Best early-onset Parkinson dementia predictor using ensemble learning among Parkinson's symptoms, rapid eye movement sleep disorder, and neuropsychological profile

Table 1 Measurement and definition of variables

Variable	Measurement	Characteristics
Sociodemographic factors	Age	Continuous variable
	Gender	Male or female
	Education	Middle school graduate and below or high school graduate and above
	Mainly used hand	Left hand, right hand, or both hands
	Family dementia history	Yes or No
	Family PD history	Yes or No
Environmental factors	Exposure to pesticide	Never, currently not exposed but exposed previously, or currently exposed to pesticide
Health behaviors	Pack-years	Non-smoking, 1-20, 21-40, 41-60, or ≥ 61 pack-years
	Coffee-drinking	Yes or No
	Mean coffee intake per day (cups/d)	No, ≤ 1, 2-3, or ≥ 4 cups
	Coffee drinking period (yr)	No, ≤ 5, 6-9, or ≥ 10
Disease history	Carbon monoxide poisoning	Yes or No
	Manganese poisoning	Yes or No
	Encephalitis	Yes or No
	Traumatic brain injury	Yes or No
	Stroke	Yes or No
	Alcoholism	Yes or No
	Diabetes	Yes or No
	Hypertension	Yes or No
	Hyperlipidemia	Yes or No
	Atrial fibrillation	Yes or No
Neuropsychological characteristics	Total score of KMMSE	Continuous variable
	Total score of KMoCA
	Global CDR score
	Sum of boxes in CDR
	K-IADL
	Total score of UPDRS
	Motor score of UPDRS
	H&Y staging
	Schwab & England ADL
Sleep behavior disorders	REM sleep behavior disorders	Yes or No
Exercise characteristics related to PD (PD related motor signs)	Tremor	Yes or No
	Rigidity	Yes or No
	Bradykinesia	Yes or No
	Postural instability	Yes or No
	LMC	Yes or No

PD: Parkinson’s disease; KMMSE: Korean Mini Mental State Examination; KMoCA: Korean Montreal Cognitive Assessment; CDR: Clinical Dementia Rating; K-IADL: Korean Instrumental Activities of Daily Living; UPDRS: Score of Untitled Parkinson’s Disease Rating; H&Y staging: Hoehn and Yahr staging; Schwab & England ADL: Schwab & England Activities of Daily Living scale; REM: Rapid eye movement; LMC: Late motor complications.

Table 2 General characteristics of the subjects (n = 342)

Characteristics	n (%)
Age, mean ± SD (yr)	57.3 ± 5.7
K-MMSE, mean ± SD	25.6 ± 4.0
K-MoCA, mean ± SD	21.2 ± 5.1
Global CDR score, mean ± SD	0.4 ± 0.3
Sum of boxes in CDR, mean ± SD	1.5 ± 1.7
K-IADL, mean ± SD	1.0 ± 2.4
Total score of UPDRS, mean ± SD	41.3 ± 21.8
Motor score of UPDRS, mean ± SD	23.1 ± 11.1
H&Y staging, mean ± SD	2.3 ± 0.6
Schwab & England ADL, mean ± SD	77.5 ± 15.0
Gender
Male	174 (50.9)
Female	168 (49.1)
Education
Middle school graduate and below	195 (57.0)
High school graduate and above	147 (43.0)
Handness
Right	318 (93.0)
Left	15 (4.4)
Both hands	9 (2.6)
Family PD history
No	279 (94.9)
Yes	15 (5.1)
Family dementia history
No	264 (92.6)
Yes	21 (7.4)
Smoking (pack year)
1-20	18 (7.9)
21-40	9 (2.6)
41-60	3 (0.9)
61+	303 (88.6)
Coffee consumption
No	174 (50.9)
Yes	168 (49.1)
Carbon monoxide poisoning
No	294 (93.3)
Yes	21 (6.7)
Traumatic brain injury
No	306 (97.1)
Yes	9 (2.9)
Diabetes
No	276 (82.3)
Yes	60 (17.7)
Hypertension
No	249 (73.5)
Yes	90 (26.5)
Hyperlipidemia
No	303 (89.4)
Yes	36 (10.6)
Atrial fibrillation
No	336 (99.1)
Yes	3 (0.9)
Tremor
No	120 (36.0)
Yes	213 (64.0)
Rigidity
No	24 (7.2)
Yes	309 (92.8)
Bradykinesia
No	21 (6.3)
Yes	312 (93.7)
Postural instability
No	159 (50.5)
Yes	156 (49.5)
REM sleep behavior disorders
No	195 (61.3)
Yes	123 (38.7)
Late motor complications
Only ON-OFF/Wearing OFF	57 (17.9)
Only levodopa-induced dyskinesia	12 (3.8)
Both ON-OFF/Wearing OFF and levodopa-induced dyskinesia are present	48 (15.1)
Both ON-OFF/Wearing OFF and levodopa-induced dyskinesia are absent	201 (63.2)
Depression
No	147 (67.1)
Yes	72 (32.9)

K-MMSE: Korean Mini Mental State Examination; K-MoCA: Korean Montreal Cognitive Assessment; CDR: Clinical Dementia Rating; K-IADL: Korean Instrumental Activities of Daily Living; UPDRS: Score of Untitled Parkinson’s Disease Rating; H&Y staging: Hoehn and Yahr staging; Schwab & England ADL: Schwab & England Activities of Daily Living; PD: Parkinson’s disease; REM: Rapid eye movement.

Table 3 Error of Out-Of-Bag

Mtry (n)	Error of Out-Of-Bag
3	0.140
4	0.105
5	0.149
6	0.132
7	0.140
8	0.123
9	0.149
10	0.123
11	0.140
12	0.158
13	0.149

Table 4 The normalized importance of variables in the random forest model

Variables	Mean decrease Gini
K-MMSE	7.224
K-MoCA	2.992
Sum of boxes in CDR score	2.872
Global CDR score	2.304
Motor UPDRS	2.104
K-IADL	1.720
Total UPDRS	1.587
Schwab & England ADL	1.258
H&Y staging	1.040
Late motor complications	0.775
Consumption of coffee	0.699
Education level	0.527
Pack year	0.505
BDI	0.409
Tremor	0.338
Postural instability	0.338
Rigidity	0.331
Gender	0.255
REM sleep behavior disorders	0.249
Hypertension	0.168
Handness	0.151
Diabetes	0.146
Hyperlipidemia	0.129
Carbon monoxide poisoning	0.124
Family PD history	0.074
Family dementia history	0.066
Bradykinesia	0.034
Manganese poisoning	0.013
Traumatic brain injury	0.002
Atrial fibrillation	< 0.001

K-MMSE: Korean Mini Mental State Examination; K-MoCA: Korean Montreal Cognitive Assessment; CDR: Clinical Dementia Rating; K-IADL: Korean Instrumental Activities of Daily Living; UPDRS: Score of Untitled Parkinson’s Disease Rating; H&Y staging: Hoehn and Yahr staging; Schwab & England ADL: Schwab & England Activities of Daily Living; PD: Parkinson’s disease; REM: Rapid eye movement; BDI: Beck Depression Inventory.