“Young Onset Parkinson’s Disease (YOPD) Dementia” – Webinar notes

“Young Onset Parkinson’s Disease (YOPD) Dementia” – Webinar notes

On April 15 the Davis Phinney Foundation YOPD Council Series hosted a webinar with Rodolfo Savica, MD, PhD, on the topic of Young Onset Parkinson’s Disease (YOPD) Dementia.  Dr. Savica had some very interesting things to say.

Essentially, Dr. Savica said YOPD is not the same disorder as older-onset Parkinson’s.  Dementia is rarely seen in those with YOPD, unless an individual has a specific inherited genetic mutation.  People with YOPD have the same life expectancy and develop the same types of dementia at the same ages as the general population.

Dr. Savica emphasized the importance of exercise in creating new pathways in the brain to enable movement for as long as possible.  He encourages people with YOPD to exercise vigorously with their peers, rather than with elderly Parkinson’s folks.  

There are times when those with YOPD exert themselves physically, like running a marathon, or are under increased stress at work.  During these times Dr. Savica supports taking more dopaminergic medication to support the body while it is being taxed, even if it is very brief, like just mornings that are crazy busy at work, but afternoons are quiet.

The webinar was recorded and can be viewed on the Davis Phinney Foundation’s YouTube channel.  

The Stanford Parkinson’s Community Outreach Program has more information about Young Onset Parkinson’s Disease and cognitive changes in Parkinson’s Disease.

And now, on with my notes…

– Denise Dagan

“Young Onset Parkinson’s Disease (YOPD) Dementia” – Webinar notes

Webinar Host: Davis Phinney Foundation

Webinar Date: April 15, 2021

Summary by Denise Dagan, Stanford Parkinson’s Community Outreach

Moderator: Mel Dizon


Rodolfo Savica, MD, PhD                 

Tom Palizzi, DPF Ambassador, Diagnosed with YOPD at age 48

Mel:  Dr. Savica, what is YOPD and is it different enough to be considered a different disorder from later onset Parkinson’s disease?

Dr. Savica:  I would use the term Early Onset Parkinson’s to indicate someone who is diagnosed younger than the usual onset of the motor symptoms of Parkinson’s, which is over age 65.

In the literature, you may see the term Young Onset to consider someone diagnosed with the motor symptoms of Parkinson’s at age 60 or below.  In some literature the age is 55 and below, which is more conservative.  In some literature the age is even 40 and below. 

We are trying to define the nomenclature and harmonize the terminology in one way.  Every country is different.  It is very confusing!

When you move beyond mere nomenclature to the biological terminology used in research, regulatory agencies, or for funding purposes, clearly later onset Parkinson’s disease is considered a diagnosis at age 65-70 years.  

Compared to diagnoses made when a person is in their 40s or 50s, it is a completely different disease.  The outcome is the same: damage to the substantia nigra and the basal ganglia.  But the cause of the damage is different, making them different diseases with different biology and different organelles that are involved.

Everybody listening knows that the presence of Lewy Bodies is the hallmark of Parkinson’s.  If you open the brain of younger patients, you may not see any Lewy Bodies at all.  

In those with later onset Parkinson’s, there are several non-motor symptoms that precede the motor symptoms by as much as 10-20 years prior to the start of motor symptoms.   These include loss of the sense of smell, constipation, REM sleep behavior disorder, depression, anxiety, etc.  In early and young onset Parkinson’s disease, these non-motor symptoms prior to motor symptoms are not very common.  

The presentation of symptoms between early/young onset and later onset Parkinson’s is different too.  In those with later onset of motor symptoms, the motor symptoms are commonly tremor, stiffness, maybe frozen shoulder, slowness of gait, falling, etc.  In younger people one of the most common initial symptoms is muscle cramps when exercising.  This is dystonia, but initially it looks like a muscle cramp. 

There is epidemiological data that supports the difference between young/early onset, and late onset.  We also have biological data that distinguishes early onset from late onset.  We have some genetic data; however, it was one of the original sins of the literature to say every young onset person had a strong family history.  Actually, familiar cases are less common compared to the number of sporadic cases.  

So epidemiological, biological, genetic, and clinical symptoms are different between the two.  When we talk about clinical symptoms we are talking about treatment or symptom management.  

