Introduction: The neutrophil-to-lymphocyte ratio (NLR) is widely regarded as a proxy for system inflammation. The previous study indicated that the NLR might be higher in Parkinson’s disease (PD) compared to healthy controls (HC). The study aimed to assess the role of system inflammation indicated by NLR in the incidence and progression of PD. Methods: We included participants from the longitudinal population-based cohort, UK Biobank, to analyze the association of NLR and the risk of PD. We conducted the Cox proportional hazards analyses as the primary analysis to determine the association between baseline NLR value and the risk of PD in UK Biobank. Then we further used data from a disease-specific longitudinal cohort, Parkinson’s Progression Markers Initiative (PPMI), to evaluate the differences between individuals with higher PD risk, and early-stage PD patients in the values of NLR. Patients with PD were divided into two groups according to the median value of NLR (2.35). Linear mixed models (random intercept and random slope) were used to evaluate the relationship between the high/low NLR groups and the disease progression. Results: A number of 288,837 participants from UK Biobank were included and 1,429 were diagnosed with incident PD. Among them, higher NLR was associated with an increased risk of incident PD in HC (per SD increment hazard ratio [HR], 1.041; p < 0.001). A total of 349 early-stage PD patients, 438 individuals with higher PD risk, and 207 HC were included from PPMI. PD patients and individuals with higher PD risk had a significantly higher NLR compared to HCs. Higher NLR group was associated with a faster deterioration of the Montreal Cognitive Assessment score in PD patients in 2 years (β [SE] = −0.225 [0.080], p = 0.005). Conclusion: Increased NLR in HC was linked with a higher risk of incident PD, and higher NLR was associated with a faster cognitive decline in PD patients, which indicated that inflammation was involved in the incidence of PD and the cognitive decline in early-stage PD.

1.
Gelders
G
,
Baekelandt
V
,
Van der Perren
A
.
Linking neuroinflammation and neurodegeneration in Parkinson’s disease
.
J Immunol Res
.
2018
;
2018
:
4784268
.
2.
Mogi
M
,
Harada
M
,
Riederer
P
,
Narabayashi
H
,
Fujita
K
,
Nagatsu
T
.
Tumor necrosis factor-alpha (TNF-alpha) increases both in the brain and in the cerebrospinal fluid from parkinsonian patients
.
Neurosci Lett
.
1994
;
165
(
1–2
):
208
10
.
3.
Brodacki
B
,
Staszewski
J
,
Toczyłowska
B
,
Kozłowska
E
,
Drela
N
,
Chalimoniuk
M
, et al
.
Serum interleukin (IL-2, IL-10, IL-6, IL-4), TNFalpha, and INFgamma concentrations are elevated in patients with atypical and idiopathic parkinsonism
.
Neurosci Lett
.
2008
;
441
(
2
):
158
62
.
4.
Chen
X
,
Hu
Y
,
Cao
Z
,
Liu
Q
,
Cheng
Y
.
Cerebrospinal fluid inflammatory cytokine aberrations in Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis: a systematic review and meta-analysis
.
Front Immunol
.
2018
;
9
:
2122
.
5.
Karpenko
MN
,
Vasilishina
AA
,
Gromova
EA
,
Muruzheva
ZM
,
Miliukhina
IV
,
Bernadotte
A
.
Interleukin-1β, interleukin-1 receptor antagonist, interleukin-6, interleukin-10, and tumor necrosis factor-α levels in CSF and serum in relation to the clinical diversity of Parkinson’s disease
.
Cell Immunol
.
2018
;
327
:
77
82
.
6.
Jensen
MP
,
Jacobs
BM
,
Dobson
R
,
Bandres-Ciga
S
,
Blauwendraat
C
,
Schrag
A
, et al
.
Lower lymphocyte count is associated with increased risk of Parkinson’s disease
.
Ann Neurol
.
2021
;
89
(
4
):
803
12
.
7.
Galiano-Landeira
J
,
Torra
A
,
Vila
M
,
Bové
J
.
CD8 T cell nigral infiltration precedes synucleinopathy in early stages of Parkinson’s disease
.
