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Summary

Parkinson disease (PD): affects 1 in 15 people in their lifetime, particularly men; has the most rapidly increasing prevalence among neurologic disorders; data suggest rates have doubled over 25 yr (1990-2015) and predict another doubling between 2015 and 2040, affecting ≈13 million individuals; longer lifespans increase the likelihood of developing degenerative diseases; life expectancy has doubled over the past 100 yr; age is a major risk factor but not the only factor

Models of Care

Classifications: transdisciplinary — separate disciplines unite to holistically contribute to patient care; multidisciplinary — a group of specialists collaborate through the sharing of documentation; interdisciplinary — highest level of care, marked by interaction in real time

ParkinsonNet: multidisciplinary model developed in the Netherlands which includes ≈70 regional networks with trained professionals across multiple disciplines; provides care for people residing anywhere in the Netherlands

Service and science hub model: interdisciplinary model implemented at the Norman Fixel Institute for Neurological Diseases at the University of Florida; a centralized location houses all specialists; each specialist develops a patient-specific health plan; all research opportunities are tracked in a database (ie, each patient becomes a research opportunity); represents an attempt to model a bidirectional patient-physician relationship; plans are designed for local implementation

Goals for models of care: for patients with complex neurologic disorders, these include centralized location, patient-specific care plans, consideration of every patient as a potential research participant, tracking of outcomes, and establishing bidirectional relationships between the patient and clinician

Establishment of a Care Model

Delivering care to a patient with PD: Bloem et al (2021) emphasizes the patient with PD and his or her family as the center of focus, around which clinicians rotate to provide the best possible care; Dorsey et al (2013) reviewed randomized controlled trials of telemedicine or virtual house calls for PD; many methods exist for remote delivery of care, follow-up, and monitoring of patients

Challenges

Regional concerns: providers must understand the governing laws, provisions, hospital systems, and insurance products that are available

Financing for services not covered: grants — may be a year-to-year or month-to-month solution but have potential for slow turnaround time and may lead to difficulty hiring and retaining staff; multiyear grants would be optimal but may not be sustainable over the long term; clinical research — consider negotiation with the health care system or local payers through data collection to support a value proposition; support from philanthropists — through an endowment (money deposited in an account, with funds sufficient to cover salary, benefits, and cost-of-living adjustments for staff; interest covers operating expenses) or cash (needs to be secured for multiple years); local councils or groups — can help determine what is best for the community; universities or community colleges — consider establishing a training program for students in exchange for provision of needed services by the school (eg, social workers for patients) to provide benefits to all stakeholders to achieve sustainability

Clinician time: proper review of PD medications can take ≥15 min per encounter; a multidisciplinary approach requires more time; possible solutions — consider adopting an “all-under-one-roof” model; reserve some elements of care for subsequent visits; delegate different tasks to different team members (facilitates development of trusted relationships while eliminating redundancy); collection of outcomes data — allows tracking of downstream revenue and quantification of diagnostic tests and procedures performed; data can help during negotiation of tradeoffs (eg, longer appointments in exchange for fewer hospitalizations or shorter hospital stays); spending more time with patients is more costly up front but can yield economic benefits over time

Profitability: arguing in favor of building a multidisciplinary or interdisciplinary care team only on the basis of the revenue to be generated within the health care system is unlikely to be successful; instead, address added value for clinicians who treat PD, including savings from diverting care from inpatient to outpatient care and benefits of acquiring a system-wide reputation of caring for the community (which attracts patients to the health care system and ultimately increases downstream revenues); self-advocacy of patients — can be encouraged by, eg, providing a kit from the Parkinson’s Foundation that contains information about eg, appropriate medications, imaging requirements; another strategy for reducing the frequency of hospital visits, thereby skewing the economics in favor of a multidisciplinary or interdisciplinary approach to care

Summary of strategies for gaining approval: construct a vision and plan to move forward; be persistent; consider placement of services under one roof or adding one service at a time, then provide data to support the value proposition over time; emphasize the long-term benefits (ie, improved quality of care, reduced complications, lower costs)

Research into Therapies for PD

Strategies for advancing treatment: to procure funding, researchers involved in, eg, HIV, polio, used the “PACT” (Prevention, Advocacy, Care, [development of new] Treatments [and research]) formula; treatments aside from surgeries, medication, and gene therapies should be considered; simple measures (eg, exercise) can have beneficial effects; for example, a study (Sowalsky [2017]) found the use of metronomes helpful for influencing movement in patients with PD; research into PD is underfunded (≈$200-$250 million annually), compared with that for HIV (≈$3 billion annually); there is a need to improve funding at least 10 fold

