Parkinson’s Disease Dementia (Tremor Paralysis Dementia)

Etiology

(1) Causes of Disease
The exact cause of primary Parkinson’s disease remains unclear, but it is generally believed to be related to aging, genetic factors, and environmental influences. Pathological changes mainly involve a significant reduction in dopamine (DA) levels in the striatum, leading to an imbalance between the DA system and the cholinergic system. This causes damage in the brain, particularly in regions like the substantia nigra, globus pallidus, caudate nucleus, putamen, and the locus coeruleus.

1. Genetic Factors: Some cases (10%-15%) follow a dominant autosomal inheritance pattern. However, despite advancements in genetic research, there is still much debate, and it is thought that multiple genes may be involved. This is an area requiring further research.
2. Free Radical Damage and Oxidative Phosphorylation Deficits: Experimental studies have shown that free radicals are elevated in Parkinson’s patients compared to controls, and there are defects in mitochondrial complex I’s oxidative phosphorylation. These factors are related to damage to mitochondrial DNA and other macromolecules.
3. Environmental Risk Factors: Clinical and experimental studies have shown that exposure to a substance known as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is associated with Parkinson’s disease. MPTP is used to create experimental models of Parkinson’s disease.

Overall, while current research suggests that Parkinson’s disease mainly arises from degeneration of dopamine neurons in the substantia nigra (resulting in 65%-70% neuronal loss) and the reduction of dopamine in the striatum, there is evidence indicating other neurotransmitters like norepinephrine (NE), serotonin (5-HT), and gamma-aminobutyric acid (GABA) may also play roles in the disease’s development.

(2) Mechanism of Disease
The mechanism remains unclear due to the unknown cause of Parkinson’s disease. However, it is currently believed that the degeneration of dopamine neurons in the substantia nigra leads to a decrease in dopamine in the striatum, causing an imbalance between dopamine and acetylcholine (ACh), which results in the disease’s onset. Biochemical research indicates a significant reduction of dopamine in the striatum of Parkinson’s patients. Further studies suggest that the tremors and paralysis symptoms are linked to the imbalance between dopamine and acetylcholine, with cholinergic activity becoming dominant. Neuropathologists have identified changes in the midbrain substantia nigra and the locus coeruleus, observing a lightening of color in these regions, loss of pigmented neurons, and the appearance of Lewy bodies, which are distinctive cellular inclusions found within neurons.

Recent studies confirm that dopamine accumulation within the cytoplasm can lead to neuronal death. The vesicular monoamine transporter (VMAT) plays a protective role for dopamine neurons. Experimental studies on rats and cell cultures have shown that neurotoxic substances like MPP+ have a strong affinity for VMAT, affecting dopamine storage and causing an increase in dopamine in the cytoplasm, which in turn produces free radicals that lead to neuronal degeneration.

Symptoms

1. Neurological Symptoms and Signs:
   • Bradykinesia and Akinesia: Common symptoms of Parkinson’s disease, presenting with slow movement or inability to move. These symptoms typically begin with one limb or one side of the body, characterized by reduced movement and slow actions.
   • Muscle Rigidity: This is another hallmark symptom, often accompanied by abnormal posture and reflex disturbances. Rigidity in Parkinson’s disease is due to increased muscle tension, where both flexor and extensor muscles are affected.
   • Tremors: The most common symptom, occurring in 70%-80% of patients. It typically starts in one hand or arm and presents as resting tremors, which disappear when the individual is engaged in purposeful movements.
   • Other Symptoms: Some patients experience discomfort like shoulder and back pain, especially in the early stages. Some may also have irregular leg movements while at rest, which can affect sleep.
2. Psychiatric and Cognitive Symptoms:
   • Patients may experience a decrease in attention, memory, and cognitive abilities, which can progress to full-blown dementia. About 15%-20% of patients may develop significant cognitive impairments.

Diet and Healthcare

1. Dietary Recommendations:
   • Protein Restriction: Patients on dopamine treatments should limit protein intake, as proteins can interfere with dopamine absorption.
   • Hydration: It’s crucial for Parkinson’s patients to stay hydrated to counteract medication side effects and maintain overall health.
   • Increasing Fiber and Vitamin-Rich Foods: Consuming vegetables, fruits, and honey can alleviate constipation and provide essential nutrients.
2. Foods to Avoid:
   • Limit Alcohol and Caffeine: Avoiding stimulants and alcohol is recommended.
   • Avoid Saturated Fats and Animal Organs: Reducing intake of these foods can help prevent negative effects on health and may improve the efficacy of Parkinson’s treatments.

Treatment

There is no definitive cure for Parkinson’s disease. However, appropriate medication, such as levodopa, and other treatments can help manage symptoms and slow progression.

Differential Diagnosis

Parkinson’s disease must be differentiated from other similar conditions such as drug-induced Parkinsonism, vascular Parkinsonism, and progressive supranuclear palsy. Diagnostic imaging such as CT and MRI is often used to aid in the differentiation of these conditions.

Complications

The disease progresses slowly and can lead to a decline in quality of life, with complications like pneumonia and urinary tract infections being common in advanced stages. About 25% of patients may also suffer from depression.