Part 8. Parkinson’s Disease Is Not Only a Movement Disorder
— Why can it affect sleep, the gut, bladder, mood, and cognition?
When people hear “Parkinson’s disease,” the first thing that comes to mind is movement.
The hand trembles.
The body stiffens.
Movements slow down.
Steps become shorter, and the first step can be hard to take.
For a long time, Parkinson’s disease has therefore been described as a movement disorder.
I thought of it that way at first too.
Dopamine neurons in the substantia nigra decline,
the basal ganglia circuit stops working normally,
and movement becomes impaired.
That explanation is not wrong.
But the longer you look at Parkinson’s disease, the more symptoms appear that cannot be explained by movement alone.
Sleep changes.
The sense of smell may weaken.
Constipation appears.
Blood pressure becomes unstable.
Urinary symptoms develop.
Pain and fatigue appear.
Mood and motivation can change.
The speed of thought and attention can also be affected.
Some of these symptoms may even appear before hand tremor.
So the question changes.
Is Parkinson’s disease really only a movement disorder?
No.
Parkinson’s disease is not a disease of the substantia nigra alone,
and it is not a disease of dopamine alone.
Seen more broadly,
it is better understood as a disease in which multiple neural systems are affected together over time.
That broader view explains the patient’s lived body much better.
1. Looking only at the substantia nigra shows only half of Parkinson’s disease
One of the most important structures for understanding the motor symptoms is the substantia nigra pars compacta.
Dopamine produced there is delivered to the striatum,
and as dopaminergic neurons are lost, basal ganglia motor circuits become disrupted.
That is why typical symptoms such as bradykinesia and rigidity appear.
But the changes of Parkinson’s disease are not limited to the substantia nigra.
Multiple brainstem nuclei,
the autonomic nervous system,
the olfactory system,
the limbic system,
the cerebral cortex,
and even the peripheral autonomic nervous system can be affected.
And dopamine is not the only neurotransmitter system involved.
Noradrenaline,
serotonin,
and acetylcholine
can also be involved.
Seen this way, the large number of non-motor symptoms in Parkinson’s disease begins to make more sense.
2. It may begin before motor symptoms appear
There is an interesting fact about Parkinson’s disease.
Some non-motor symptoms may appear years before the typical motor symptoms such as hand tremor or bradykinesia.
Well-known examples include
reduced sense of smell,
constipation,
and REM sleep behavior disorder.
Of course, having these symptoms does not mean that a person will necessarily develop Parkinson’s disease.
Constipation and reduced smell are common symptoms.
They cannot diagnose Parkinson’s disease on their own.
But when we look back at the history of people who later develop Parkinson’s disease,
we often find that such changes were present long before the motor syndrome became obvious.
That has an important implication.
The pathological process of Parkinson’s disease
may not have suddenly begun on the day the hand started to tremble.
3. Losing the sense of smell is also neuroanatomy
Reduced smell is one of the common non-motor symptoms of Parkinson’s disease.
What could smelling have to do with walking?
At first glance, they seem completely unrelated.
But if Parkinson’s disease is viewed as a disorder of the nervous system as a whole, this is not so strange.
Structures involved in processing olfactory information can also be related to Parkinsonian pathology.
This gives us an important clue.
The disease does not necessarily progress in one simple direction:
substantia nigra → motor impairment.
Different neural systems may be affected at different times.
4. The gut and the brain are more closely connected than they seem
Constipation is very common in people with Parkinson’s disease.
It is easy to assume that this happens simply because they move less.
Reduced activity can certainly contribute.
But that is not enough to explain it.
Gastrointestinal motility is regulated by the autonomic and enteric nervous systems.
These systems can also be affected in Parkinson’s disease.
The gut itself can therefore become slower.
And another issue follows.
The gut is not merely an organ that causes discomfort.
It is the route levodopa must pass through in order to be absorbed.
Even after the medication is swallowed, if it remains in the stomach for a long time, it reaches the small intestine later.
That delays the onset of medication effect.
This may help explain why the same medication taken at the same time
works quickly on some days,
slowly on others,
and on some days does not produce a full ON state at all.
5. The gastrointestinal tract is part of the medication-effect curve
As I studied Parkinson’s medication response, I increasingly felt that I could not look at the medication alone.
A levodopa tablet does not immediately arrive in the brain.
It has to leave the stomach and enter the small intestine.
It has to be absorbed there.
It has to travel through the bloodstream.
It has to cross the blood–brain barrier.
Only then can it affect the brain’s dopaminergic system.
So if gastric emptying is delayed or irregular,
the medication-effect curve can also become irregular.