Targets of research

Genetics: multiple therapies target specific gene mutations (eg, LRRK2, GBA); understanding the relevant genetic mutations, targets, and pathways in the brain is necessary for development of new therapies; PD GENEration (an initiative by the Parkinson’s Foundation) and several other similar initiatives help to obtain patient genotypes to search for these mutations (found in ≈15% of all patients with PD)

New drug targets: may provide relief not only for motor symptoms (eg, tremors, stiffness, slowness) but also for nonmotor aspects that can be more disabling; levodopa does not halt progression of manifestations of PD related to “walking, talking, and thinking” (in addition to drugs, devices are being explored to address these symptoms); epidemiologic studies demonstrate that certain medications that influence inflammation or the neuroimmune system (eg, tumor necrosis factor-α inhibitors) may reduce risk for the development of PD (research is ongoing); slowing the progression of symptoms is a key area of research; high-throughput screening of drugs used to treat malaria, diabetes, gout (eg, inosine), and high blood pressure (eg, isradipine) has failed to demonstrate significant disease-modifying effects with respect to PD; exenatide, an antidiabetes agent, is still under investigation by Foltynie et al (2021)

Circuitopathies (abnormal circuits in the brain): researchers are able to “listen” to cells surrounding an electrode and are attempting to match these signals to different symptoms of PD; with decoding of the signals, it may be possible to deliver electricity only when necessary (rather than during a deep brain stimulation [DBS] treatment session), allowing disruption of symptoms with decreased risk for adverse events; optogenetics — combines genetics, engineering, light optics, and light-sensitive molecules to achieve precise control of cellular activity; the term “optogenetically inspired DBS” refers to use of this strategy to better understand the circuits and thereby guide targeting of therapies

Designer receptors: under investigation as potential targets for treatment of cancer; exclusively activated by designer drugs; may be another pathway for design of PD therapies

Immunotherapy: vaccine-based approaches — allow targeting of proteins (eg, α-synuclein) deposited in the brain; however, effects on symptoms and progression of PD have not yet been determined; neuroimmunology — this approach may involve administering antibodies to target areas in the brain and reduce inflammation

Summary of targets for emerging therapies: include genes, misfolded α-synuclein, throwaway pathways in the brain, ions that have stabilizing effects, mitochondria, neurotrophic factors, vaccines, neuroinflammatory therapies, diets, microbiomes, cannabinoids, novel druggable targets, gene therapies, and the next generation of adaptive DBS

Biomarkers: for PD, having biomarkers that gauge disease progression (ie, to determine the efficacy of therapies) is more critical than identifying biomarkers for diagnosis; a National Institutes of Health multicenter study (Birciu et al, 2017) used an imaging biomarker; other potential biomarkers include those present in blood, saliva, and skin; measurements made using highly sensitive markers could drastically reduce the number of patients required for clinical trials

Questions and Answers

Meeting with specialists: not every visit needs to include the entire specialist team; from a public health perspective, it would be useful to meet with the entire team once annually or every 6 mo to determine needed services; it is reasonable to have a system in which a few core specialists perform screening at the initial visit to establish a treatment plan; setting up visits with multiple specialists in a 3- to 4-hr timeframe vs seeing one specialist adds considerable value and increases synergy among the specialists; considering the disorganization of the American health care system, setting up multiple (as many as 6-7) visits at one time adds value for the patient

Assessment of gait and balance: timed “up and go” test, the walking portion of the Unified Parkinson Disease Rating Scale, Berg Balance Scale, electronic gait mat (not as useful), and pull test (failure indicates increased risk for falls); not all assistive devices are appropriate for individuals with PD, and these may require modification over time; be consistent in assessment for balance, gait, freezing, posture, and fall risk

Most promising therapies: for nonpharmacologic approaches, exercise has shown the most potential; monoamine oxidase-B inhibitors may be helpful, but the effect size is small; combination therapies — have not been explored; with more investment, it may be reasonable to combine, eg, a neuroimmunologic approach with pharmacologic targets and/or behavioral or modulation therapy; premotor (preclinical) aspects of PD — more attention is needed; failures of disease-modulating treatment may relate to focus on motor symptoms; because motor symptoms do not develop until patients have lost 50% to 80% of dopamine reserves, targeting them as if they represent the onset of the disease is illogical; other neurotransmitter systems should be explored for their potential to help modulate disease progression because many premotor symptoms are nondopaminergic in nature

Physical medicine and rehabilitation (PM&R) specialists: should be included to a greater extent, along with geriatricians, psychiatrists, and neurologists; PM&R specialists are classically thought of in association with admission to rehabilitation hospitals; services can be helpful in addressing walking dysfunction and demoralization (occurs in 1 in 5 to 1 in 6 people, sometimes without depression or anxiety); encourage increased involvement of PM&R specialists and learn from their approaches to rehabilitation; use of multidisciplinary care by PM&R specialists predates integration into treatment of PD