Questions About Parkinson’s Disease & Cognitive Impairment

Changes in cognition can unfortunately be a common non-motor symptom of Parkinson’s disease (PD).

Mild cognitive impairment (MCI) is an early stage of cognitive difficulty that does not interfere with a person’s ability to perform activities independently but can nevertheless affect a person’s performance of more complex cognitive tasks.

Dementia refers to cognitive difficulty that does interfere with a person’s independence.

On a recent episode of APDA’s Dr. Gilbert Hosts, I spoke with Dr. Jasdeep Hundal, a neuropsychologist with expertise in the cognitive challenges of PD. We covered a lot of ground and during the broadcast and answered questions from the audience. In this blog, we are answering the questions we didn’t have time for.

Highlights from the Episode

It was a very informative conversation, and we encourage you to watch the full episode, but for your convenience we’ve listed the topics and questions from the episode below with timestamps, so you can skip to what interests you most:

Overview

• 2:15 Dr. Hundal’s presentation

Medication

• 18:41 I find that carbidopa/levodopa helps my movements but makes my cognition worse. Why is that?
• 23:38 Does taking the antidepressant bupropion accelerate cognitive decline?
• 25:10 Do you have any suggestions about a medication dispenser for those who have difficulty remembering to take their medications?
• 39:36 There are many nutritional supplements and compounds available for purchase that claim to be good for cognition. How do I choose?
• 45:00 There is a new drug available for Alzheimer’s disease. Will this be used for people with PD and dementia?

Aging

• 19:41 How do you distinguish between normal aging and MCI?
• 24:02 Does the information presented today apply to those with young onset Parkinson’s disease?

Care for Another Individual

• 21:23 For family members who suspect MCI in their loved one, what advice do you have to broach the topic with the person affected and their health care provider?

Symptoms

• 26:56 Are people who have had deep brain stimulation more or less likely to develop cognitive decline?
• 31:39 What is Lewy body dementia and how does it differ from PD dementia?

Mood Changes

• 28:58 One of my major problems is lack of motivation or apathy – does that relate to cognitive decline?
• 38:11 How can you distinguish between mood changes and cognitive changes?

Cognitive Practices

• 33:32 What cognitive practices can you do to improve your cognition?
• 37:01 Do you recommend a specific online cognitive program to improve cognition?

Speech Difficulty

• 30:22 I have difficulty retrieving the right words when I speak. Do you have any exercises or therapies to help?
• 35:51 Is stuttering and stammering part of MCI?

Testing

• 41:19 What kind of testing do you do to determine what type of Parkinson’s a person has?

Physical Activity

• 43:10 My wife does not think I should drive anymore but I think that she is over-reacting. What should I do?

Additional Audience Questions

Here we have answered the many audience questions and comments about Parkinson’s and cognitive impairment that we didn’t have time to address during the live broadcast.

Symptoms | Physical Activity

Q: I struggle with multi-tasking. I feel easily frustrated or overwhelmed and I need to take frequent breaks.

A: Multi-tasking requires intact executive functioning, which is the cognitive processes that allow us plan, organize, and pay attention. This set of cognitive skills can be affected early on in PD. Cognitive rehabilitation can teach you alternative methods to get things done, so ask you neurologist for a referral for this type of therapy.

Q: I was diagnosed five years ago, and I feel that my cognitive problems are progressing very rapidly. Is this normal?

A: I would discuss this with your neurologist who may want to refer you for neuropsychiatric testing. This type of testing would help you and your doctor better understand the cognitive changes that you are experiencing. 

Q: My husband has MCI and has difficulty using his cell phone. He is unable to set alarms or reminders and I am not always at home. This is a challenge for us.

A: I would ask your neurologist for a referral for cognitive rehabilitation with an occupational therapist. The sessions could focus on working with your husband and his cell phone to find settings that are easy for him to access and manipulate.

Light Therapy

Q: Does light therapy help cognition in PD?

A: Light therapy refers to the use of light as a treatment for disease. Light therapy is being studied for various motor and non-motor symptoms of PD. To my knowledge however, the studies are not looking to see if cognitive function is improved, but instead are focused on sleep, mood, and motor function.

Multiple system atrophy (MSA)

Q: Does Multiple system atrophy (MSA) have the same cognitive issues as PD?

A: In the past, cognitive issues were not considered a major part of MSA. In fact, appearance of cognitive issues was a reason to reconsider the diagnosis. However, more recent research suggests that people with MSA can have cognitive issues that are like those in PD.

Dementia

Q: If we experience MCI early on in our diagnosis, is it likely it will progress to dementia?

A: Different studies report different rates of progression, but it may be as high as a 50% conversion from MCI to dementia over a five-year period. It is worth noting however, that some studies show that about 10% of people with MCI reverted to normal cognition over time, indicating that MCI is a complex and varied state that is not completely predictable.

Medication

Q: Do anticholinergic medications contribute to cognitive impairment?

A: Reversible side effects (meaning the side effect will stop when the medication is stopped) of anti-cholinergic medications include memory loss and confusion. There remains debate however, about whether these medications could also contribute to the risk of dementia in a way that is not reversible (persisting even if the medication is stopped.)

The fact that anti-cholinergic medications can cause memory complaints as a reversible side effect is not surprising. Anti-cholinergics act by blocking acetylcholine signaling in the brain, which is thought to be an important brain chemical for cognition. In fact, the one medication that is currently approved for cognitive decline in PD is rivastigmine, which is an acetylcholinesterase – a medication that increases acetylcholine in the brain. So, blocking acetylcholine can have the opposite effect.

