The Effect of Cilostazol on the Clinical Outcome of Patients with Parkinson's Disease

Parkinson's disease (PD) is the second most common neurodegenerative disease, affecting about 1% of the elderly population, with 5 to over 35 new cases in 100,000 per year diagnosed with PD, with a prevalence of over 10 million people worldwide. This number is projected to increase to more than 12 million by 2040. The incidence of PD increase with age but it can affect people less than 50 years old. In the Eastern Mediterranean Region (EMR), the prevalence rate of PD increased by 42.3% over the period 1990-2016, and reached 87.1 per 100,000 in 2016. Factors that cause PD are multifactorial including genetic predispositions, environmental toxins, and aging leading to disease initiation and progression.

Parkinson's disease is a chronic condition characterized by the slow progression of the dopaminergic neuronal degeneration with irreversible loss of dopamine (DA). It is associated with motor symptoms as bradykinesia, resting tremor, rigidity, and postural instability. It also affects other extra-nigral dopaminergic, cholinergic and serotoninergic tracts, leading to non-motor symptoms as anosmia, sleep disorders and constipation as well as cognitive and psychiatric symptoms like cognitive impairment, dementia and depression.

Cognitive decline is a common non-motor symptom in PD, and an important source of patient disability and caregiver burden. The pathophysiology of cognitive impairment in PD is complex and likely involves a disruption of several distinct neuronal networks occurring over time. The timing, profile and rate of cognitive decline vary widely among individuals with PD and can range from normal cognition to mild cognitive impairment and dementia.

The pathogenesis of PD is not fully understood, however, several studies have revealed that the inflammation, oxidative stress, and neuronal apoptosis have a major role in its progression. In addition, PD was found to be linked with the reduction of the regional cerebral blood flow (rCBF). This reduced cerebral blood flow has been found to be associated with the occurrence of cognitive impairment and dementia.

Neuroinflammation in PD has been evidenced through several human and animal studies. It may result from the consequences of ongoing neuronal cell death in PD, the aggregation of misfolded α-Synuclein, microgliosis and astrogliosis, peripheral inflammation and PD-risk-associated genes. Any of these factors will result in the activation of microglia, CNS-resident macrophages important for normal CNS functioning, and production of pro-inflammatory mediators as cytokines (IL1, IL6, and TNFα) chemokines and reactive oxygen species, leading to the exacerbation of DA neuron degeneration.