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Tzu Chi Medical Journal

TZU CHI MED J June 2010 Vol 22 No 2

2010 Buddhist Compassion Relief Tzu Chi Foundation

Review Article

The Epidemiology of Parkinsons Disease

Shin-Yuan Chen1,2,3*, Sheng-Tzung Tsai1,2,3

1Department of Neurosurgery, Buddhist Tzu Chi General Hospital, Hualien, Taiwan2Division of Functional Neuroscience, Buddhist Tzu Chi General Hospital, Hualien, Taiwan3Department of Medicine, Tzu Chi University, Hualien, Taiwan

Abstract

Parkinsons disease (PD) is the second most common neurodegenerative disorder and manifests as bradykinesia, rigidity, resting tremor and posture instability. Although the disease symptomatology can be well controlled by levodopa, related medications and deep brain stimulation, the etiology of PD remains obscure. The epidemiological features have been discussed in depth in the literature, but the methodologies used to approach the issues have varied greatly, and the results cover a wide range of factors and are generally inconclusive. The crude prevalence rate of PD has been reported to range from 15 per 100,000 to 12,500 per 100,000, and the incidence of PD from 15 per 100,000 to 328 per 100,000, with the disease being less common in Asian countries. Risk factor studies have pinpointed cigarette smoking, coffee/tea consumption and alcohol drinking as being mostly related to a lower risk of PD. The relationship between a higher risk of PD and drinking well-water and being exposed to herbicides/pesticides is controversial. Systemic diseases including gout, hyperlipidemia and hyper-tension may be related to a reduced risk of PD. A family history of PD, tremor, depression and head injury are related to a higher risk of PD. Genetic studies of the glucocerebrosidase, parkin and LRRK2 genes have contributed to our understanding of familial PD but not of sporadic PD. The health-related quality of life of PD patients is related not only to their motor disability, but also to their non-motor symptoms of depression, sleep disturbance, bladder and sexual dysfunction. The economic burden of PD is enormous, and the annual cost of medical service per PD patient can reach c13,804 (NT$599,547). [Tzu Chi Med J 2010;22(2):7381]

Article info

Article history:Received: December 21, 2009Revised: April 1, 2010Accepted: April 20, 2010

Keywords:ComorbidityEconomic burdenEpidemiologyParkinsons diseaseQuality of lifeRisk factorSystemic disease

*Corresponding author. Department of Neurosurgery, Buddhist Tzu Chi General Hospital, 707, Section 3, Chung-Yang Road, Hualien, Taiwan.E-mail address: william.sychen@msa.hinet.net

1. Introduction

Parkinsons disease (PD) is the second most common neurodegenerative disease and manifests as brady-kinesia, resting tremor, cogwheel rigidity and posture instability. The slowly progressive character of the dis-ease means that development may last for 20 years.

Although the motor symptoms of PD can be well con-trolled by levodopa and other adjunctive medications in the early stages of the disease, treatment-related complications will inevitably occur after 57 years. As the disease progresses, the cardinal motor symptoms of PD as well as cognitive decline, neuropsychological problems, autonomic failure and treatment-related

74 TZU CHI MED J June 2010 Vol 22 No 2

complications associated with levodopa will enor-mously reduce the patients activities of daily living (ADL) and health-related quality of life (HR-QoL) [1]. The World Health Organization has conducted numer-ous projects to raise awareness of the public health importance of PD since 1997. One of the completed projects is the Global Parkinsons Disease Survey (GPDS), a multinational survey across three continents (and including Canada, Italy, Japan, Spain, UK and USA), which showed that the QoL of PD patients was intimately associated not only with the severity of the disease and its treatment, but also with patients satis-faction with the explanation of their diagnosis, their emotional state and the current level of their optimism about the disease. The burden and public health im-portance of neurological diseases such as PD has been underestimated [2]. The task of carrying out public health investigations into PD needs enthusiasm to carry on. In this context, multidisciplinary teamwork is able to improve the wellbeing of PD patients. In this review, we will focus our attention on the current understand-ing of the risk factors of PD, its comorbidities, the eco-nomic burden of PD, and the HR-QoL of PD patients.

2. Prevalence and incidence

Prevalence is defined as the total number of persons with a disorder within a given population at a fixed point in time. Incidence is defined as the number of new cases of a disorder diagnosed during a specific time period [3]. The crude prevalence rate of PD in European countries has been found to range from 65.6 per 100,000 to 12,500 per 100,000, and the incidence from 5 per 100,000 to 346 per 100,000 [312]. In Asian countries, the crude prevalence rates seem to be lower and range from 15 per 100,000 to 328 per 100,000 [6,1316]. Interestingly, the wide ranges for the prevalence and incidence rates for PD from various research groups might be due to differ-ences in their research methodologies; these include case finding protocols, diagnostic criteria and the age of the study population [5]. How ever, in this context, it seems likely that the ethnic difference may be at-tributed to different environmental exposure risks or interethnic differences in genetic susceptibility genes.