Brain
.
2020
;
143
(
12
):
3717
33
.
8.
Jiang
S
,
Gao
H
,
Luo
Q
,
Wang
P
,
Yang
X
.
The correlation of lymphocyte subsets, natural killer cell, and Parkinson’s disease: a meta-analysis
.
Neurol Sci
.
2017
;
38
(
8
):
1373
80
.
9.
Zahorec
R
.
Neutrophil-to-lymphocyte ratio, past, present and future perspectives
.
Bratisl Lek Listy
.
2021
;
122
(
7
):
474
88
.
10.
Inci
I
,
Kusbeci
OY
,
Eskut
N
.
The neutrophil-to-lymphocyte ratio as a marker of peripheral inflammation in progressive supranuclear palsy: a retrospective study
.
Neurol Sci
.
2020
;
41
(
5
):
1233
7
.
11.
Jin
H
,
Gu
H-Y
,
Mao
C-J
,
Chen
J
,
Liu
C-F
.
Association of inflammatory factors and aging in Parkinson’s disease
.
Neurosci Lett
.
2020
;
736
:
135259
.
12.
Akıl
E
,
Bulut
A
,
Kaplan
İ
,
Özdemir
HH
,
Arslan
D
,
Aluçlu
MU
.
The increase of carcinoembryonic antigen (CEA), high-sensitivity C-reactive protein, and neutrophil/lymphocyte ratio in Parkinson’s disease
.
Neurol Sci
.
2015
;
36
(
3
):
423
8
.
13.
Sanjari Moghaddam
H
,
Ghazi Sherbaf
F
,
Mojtahed Zadeh
M
,
Ashraf-Ganjouei
A
,
Aarabi
MH
.
Association between peripheral inflammation and DATSCAN data of the striatal nuclei in different motor subtypes of Parkinson disease
.
Front Neurol
.
2018
;
9
:
234
.
14.
Kara
SP
,
Altunan
B
,
Unal
A
.
Investigation of the peripheral inflammation (neutrophil-lymphocyte ratio) in two neurodegenerative diseases of the central nervous system
.
Neurol Sci
.
2021
;
43
(
3
):
1799
807
.
15.
Muñoz-Delgado
L
,
Macías-García
D
,
Jesús
S
,
Martín-Rodríguez
JF
,
Labrador-Espinosa
M
,
Jiménez-Jaraba
MV
, et al
.
Peripheral immune profile and neutrophil-to-lymphocyte ratio in Parkinson’s disease
.
Mov Disord
.
2021
;
36
(
10
):
2426
30
.
16.
Hosseini
S
,
Shafiabadi
N
,
Khanzadeh
M
,
Ghaedi
A
,
Ghorbanzadeh
R
,
Azarhomayoun
A
, et al
.
Neutrophil to lymphocyte ratio in Parkinson’s disease: a systematic review and meta-analysis
.
BMC Neurol
.
2023
;
23
(
1
):
333
.
17.
Ataç Uçar
C
,
Gökçe Çokal
B
,
Ünal Artık
HA
,
İnan
LE
,
Yoldaş
TK
.
Comparison of neutrophil-lymphocyte ratio (NLR) in Parkinson’s disease subtypes
.
Neurol Sci
.
2017
;
38
(
2
):
287
93
.
18.
Liu
Z
,
Fan
Q
,
Wu
S
,
Wan
Y
,
Lei
Y
.
Compared with the monocyte to high-density lipoprotein ratio (MHR) and the neutrophil to lymphocyte ratio (NLR), the neutrophil to high-density lipoprotein ratio (NHR) is more valuable for assessing the inflammatory process in Parkinson’s disease
.
Lipids Health Dis
.
2021
;
20
(
1
):
35
.
19.
Muñoz‐Delgado
L
,
Labrador‐Espinosa
,
Macías‐García
D
,
Jesús
S
,
Benítez Zamora
B
,
Fernández‐Rodríguez
P
, et al
.
Peripheral inflammation is associated with dopaminergic degeneration in Parkinson’s disease
.
Mov Disord
.