The progression is slightly different, the prognosis is very different, the life expectancy is completely different, and the social needs are completely different.  The needs of our patients in their 40s, 50s, even 60s is very different from those in their 70s and older.  YOPD people have responsibilities for work, family, children, and 40 years ahead of them to live life.  That is different than having Parkinson’s in your 70s.  So, they are two different conditions that only have a name in common.  

Mel:  So, once you’re YOPD, you’re always YOPD because even when you’re 70, if you were diagnosed when you were 40 your symptoms and progression are different than those who are diagnosed at age 70.

Dr. Savic:  Absolutely!  This is a very important thing.  Patients in their in their 70s and 80s who have had PD for 30-40 years still have young onset Parkinson’s.  The age when the motor symptoms start determines which type of Parkinson’s you have.

Mel:  YOPD and dementia are not frequently discussed together,.  Let’s do a relative comparison between what dementia looks like for later onset Parkinson’s and what does it looks like in those diagnosed with YOPD?

Dr. Savic:  Memory loss and dementia is a complex phenomenon in the general population.  It is even more complex in those with Parkinson’s.  We have three processes to consider in those with Parkinson’s.  That is 1) aging, 2) plaques and tangles of Alzheimer’s disease, and 3) later in Parkinson’s disease there is the presence of Lewy Bodies that cause cellular damage and can cause memory loss.  And we have vascular changes occurring at the same time and causing additional damage.

If we talk only about the damage caused by the Lewy Bodies (setting aside for the moment Alzheimer’s and vascular changes) I can totally say that the memory loss we see in Parkinson’s disease is completely different than what we see in Alzheimer’s.  Dementia is memory loss that is interfering with our activities of daily living when patients may or may not have insight about the problem.  

The memory loss we see in Parkinson’s is completely different from Alzheimer’s.  It is not like forgetting a name or misplacing things.  It has more to do with psychomotor slowing.  Parkinson’s disease causes bradykinesia, or slowness of movement, but it also causes slowness of thinking.  Psychomotor slowing impacts a person’s ability to multi-task and plan ahead.  

The other aspect of memory that is affected is visuospatial memory.  That is having good perception of where our body is in space and spatial awareness of objects with respect to each other.  Theis is also very different than what we see in Alzheimer’s where usually working memory, or short-term memory is the first domain to be affected.

Some of these memory problems, especially planning, or executive function may respond to carbidopa levodopa.  When I see someone in their 70s or 80s with Parkinson’s and they say their memory is not good.  I try to optimize their carbidopa levodopa and see if the memory loss persists.  If it does, we have to try something else, but if it doesn’t, they should have less cognitive fogginess, better attention, and be better able to keep up with conversations, etc.  We are talking about treating later onset Parkinson’s where the pathology involves Lewy Bodies.  In that population about 39% of people will have some degree of memory loss (from mild to severe) 8 years after diagnosis.  

If we try dopamine replacement to treat cognitive slowing in the Young Onset group, it will not be effective because that population doesn’t have Lewy Bodies.  Young Onset people are working and still an integral part of society.  Their cognitive needs are higher, and they require more functional abilities to cope with a higher level of stimuli.  The most common cognitive symptom of Early Onset Parkinson’s is what they call brain fog.  They say they are able to get things done but it’s taking longer or it’s more difficult to accomplish tasks.  

If you ask me how frequently I see dementia in Early Onset Parkinson’s, I will say it is not very common.  If you say, what about 20 or 30 years later?  Then, you’ve had YOPD for 40 years and you may have Alzheimer’s because now you are 80.  At that age people also have vascular changes that affect memory and cognition.

Are there forms of Early Onset Parkinson’s that cause dementia?  Yes, but only in cases of inherited genes that produce too much alpha synuclein and the accumulation of Lewy Bodies in the brain.  Then, for sure you may have earlier onset of memory loss.  But without that genetic influence we don’t see atrophy, or shrinkage of the brain causing dementia, excepting the normal shrinkage due to aging.

