Parkinson’s disease (PD)

The challenge: a radical improvement in the early diagnosis of Alzheimer’s and Parkinson’s diseases (AD and PD)

  • Parkinson's disease (PD) is a neurodegenerative brain disorder that progresses slowly in most people. Most people's symptoms take years to develop, and they live for years with the disease. Parkinson disease (PD) has an estimated overall prevalence of 0.3%, increasing to 1% in the over 60 years of age in Europe. The results of the Global Burden of Disease 2010 report demonstrated that between 1990 and 2010, the number of deaths attributed to PD more than doubled.
    Normally, there are brain cells (neurons) in the human brain that produce dopamine. These neurons concentrate in a particular area of the brain, called the substantia nigra. Dopamine is a chemical that relays messages between the substantia nigra and other parts of the brain to control movements of the human body. Dopamine helps humans to have smooth, coordinated muscle movements. When approximately 60 to 80% of the dopamine-producing cells are damaged, and do not produce enough dopamine, the motor symptoms of Parkinson's disease appear. (Source:

    Read more

  • There is no “one way” to diagnose Parkinson’s disease (PD). However, there are various symptoms and diagnostic tests used in combination. One of the most important things to remember about diagnosing PD is that there must be two of the four main symptoms present over a period of time for a neurologist to consider a PD diagnosis.

    Four Main Motor Symptoms of PD:

    • Shaking or tremor
    • Slowness of movement, called bradykinesia
    • Stiffness or rigidity of the arms, legs or trunk
    • Trouble with balance and possible falls, also called postural instability

    The bedside examination by a neurologist remains the first and most important diagnostic tool for patients suspected of having PD. When questions arise, some newer imaging modalities such as PET and DAT scans may aid diagnosis, when performed by an expert in neuroimaging. DATscan is FDA-approved for differentiating PD from essential tremor, but it cannot distinguish between PD and parkinsonian subtypes.

  • The importance of early detection of PD is evident: currently ultimate therapies for PD are not available, despite medicines improving the symptoms or temporarily slowing down the disease progression in some people have been developed (

    The goal of medical management of Parkinson disease is to provide control of signs and symptoms for as long as possible while minimizing adverse effects. Studies demonstrate that a patient's quality of life deteriorates quickly if treatment is not instituted at or shortly after diagnosis.
    Pharmacologic treatment of Parkinson disease can be divided into symptomatic and neuroprotective (disease modifying) therapy. At this time, there is no proven neuroprotective or disease-modifying therapy.
    Levodopa, coupled with carbidopa, a peripheral decarboxylase inhibitor (PDI), remains the gold standard of symptomatic treatment for Parkinson disease. Carbidopa inhibits the decarboxylation of levodopa to dopamine in the systemic circulation, allowing for greater levodopa distribution into the central nervous system. Levodopa provides the greatest antiparkinsonian benefit for motor signs and symptoms, with the fewest adverse effects in the short term; however, its long-term use is associated with the development of motor fluctuations (“wearing-off”) and dyskinesias. Once fluctuations and dyskinesias become problematic, they are difficult to resolve. Monoamine oxidase (MAO)-B inhibitors can be considered for initial treatment of early disease. These drugs provide mild symptomatic benefit, have excellent adverse effect profiles, and, according to a Cochrane review, have improved long-term outcomes in quality-of-life indicators by 20-25%. [40]
    Dopamine agonists (ropinirole, pramipexole) provide moderate symptomatic benefit and delay the development of dyskinesia compared with levodopa. Proactively screen patients receiving oral dopamine agonists for adverse events. A review of the Cochrane and PubMed databases from 1990 to 2008 found that these agents caused a 15% increase in adverse events such as somnolence, sudden-onset sleep, hallucinations, edema, and impulse control disorders (eg, pathologic gambling, shopping, and Internet use; hypersexuality; and hoarding). [41] Note that patients may be reluctant to mention these events or may not attribute them to their treatment.
    Symptomatic anti-Parkinson disease medications usually provide good control of motor signs of Parkinson disease for 4-6 years. After this, disability often progresses despite best medical management, and many patients develop long-term motor complications, including fluctuations and dyskinesias. Additional causes of disability in late disease include postural instability (balance difficulty) and dementia. Thus, symptomatic therapy for late disease requires different strategies.
    Neuroprotective therapy aims to slow, block, or reverse disease progression; such therapies are defined as those that slow underlying loss of dopamine neurons. Although no therapy has been proven to be neuroprotective, there remains interest in the long-term effects of MAO-B inhibitors. Other agents currently under investigation include creatine and isradipine.

  • There are a lot of promising areas in PD research, but one of the most exciting is genetics. Researchers have identified a number of genes and chromosomal regions believed to play a role in PD. Studying the gene mutations responsible for inherited cases can help researchers understand both inherited and sporadic types of the disease. Identifying gene defects may be able to help researchers develop animal models that accurately mimic the neuronal death in human PD, identify new drug targets and improve diagnosis. Based on genetic findings, investigators have already developed improved animal models, so essential for our understanding of what causes the disease and for testing new treatments, and have made breakthroughs in cell biology that are helping to elucidate the various neurodegenerative processes and mechanisms in PD. In the future, it may become possible to test for individual gene differences in order to customize treatment of individual PD patients. And these basic research successes are translating into the clinic: We now have a number of new and exciting therapeutic strategies at or near the point of clinical testing. These include neuroprotection using various medications, other substances, or nerve growth (neurotrophic) factors and gene therapy. Other potential therapies still being tested in animals include a vaccine to modify the immune system in a way that can protect dopamine-producing neurons, stem cell therapy and inhibition of inflammatory enzymes, including COX-2.