Precision medicine to identify optimal diagnostic and therapeutic interventions for Parkinson's Disease

Abstract

Objective: Parkinson's disease, the second most common neurodegenerative disorder afflicting 10 million people worldwide and the fourteenth leading cause of death in the United States, is caused by the death of dopaminergic neurons that regulate movement in the substantia nigra pars compacta. Mechanisms contributing to the development of Parkinson’s disease in vulnerable individuals include protein misfolding, protein aggregation, and mitochondrial dysfunction. In order to develop guidelines for clinicians to utilize precision medicine to develop treatment plans to address the specific needs of individuals with Parkinson’s disease and related conditions, we have developed algorithms for diagnosis and treatment based on their view of available knowledge. We reviewed the key literature on the pathogenesis of Parkinson’s disease on PubMed and google scholar in order to propose guidelines for the development of diagnostic and therapeutic interventions for people with Parkinson’s disease and related conditions. In about 25 percent of patients, clinicians incorrectly diagnose Parkinson’s disease. Causes of misdiagnosis include a lack of algorithms and inadequate use of diagnostic modalities. Four main mechanisms that may contribute to the development of Parkinson's disease (misfolding of alpha-synuclein, mitochondrial dysfunction, dysfunctional ubiquitin proteasomal pathways, and abnormal autophagy) and different diagnostic modalities (structured interview and examination, laboratory assessments, neuropathology, genetic testing, neuroimaging) will form the basis for our algorithm for the diagnosis and treatment of Parkinson’s disease and related conditions. Clinicians, administrators, policy planners, advocates, and other concerned individuals will benefit from the adoption of our guidelines for the diagnosis and treatment of Parkinson’s disease and related conditions.

Guidelines for the Diagnosis and Treatment of Parkinson’s Disease

“…(Figure 1). Careful evaluation of persons with PD requires medical and family history [4], examination, structured movement assessments by visual observation [5,6], instrumentation [7], and neuroimaging [3].…”

“…movement assessments by visual observation [5,6], instrumentation [7], and neuroimaging [3]. Clinicians will then benefit from the systematic consideration of potential therapies for PD to apply the principles of precision medicine to develop an optimal treatment plan (Figure 2).…”

“…Additionally, future investigations will explore the development of handwriting analysis and other potential digital biomarkers other tools for the diagnosis of PD. We anticipate that clinicians, administrators, policy planners, advocates, and other concerned individuals will benefit from the adoption of our guidelines for the diagnosis and treatment of Parkinson's disease and related conditions [3].…”

“…Parkinson's disease (PD), the second most common neurodegenerative disorder afflicting 10 million people worldwide [1] and the fourteenth leading cause of death in the United States [2], is caused by the death of dopaminergic neurons that regulate movement in the substantia nigra pars compacta. Mechanisms contributing to the development of PD in vulnerable individuals include protein misfolding, protein aggregation, and mitochondrial dysfunction [3].To facilitate an organized approach for clinicians to utilize precision medicine to develop treatment plans to address the specific needs of individuals with PD and related conditions, we have developed guidelines for diagnosis and treatment based on the review of available knowledge [3].…”

Classification of extremity movements by visual observation of signals and their transforms

“…The incidence of PD, a condition afflicting 1% of people aged 60 years and older throughout the world, increases with age [1] . The evaluation of individuals with possible PD includes a comprehensive assessment of the medical and family histories, the physical and neurological examinations, and laboratory evaluations [2 , 3] . The administration of structured assessments to provide quantitative measurements constitutes a key component for the diagnosis and treatment of people with PD and related conditions.…”