Are there cases of Lewy Body Dementia, involving hallucinations, delusions, and cognitive fluctuations in those with YOPD?  Yes, but it is incredibly rare.  To be honest, we are publishing a paper on early onset Lewy Bodies and there’s nothing out there.  It has not been very well described because there are only a handful of cases in their 40s & 50s.  Likely these people have some genetic predisposition and some environmental effect on their genes causing an acceleration of these processes. 

Mel:  Tom, you smiled a little bit when Dr. Savica was talking about brain fog.  Can you tell us a little bit about that experience for you?

Tom:  It’s a common thing.  I think all of us with Parkinson’s experience that at some time, maybe some sooner than others.  Brain fog feels like my head’s a puzzle and all the pieces are pulled apart.  Like the doctor said, it’s hard to describe it. 

Mel:  If I remember right, Tom, your diagnosis was fairly quick.  You went to your doctor, and you got your diagnosis, but was brain fog something you felt for a while before you got diagnosed?

Tom:  No, early on there was very little brain fog.  The brain fog developed as time went on.  Lately it’s getting to be more visible, more and more there.  Early on I functioned basically normally.  I think the non-motor symptoms developed just like the motor symptoms.  They get worse and worse as things go.  What I suffer more from mostly now is memory loss.  My wife will say, “I told you we were doing this,” and I say, “Woah! when did you tell me that?”  The ongoing argument ensues, and I usually lose.  I hear that from my kids, too.  My son will say, “Dad, we talked about this the other day.”  So, yeah, you really need to pay close attention because there’s brain fog and attention issues that all come into play.

Dr. Savica:  Tom, you used a term that is crucial, “attention.”  We have an attention network to keep us aware of what’s going on around us during the day.  This network, in the frontal lobe of the brain, requires dopamine to function.  

Some people report they have a constant memory loss.  Others report that when the medication drops the memory loss is worse and when the medication is active the memory loss is better.  That makes memory a non-motor symptom with ON/OFF medication fluctuations.  This is valid for other non-motor symptoms as well, like anxiety and depression.  It has to do with the pathway that goes from the center of the brain to the frontal lobe, which is responsible for mood, memory, and attention.

There are some medications that are known to worsen memory slightly, like dopamine agonists, ropinirole/Requip and rotigotine/Neupro patch.  If taken at a high dose they can cause memory problems.  

One reason people using carbidopa levodopa/Sinemet don’t function very well, regardless of age, is persistent low blood pressure.  Systolic blood pressure of 100 or 110, along with physical activity, causes low profusion in the brain.  Lack of profusion can cause brain fog.

So, to reduce brain fog, correct low blood pressure, maximize medication levels, and minimize any medications that can cause memory loss.

Mel:  A listener says his wife was diagnosed at age 37 and died at age 66.  For the last 1.5 years she had paranoia.  As a result, she refused to eat.  Is this unusual?

Dr. Savica:  Clearly the damage unfortunately has built up through 30 years.  I wouldn’t be very surprised if you were told the paranoia was present for 25 years.  If it wasn’t 25 years, maybe the diagnosis should be revised.  

For the last 1.5 years with accumulation of proteins, the biochemical damage has been built up.  Some of the areas of the brain responsible for hallucinations and psychosis can be affected.  

It is not uncommon that paranoia would lead her to not want to eat.  There are many psychiatric syndromes that affect those with late-stage Parkinson’s.  

  • Some believe their spouse is an imposter.  This is called Capgras syndrome.  
  • Others have reduplicative paramnesia, which is the belief that a place of location has been duplicated, existing in two or more places simultaneously, or that it has been ‘relocated’ to another site.  
  • Still others have Othello syndrome, or paranoid jealousy toward their spouse or partner.  

Again, in Early Onset Parkinson’s I’m not expecting these psychiatric syndromes.  It can happen but I would expect these much later in life.  In one of our recent studies, it was shown that the median survival time from Early Onset Parkinson’s diagnosis is 38 years.  This is exactly what this listener commented.  If you’re somebody diagnosis is at age 45 their life expectancy is 38 years later, they will be 83 when they die.  That it is different than late-onset Parkinson’s disease.

Mel:  Can you say more about optimizing medications to work with memory loss?  Is it a matter of working with the doctor by a process of trial and error to determine the appropriate dose of medication?  
Another listener wants to know if executive function is a form of dementia?

