Supplements Parkinson’s Disease: Quality Assessment and Improvement of Care
Part 1: Pathophysiology, Symptoms, Burden, Diagnosis, and Assessment
Parkinson’s disease (PD) is a chronic neurodegenerative disease associated with substantial morbidity, increased mortality, and high economic burden. Of importance to managed care is that the number of cases of PD are on the rise, paralleling the advancing age of the population, and misdiagnosis is common. Effective management of PD can minimize disability and potentially improve long-term outcomes, which would minimize long-term healthcare costs and medical resource utilization. This article provides a brief review of the epidemiology, pathophysiology, clinical course, and burden of PD.
(Am J Manag Care. 2008;14:S40-S48)Parkinson’s disease (PD) is a chronic, progressive, neurodegenerative disease with a multifactorial etiology. Characterized by hallmark signs of bradykinesia, rigidity, tremor, and postural instability, it is superseded only by Alzheimer’s disease as the most common neurodegenerative disorder.1-5 PD exacts a substantial burden on patients, families of patients, and caregivers,6 and is associated with a significant increase in morbidity and disability; mortality rates are higher and life expectancy lower relative to the general population.5,7-9 The economic burden of the disease is substantial, related to direct/indirect costs and medical resource utilization.6,8,10
Managed care providers and health plans need a broad understanding of PD and its management for 3 principal reasons:
1. The prevalence of PD increases with age.4,11 This is of growing concern, since the number of cases of PD is increasing as a result of the longer life expectancy in many populations, including the United States, with an increased need for healthcare resources.2,12
2. The diagnosis of PD can be easily missed, and misdiagnosis is common.11,13
3. Healthcare costs related to PD are projected to rise dramatically in the near future.10
This 3-part supplement is being provided to managed care providers to assist them in addressing issues relative to improving the care of patients with PD.
The prevalence of PD rises from 0.3% in the general US population to 1% to 2% in persons 65 years of age or older; some data indicate a prevalence of 4% to 5% in individuals >85 years.2,4,5 The usual age of onset is the early 60s, although up to 10% of those affected are 45 years of age or younger; the latter group is referred to as “youngonset” PD.5,11 In the United States, there are currently up to 1 million with diagnosed PD, which is greater than the combined number of cases of multiple sclerosis, amyotrophic lateral sclerosis (ALS), and muscular dystrophy.1 About 40,000 cases of PD are diagnosed annually, which by definition does not include the thousands of new cases that remain undetected.1 The lifetime risk of PD in males is 2.0% and 1.3% for women.8 Incidence of the disease appears to be lower in African Americans than Caucasians.5
Etiology and Risk Factors
Parkinsonian symptoms can arise from either the neuropathologic condition of PD (idiopathic PD [iPD]) or other forms of parkinsonism. For neuropathologic PD, about 90% of cases are sporadic, with no clear etiology; an additional 10% have a genetic origin, and at least 11 different linkages with 6 gene mutations have been identified.11,14,15 Genetic forms of PD are seen more frequently in young-onset PD.5 A combination of environmental factors or toxins, genetic susceptibility, and the aging process may account for many sporadic cases.11,14,16
Secondary forms of parkinsonism can be caused by medications, the sequelae of central nervous system infection, toxins, or vascular/metabolic disorders. Certain neurodegenerative conditions may also exhibit parkinsonian features; these are labeled parkinson-plus or atypical parkinsonian syndromes, and include progressive supranuclear palsy.5,11,13
The only proven risk factor for PD is advancing age.5 Other environmental or lifestyle risk factors associated with development of PD are rural living, exposure to pesticides and herbicides, well-water drinking, and working with solvents.5,11 However, none of these factors unequivocally has been demonstrated to cause iPD.5
Pathophysiology of PD
The pathologic hallmark of PD is degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc), resulting in depletion of striatal dopamine.2,15 This neurotransmitter regulates excitatory and inhibitory outflow of the basal ganglia.2,5,15
Some surviving neurons contain eosinophilic intracytoplasmic inclusions, or Lewy bodies, which are in part composed of numerous proteins. Protein accumulation is speculated by some to play a prominent role in the pathogenesis of both familial and sporadic PD,2,14-16 and the appearance of proteins in Lewy bodies tends to support this notion. Lewy bodies appear to represent the aftermath of underlying pathology. Evidence suggests these intracytoplasmic inclusions do not appear deleterious to cells, and may even be cytoprotective.2 Neurodegeneration of the SNc can occur in the absence of Lewy bodies in both sporadic and familial cases of PD; conversely, Lewy bodies can be present in the absence of neurodegeneration.2 However, the presence of Lewy bodies is required for pathologic confirmation of a clinical diagnosis of iPD.5
The neurodegenerative process in PD is not limited to the SNc, and neuronal loss with Lewy body formation also occurs in other brain regions,5,15-17 which may account for both motor and nonmotor features of the disease.
