The Effect of Long Term Usage of Levodopa

The Effect of Long Term Usage of Levodopa on Neurodegeneration in Parkinson’s Disease Introduction Results ❖ Parkinson’s Disease is a neurodegenerative disorder where neurons that produce dopamine in the brain gradually break down. ➢ As the disease progresses, the level of severity increases drastically. ❖ Although there is no cure, levodopa is a medication used to suppress the symptoms of Parkinson’s Disease by delivering a precursor of dopamine to the brain which then temporarily bolster dopamine levels. ➢ The dopamine levels are then bolstered in the brain temporarily ❖ However, certain speculations on levodopa are skeptical of the effectiveness of the long-term use of this drug. ❖ Patient 0 = healthy ➢ Tapping frequency stays constant ➢ Dopaminergic input remains the same Patient 1 and Patient 2’s Levodopa Levels Methods ❖ We used a MATLAB connectionist network of the basal ganglia model ➢ Allows simulation of dopamine in Parkinsonian subjects ❖ Originally the model had two Parkinson’s patients: one with more exposure to levodopa than the other ❖ We modified the model to add an additional patient [patient 0], as a control (mimics a healthy person) ➢ Parameters: ■ Dop_tonic_PD = 0.55 ■ Dop_max = 0 ■ Dop_50 = 0 ■ N=2 ❖ The model simulates the Alternate Finger Tapping motor task as an indicator of bradykinesia (slowness in movement; often present in parkinson’s disease) ➢ We utilized this as an indication of neurodegeneration, since the substantia nigra is the brain structure of the basal ganglia (BG) in which the death of dopaminergic neurons is responsible for the major motor symptoms of the disease. ➢ When a patient’s finger tapping frequency decreases, we can conclude that neurodegeneration is happening . ❖ Patient 1 = Parkinson’s Disease Patient ➢ Recently went on levodopa ➢ Dopaminergic input maximizes at around 0.76 ■ Gradually declines ➢ Tapping frequency reaches a max of 173 taps per minute ❖ Patient 2 = Long term Parkinson’s Disease Patient ➢ Took levodopa treatment for a longer period of time ➢ Dopaminergic input maximizes at around 0.6 ■ Decreases at a much faster rate ➢ Tapping frequency reaches a max of 164 taps per minute ■ Also slows back down rather quickly ■ Max is lower than Patient 1 ● Shows that levodopa is more effective when it is used for a shorter period of time Discussion/Conclusions ❖ Patient 1 and Patient 2 receive the same amount of levodopa dosage ➢ However, the difference between patient 1 and 2 is that patient 2 is further along in the disease ❖ The model illustrates how levodopa is not as effective in increasing dopamine levels as high or as long in patients with more degeneration ➢ The patient’s performance is not as improved ❖ According to a BMJ Journal study, clinicians realized that within a few years of introducing levodopa, several problems associated with its continued use were found. ➢ As Parkinson’s develops further, the response to levodopa lessens ➢ Symptoms arise with further progression of the disease ■ More unpredictable complications, such as motor fluctuations, “on/off” phenomena, and dyskinesias appear. ➢ Our results correspond to the results of this study