Dr. Savica:  There are four main domains in neuropsychology to explain memory.  They are:

  • executive function – planning
  • language – the ability to understand and talk
  • visuospatial – spatial awareness, knowing where you are and understanding the space around you
  • working memory – the ability to recall something once you learn it

If any one of these four domains is nonfunctioning, you can have dementia.  
For example: aphasia is the primary language disorder when people are not able to speak because the language center of the brain has been damaged.  

If aphasia interferes with a person’s ability to perform the activities of daily living independently, they are considered to have dementia despite the other three domains being intact.  

If aphasia only minimally interferes with a person’s ability to perform the activities of daily living, they are considered to have mild cognitive impairment (MCI). 

Activities of daily living include: 

  • personal hygiene (bathing, grooming, nail care, and oral care)
  • dressing (selecting appropriate attire and physically able to dress and undress oneself)
  • eating (though not necessarily the capability to prepare food)
  • maintaining continence (using the restroom independently)
  • transferring/mobility (standing from a sitting position, getting in and out of bed, walking independently)

Working memory is the first domain to be impacted when someone has Alzheimer’s disease.  Since Alzheimer’s is the most common form of dementia it is the one people are most familiar with.   As soon as someone has memory loss, it is assumed that person has Alzheimer’s.  But there are other forms of dementia that are less common and can occur with impairment of just one of the four domains.

Dr. Savica:  The other question asked was about maximizing medications.  Obviously, you need to work with your doctor.  He or she should be customizing a medication regimen for you.  When I do this for my patients I needs to know:

  • How long does the medication last?
  • How long does it take to kick in?
  • What kind of diet does the person eat?
  • What kind of dose seems to be having an effect?
  • Are there dose phenomena, like dyskinesia or dystonia?

Once you tell your doctor this information, he or she should be able to find the best medication regimen for you.  
On the other hand, sometimes it’s not easy.  Sometimes it is an art that requires some time.  If your doctor doesn’t spend enough time with you, it is very difficult to individualize this part.  Especially if the person with YOPD has a job requiring multi-tasking or a high level of attention, or if somebody is an athlete.  The requirement of the medication is different during these high-demand activities.  

I have a patient who runs marathons.  I give him 1/2 or 1 tab more of Sinemet prior to the race in anticipation of the increased physical demands and to prevent wearing off during the race.  

Likewise, somebody who says their work mornings are always difficult with many demands on their attention, but the afternoons are calm.  Or someone may say their schedule next week will be incredibly stressful due to an important presentation.  The week prior to the presentation that person can speak with their doctor about what medication adjustment would be needed to handle the additional, temporary stress.

It’s like diabetes.  When someone with diabetes has a high glucose level, we have ways to measure the real time level of glucose in the bloodstream.  There are ways to give different amounts of insulin to meet the requirement.  We should do the same with Parkinson’s disease.  When there is need, we can do more.

Mel:  Is there a similar thing you can do depending upon a certain diet someone has?  Like vegans?  Do you do that?

Dr. Savica:  This is a great point.  Diet is getting more and more important.  To be honest, it doesn’t matter whether someone is vegan, gluten free, vegetarian, pescatarian, or omnivore.  You name it!  The list is endless.  There are a couple things I recommend.  

The gold standard medication is carbidopa levodopa.  It is usually given on an empty stomach.  That means 1 hour before meals, or 2 hours after meals.  This is not possible at times, especially if you take the medication every 3 hours.  

I recommend a low protein diet, a minimal breakfast with coffee (no milk, or delayed an hour to have coffee with milk), a minimal lunch with just carbohydrates, and a larger meal with protein at night.  

However, especially in Early Onset Parkinson’s, there is mounting animal study evidence that intermittent fasting seems to work better.  In mice intermittent fasting seems to be delaying the damage caused by the mitochondria hyperactivity.  In Early Onset Parkinson’s the mitochondria organelle may be the most likely target of our disease and driving, more than in late-onset Parkinson’s, the energetic crisis leading to cell damage.  So intermittent fasting is something that can impact this particular pathway and is something that can help quite a lot.  

Intermittent fasting is something you can see online how to do it.  People are going 24hrs without eating.  Personally, I eat one big meal at night, skip breakfast, have an apple for lunch.  Interesting, without getting too philosophical, even the major religions endorse fasting. 

