Clinical characteristics of subjects
A total of 121 consecutive patients with CSVD were screened for recruitment. Of these, 37 patients were excluded based on the following patient-selection criteria: presence of OSAS (n=11); presence of other medical conditions that interfere with sleep (n=2); patients taking sleep pills (n=12); (4) presence of major depression (n=4); refusal to participate (n=8). A total of 84 patients and 24 healthy controls were finally enrolled in the study. There were no significant between-group differences with respect to demographic characteristics (p > 0.05) (Table 1). Among the 84 CSVD patients, 63 complained about poor sleep quality and 54 patients qualified the DSM-5 criteria for chronic insomnia.
Table 1 Demographic and clinical characteristics of the study population
Groups
|
n
|
Age, mean (SD)
|
Male, n (%)
|
BMI ≥25, n (%)
|
Single, n (%)
|
Study group
Control group
t/χ2
P
|
84
24
|
60.1±8.4
61.8±10.2
0.136a
0.728
|
47(56.0%)
14(58.3%)
0.043b
0.836
|
37(44.0%)
11(45.8%)0.024b
0.877
|
7 (8.3%)
4 (16.7%)
1.417b
0.234
|
Groups
|
n
|
Retirement, n (%)
|
Education <12 years, n (%)
|
Insomnia complaints, n (%)
|
Insomnia, n (%)
|
Study group
Control group
t/χ2
P
|
84
24
|
38 (51.4%)
11 (45.8%)
0.221b
0.638
|
41 (48.8%)
15 (62.5%)
1.401b
0.236
|
63 (75.0%)
9 (37.5%)
11.813
0.001
|
54 (64.3%)
7 (29.2%)
9.366
0.002
|
a t value, b χ2 value.
SD, standard deviation; BMI, body mass index
PSG parameters
Subjects in the study group showed significantly lower SE and N-3 ratio compared to the control group; the WASO, N-1 ratio, ArI, PLMSI, and PLMAI of the study group were significantly higher than that in control group (p < 0.05). These findings indicated that CSVD patients had more severe objective sleep fragmentation than normal controls, especially during the slow wave sleep (Table 2).
Table 2 Comparison of PSG measures
Groups
|
n
|
SOL, min
|
TST, min
|
SE, %
|
WASO, min
|
AHI, per hour
|
PLMSI
|
Study group
Control group
t
P
|
84
24
|
25.3±14.5
19.8±13.8
1.054
0.095
|
314.8±88.5
368.6±98.2
0.796
0.195
|
61.5±10.8
72.4±13.4
1.985
0.031
|
131.5±51.2
96.8±42.1
2.325
0.011
|
3.4±1.5
3.8±1.2
0.124
0.957
|
10.3±8.7
6.7±5.9
2.305
0.019
|
Groups
|
n
|
REM(%)
|
NREM-1(%)
|
NREM-2(%)
|
NREM-3(%)
|
ArI, per hour
|
PLMAI
|
Study group
Control group
t
P
|
84
24
|
16.4±4.7
19.5±5.5
1.942
0.045
|
19.2±3.4
12.1±1.2
4.241
0.000
|
52.2±11.4
53.4±9.5
0.285
0.657
|
10.4±4.5
13.5±5.2
2.214
0.039
|
26.9±7.4
19.8±7.7
2.472
0.021
|
5.6±5.2
3.7±2.8
2.117
0.036
|
|
|
|
|
|
|
|
|
|
Abbreviations: SOL, sleep onset latency; TST, total sleep time; SE, sleep efficiency; WASO, wake after sleep onset; REM, rapid eye movement sleep; NREM, non rapid eye movement sleep; AHI, apnea–hypopnea index; ArI, arousal index; PLMSI, periodic limb movement in sleep index; PLMAI, periodic limb movement related arousal index.
PSQI measures
Participants in the study group had significantly lower SE, worse daytime dysfunction, and higher PSQI total score than the control group (p < 0.05). These findings indicated that patients with CSVD had worse subject sleep quality than normal controls (Table 3).