Q: My husband was in the sage-718 trial. It Made a huge difference in his MCI. Hopefully it will be available soon!

A: SAGE-718 is an NMDA receptor positive allosteric modulator, a molecule that enhances the activity of the NMDA receptor. This is a type of receptor that interacts with the brain chemical glutamate which plays a role in learning and memory. A Phase 2 open label trial for people with PD and mild cognitive impairment (NCT04476017) is now complete. The results of that study were presented at the Annual Meeting of the American Academy of Neurology in April 2022 and demonstrated that the compound was well-tolerated and associated with improvement on multiple tests of cognitive performance, learning and memory.

A randomized, double blind, placebo-controlled Phase 2 trial to evaluate SAGE-718 in PD-MCI is now underway. NYX-458 is another NMDA receptor modulator that is being studied in a randomized, double blind, placebo-controlled Phase 2 trial for PD-MCI or PD with mild dementia.

We look forward to seeing the results of these trials!

Medical Procedures

Q: Is there are reason to get a brain MRI or spinal tap if you have PD and are concerned about MCI?

A: Brain MRI shows the structure of the brain. In most cases of PD as well as PD with MCI, the standard sequences of brain MRI will be normal. However, research efforts are underway to define MRI sequences that can be used to identify PD, as well as the cognitive issues of PD.

Currently, there is a diagnostic test that can be performed on spinal fluid that can help make the diagnosis of Parkinson’s and related disorders (not specifically MCI in PD though). You can read more about this test as well as a test on skin biopsies here.

Q: My thyroid was removed due to cancer. Now my thyroid levels can run low. Does this affect my cognition?

A: When someone has a cognitive issue of any type, whether they have PD, one of the first things to check are thyroid levels. An underactive thyroid by itself can cause cognitive problems. In addition, if someone has MCI or dementia from another cause and has an underactive thyroid, their cognitive issues can be worse. So, treating an underactive thyroid with thyroid hormone replacement is very important.

Q: Is stem cell therapy used for cognitive issues in PD?  

A: There are no stem cell treatments that are approved for use in PD, PD with MCI or PD with dementia. However, there are stem cell treatments that are currently being tested in clinical trials. These trials are fraught with complexity. There are multiple variables to consider – among these are: what type of stem cell is being used and how are the cells being introduced into the body. If you look on clinicaltrials.gov, which is an international database of all clinical trials, there are several trials that are registered that involve PD and stem cells. You can read about the most promising ones on cell therapy and stem cells. As the field evolves, there will likely be more relevant clinical trials to try to bring these therapies closer to the clinic.

Q: What is the value of a DaTscan and is it useful to diagnose MCI?

A: DaTscan is an imaging test which detects the presence of the dopamine transporter on dopamine neurons. It can be helpful in the diagnosis of PD and related disorders. However, there are other brain chemicals besides dopamine that are involved in the cognitive problems of PD. Therefore, looking only at the dopamine system with DaTSCAN is not particularly useful in diagnosing MCI. 

Homocysteine

Q: What is the relationship between homocysteine and cognitive difficulties in PD?

A: Homocysteine is a normal byproduct of cells. Elevated levels of homocysteine are linked to stroke and vascular damage to the brain. Elevated homocysteine is typically linked to low levels of vitamin B12 and folate and taking these can improve homocysteine levels.

Vascular damage to the brain, which can impede healthy blood flow to the brain, is highly linked to cognitive problems. Therefore, although there is no clear link between homocysteine and the MCI that comes specifically from PD, it certainly makes sense for someone with PD to take steps to limit vascular damage to the brain as well. Controlling blood pressure and diabetes as well as homocysteine are all important steps to make sure that there is good blood flow to the brain. 

Low Blood Pressure

Q: Can the low blood pressure which is common in PD be associated with cognitive problems?

A: Low blood pressure can be a side effect of PD medications and can be a symptom of PD itself (it’s also called orthostatic hypotension.) When someone’s blood pressure is too low, then the brain is not well-perfused, and this can cause dizziness and sometimes passing out. Low blood pressure can also cause confusion and can exacerbate cognitive issues. This does not happen to everyone but can be a major issue for some people. If you are concerned that this is happening to you, talk with your neurologist. He or she may suggest that you keep a daily diary of blood pressures taken sitting and then standing. If your blood pressure falls upon standing, there are multiple lifestyle changes that can help to mitigate this problem, such as rising slowly, increasing fluids and salt intake, or using compression stockings. There are even medications that can be prescribed if necessary.

Tips and Takeaways

• Cognitive issues are a common non-motor problem in PD. If you are experiencing changes in your cognition, bring this to the attention of your neurologist. Then any reversible causes to be addressed and you can access cognitive rehabilitation, medications, or clinical trials
• For a summary of PD and MCI, see this helpful factsheet
• For a summary of PD and cognitive problems in general, see this helpful factsheet
• You can learn more by viewing the Dr. Gilbert Hosts episode about mild cognitive impairment
• You can track your PD symptoms using the APDA Symptom Tracker app, available for free through the Apple Store or Google Play
• If you have a PD-related question, you can submit it to our Ask A Doctor portal
• To make sure you don’t miss the next episode of Dr. Gilbert Hosts, subscribe to APDA’s YouTube channel, and check our Virtual Events Calendar