Parkinson’s disease
Parkinson’s disease is the second most common neurodegenerative disorder after Alzheimer’s disease. Parkinson’s disease involves both motor and nonmotor symptoms. The disease is characterized by degeneration and loss of dopamine-producing neurons located in the Substantia nigra. About 50–70% of these neurons are lost before major symptoms appear.
It mainly affects people older than 55 years, but younger adults and, rarely, children can also develop it. Globally, Parkinson’s disease affects approximately 1–3 people per 100 individuals over 60 years of age. The disease not only affects patients but also caregivers, who often experience emotional and physical stress.
Signs and symptoms
Parkinson’s disease is a serious disorder that gradually damages motor and nonmotor functions of the body over many years. The disease develops slowly and symptoms worsen over time.
Motor symptoms
The main motor symptoms include:
- Bradykinesia
- Rigidity
- Resting tremor
- Postural instability
The above symptoms usually appear only after a major loss of dopamine-producing nerve cells in the brain. In substantia nirgra, about 50–60% of dopamine neurons are already damaged and around 60–80% of nerve endings in the striatum are lost before symptoms become obvious.
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Non-motor Symptoms
Besides movement problems, Parkinson’s disease can also cause many symptoms not directly related to movement, such as:
- Sleep disturbances
- Depression
- Psychological impairment
- Anosmia
- Constipation
- Incontinence
- ANS dysfunctions
Motor and non- motor symptoms in detail
Primary Motor Symptoms
These are the main movement-related symptoms of Parkinson’s disease.
Tremors
According to many healthcare professional, tremors is considered as the main signs of Parkinson’s disease. Tremors are involuntary shaking or trembling movements, usually affecting hands, arms, fingers, feet, legs, head and jaw.
Resting tremors
In Parkinson’s disease, these are called “resting tremors” because the shaking occurs when the body part is relaxed or at rest. the tremor often decreases or stops when the person intentionally moves that body part. Tremors may worsen during stress, excitement, and fatigue.
In the hands, the tremor often produces a characteristic supination–pronation movement, meaning the hand rotates back and forth, sometimes called a “pill-rolling tremor“.
The tremor is strongest when the body part is resting. It usually decreases during voluntary movement, and during sleep.
Postural Tremor
Patients with Parkinson’s disease may also develop a postural tremor. Tremor appears when a person tries to maintain a posture against gravity, such as holding the arms stretched forward.
Postural tremor can sometimes be more noticeable than rest tremor, it may even appear as an early sign of Parkinson’s disease.
Both rest tremor and postural tremor in Parkinson’s disease usually occur at 4–6 Hz frequency (4–6 shaking movements per second). These tremors often improve with dopaminergic therapy (medications that increase dopamine activity).
Bradykinesia
Bradykinesia means slowness of voluntary movement and is considered one of the most important motor symptoms of Parkinson’s disease. Over time, it becomes difficult to start movements, and complete movements.
It can also affect facial muscles, producing a reduced facial expression and “mask-like face” appearance. It occurs because of the loss of nerve cells in the substantia nigra (SN), a brain region responsible for producing dopamine.
People with bradykinesia may experience slow body movements, reduced movement size or amplitude, difficulty with fine motor activities such as writing, buttoning clothes and handling small objects
Patients cannot generate enough nerve signals and muscular energy to perform quick and smooth movements.
Initial symptoms may include delayed reaction time, difficulty performing multiple tasks at the same time, reduced facial expressions and gestures, decreased blinking, swallowing difficulties
Bradykinesia can worsen depending on the patient’s emotional state including stress, anxiety, and lack of motivation. Patients may need stronger external cues or stimulation to initiate movement. The severity of bradykinesia is closely linked to dopamine deficiency; lower dopamine levels generally result in more severe movement slowing.
Rigidity
Rigidity means stiffness or inflexibility of muscles. It commonly affects limbs (arms and legs), neck, and trunk (body core). Rigidity is considered the second most common primary motor symptom of Parkinson’s disease.
Stiffness in muscles cause muscle pain, cramps, difficulty in movement. loss of fine hand movement may lead to micrographia (small cramped handwriting) and difficulty in eating.
Difference Between Bradykinesia and Rigidity
In bradykinesia, movement becomes slow. In rigidity, movement range becomes restricted, muscles remain stiff and resist movement.
So, in rigidity, the joints cannot move freely, muscles fail to relax properly. Rigidity may lead to muscle stiffness, discomfort, pain, and reduced flexibility.
Such as in painful shoulders sometimes mistakenly diagnosed as arthritis, because both conditions can cause pain and stiffness.