That is why gastrointestinal problems and motor fluctuations are not always completely separate issues in Parkinson’s disease.
The gut sits at the front end of the medication-effect curve.
6. Why protein can affect medication response
Levodopa is structurally related to amino acids.
During intestinal absorption and transport across the blood–brain barrier, it shares transport systems with large neutral amino acids.
As a result, some patients may notice that when a protein-rich meal overlaps with levodopa dosing, the medication works more slowly or less effectively.
Not every patient is affected in the same way.
But in people with marked motor fluctuations, it can be worth examining the relationship between meal timing and medication response.
This again shows something important.
In Parkinson’s disease, medication response is not only a matter of the brain.
It is the result of a whole process that begins in the gastrointestinal tract and continues through the blood to the brain.
7. Bladder symptoms are not unrelated to movement
Parkinson’s disease can cause urinary frequency,
urgency,
and nocturia.
The bladder is not simply a bag that empties when it becomes full.
Urination is controlled by a complex neural network.
The cerebral cortex,
the basal ganglia,
the brainstem,
the spinal cord,
and the peripheral autonomic nervous system all participate.
Normally, higher neural centers help prevent the bladder from contracting at inappropriate times.
If those control circuits are affected, problems such as bladder overactivity can appear.
So when a person with Parkinson’s disease says,
“I need to urinate too often,”
it should not automatically be attributed only to age or prostate disease.
Other urologic causes must of course also be considered,
but changes in Parkinsonian neural circuits themselves can be one contributor.
8. Blood-pressure regulation is also a nervous-system function
When we stand up suddenly from a lying position, gravity pulls blood downward.
A normal body detects this immediately,
constricts blood vessels,
adjusts cardiac output,
and maintains blood flow to the brain.
The autonomic nervous system is essential to this process.
In some patients with Parkinson’s disease, this regulation becomes impaired and orthostatic hypotension can occur.
On standing,
the person may feel dizzy,
the vision may darken,
strength may suddenly disappear,
and in severe cases fainting can occur.
The important point is that these symptoms are not simply motor impairment.
When someone says, “I can’t walk well,” the cause may not be only one thing.
It could be bradykinesia.
It could be freezing.
Or the person may feel weak because blood pressure has fallen.
Different circuit problems can hide inside the same phrase: “I can’t walk.”
9. Parkinson’s disease is present even during sleep
Sleep is not a time when the brain is simply switched off.
Sleep itself is a state produced by complex neural circuits.
Parkinson’s disease can be associated with
difficulty falling asleep,
frequent awakenings,
nighttime motor problems,
and daytime sleepiness.
One especially important problem is REM sleep behavior disorder.
During normal REM sleep, most skeletal muscles are suppressed even while dreaming, so dream activity does not become actual body movement.
When that suppression system fails,
a person can physically act out the dream.
They may shout,
swing their arms,
or kick.
This phenomenon shows that brainstem sleep-regulating circuits can also be involved in Parkinson’s disease.
10. Why can the body feel different at night and during the day?
Symptoms in Parkinson’s disease are not constant across the day.
Day and night can feel different,
and the body can also change depending on how well a person slept.
Sleep deprivation can affect
attention,
motor performance,
fatigue,
pain perception,
and emotional state.
So when the body feels poor in the morning, it should not automatically be interpreted as a medication-dose problem.
In Parkinson’s disease,
medication effect,
sleep,
autonomic function,
activity level,
and meals
can all interact to shape the state of the day.
11. Pain can also be part of Parkinson’s disease
It is easy to think of Parkinson’s disease and pain as separate problems.
But pain is a non-motor symptom experienced by many patients.
Muscles and joints can hurt because of rigidity.
Dystonia can also cause pain.
But that is not the whole story.
Changes in the central nervous system that processes and modulates pain may also contribute.
The same peripheral stimulus can therefore be processed differently by the brain.
Pain in Parkinson’s disease may need to be considered in several categories,
including muscular pain,
joint pain,
dystonic pain,
neuropathic pain,
and central pain.
12. Fatigue is not simply a lack of strength
Fatigue in Parkinson’s disease is difficult to describe.
It cannot always be explained as reduced muscle strength.
A person may feel exhausted even after adequate sleep.
The body may feel heavy even without much physical activity.
This may reflect the combined influence of multiple systems,
including arousal,
motivation,
autonomic function,
sleep,
and mood.
This is one reason why it is difficult in Parkinson’s disease to match each symptom to a single anatomical structure.
13. Dopamine does more than control movement
When we think of dopamine, movement comes to mind easily.
But there is more than one dopamine pathway.