Tom:  I think most people like me are going to want to know is; I was diagnosed with YOPD and does that impact my life worse in the future?  I think you answered that earlier that there’s no real evidence to support that.

Dr. Savica:  I am talking about big numbers.  I’m not talking about individual patients.  Clearly everybody is different and there are exceptions within the big numbers.  

We have been looking at the population in Southeast Minnesota that lives around Olmsted County.  We are able to follow them from the moment they are born or moved there to the moment they die.  We have 30-40 years of observation and medical records.  This population is Caucasian with northern European heritage, so the information may not apply to everyone, but it gives us a good snapshot.  What we know is that diagnosis of Early Onset Parkinson usually does not progress as fast as late-onset Parkinson’s.  The survival timing is 38 years from diagnosis.  If your diagnosis is at age 40 or 45, you’re living until 78 or 83.  That’s as long as the general population.

The important thing is quality of life.  Generally speaking, we don’t see the same kind of decline in YOPD that we see in late-onset Parkinson’s.  Obviously, late-onset patients are older and have comorbidities that impact their longevity.  

Also, it seems the patient with Early Onset Parkinson’s always respond to medications.  It’s just a matter of adjusting them.  Complications, such as dyskinesia (for example), that are very feared are present in only 12% of YOPD patients.  That is a much smaller than we see in late-onset cases. 

If you’re a woman, you have a better prognosis, generally speaking.  

If your initial symptom is tremor, it seems the prognosis is better than those who have no tremor at all and there is mounting biological evidence to support why this is happening.  

There are some genetic forms that cannot take a smidge of carbidopa levodopa without experiencing major side effects, like dystonia, dyskinesia, and so forth.  Unless we do a genetic analysis, we don’t know if that is the cause of side effects but if you or any patients do not have this mutation levodopa will always work.

Dr. Savica:  Exercise and working out is the best thing you can do to stay flexible, minimize symptoms and slow progression.  I don’t want those with YOPD to work out like they are already elderly.  I want them to find something they love doing and want to continue to be able to do.  

If you enjoy biking, bike with people who are your age and take enough medication to keep up with them!
I love the Parkinson’s boxing programs.  They are fantastic!  If you love boxing and you are in your 30s or 40s don’t sign up for Parkinson’s boxing.  You do regular boxing!

If you like martial arts do Grappling Brazilian Jiu Jitsu.  

Those are all fantastic activities because they allow the proprioception to be constantly stimulated, prevent falls.  Tell the trainer you have Parkinson’s disease so maybe you’re not the fastest, but you still want to measure yourself against people your age, not people in their 80s where you don’t relate to them at all.

Mel:  A listener says that when they exercise really hard, right afterward they have increased brain fog.  After they recover, their motor and non-motor symptoms are more comfortable.  Is that common?

Dr. Savica:  Very common.

Mel:  What’s happening to make the brain fog?  Is it just that you’ve metabolized all your medicine with the exertion?

Dr. Savica:  Likely there’s a bioenergetic requirement that is higher, so immediately there’s a lack of dopamine or any other chemicals.  But then the exercise helps the surge back on these particular chemicals.  It’s very common to hear, “Right after exercise I’m fatigued, but the last five minutes I feel great.”

Tom:  That’s definitely the case.  I do a lot of cycling.  I run a pedaling for Parkinson’s class three days a week.  The idea is to push it, not just pedal.  

Tom:  A listener posted an interesting question about plasticity and the possibility of creating new pathways.

Dr. Savica:  Absolutely!  It’s kind of complex.  I’ll try to simplify.  The basal ganglia is a system that regulates and cleans out the noise around movement and action.  When the basal ganglia is working well movements are very precise.  There is no superfluous movement, like tremor.    

The brain has a big cortex and the little basal ganglia did not evolve to be as large as the cortex.  So, everything goes through this narrow path of the basal ganglia, which is very difficult to manage.  

What we want to do when we age is to make sure the noise surrounding the basal ganglia is removed.  And we want to make sure the basal ganglia is getting more information about the noise from somewhere.  That is why it’s crucial to take advantage of the plasticity of the brain to build new pathways.  

