cognitive decline.
Question-and-Answer
Q: What is the difference between Alzheimer’s and dementia with Parkinson’s disease?
A: Alzheimer’s is characterized by amyloid proteins forming plaques, tau proteins forming tangles, and brain cell loss in regions affecting memory and that leads to symptoms that include short term memory problems. On the other hand, Parkinson’s is characterized by changes to a different protein, alpha synuclein proteins forming Lewy bodies and cell loss of dopamine producing neurons that affects brain regions responsible for movement which lead to a different profile of symptoms.
There are parallels where both diseases are characterized by abnormal proteins, both have neurodegeneration or cell loss, and they are both progressive. However, there are important differences where the key proteins are different and the different brain regions where the proteins accumulate are different.
As disease progresses, there can be changes in other regions of the brain which lead to a wider variety of symptoms. In Alzheimer’s disease, symptoms can progress from memory and concentration to include language and movement. For Parkinson’s, 75% of people who have had Parkinson’s disease for over 10 years go on to develop Parkinson’s disease dementia, so this is where the changes in cognition meet a level of severity and interfere with their day to day lives.
Additionally, mixed dementia is also common. Between a third to a half of clinically diagnosed cases of Alzheimer’s show at least some degree of Lewy body pathology at autopsy. Studies also show that between 20-60% of people with Parkinson’s disease dementia also have Alzheimer pathology (meaning they have amyloid protein or tau protein in the brain).
Comment by moderator (Dr. Gilbert): There are anti-amyloid therapies that are now being used in clinics for Alzheimer’s and there are anti-alpha synuclein therapies in research development for Parkinson’s. We are hoping that the therapies being studied for Parkinson’s proceed along the same pathway as the anti-amyloid therapies in Alzheimer’s. Similarly, there are biomarkers for Alzheimer’s and Parkinson’s is a little behind as we are still working on developing biomarkers for Parkinson’s. Therefore, understanding how the Alzheimer’s community is taking these advances and then applying those to Parkinson’s disease is very exciting.
Q: How often are both Alzheimer’s and Parkinson’s brain changes found?
A: It is common for people to have more than one change in the brain. There can also be vascular changes in the brain as well. Across the field, we are gaining better insight into the biology of the changes. We are going from an understanding of the disease that was centered on the clinical symptoms to seeing the symptoms and thinking about what could be causing them in the brain to having more of a biologic staging of these diseases looking what proteins there are and accompanying changes and working towards targeting those issues. The field continues to grow and evolve.
Q: What is the difference between Lewy body dementia and Parkinson’s disease dementia and how is that related to Alzheimer’s disease?
A: Lewy body dementia is an umbrella term that includes both Parkinson’s disease and dementia with Lewy bodies. Both are characterized by alpha synuclein protein in the brain. What differs between these two is what types of symptoms emerge first. With Parkinson’s there can be movement changes first and then changes in cognition later in the disease. Whereas with dementia with a Lewy body there tends to be cognitive changes first and then changes with movement later. These are tricky diagnoses to make. In the Alzheimer’s field, with the advances in PET scans, CSF tests, and blood tests, we can identify amyloid and tau proteins. Similarly in the Parkinson’s disease field, there are tests in development to measure alpha synuclein and once those are available clinically, that it will be a game changer in term of being able to aid in early diagnosis, used in the development of new treatments by ensuring that the right people are enrolled in clinical trials, and evaluating the success of treatments.
Q: Can you talk about the controversy surrounding some of the new Alzheimer’s medications and about the safety?
A: There are multiple drugs now targeting amyloid in the brain and these are extremely effective in removing amyloid from the brain. In terms of clinical implications, these are not a cure all. Alzheimer’s is a complex disease, it is not characterized by amyloid but also by tau, and we can see other changes in the brain as the disease progresses, so there’s not one simple cure. These treatments are an important first step. In terms of side effects, there are side effects. It’s important to discuss whether the side effects and treatments would be right for the individual and that would be a discussion between the individual and the doctor. The new drug is currently taken by infusion and there can be a reaction to the infusion and there is amyloid related abnormalities related imaging aka ARIA (areas of swelling in the brain) that can happen, so if someone is getting the new treatment, they would also get a series of MRI scans so incidents of ARIA can be detected and monitored.
Comment by moderator (Dr. Gilbert): It is important to highlight that there has been such a slow process for the past few decades in treatment of dementia, and we are at the very beginning of finding these advances related to dementia. These advances in the Alzheimer’s community are huge for both the Parkinson’s community and Alzheimer’s community because of the burden and struggle that dementia carries. There are going to be bumps with the new treatments that come out, but we are all eager for more to come. The Parkinson’s community can learn so much from the Alzheimer’s community.
Q: How do Parkinson’s scientists and Alzheimer’s scientists talk to each other and know what is going on in each other’s fields?
A: Yes, we talk and collaborate in several different ways. There are also researchers who are working on both conditions. The Alzheimer’s Association also funds research into Parkinson’s dementia and dementia with a Lewy body. At [professional] conferences there are networking events and organizations host collaborations.