2023
;
38
(
5
):
755
63
.
20.
Zhang
L
,
Cao
B
,
Hou
Y
,
Wei
Q
,
Ou
R
,
Zhao
B
, et al
.
High neutrophil-to-lymphocyte ratio predicts short survival in multiple system atrophy
.
NPJ Parkinsons Dis
.
2022
;
8
(
1
):
11
.
21.
Parkinson Progression Marker Initiative
.
The Parkinson progression marker initiative (PPMI)
.
Prog Neurobiol
.
2011
;
95
(
4
):
629
35
.
22.
Paul
KC
,
Schulz
J
,
Bronstein
JM
,
Lill
CM
,
Ritz
BR
.
Association of polygenic risk score with cognitive decline and motor progression in Parkinson disease
.
JAMA Neurol
.
2018
;
75
(
3
):
360
6
.
23.
Jost
ST
,
Kaldenbach
M-A
,
Antonini
A
,
Martinez-Martin
P
,
Timmermann
L
,
Odin
P
, et al
.
Levodopa dose equivalency in Parkinson’s disease: updated systematic review and proposals
.
Mov Disord
.
2023
;
38
(
7
):
1236
52
.
24.
Kwak
SG
,
Kim
JH
.
Central limit theorem: the cornerstone of modern statistics
.
Korean J Anesthesiol
.
2017
;
70
(
2
):
144
56
.
25.
Portugal
B
,
Artaud
F
,
Degaey
I
,
Roze
E
,
Fournier
A
,
Severi
G
, et al
.
Association of physical activity and Parkinson disease in women: long-term follow-up of the E3N cohort study
.
Neurology
.
2023
;
101
(
4
):
e386
98
.
26.
Dettori
JR
,
Norvell
DC
,
Skelly
AC
,
Chapman
J
.
Heterogeneity of treatment effects: from “ow to treat” to “Whom to treat”
.
Evid Based Spine Care J
.
2011
;
2
(
2
):
7
10
.
27.
Allwright
M
,
Mundell
H
,
Sutherland
G
,
Austin
P
,
Guennewig
B
.
Machine learning analysis of the UK Biobank reveals IGF-1 and inflammatory biomarkers predict Parkinson’s disease risk
.
PLoS One
.
2023
;
18
(
5
):
e0285416
.
28.
Liu
J-H
,
Zhang
Y-J
,
Ma
Q-H
,
Sun
H-P
,
Xu
Y
,
Pan
C-W
.
Elevated blood neutrophil to lymphocyte ratio in older adults with cognitive impairment
.
Arch Gerontol Geriatr
.
2020
;
88
:
104041
.
29.
Ramos-Cejudo
J
,
Johnson
AD
,
Beiser
A
,
Seshadri
S
,
Salinas
J
,
Berger
JS
, et al
.
The neutrophil to lymphocyte ratio is associated with the risk of subsequent dementia in the framingham heart study
.
Front Aging Neurosci
.
2021
;
13
:
773984
.
30.
Hou
J-H
,
Ou
Y-N
,
Xu
W
,
Zhang
P-F
,
Tan
L
,
Yu
J-T
, et al
.
Association of peripheral immunity with cognition, neuroimaging, and Alzheimer’s pathology
.
Alzheimers Res Ther
.
2022
;
14
(
1
):
29
.
31.
Mak
E
,
Su
L
,
Williams
GB
,
Firbank
MJ
,
Lawson
RA
,
Yarnall
AJ
, et al
.
Longitudinal whole-brain atrophy and ventricular enlargement in nondemented Parkinson’s disease
.
Neurobiol Aging
.
2017
;
55
:
78
90
.
32.
Becker
S
,
Granert
O
,
Timmers
M
,
Pilotto
A
,
Van Nueten
L
,
Roeben
B
, et al
.
Association of hippocampal subfields, CSF biomarkers, and cognition in patients with Parkinson disease without dementia
.
Neurology
.
2021
;
96
(
6
):
e904
15
.
33.
Kandiah
N
,
Zainal
NH
,
Narasimhalu
K
,
Chander
RJ
,
Ng
A
,
Mak
E
, et al
.