Postural instability
Postural instability means difficulty maintaining balance and posture, impaired body reflexes needed to stay upright. It occurs because the normal postural reflexes become weakened or lost.
Postural instability usually appears in the later stages of Parkinson’s disease. It becomes more severe as the disease progresses. Because balance control is impaired, patients may stumble easily, have difficulty turning or standing, and experience frequent falls.
This symptom is the main cause of falls in Parkinson’s disease patients. Falls can lead to serious complications such as hip fractures, injuries, and reduced mobility.
Secondary Motor Symptoms
These are additional movement-related problems that may develop:
- Freezing of gait- Sudden inability to move while walking, as if the feet are “stuck” to the floor.
- Micrographia- Very small and cramped handwriting.
- Unwanted increasing velocities- Uncontrolled speeding up of movements, especially while walking (called festination).
- Speech trouble- Soft, unclear, or slurred speech.
- Dystonia-Painful muscle contractions causing abnormal postures or twisting movements.
- Dysphagia-Difficulty swallowing.
- Sexual dysfunction- Problems related to sexual performance or desire.
Non-Motor Symptoms
Emotions
Non-motor symptoms affect emotions, thinking, and automatic body functions such as anxiety, depression, dementia and psychosis.
Rapid Eye Movement Sleep Behavior Disorder (RBD)
Sleep problems are very important early nonmotor symptoms of Parkinson’s disease and may help predict who is likely to develop the disease.
People with Parkinson’s disease often experience sleep disorders such as REM Sleep Behavior Disorder (RBD), restless leg syndrome, and sleep apnea. Among these, RBD has the strongest connection with Parkinson’s disease progression.
RBD is a sleep disorder in which people physically act out their dreams, make sudden movements, and talk, shout, punch, or kick during sleep.
Normally during REM sleep, muscles become temporarily paralyzed (called muscle atonia), preventing body movement during dreams.
In RBD, this paralysis is lost, so the person can move while dreaming. RBD is sometimes confused with sleepwalking, but they are different because sleepwalking usually occurs during non-REM sleep and is not strongly associated with vivid dreaming.
Doctors use Polysomnography (a sleep study) and electromyogram (EMG) recordings to detect abnormal muscle activity during REM sleep.
Why is RBD important in Parkinson’s disease?
RBD is strongly associated with disorders called synucleinopathies, which involve abnormal alpha-synuclein protein accumulation, including Parkinson’s disease, Dementia with Lewy bodies, and Multiple System Atrophy.
People with RBD have a much higher risk of later developing Parkinson’s disease than the general population. If Parkinson’s disease develops in someone with RBD, motor symptoms often progress faster.
Constipation
Constipation is one of the earliest and most common nonmotor symptoms of Parkinson’s disease and may appear years before movement problems begin. Constipation results infrequent bowel movements, difficulty passing stool, or incomplete bowel emptying.
More than 60% of people with Parkinson’s disease experience constipation. Parkinson’s disease affects not only the brain but also other body systems, including the gut.
Why does constipation occur in Parkinson’s disease?
There several factors that cause constipation in Parkinson’s diseases, such as:
- dysfunction of the autonomic nervous system
(the part of the nervous system controlling automatic body functions like digestion), - reduced physical activity or weakness,
- low fluid intake,
- side effects of medications such as Trihexyphenidyl,
- and accumulation of abnormal alpha-synuclein protein in nerves involved in the digestive system.
Why is constipation important clinically?
Compared with REM Sleep Behavior Disorder:
- constipation is easier and cheaper to screen for,
- often a simple questionnaire or single screening question is enough,
- whereas RBD usually requires an expensive sleep study (polysomnography).
Urinary dysfunction
Urinary problem is another possible early symptom or risk factor in Parkinson’s disease.
However, urinary issues may sometimes occur secondary to chronic constipation rather than directly from Parkinson’s disease itself.
Olfactory Dysfunction
Loss of smell is one of the earliest and most important nonmotor symptoms of Parkinson’s disease and may appear many years before movement symptoms develop.
Scientists first linked reduced smell sensitivity with Parkinson’s disease in 1975. Today, olfactory dysfunction (problems with smelling) is considered a major early sign of Parkinson’s disease.
Hyposmia- It is the condition where person has reduced ability to smell odors and more than 80% of Parkinson’s patients experience hyposmia. Because it appears early, hyposmia is considered a sensitive prodromal marker (early warning sign) of the disease.
Why does smell loss occur?
The olfactory receptor neurons detect odors, and send signals to the brain through long unmyelinated nerve fibers. These neurons may be especially vulnerable to neurodegeneration.