3. Risk factors

The unknown basis of the etiology of PD makes the disease incurable. It is now considered to be a multi-factorial disease resulting from both environmental ex-posure to various factors and differences in genetic susceptibility. Multiple environmental factors that may be related to the etiology of PD include exposure to pesticides and herbicides, intake of various metals

(copper, lead-copper, lead-iron, iron-copper), drinking well-water and exposure to a neurotoxin (1-methyl-1-4 phenyl-1,2,3,6-tetrahydropyridine), yet none of these has been identified as the sole causative agent of PD [1721].

Although mutations in the parkin, LRRK2, and glucocerebrosidase genes are commonly found in multiethnic populations with familial early PD, such mutations are rare in sporadic early PD, which accounts for most patients with PD [2224]. Thus, environmental factors may be more important than ethnicity and genetic factors in the etiology of PD [25].

In contrast to the high risk factors associated with PD, many epidemiological studies have shown that cigarette smoking is inversely associated with the oc-currence of PD [19,20,26,27], even in a population characterized by a high prevalence of pesticide expo-sure [26], although pesticides or herbicides may not necessarily be associated with PD [19,21]. Coffee and tea drinking have also been suggested to be associ-ated with a lower risk of PD [28]. Physical activities may also be an issue such that a higher level of activ-ity may lower the risk of PD [29]. Also mentioned in one paper is the possibility that an increase in body mass index is positively associated with a higher risk of PD [30] (Tables 13 [1924,26,2838]).

4. Comorbidity

4.1. Neuropsychological events

PD as a neurodegenerative disease is characterized clinically by motor symptoms, which are related to dopamine deficiency; this occurs as a consequence of the degeneration of the substantia nigra pars com-pacta and has gained much attention in terms of treatment intervention.

It is estimated that neurologists overlook discuss-ing crucial non-motor symptoms of PD (including de-pression, anxiety, fatigue, and sleep disturbance) with their patients more than 50% of the time; this esti-mate comes from a prospective study of 101 patients [39]. However, only 12% of the sample had no non-motor symptoms in a brief report describing 99 non-demented PD patients [40]. Indeed, associated non-motor comorbidity in PD patients is a significant source of disability and impaired QoL. The non-motor symptom complex of PD includes neuropsychiatric symptoms, sleep disorders, dysautonomia and sen-sory complaints [41]. These non-motor symptoms are usually correlated with advancing age and disease severity, while other non-motor symptoms such as olfactory dysfunction, REM sleep behavior disorder, depression and gastrointestinal symptoms can occur early in the disease and deteriorate in parallel with the motor symptoms [4144].

TZU CHI MED J June 2010 Vol 22 No 2 75

Table

1

Sm

okin

g, dri

nkin

g, vit

am

ins

and t

he r

isk o

f Park

inso

ns

dis

ease

Ris

k f

acto

r Ris

k

Stu

dy

peri

od

Stu

dy

desi

gn

Stu

dy

popula

tion

Countr

y D

esc

ription

Refe

rence

Cig

arett

e s

mokin

g Lo

wer

19922

001

Prosp

ect

ive

M =

63

,34

8; F

= 7

9,9

77

U

.S.

N =

41

3 h

ad d

efi

nite o

r pro

bab

le P

D d

uri

ng

follo

w-u

p p

eri

od

31

(no P

D s

/s a

t b

aselin

e)

1.

Cig

arett

e s

mokin

g Lo

wer

19811

998

Prosp

ect

ive c

ohort

N

= 1

3,9

79

U

.S.

No. of

PD =

39

5; co

ntr

ol =

2320; O

R =

0.4

2 (

95%

CI =

0.2

20

.80)

for

20

2.

Coff

ee c

onsu

mption

case

-contr

olle

d

(no P

D s

/s a

t b

aselin

e)

cu

rrent

smoke

r 1

+ p

ack/d

; O

R =

0.7

1 (

95%

CI =

0.5

20

.95)

for

3.

Alc

ohol co

nsu

mption

co

ffee d

rinke

r 2

+ c

ups/

d; O

R =

0.7

7 (

95%

CI =

0.5

81

.03)

for

alco

hol

4.