Clinical Expression and Course
Four cardinal motor manifestations are the central features of PD: (1) resting tremor, (2) bradykinesia (slowness of movement), (3) rigidity often with a cogwheel quality, and (4) postural instability (impairment of postural reflexes), which occurs later in the disease.5,18 Symptoms reported by patients when the dominant hand is involved include micrographia (abnormally small, cramped handwriting) and impairment in other fine tasks, such as fastening buttons. Motor symptoms usually begin asymmetrically but gradually spread to the contralateral side,5,11 although the side of initial involvement tends to remain the most severely affected throughout the course of the disease. Characteristics of these cardinal motor features are shown in Table 1.4,5,11,13 Although these features may also be present in other forms of parkinsonism, asymmetric onset, gradual progression, and response to levodopa in the absence of neurologic findings other than parkinsonism are clues that the patient has iPD.
Clinical presentation may vary from patient to patient, and it is not uncommon for PD symptoms to go unrecognized or unreported for years.18 A common initial symptom is asymmetric rest tremor (70%-90% of patients).5,11 This usually involves the thumb or wrist.4,5,13 A “pill-rolling” motion of the forefinger and thumb at a frequency of 3 to 6 cycles/second is the classical presentation. Tremor is more likely to be the presenting symptom in younger patients, whereas older patients may have more prominent bradykinesia. Tremor may be the most visible sign of PD, but it rarely is the major cause of disability.5
Bradykinesia is the most disabling feature of the disease; it contributes to the inability to arise from a chair or difficulties getting in and out of a car.11 The extreme of bradykinesia is akinesia, or the inability to initiate movement.5 Bradykinesia, particularly when combined with rigidity, may manifest as micrographia if the dominant hand is involved. Bradykinesia also presents as very slow movement, hypophonia (weak voice or whispering as a result of un-coordination of muscles of vocalization), reduced dexterity, a masked face and drooling, decreased blink rate, and a slow, shuffling gait.5,11
The “cogwheel pattern” of rigidity (fluctuating intensity of resistance while limb is passively moved) is often best detected in the distal part of the limbs, mainly the wrist joint.5 Postural instability is a sign of more advanced PD, and one of the most disabling motor features.
Postural instability and falls, although initially responsive to treatment, often become treatment resistant. If prominent postural instability occurs early in the disease, the diagnosis of iPD should be questioned.5,11
Nonmotor Features. The clinical course of PD is not limited to motor symptoms. A variety of nonmotor symptoms and disorders (Table 2) are common and significantly affect health-related quality of life (HRQOL) of both patient and caregiver.3,5,9,11,13,19,20 Surveys in PD patients have revealed that close to 90% have at least 1 nonmotor symptom, with about 10% exhibiting 5 nonmotor symptoms.3
Increasingly, it is recognized that nonmotor symptoms, especially depression, dementia, and psychosis, contribute to excess disability in PD.3,9,21 Nonmotor symptoms dominate the clinical picture as PD progresses and may also contribute to shortened life expectancy.7,9 Most do not respond to, and may be exacerbated by, dopamine replacement therapy.9 Of concern is that, in contrast to motor symptoms, nonmotor symptoms of PD are frequently unrecognized and either untreated or poorly treated in clinical practice, ultimately leading to increased healthcare costs and utilization.9
Depression is frequent in PD and the most common neuropsychiatric disorder, affecting up to 50% of patients.5,9,19-21 Depression is often comorbid with anxiety and can occur at any stage of the illness, including prior to onset of motor symptoms. Other nonmotor features that may occur early in PD are autonomic dysfunction, cognitive impairment, and olfactory dysfunction (hyposmia, a reduced ability to smell odors, or anosmia, which is loss of smell).
Cognitive impairment in PD is characterized by deficits in executive abilities, memory retrieval deficits, and impairments in attention and visuospatial abilities, with advancing age being the primary risk factor.5,19 During long-term follow-up of PD patients, a substantial proportion will eventually develop dementia; a prevalence of 78% was reported in a recent long-term prospective study.20 Dementia is rare in early iPD, and its early occurrence should call into question the diagnosis of PD and may suggest a diagnosis of dementia with Lewy bodies (DLB).5,13 Anosmia and hyposmia are so common in PD that smell-testing is undergoing evaluation as an early biomarker to identify patients at risk of developing PD; loss of smell is also a sign that has usefulness in differential diagnosis, helping to distinguish PD from other conditions.5,9 Anosmia does not respond to dopaminergic therapy.5
Psychosis, specifically hallucinations and delusional thinking, is also common in PD, seen in 15% to 40% of treated patients20 and tending to occur later in the disease course. Although there is a clear association between dopaminergic therapy and psychosis, the etiology of psychosis is complex.20 Other reported risk factors for psychosis include older age, cognitive impairment, visual impairment, sleep disturbances, comorbid depression, and longer duration and increasing severity of PD.19,20
Impulse control disorders (ICDs) (Table 2) are increasingly recognized as a relatively common psychiatric disorder in PD, occurring in up to 10% of patients at any given time. The most commonly reported ICDs in PD are compulsive gambling, buying, sexual behavior, and eating, and their occurrence can be devastating to patients and caregivers. Recent research suggests an association between dopamine agonist use and ICDs in PD.