Table 3 Comparison of PSQI measures
Groups
|
n
|
Total score
|
Sleep quality
|
Sleep latency
|
Sleep time
|
Study group
Control group
t
p
|
84
24
|
9.3±5.2
5.9±2.1
2.094
0.015
|
1.5±1.0
0.9±0.4
1.332
0.084
|
1.3±1.2
0.8±0.6
1.742
0.062
|
1.7±1.1
1.2±0.7
0.834
0.452
|
Groups
|
n
|
Sleep efficiency, %
|
Sleep disturbances
|
Medication use
|
Daytime dysfunction
|
Study group
Control group
t
p
|
84
24
|
65.3±13.4
76.2±8.2
1.893
0.031
|
1.7±0.6
1.0±0.3
1.022
0.104
|
-
-
-
-
|
1.5±0.8
1.1±0.3
1.983
0.030
|
Imaging markers in CSVD patients with different level of ArI
Among the 84 CSVD patients, 23 (27.4%) patients had lacuna, 25 (29.8%) had CMB, 42 (50%) had WMH (DWMH Fazekas 2–3 and/or PWMH Fazekas 3), and 40 (47.6%) had PVS. There was no significant difference between patients with higher and lower ArI with respect to age, sex, education level, BMI, or vascular risk factors (p > 0.05). Patients with higher ArI showed significantly more severe PWMH and PVS than those with lower ArI (p < 0.05) (Table 4).
Table 4 Comparisons of CSVD markers in patients with different ArI level
Groups
|
n
|
CSVD burden
|
Lacuna
presence
|
CMB
Presence
|
WMH
presence
|
PWMH
severity
|
DWMH
severity
|
PVS
severity
|
PVS
presence
|
Higher ArI
Lower ArI
t/χ2
P
|
53
31
|
1.7±0.7
1.5±0.7
0.123a
0.804
|
15(28.3%)
8(25.8%)
0.061b
0.805
|
18(34.0%)
7(22.6%)
1.212b
0.271
|
27(50.9%)
15(48.4%)
0.051b
0.821
|
1.9±0.9
1.3±1.0
2.043a
0.045
|
1.4±1.0
1.6±1.1
0.723a
0.175
|
2.4±1.1
1.6±0.9
2.426a
0.037
|
28(52.8%)
15(48.4%)
0.155b
0.694
|
Abbreviations: CSVD, cerebral small vessel disease; CMB, cerebral microbleed; WMH, white matter hyperintensities; PWMH, periventricular WMH; DWMH deep WMH; PVS, perivascular space.
a t value, b χ2 value.
Relationship between sleep fragmentation and CSVD imaging markers regression
Ordinal logistic regression was performed to evaluate the association between sleep fragmentation and CSVD markers of patients in the study group. PWMH severity and PVS severity were the outcomes; ArI (≥19.8/h or <19.8/h) was the exposure; and potential confounders [TST (≥6h or <6h), WASO (≥30 min or <30 min), SE (≥85% or <85%), N-3 sleep ratio, PLMSI, and PLMAI] were the independent variables. The results showed that higher ArI was significantly associated with PWMH severity (odds ratio [OR] 1.121, 95% confidence interval [CI] 0.138–2.185) and PVS severity (OR 2.108, 95% CI 1.032–4.017), after adjusting for all independent variables. These findings indicated that sleep fragmentation may aggravate pathological process of CSVD (Table 5).
Table 5 Results of ordinal logistic regression showing the relationship of sleep parameters and CSVD imaging markers
Variables
|
ArI
|
TST
|
WASO
|
SE
|
%, N-3
|
PLMSI
|
PLMAI
|
PWMH severity
OR
95% CI
P
|
1.121
0.138–2.485
0.034
|
0.754
0.369–2.151
0.637
|
2.835
0.728–4.685
0.152
|
0.825
0.367–2.010
0.670
|
0.756
0.235–1.423
0.431
|
0.703
0.181–2.733
0.611
|
0.613
0.143–2.632
0.511
|
PVS severity
OR
95% CI
P
|
2.108
1.032–4.017
0.027
|
0.964
0.204–2.258
0.568
|
1.428
0.439–2.284
0.339
|
0.965
0.312–1.941
0.785
|
1.052
0.534–2.294
0.654
|
1.185
0.982–1.430
0.086
|
1.241
0.909–1.532
0.255
|
Abbreviations: PWMH, periventricular white matter hyperintensities; PVS, perivascular space; ArI, arousal index; TST, total sleep time; WASO, wake after sleep onset; SE, sleep efficiency; N-3, non rapid eye movement sleep-stage 3; OR, odds ratio; CI, Confidence interval; PLMSI, periodic limb movement in sleep index; PLMAI, periodic limb movement related arousal index.