According to the Braak staging theory, abnormal alpha-synuclein accumulation, and Lewy body pathology begin in the Olfactory bulb during the earliest stage of Parkinson’s disease.
This suggests that smell loss may not only be an early symptom, but potentially one of the first detectable signs of neurodegeneration.
Why is this clinically important?
If olfactory loss is identified early, doctors and researchers may be able to start future neuroprotective therapies earlier, potentially slowing disease progression before severe motor symptoms appear.
Compared with other prodromal symptoms like, REM Sleep Behavior Disorder, or constipation,
olfactory testing has advantages because simple smell-testing kits are available, testing does not require a neurologist or sleep laboratory, and most important it is inexpensive and easy for large-scale screening.
Limitation
Smell loss is not unique to Parkinson’s disease, and it can also occur in other neurodegenerative disorders and even aging. Therefore, olfactory dysfunction alone cannot definitively predict Parkinson’s disease, but it is still a very useful early indicator.
Depression
Depression is an important nonmotor symptom of Parkinson’s disease and may appear before or during the progression of the disease.
Depression is a mood disorder that affects emotions, thoughts, motivation, and behavior. It is commonly linked to imbalance of brain neurotransmitters such as serotonin, norepinephrine, and dopamine.
These chemical changes can cause persistent sadness, loss of interest or pleasure, low motivation, and emotional distress. Approximately 50% of people with Parkinson’s disease experience depression, and symptoms may worsen progressively over time.
Depression in Parkinson’s disease is often associated with anxiety, panic attacks, fatigue, and apathy (lack of motivation or emotional interest). These symptoms may even appear before the classic motor symptoms of Parkinson’s disease.
Depression assessed through Geriatric Depression Scale-15 (GDS-15) and Montgomery-Asberg Depression Rating Scale (MADRS). These scales help clinicians evaluate the severity of depression, but they usually require trained professionals or experts to administer and interpret them.
Neuroanatomical Classification
Different symptoms arise from damage to different parts of the nervous system.
Cortex associated with psychosis and cognitive (thinking) impairment.
Basal ganglia associated with impulse control problems, apathy (lack of motivation) and restlessness.
Brainstem associated with depression, anxiety, and sleep disorders.
Spinal cord associated with orthostatic hypotension (drop in blood pressure when standing)
Peripheral nervous system associated with pain, constipation.
Thus, Parkinson’s disease affects not only movement but also emotions, cognition, sleep, digestion, and many other body systems.
Prodromal Symptoms
Scientists believe that the damage in Parkinson’s disease starts many years before diagnosis. The disease gradually spreads through both the central nervous system (brain and spinal cord) and the peripheral nervous system.
Early in the disease, nerve cells in the Substantia nigra begin to degenerate, but there are no obvious symptoms yet.
The progression is divided into 3 stages:
Preclinical stage
Neurodegeneration has already started.
Dopamine-producing neurons are being damaged.
No visible symptoms appear yet.
Prodromal stage
This stage may last more than 10 years.
Neuronal loss continues.
Early nonmotor symptoms appear, such as:
Constipation
Reduced sense of smell
Depression
Rapid eye movement sleep behavior disorder (RBD)
Clinical stage
By this point, around 40–60% of dopamine-producing neurons are already lost.
Typical motor symptoms appear:
Bradykinesia
Rigidity
Tremor
Parkinson’s disease is usually diagnosed at this stage.
Brain regions that are affected in Parkinson’s disease
Parkinson’s disease does not affect only one brain region. Other areas of the central nervous system (CNS) are also damaged, including dorsal motor nucleus of the vagus nerve, nucleus basalis of Meynert, locus coeruleus, and hypothalamus. The disease can even affect areas outside the brain, such as the myenteric plexus in the digestive system.
Lewy bodies are the abnormal protein clumps (mainly alpha-synuclein protein) found inside nerve cells, which are the characteristic feature of Parkinson’s disease. These protein deposits indicate degeneration of neurons.
Causes of dopamine neuron death in Parkinson’s disease
Various factors that believed to contribute to the death of dopamine-producing neurons in Parkinson’s disease including
mitochondrial dysfunction – the cell’s energy-producing structures do not work properly,
Oxidative stress (oxidative pressure) – harmful free radicals damage cells,
Neuroinflammation (nerve aggravation) – chronic inflammation in the nervous system
Impaired autophagic-proteasomal degradation – the cell’s waste-removal and protein-cleaning systems fail, leading to accumulation of toxic proteins
Together, these processes gradually damage and kill neurons involved in dopamine production.
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