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Parkinson's disease (PD), also known as parkinsonism, is a complex neurodegenerative disease (also known as cognitive disorder) second only to Alzheimer's disease [1], which mainly affects the neurons of dopamine production (dopaminergic) in specific areas of the brain (substantia nigra). The disease can cause progressive dyskinesia and non-dyskinesia. Clinical symptoms are bradykinesia, trembling at rest or stiffness [2].
Parkinsonism is a term for a disease that has similar symptoms to Parkinson's disease. Mainly includes the following types:
It is the most common type of parkinsonism. Idiopathic means that the cause is unknown. The main symptoms of idiopathic Parkinson's are tremor, rigidity (stiffness) and slowness of movement.
Vascular parkinsonism (also known as arteriosclerotic parkinsonism) affects people with restricted blood supply to the brain - usually older people who have health issues such as diabetes. The main symptoms are difficulty walking, urinary incontinence and memory problems.
A small percentage (about 7%) of people who diagnosed with Parkinson's disease develop symptoms after receiving specific medications.
Multiple system atrophy (MSA)
Multiple system atrophy (MSA) is an adult-onset, sporadic neurodegenerative disease. Its clinical manifestations include autonomic nerve dysfunction, Parkinson's syndrome, cerebellar ataxia and pyramidal tract signs.
Progressive supranuclear palsy (PSP)
Progressive supranuclear palsy affects eye movement, balance, movement, speech and swallowing. It is sometimes called the Steele - Richards - Olszewski syndrome.
Normal pressure Hydrocephalus
The symptoms of normal pressure hydrocephalus mainly affect the lower body. Common symptoms are difficulty walking, urinary incontinence and memory problems.
Figure 1 Diseases easily confused with Parkinson's
Epidemiology showed that the prevalence rate was 15 ~ 328/100,000 population, and about 1% of > 65-year-old population. The incidence is 10 to 21 per 100,000 population per year. In the United States, the incidence is 21 cases per 100,000 people [3]. Given the increase in global life expectancy, the number of people affected by Parkinson's disease and the consequent personal, social and economic burden are expected to increase dramatically by 2030 [4]. By 2020, nearly one million people in the United States will have Parkinson's disease, and about 60,000 Americans are diagnosed with Parkinson's disease each year. More than 10 million people worldwide suffer from Parkinson's disease.
Age: Parkinson's disease occurs mainly in the elderly, although Parkinson can be developed among young people, but it is estimated that only 4% of people with Parkinson's disease were diagnosed before the age of 50. The average age of onset of Parkinson's disease is 60 years, and its incidence increases with age.
Gender: Men are 1.5 times more likely than women to have Parkinson's disease.
People with Parkinson's disease in their parents or siblings may double their chance of developing Parkinson's disease because of genetic mutations.
Race: There is a racial difference in prevalence, with whites being the highest, followed by yellows and blacks being the lowest.
Figure 2 Facts about Parkinson's disease
When famous people disclose their illness, it helps to raise people's attention to the disease and increase their awareness and understanding of the disease.
Muhammad Ali (diagnosed as 1984) was diagnosed with Parkinson's disease three years after he left the boxing campaign. He has raised awareness of Parkinson's disease worldwide and helped establish the Muhammad Ali Parkinson Center in Phoenix, Arizona.
Michael j fox (diagnosed in 1991) is one of the world's most famous patients with Parkinson's disease. He devoted his life to the further development of Parkinson's research and established the Michael j fox Parkinson research foundation.
Brian Grant (diagnosed as Parkinson's disease in 2008) and established the Brian Grant Foundation to help others do the same.
In addition, George H. Bush, Billy Connolly, Alan Arda, Neil Diamond and Pat Torpey were also diagnosed as Parkinson.
There are several theories:
In conclusion, multiple factors in the above pathogenesis synergize, mutually cause and effect each other, and the vicious cycle leads to selective destruction of substantia nigra neurons, neurobiochemical changes such as dopamine synthesis and secretion reduction, as well as a series of changes in basal ganglia loop, and eventually a variety of clinical manifestations of Parkinson's disease.
Although the etiology of Parkinson's disease is still under investigation and has not been fully established, the absence of neurotransmitter dopamine is the main cause. It is also related to genetic factors, environmental factors, patient factors and so on.
Figure 3 The main cause of Parkinson's disease
Pathogenic mutations of autosomal dominant Parkinson's disease genes SNCA, LRRK2 and VPS35 account for about 0.1% to 30% of Parkinson’s disease, which depends on family history, age of onset and population background [5] [6].
Autosomal recessive inheritance: PARK7, PINK1, PRKN.
Mutations in the gene encoding glucocerebrosidase are the strongest genetic risk factors for this disease [7].
The enrichment of rare inherited variation in the pathway controlling mitochondrial DNA replication and repair influences the risk of PD，Most mutations in genes that cause familial PD, including SNCA [8], LRRK2, PINK1, PRKN, and VPS35, have been shown to disrupt mitochondrial quality control. The induction of Parkinson phenotype in zebrafish larvae supports the contribution of mitochondrial superoxide generation to PD development [9].
Nervous system problems: supranuclear palsy, Wilson's disease, Huntington's disease, Haller Walden-Spartz syndrome, and Alzheimer's disease can also cause Parkinson's disease.
