Annals of Long-Term Care: Clinical Care and Aging. 2015;23(10):41-43.
Parkinson’s disease (PD) is a neurological disorder, caused by the degeneration of dopaminergic neurons in the brain, that affects ~1 million people in North America.1 PD is the second most common neurodegenerative disorder, yet its causes still remain largely unknown.2
Older adults approaching 60 years of age are the most at risk, with males being twice as likely to develop PD as women.3 The most common symptom associated with the disease is tremors in the hands, arms, legs, jaw, and face, but one might also experience a number of other symptoms such as slowness of movement, rigidity of limbs, and impaired balance.1 However, in addition to impaired motor functioning, people with PD often face numerous other challenges, including depression, anxiety, and sleep disorders, hindering opportunities for healthy living.4 Complicating the disease further is the fact that non-motor symptoms of PD often go unnoticed by caregivers and practitioners, due to lack of complaints by patients and nonspecific questioning by doctors.5
The causes of PD are still widely debated, with a definitive answer still unknown, but certain studies have identified different factors that contribute to the symptoms associated with the disease. Currently, much of the focus among researchers centers on the presence of the protein α-synuclein in Lewy bodies, which are distinctive neuronal inclusions found within specific brain regions and are believed to be one of the main causes of PD.6 An early study of PD found that the prevalence of Lewy bodies increases as people age.6 Other, more recent studies have since implicated α-synuclein as the major component of Lewy bodies and as being responsible for accelerating cell death and dysfunction in the onset of PD.7 Although much ground has been gained in the search for new viable treatments for PD, patients with this disease continue to struggle, and often do so within the long-term care setting.
To better understand the disease and ways to treat and care for patients with PD, Annals of Long-Term Care: Clinical Care and Aging® (ALTC) spoke with Fulvio Lauretani, MD, University Hospital of Pharma, Italy. Dr. Lauretani is an accomplished physician with a background in geriatrics and has written extensively about the subject of Parkinson’s disease. He is also a professor at the University Hospital of Parma, Italy, where he teaches a course for graduate students on the importance of data analysis in a clinical perspective.
ALTC: Are there any genetic or environmental factors that have been recognized as potential contributors to risk for PD?
Dr. Lauretani: The most important risk factor for PD is age.8 Results of a meta-analysis examining 30 different potential risk factors identified 11 environmental factors that significantly altered the risk of PD. The factors that increase risk (in decreasing order of strength of association) were pesticide exposure, prior head injury, rural living, β-blocker use, agricultural occupation, and drinking well water.
The contribution of genetics to PD is suggested by the increased risk of disease associated with a family history of PD or tremor. The most convincing evidence came with the discovery of monogenic forms of PD. SNCA, which encodes the protein α-synuclein, was the first gene to be associated with inherited PD. Mutations in LRRK2 and PARK2 are the most common causes of dominantly and recessively inherited PD, respectively.
What are some of the signs and symptoms that can be used to identify PD early in the disease progression? Are there different stages in regard to the progression or severity of PD?
In the latest decade, the approach to PD was dramatically changed.9 In fact, although for many years PD has been considered only a disease that affects walking, with a key role of the neurotransmitter dopamine, the neurological approach recently has been modified. The disease is not only a neurological issue. In the early phase, symptoms such as constipation and hyposmia frequently occur, even 10 years before of the development of motor symptoms, and a multidisciplinary evaluation should be recommended.9
The term “Parkinson’s disease” has been changed to “Parkinson’s diseases” in order to demonstrate that different clinical entities have been observed in studies, suggesting the existence of PD subtypes.10 PD patients could be grouped based on clinical features; for example, considering only motor symptoms, patients are classically divided in two groups: the “tremorigen-form,” in which resting tremor is the motor predominant symptom, and the “akinetic-rigidity-form,” in which akinesia/bradikynesia and rigidity are motor predominant symptoms.11
The first form is actually considered a “benign form” in terms of delay of appearance of cognitive and psychotics problems with evidence of low rate of institutionalization, whereas the second form is more prone to early development of cognitive impairment, with a high rate of falls and a more rapid progression toward activities of daily living (ADL) disability and institutionalization.11
What are some of the non-motor symptoms of PD?
