The Highs, Middles, and Lows of a Day With Parkinson’s

“Everything I know now . . . the pitfalls, the highs and lows, everything . . . it taught me and made stronger.” Ray Allen

“There is no black-and-white situation. It’s all part of life. Highs, lows, middles.” Van Morrison

Start of the Story: I play Monday and Wednesday in two Men’s Golf Groups. It is both fun and competitive. For several months, I have been writing a review article about exercise and Parkinson’s. [Why do we need another article about exercise? Wait and see if you think it might be different and valuable to your understanding of exercising with Parkinson’s.]

I had been writing late into Tuesday night/morning when I went to sleep, knowing I had a tee time at 8:35 AM Wednesday. Surprisingly, I woke up at 8:25 AM and realized that I could not make it there for the start. I called the golf club and told them the situation; they called the starter at the first hole and said he’d direct me to the players on my team for the day. I got there at ~9:00 AM, barely dressed, with no coffee and no warm-up, and I got down 2.5 tablets of carbidopa/levodopa and joined my three golf mates on the third hole. They rode me hard for a few minutes about arriving late. However, it was all in jest. They were happy to see me.

I made par on the first and third holes I played, and the rest of the day went like that. There were a lot of good golf shots. No warm-up, no stretching, yet I played well. On the 18th hole, I hit a good drive in this par four hole, leaving me 102 yards to the green by measurement, but with a giant sand trap between my ball and the pin. I started thinking, take one more club down and make sure you clear the sand trap. It worked, and the ball ended up about 2 inches from the pin, a tap-in-birdie 3. The entire morning, with an arthritic hip, torn cartilage in my right knee, and lower back stiffness, was a sheer delight; fun playing partners, beautiful spring morning, and my golf game worked so well. I was in little body pain—the wonders of dopamine help to mask the pain and keep the body functioning. But dopamine is quickly consumed when dealing with pain (I am convinced of that). Yes, this was a high.

I made it home by 1:00 p.m., took some carbidopa/levodopa, ate lunch, and then felt listless, drained, and tired. I went to the bedroom and slept for at least four hours. This one could be called my low of the day.

I woke up refreshed, alert, and feeling like a new person. I took some more carbidopa/levodopa and balanced my mind and thoughts. This was the in-between, the middle feeling. For the rest of the evening, I was feeling almost normal, regardless of the signals Parkinson’s was sending me.

“I still have highs and lows, just like any other person. What’s missing is the lack of control over the super highs, which became destructive, and the super lows, which are immediately destructive.” Patty Duke

A More Typical Day: Many people ask me what it feels like to have Parkinson’s. I respond that I can typically have good (high) days and bad (low) days. These occur regardless of my medical regimen that day. Even more likely, I can have some days where my high fluctuates, going from high to middle to low and back up to high over several hours. 

What is difficult for me to understand is the dopamine stored in my brain and the daily up-and-down that I described above, going from high to middle to low. Are those just the emotions that I am feeling at the moment? Or is this related to my Parkinson’s and the ratio of dopamine present to levodopa taken each time? Or am I just missing something? I present three possibilities: (i) Parkinson’s progression and the role of levodopa, (ii) Neurotransmitters and emotions, and (iii) Dopamine and other neurotransmitters. I have three ideas because I do not have an answer for you. Thus, it is intriguing to present these three possible reasons and go from there.

“I still get very high and very low in life. Daily. But I’ve finally accepted the fact that sensitive is just how I was made, that I don’t have to hide it and I don’t have to fix it. I’m not broken.” Glennon Melton

Some Benchmarks of the Progression of Parkinson’s: In a 2024 article, Dr. J. Eric Ahlskog provides his usual stellar commentary on the progression of Parkinson’s. The earliest non-motor symptoms can present many years before the clinical motor-derived symptoms. The typical results suggest a 20-30-year interval occurs before Parkinson’s manifests itself. The third stage typically begins with levodopa (carbidopa) therapy; levodopa initially has a “long-duration” effect; that is, it works continuously without pause and overlaps with the next dose. However, you continually lose the dopaminergic nigrostriatal region. The response to treatment and the response to levodopa is constant and reliable. Next, as time progresses, this could be 5-10 years, dyskinesia can begin, and you get the “slow response” of levodopa-carbidopa. It is important to note that dyskinesia is strongly linked to older age and the onset of symptoms rather than young-onset Parkinson’s patients.