Brain injury: traumatic brain injury, which causes changes in consciousness levels, increases the risk of PD in the years following injury [10].
Living area: there are differences in the geographical distribution of PD. This may be due to differences in environmental and genetic risk factors.
Occupations: certain occupational categories or titles are associated with higher rates of PD. Stress at work increases the risk of Parkinson's disease.
Pesticide exposure: Pesticides (including cypermethrin and hexachlorocyclohexane) have been reported most consistently in all chemical exposures associated with Parkinson's disease.
Contact with metals: Occupational exposure to various metals is considered to be related to the development of PD.
Age: is the biggest risk factor for Parkinson's disease. Parkinson's disease mainly affects the elderly, especially those between the ages of 55 and 65.
Gender: men are more likely than women to develop Parkinson's disease.
Parkinson's disease has a classic progressive stage. Symptoms of PD are usually divided into five stages: early stage, primary exercise, secondary exercise, primary and secondary non-exercise symptoms [11].
Figure 4 Five stages of Parkinson's disease
Resting tremor (arm, lower limb tremor), bradykinesia, muscle rigidity (face stiffness or limb stiffness) and posture gait disorder. As the disease progresses, further gait defects may occur, such as hesitation, transition, and frozen gait at the beginning of the exercise.
The incidence of Parkinson's disease increases with age, with 1% of people over 65 years old and 3% of people over 80 years old affected [15]. Young Onset Parkinson Disease (YOPD) occurs in people under 50 years of age. In rare cases, Parkinson-like symptoms may occur in children and adolescents. People diagnosed with YOPD have a more frequent family history of Parkinson's disease and a longer survival period.
Figure 5 Symptoms of Parkinson's disease
If you're worried that you might have Parkinson's disease, you should see a Parkinson's specialist for a diagnosis.
The disease is difficult to diagnose, especially in its early stages, and it is often diagnosed through medical history assessments, neurological tests, and in some cases, brain scans or laboratory tests.
Clinicians should perform a complete neurological examination of patients with suspected Parkinson's disease. Special attention should be paid to the assessment of extraocular movements, facial expressions, volume, torso and limb movement speed, muscle tone and gait [16].
If you have at least two of the following three symptoms, you may be diagnosed with Parkinson's disease.
If your symptoms improve after taking a drug called levodopa, you are more likely to develop Parkinson's disease.
In addition, scientists are looking for ways to identify PD's biomarkers that can lead to earlier diagnoses and more targeted treatments to slow the disease's progression. Eyesight abnormalities in Parkinson's disease have potential value as biomarkers [17].
If you're a Parkinson's patient or suspected of Parkinson's, you can contact Parkinson UK, Parkinson supports and research charities.
Parkinson's UK website: https://www.parkinsons.org.uk/.
Hoehn & Yahr scale: The severity of Parkinson's disease is generally assessed using a Hoehn & Yahr (H&Y) scale. Clinicians use it to describe the progression of motor symptoms in Parkinson's disease. The symptoms are divided into 1 to 5 levels. In this scale, 1 and 2 represent early, 2 and 3 represent metaphase, and 4 and 5 represent advanced Parkinson's disease.
The unified Parkinson's disease rating scale (UPDRS) is a more comprehensive tool for describing non-motor symptoms, including mental function, emotional and social interactions, cognitive difficulties, daily activity, and treatment complications.
Treatment can be divided into non-drug treatment and drug treatment, surgical treatment.
Parkinson's disease medications list:
Such as deep brain stimulation or tissue resection.
Non - pharmacological treatments includes awareness and understanding of the disease, nutritional supplements, exercise enhancement, confidence in combating the disease, and understanding, care and support from society and family.
A healthy and balanced diet can improve overall health. Many people with Parkinson's disease, including the famous advocate Michael J. Fox, say that a healthy diet helps to alleviate symptoms.
Parkinson's disease diet: The ketogenic diet may even be beneficial for diabetes, cancer, epilepsy and Alzheimer's disease [18] [19]; Green tea may have a protective effect on neurons; people who drink coffee [20] are at a much lower risk of developing Parkinson's disease.
Supplements: Certain supplements may help reduce Parkinson's symptoms, including:
Reduce toxicity and chemical exposure: Studies have shown that rural living, well water exposure, pesticide and herbicide exposure are all linked to Parkinson's disease, so eating more or all organic food is very beneficial and protective. Chelation also helps reduce the accumulation of heavy metals and the presence of other toxins.
Exercise therapy may be helpful in improving the symptoms of Parkinson's disease and even delaying the progression of the disease [21]. Patients with Parkinson's disease often have gait freezing, posture balance disorder, language and/or dysphagia, and can perform rehabilitation or exercise training according to different mobility disorders. Perform language barrier training, gait training, posture balance training, etc. Exercise and physical therapy are key to gait and balance symptoms that cannot be improved with medication.
Patients with Parkinson's disease often have psychological disorders such as depression, which is one of the main risk factors affecting the quality of life of patients. Therefore, effective psychological counseling and antidepressant medication for patients with Parkinson's disease can achieve a more satisfactory therapeutic effect.
In addition, there are music therapy [22] and speech therapy for Parkinson's disease [23].
Gene therapy may be a promising PD treatment strategy. In recent years, several gene therapy methods for PD have entered clinical trials. Some gene therapy methods for PD include:
References
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