Non-motor symptoms (NMSs) are often an integral part of the disease and some of them, such as depression, anxiety and hyposmia, can precede the onset of parkinsonism. Other NMSs, such as psychosis, dementia, impulse-control disorders (ICDs), sleep disorders and autonomic dysfunctions, are almost invariably present in advanced disease and in various combinations they may represent the principal complaints and therapeutic challenges. If untreated, they may impair quality of life and represent a major cause of hospitalization and institutionalization. Recently, it has been proposed PD subtypes including motor and non-motor symptoms. Cluster analysis revealed the presence of distinct subtypes of patients profiled according to the relevance of both motor and non-motor symptoms.11
Are there certain activities patients with PD should avoid so as not to injure themselves or those around them?
Risk of falling is one of the most important risk of these patients, with high probability of hip fractures and subsequent ADL disability. When balance problems appear, patients should be instructed to avoid movements, such as rapid changes in direction during walking, that can pose a risk of falling. Aerobic physical activity as well as exercises that produce increased mass muscle and strength, especially resistance training, should be encouraged.12
Currently, what are some of the most effective approaches for the treatment or management of PD?
Overall, the randomized control trial in PD showed that levodopa remains the most effective drug for the treatment of motor symptoms of PD. However, compared to placebo, adjuvant therapy reduces off-time, levodopa dose, and improves UPDRS scores in PD patients who develop motor complications on levodopa therapy. It is well established that the utilization of levodopa is at the expense of increased dyskinesia and numerous other side effects. Many authors showed that the risk of motor complications with levodopa therapy significantly increased when the dosage is higher than 400 mg per day.13
Indirect comparisons suggest that dopamine agonist therapy may be more effective than catechol-O-methyl transferase inhibitors and monoamine oxidase type B inhibitors, which have comparable efficacy. However, as indirect comparisons should be interpreted with caution, direct head-to-head randomized trials assessing the impact of these different drug classes on overall patient-rated quality of life are needed. It has been realized that adequate clinical trials that include more people at an advanced age, as showed by the incidence age of this disease, are necessary. Additionally, rather than considering a class effect, clinical trials of singular drugs are needed; this is especially true for dopamine agonists, because each specific drug has different reported adverse effects.14
Deep brain stimulation is a well-established treatment for the motor symptoms of PD. Findings of several clinical trials have shown that deep brain stimulation of either the subthalamic nucleus or globus pallidus internus is effective in moderate-to-severe PD.
What are some of the more promising developments for the future of care for patients with PD?
The motor and non-motor symptoms of late-stage PD typically respond poorly to levodopa. Abnormalities in non-dopaminergic neurotransmitters, including acetylcholine, glutamate, norepinephrine, and serotonin, contribute to the symptoms of PD. Expression of these levodopa-resistant symptoms probably involves some of these other neurotransmitter systems. In particular, reduction in acetylcholine due to degeneration of cholinergic structures might be associated with dementia as well as gait dysfunction and falls in late-stage PD.15 Accordingly, the cholinesterase inhibitor rivastigmine is efficacious for the treatment of dementia in PD. Variable results have come from studies using donepezil, another cholinesterase inhibitor. Findings from a small trial of donepezil for treatment of falls support the hypothesis that a rise in cholinergic tone might improve postural stability in Parkinson’s disease.
Further understanding of the molecular and cellular pathways involved in the neurodegenerative process are expected to yield useful biomarkers for the diagnosis of early prodromal disease, although a single biomarker is likely to be insufficient. The ultimate deliverable from ongoing research is the development of disease-modifying therapies, which we anticipate will need to be combined, and possibly individualized, to be effective.
Investigations into the use of stem cells to treat PD are still ongoing, and we await definitive data to guide their application in clinical practice.