Citation: Ahlskog, J. Eric. “Parkinson’s disease progression is multifaceted: Evidence for the underlying benchmarks.” Parkinsonism & Related Disorders (2024): 106037.

“I think my life in general, like that of any human being, has highs and lows, has moments of great light and moments of great darkness.” Thalia

Dopamine and Other Neurotransmitters: Could some of the symptoms and time of expression be related to something other than the dopaminergic nigrostriatal region of the brain? We know that Parkinson’s is more than just the death of dopaminergic neurons; the involvement of serotonergic and cholinergic systems also marks the pathology of Parkinson’s. This pathology includes the neurons in the locus coeruleus in the brain, the central site for the noradrenergic region. In a well-defended paper, Romelfanger and Weinshenker (2007) present a case for the importance of norepinephrine during the progression of Parkinson’s. Significantly, norepinephrine strongly affects brain inflammation, oxidative stress, and the function of several other proteins implicated in the role of Parkinson’s. Thus, a role can be established for losing norepinephrine, similar to dopamine in Parkinson’s.

Interestingly, norepinephrine and dopamine share the same synthesis machinery. They are not saying that dopamine loss is not involved in Parkinson’s; in some studies with norepinephrine, it was found to slow the progression of Parkinson’s. Therefore, it is essential not to wear blinders on our heads and see only dopamine as involved in Parkinson’s; it is a multifaceted disease, and we must include other neurotransmitters, like norepinephrine.

Citation: Rommelfanger, K. S., and D. Weinshenker. “Norepinephrine: the redheaded stepchild of Parkinson’s disease.” Biochemical pharmacology 74, no. 2 (2007): 177-190.

“When you understand the purpose [of life], then you can deal and journey through the obstacles, the rejections, the stops and starts, highs and lows with a different lens because you know that you’re moving in what you’re supposed to do.” Aisha Hinds

Neurotransmitters and Emotions: We must admit our emotions are essential for the existence of humans. However, we still lack a good definition of emotion, how many emotions there are, and whether ‘physiological signatures’ are associated with each emotion. In a twist away from existing dogma on emotions, Wang et al. (2020) suggest an approach using neuromodulators to define and study emotions. They suggest that emotions are derived from neuromodulators dopamine (DA), serotonin (5-HT), and norepinephrine (NE).

They suggest we have a “three primary color model” for emotions, namely, such that DA is a self-indulgent signal for salient stimuli, such as food, sex, and other needs; 5-HT is related to disgust or punishment, and that NE is the backbone for emotions that trigger ‘fight or flight.’ Other neuromodulators could also play a part in the expression of feelings. Their article introduces 11 other reviewed papers describing the emotional function and linkage to neurotransmitters. Look and see if this makes sense to you, especially as one of the founding emotions is linked to dopamine.

Citation: Wang, Fushun, Jiongjiong Yang, Fang Pan, Roger C. Ho, and Jason H. Huang. “Neurotransmitters and emotions.” Frontiers in psychology 11 (2020): 497253.

“Everything tends to make us believe that there exists a certain point of the mind at which life and death, the real and the imagined, past and future, the communicable and the incommunicable, high and low, cease to be perceived as contradictions.” Andre Breton

Final Comments: This post described how one’s day can go, leading to highs, lows, and sometimes in the middle. I started thinking, does this relate to dopamine levels and our taking of carbidopa/levodopa every day to deal with our Parkinsons? Or could it be something totally and tangentially associated with dopamine replacement, which led to the description of the three articles cited here? I had fun reading about the idea, but it consumed most of the day when I should have been doing other things around the house; I will do them tomorrow. I don’t know which makes the most sense regarding the cause of the variation from feeling high to middle to low. It may not be anything I wrote about today in this post.

“When people see some things as beautiful, other things become ugly. When people see some things as good, other things become bad. Being and non-being create each other. Difficult and easy support each other. Long and short define each other. High and low depend on each other. Before and after follow each other. Therefore the Master acts without doing anything and teaches without saying anything. Things arise and she lets them come; things disappear and she lets them go. She has but doesn’t possess, acts but doesn’t expect. When her work is done, she forgets it. That is why it lasts forever.” Laozi