There are some movements that can help increase plasticity and basal ganglia activity and there are chemicals produced during exercise.  These chemicals are the famous Brain Derived Neurotrophic Factor (BDNF) that increase dramatically and help restore new cells and sprouting new connections.

Let’s say you begin doing martial arts.  There is a great opportunity because your body would use completely different motor pathways that you never used before.  That would improve the quality of your regular movement because you’re giving more information to the basal ganglia from new sources.  

Evolutionary of the basal ganglia is delayed.  It’s about half a million years behind, compared to the rest of the cortex.  All the vertebrates have the same basal ganglia structure that is very small.  Some monkeys now seem to have something called the hyper direct pathway that goes from the basal ganglia to the frontal lobe.  It seems humans have that, but the idea is that it is a newer, yet young, yet to be developed pathway that can help compensate for some of the problems we have with movement later in life, like Parkinson’s.  

Mel:  A couple listeners are asking if deep brain stimulation (DBS) can do anything around dementia symptoms, executive function, or anything like that?

Dr. Savica:  There is an evaluation process for patients interested in DBS that includes memory loss testing and a full hour memory test.  If in the memory test patients don’t do well, there is a risk that DBS surgery will make things worse in terms of memory.  So, historically, the presence of memory loss excludes a patient as a candidate for DBS.  

DBS stimulators should not have any effect on executive functioning.  If anything, they may make things a little bit worse.  There were some studies years ago by some of the pioneers of DBS in Canada, Dr. Lozano and his team from Toronto were studying DBS in Alzheimer’s patients.  They were stimulating areas of the brain allegedly involved in memory.  They did not see any particular improvement.  The reason why is that the engrams of memories are stored everywhere in the brain and there are different kinds of memories.  So, stimulating one area doesn’t necessarily mean you will improve.

Again, there are some patients who report improvement because the dopaminergic requirement has changed.  But remember there are some DBS patients who, even though from a motor standpoint and tremor reducing point, they do not require carbidopa levodopa, they do require it because there are fluctuations of non-motor symptoms, like anxiety, depression, and memory loss.  So, DBS focuses on reducing motor symptoms, it doesn’t do anything for non-motor symptoms.

Tom:  I was diagnosed 13 years ago.  Shortly after that, maybe 10 years ago, I told my doctor that I’m mostly worried about losing cognitive capability than I am about losing mobility.  She ordered a psych test to get a baseline.  That scared me to death, but it established a benchmark, so I had something to compare my cognitive ability to later in life.  What are your feeling on that?

Dr. Savica:  Having a baseline of the 2–4-hour memory test would be good, but also a paper and pencil test done in just 10 minutes in the office of your physician can be very important, even earlier on.  If, as you say, you’re worried your cognition could get worse, having a baseline a few years prior can help you see if you’ve had a decline.

There are only a few things to consider.  Obviously, as you get older you will miss some responses.  20-30 years later your memory test must be adjusted for your current age.  Usually, they are because the tests are standardized.  People taking these tests are not always functioning at their best.  They are anxious, maybe they didn’t sleep well the night before, or their medications are not working well because they are nervous.  Sometimes, when I am worried about memory loss, I will order a PET scan.  PET scans show how a person is using glucose.  It is heavily used by behavioral neurology to see the different patterns of memory disorders.  A PET scan is not affected by anxiety.  

So, I agree getting a baseline is important.  Start with a paper and pencil test with your physician.  If the result of that quick evaluation is concerning, your doctor should order the full 2–4-hour test.  But, even if there are some issues because the patient is anxious, upset, or can’t sit for such a long test, the PET scan can be a very good alternative.

Tom:  That’s exactly what happened to me.  When I sat down to take the test beads of sweat were coming out on my forehead.  The doctor said, “Are you okay?!  Are you having a heart attack, or something?”  He gave me a 1/2 hour to settle down before starting the test.  Fortunately, I was able to get through it okay.

Mel:  I could talk to you for another 3 hours and I see listeners are typing in the chat are saying this is the best YOPD discussion we’ve ever had, so we’re really happy because Dr. Savica is going to be joining us for our YOPD Victory Summit event the end of June.  So, we’ll have more opportunities to ask you lots of questions!  Thank you for being here today.