Hig

h inta

ke o

f H

igher

dri

nke

r 2

+ d

rinks/

dvi

tam

ins

A a

nd C

Coff

ee

Low

er

19

82

19

87

C

ross

-sect

ional

N

= 2

9,3

35

Fin

land

HR

s of

PD a

ssoci

ate

d w

ith a

mount

of

coff

ee c

onsu

med d

aily

28

Tea

Low

er

19921

997

(0

, 1

4, an

d

5 c

ups)

were

1.0

0, 0.5

3 a

nd 0

.40 (

p for

trend =

0.0

05),

HR

= 0

.41

(

3 c

ups

of

tea

dai

ly)

Cig

arett

e s

mokin

g Lo

wer

19981

999

Cas

e-c

ontr

olle

d

PD =

24

7; co

ntr

ol =

67

6

Fra

nce

In

a p

opula

tion c

har

acte

rize

d b

y a

hig

h p

reva

lence

of

pest

icid

e

26

exp

osu

re; in

vers

e r

ela

tionsh

ip b

etw

een c

igar

ett

e s

mokin

g an

d

PD

(O

R =

0.6

) an

d a

lso in p

atients

with p

rofe

ssio

nal

pest

icid

e e

xposu

re (

OR =

0.5

)

Cig

arett

e s

mokin

g Lo

wer

19901

995

Cas

e-c

ontr

olle

d

PD =

19

0; co

ntr

ol =

190

Ital

y p

= 0

.00

1,

2 t

est

; p

< 0

.0001 M

cNem

ar t

est

19

Coff

ee/t

ea

re

trosp

ect

ive

(T

usc

any)

N

o d

iffe

rence

Well-

wate

r use

H

igher

1998

Cas

e-c

ontr

olle

d

PD =

13

6; co

ntr

ol =

272

Ital

y O

R =

2.0

; 9

5%

CI =

1.1

3.6

; p =

0.0

308

32

Sm

okin

g Lo

wer

OR

= 0

.7; 9

5%

CI =

0.4

1.1

; p 1

0 y

r exp

osu

re, si

gnif

ican

t in

creas

ed r

isk (

OR =

1.9

4; p =

0.0

80)

M =

mal

e; F

= fe

mal

e; PD

= P

arkin

sons

dis

eas

e; s/

s =

sym

pto

m/s

ign; U

.S. =

United S

tate

s of

Am

eri

ca; O

R =

odds

ratio; C

I = c

onfi

dence

inte

rval

; H

R =

haz

ard r

atio;

= n

ot

rela

ted.

76 TZU CHI MED J June 2010 Vol 22 No 2

Table

2

Sys

tem

ic d

isease

s and t

he r

isk o

f Park

inso

ns

dis

ease

Ris

k f

acto

r Ris

k

Stu

dy

peri

od

Stu

dy

desi

gn

Stu

dy

popula

tion

Countr

y D

esc

ription

Refe

rence

Gout

Low

er

19952

001

Prosp

ect

ive

PD =

10

52

;

U.S

.

Prev

ious

his

tory

of

gout,

low

er

risk

of

PD

36

(

in m

en o

nly

)

cas

e-c

ontr

olle

d

contr

ol =

66

34

(

Min

neso

ta)

OR

= 0

.69

; 9

5%

CI =

0.4

80

.99

In M

, O

R =

0.6

0;

95%

CI =

0.4

00

.9

In

F, O

R =

1.2

6; 95%

CI =

0.5

72

.81 (

not

reduce

d r

isk in w

om

en)

Initia

tion o

f Lo

wer

Initia

tion o

f an

ti-g

out

medic

ine, lo

wer

risk

of

PD: O

R =

0.5

7;

medic

ations

9

5%

CI =

0.1

91

.70

1.

Hyp

ert

ensi

on

Not

asso

ciate

d

19762

000

Prosp

ect

ive

F =

121,0

46

U.S

. (B

ost

on)

Self-report

ed h

isto

ry R

R =

0.9

6; 95%

CI =

0.8

01

.15

37

2. H

igh c

hole

stero

l

c

ohort

M

= 5

0,8

33

RR

= 0

.98

; 9

5%

CI =

0.8

21

.19

3.

Dia

bete

s m

elli

tus

PD

= 5

30

RR

= 1

.04

; 9

5%

CI =

0.7

41

.46

Incr

eas

ing

leve

l of

Low

er

Fro

m N

HS a

nd H

PFS

R

R =

0.8

6; 9

5%

CI =

0.7

80

.95; p for

trend =

0.0

2 (

use

of

tota

l ch

ole

stero

l (

modest

ly)

chole

stero

l-low

eri

ng

dru

gs w

as n

ot

asso

ciate

d w

ith P

D r

isk)

Hyp

ert

ensi

on

Low

er

19811

998

Prosp

ect

ive c

ohort

N

= 1

3,9

79

(no P

D

U.S

.

No. of

PD =

39

5;

contr

ol =

2320 (

OR =

0.6

2; 95%

CI =

0.4

80

.80)

20

c

ase-c

ontr

olle

d

s/s

at

bas

elin

e)

f

or

curr

ent

use

rs o

f an

tihyp

ert

ensi

ve d

rug

Incr

eas

e in B

MI

Hig

her

1972;

1977;

C

ohort

M

= 2

2,3

67

; F

= 2

3,4

39

Fin

land

HR

of

PD a

t diffe

rent

BM

I (