1.1 Impact of Parkinson’s Disease
Parkinson’s disease (PD) is the second most common degenerative disorder in the
aging brain. It affects approximately 6.3 million people worldwide. As the disease
progress, it will affect motor, autonomic, cognitive and emotional function and
eventually reduce lifespan.1, 2The cardinal symptoms of PD such as tremor, rigidity,
bradykinesia and postural instability involve motor control. Disability in PD derives
predominantly from progressive motoric disturbance which may lead the patient
become wheelchair-bound or bedridden. Such heath consequence results in a
considerable burden of illness associated with PD. Although PD is still not curable, the
advent of the levodopa raise the hope of improving both motor disability and survival in
PD.3Before the introduction of Levodopa, previous epidemiological studies report that
patients with PD had a shorter survival than the general population.4Hoehn and Yahr
reported a mortality ratio 2.9 times higher in PD patients than that of the general
population after adjustment for age, sex and race.5
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1.2 Temporal Natural History Based on Hoehn and Yahr stage
The severity of PD is usually classified by Hoehn and Yahr stage (H-Y stage).5In
the absence of treatment, the disease severity will progress to H-Y stage IV and V in 9.0
± 7.2 and 14.0 ± 3.4 years.5Previous study reported that H-Y stage at baseline were
greater in PD patients who had died during follow-up compared with that of survivors.6
Besides, patients with H-Y stage greater than III reported the impaired quality of life
and more non-motor symptoms.7This implies that H-Y stage plays an important role in
the natural history of PD for assessing both disease progression and prognosis of H-Y
stage.
In addition, those covariates associated with each transition rate between
consecutive stages were also with high interest to use them into the natural history
model to reduce the heterogeneity and also provide the information.
1.3 The Importance of Active Detective Method for
Parkinson’s Disease Classified by Hoehn and Yahr Stage
However, most studies detected PD cases by medical record review or
service-based detection, which usually detected PD case with syndrome at the late stage rather
than early stage.8-14Therefore, the incidence and prevalence of PD in door-to-door
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survey were higher than those in record-based studies.9This discrepancy implies that
outreaching surveys can yield accurate PD prevalence and incidence rates. A study in
Taiwan showed that a community-based screening program identified more early stage
PD with H-Y stage I or II than that was performed in a clinical series.15Such active
method suggested the possibility of detecting PD at early stage, and accompanied with
the effectiveness of levodopa in delaying the progression of PD, the life expectancy and
the quality of life would be expected to be improved. While temporal natural history of
H-Y-stage-based PD was proposed by Hoehn and Yahr, early detection of PD was not
envisaged at that time. In the era of preventive medicine in the 21 century, it seems
feasible as a result of effective early treatment. Screening for PD has become feasible as
Liou et al has already done in such an active detection.15With the advent of screening
for PD, PD with H-Y stage can be further divided into the screening detectable (SD)
phase and clinical detectable (CD) phase. In my thesis, the temporal natural history of
PD with H-Y stage will be classified into the SD and the CD phase for estimating the
parameters of disease progression.
1.4 Effectiveness of Early Detection and Treatment for Parkinson’s Disease
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Progression of disability on the H-Y stage has become slower with the introduction
of levodopa treatment. The progression to severe PD would be rapid for those patients
with delayed administration of levodopa therapy. 16, 17The development of therapies that
slow disease progression and improve survival makes early detection and treatment of
PD especially important. The elucidation of temporal natural history of H-Y-stage-based
PD also provide a pseudo-control group for evaluation for preventive strategy such as
screening for early PD. It has been shown that screening for early PD can lead to 51%
reduction for advanced stage of PD, and 25% mortality reduction.18Thus, early
detection could relieve medical burden from PD not only for patients themselves, but
for family members, and even the society.
1.5 Cost-effectiveness Analysis of Early Detection for Parkinson’ Disease
There are many economic evaluations for treatment of PD, but cost-effectiveness
analysis for PD screening has been scarcely addressed. Most economic evaluation
articles in PD were performed by deterministic approach although the uncertainly in
natural history of PD and also in treatment of PD was well-known in this field. Since
the advance in methodology of cost-effectiveness analysis has increasingly gained
attention over the past decades, stochastic process in decision tree and using Bayesian h ttttheheheheheiintntntntntntntttrorororororororooduddudududududuductctctctctctctctctioioioioiioioioi n n
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approach with probabilistic sensitivity analysis has also gained popularity to alleviate
concerns related to the dynamic changing of quality of life depending on disease status
and the uncertainty related to treatment and cost.
1.6 Motivation and Aims of the Study
There are few studies to depict the panorama of the natural history of PD based on
H-Y stage from various perspectives on epidemiological, clinical, and economic
aspects. Besides, the characteristics of heterogeneity in natural history and the
uncertainty in the decision analysis of early detection of PD prevention have not been
fully investigated.
The aim of this thesis includes four parts based on the principle of evidence-based
medicine.
Part I: To make use of a population and community-based cohort study to compare the two detection methods for active detecting Parkinson’s disease.
Part II: To elucidate the temporal natural history of Hoehn-Yahr-stage-based Parkinson’s
disease with stochastic process in relation to early detection of PD based on empirical data
from Part I.
Part III: To identify H-Y stage-specific factors responsible for various transitions.
Part IV: Perform cost-effectiveness and cost-utility analysis for early detection of ity y y y y tototototoaaaaaaaallllllllllllllllleveveveveveveveveviaiaiaiaiaiaiaiaiatetetetetetetetete
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Parkinson's disease through population-based screening.
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