Hippocampal volume and white matter disease in the prediction of dementia in Parkinson’s disease
.
Parkinsonism Relat Disord
.
2014
;
20
(
11
):
1203
8
.
34.
Trtica Majnarić
L
,
Guljaš
S
,
Bosnić
Z
,
Šerić
V
,
Wittlinger
T
.
Neutrophil-to-Lymphocyte ratio as a cardiovascular risk marker may be less efficient in women than in men
.
Biomolecules
.
2021
;
11
(
4
):
528
.
35.
Hurny
A
,
Michałowska-Wender
G
,
Wender
M
.
Impact of L-DOPA treatment of patients with Parkinson’s disease on mononuclear subsets and phagocytosis in the peripheral blood
.
Folia Neuropathol
.
2013
;
51
(
2
):
127
31
.
36.
Zhou
C
,
Zhou
X
,
He
D
,
Li
Z
,
Xie
X
,
Ren
Y
.
Reduction of peripheral blood iNKT and γδT cells in patients with Parkinson’s disease: an observational study
.
Front Immunol
.
2020
;
11
:
1329
.
37.
Tsukita
K
,
Sakamaki-Tsukita
H
,
Takahashi
R
.
Lower circulating lymphocyte count predicts ApoE ε4-related cognitive decline in Parkinson’s disease
.
Mov Disord
.
2021
;
36
(
12
):
2969
71
.
38.
Bowman
GL
,
Dayon
L
,
Kirkland
R
,
Wojcik
J
,
Peyratout
G
,
Severin
IC
, et al
.
Blood-brain barrier breakdown, neuroinflammation, and cognitive decline in older adults
.
Alzheimers Dement
.
2018
;
14
(
12
):
1640
50
.
39.
Sweeney
MD
,
Sagare
AP
,
Zlokovic
BV
.
Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders
.
Nat Rev Neurol
.
2018
;
14
(
3
):
133
50
.
40.
MacMahon Copas
AN
,
McComish
SF
,
Fletcher
JM
,
Caldwell
MA
.
The pathogenesis of Parkinson’s disease: a complex interplay between astrocytes, microglia, and T lymphocytes
.
Front Neurol
.
2021
;
12
:
666737
.
41.
Kouli
A
,
Camacho
M
,
Allinson
K
,
Williams-Gray
CH
.
Neuroinflammation and protein pathology in Parkinson’s disease dementia
.
Acta Neuropathol Commun
.
2020
;
8
(
1
):
211
.
42.
Chiang
P-L
,
Chen
H-L
,
Lu
C-H
,
Chen
Y-S
,
Chou
K-H
,
Hsu
T-W
, et al
.
Interaction of systemic oxidative stress and mesial temporal network degeneration in Parkinson’s disease with and without cognitive impairment
.
J Neuroinflammation
.
2018
;
15
(
1
):
281
.
43.
Cruz Hernández
JC
,
Bracko
O
,
Kersbergen
CJ
,
Muse
V
,
Haft-Javaherian
M
,
Berg
M
, et al
.
Neutrophil adhesion in brain capillaries reduces cortical blood flow and impairs memory function in Alzheimer’s disease mouse models
.
Nat Neurosci
.
2019
;
22
(
3
):
413
20
.
44.
Halliday
GM
,
Leverenz
JB
,
Schneider
JS
,
Adler
CH
.
The neurobiological basis of cognitive impairment in Parkinson’s disease
.
Mov Disord
.
2014
;
29
(
5
):
634
50
.
45.
Celik
T
.
Neutrophil-to-lymphocyte ratio in thyroid ophthalmopathy
.
Bratisl Lek Listy
.
2017
;
118
(
8
):
495
8
.
46.
Erre
GL
,
Paliogiannis
P
,
Castagna
F
,
Mangoni
AA
,
Carru
C
,
Passiu
G
, et al
.
Meta-analysis of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio in rheumatoid arthritis
.
Eur J Clin Invest
.
2019
;
49
(
1
):
e13037
.
You do not currently have access to this content.