The nigrostriatal pathway is closely related to movement,
while other dopaminergic pathways are involved in
reward,
motivation,
attention,
and behavioral choice.
That means Parkinson’s disease and its treatment can affect behavior as well as movement.
Motivation may change,
responses to reward may change,
and urges to repeat certain behaviors may increase.
In susceptible patients, some dopaminergic medications can be associated with impulse-control problems.
This should not simply be interpreted as
“a lack of willpower.”
The neural circuits that select behavior and evaluate reward are themselves influenced by dopamine.
14. Depression and anxiety are not only “problems of the mind”
Anyone living with a chronic illness for a long time can become depressed or anxious.
So it would be wrong to explain all depression and anxiety in Parkinson’s disease purely as brain pathology.
But the opposite explanation —
“they are only upset because of the illness” —
is also incomplete.
Neurotransmitter systems involved in emotion and motivation,
including dopamine,
serotonin,
and noradrenaline,
can be affected in Parkinson’s disease.
Mood changes may therefore arise from an overlap between
the psychological experience of living with the disease
and changes in the nervous system itself.
15. Thought can slow down too
The “slowness” of Parkinson’s disease does not always remain confined to the hands and feet.
In some patients, the speed of thought can also slow.
Switching from one task to another may become more difficult,
and handling several pieces of information at once may become harder.
Attention can fluctuate.
In some patients, more obvious cognitive impairment can appear as the disease progresses.
This connects to the fact that the basal ganglia are not devoted only to movement.
Alongside motor loops,
the basal ganglia also participate in
cognitive loops
and limbic loops.
The same basic architecture is used while connecting to different cortical regions.
16. Where do visual hallucinations come from?
Some people with Parkinson’s disease can develop perceptual symptoms such as visual hallucinations.
The risk may become greater when the disease has been present for a long time,
when cognitive changes are present,
or under the influence of certain medications.
This too is difficult to explain through dopamine deficiency alone.
The visual cortex that interprets visual information,
attention systems,
sleep and arousal networks,
and several neurotransmitter systems
can all be involved.
As Parkinson’s disease progresses, treatment goals therefore become more complex.
Improving motor function is not the end of treatment.
We also have to consider how medications that improve movement affect
sleep,
blood pressure,
cognition,
behavior,
and perception.
17. Multiple circuits exist at the same time in one person
Let us bring together what we have learned.
Slowness of the hands and feet depends importantly on the
basal ganglia motor circuit.
Tremor involves the
basal ganglia–thalamus–cerebellum–cortex oscillatory network.
Balance and gait involve not only the basal ganglia but also
the brainstem, cerebellum, and cerebral cortex.
Sleep involves
brainstem sleep circuits.
Blood pressure, the gut, and the bladder depend importantly on the
autonomic nervous system.
Mood and motivation involve
the limbic system and multiple neurotransmitter circuits.
Cognition depends on
prefrontal–basal ganglia circuits and broader cortical networks.
All of these coexist in one patient.
So it is only natural that Parkinson’s disease cannot be explained by a single symptom.
Non-motor symptoms, understood through the body
Before I returned to studying neuroanatomy, I evaluated Parkinson’s disease mainly through movement.
Did I walk well today?
Is my body stiff?
Am I OFF or ON?
Is there dyskinesia?
All of those are very important.
But over time, I came to understand something else.
Motor function alone does not determine my day.
How I slept,
how my gut moved,
how meals interacted with medication,
what my blood pressure and fatigue were like,
and how my concentration and mood felt
all helped shape the body I had that day.
So to understand Parkinson’s disease,
we cannot look only at the hands and feet.
We also have to look at the sleeping brain, the gut, the autonomic nervous system, and the circuits that create emotion and thought.
Parkinson’s disease is a movement disorder,
but it is not only a movement disorder.
It may be one of the clearest diseases for showing how deeply connected multiple neural systems are.
And once we understand that, symptoms that once seemed unrelated begin to fit into one larger picture.
Part 8 in one line
Parkinson’s disease can be explained as beginning with the loss of dopaminergic neurons in the substantia nigra, but the symptoms a patient actually experiences arise from changes across many neural networks — not only the motor circuit, but also the autonomic nervous system, sleep, emotion, cognition, and sensation — making it a body-wide neurological disease.
Next: Part 9
Part 9 — Where Does DBS Stimulate?
When medication alone cannot adequately control motor fluctuations or tremor, why can placing an electrode deep in the brain help regulate them?
Next, we will place the STN, GPi, and thalamus onto the actual basal ganglia circuit and examine why DBS targets those structures.