Sleep disturbance and inflammatory markers associated with post-stroke depression, anxiety, and cognitive impairment

Table 1 Baseline demographic and clinical characteristics of patients with stroke, n (%)

Characteristics	Overall cohort (n = 160)
Age, years, mean ± SD	62.24 ± 10.33
Sex
Male	62 (38.75)
Female	98 (61.25)
Stroke type
Ischemic stroke	123 (76.88)
Hemorrhagic stroke	37 (23.13)
NIHSS score, median (IQR)	5 (4, 7)
Comorbidities
Hypertension	97 (60.63)
Diabetes mellitus	47 (29.38)
Cardiovascular disease	42 (26.25)
Acute-phase inflammatory markers, median (IQR)
CRP, mg/L	8.46 (6.66, 14.21)
IL-6, pg/mL	8.32 (6.81, 10.35)
TNF-α, pg/mL	9.51 (8.04, 11.22)
NLR	2.66 (2.25, 3.74)
PSQI score, median (IQR)	7 (4, 10)

NIHSS: National Institutes of Health Stroke Scale; IQR: Interquartile range; CRP: C-reactive protein; IL-6: Interleukin-6; TNF-α: Tumor necrosis factor-α; NLR: Neutrophil-to-lymphocyte ratio; PSQI: Pittsburgh Sleep Quality Index.

Table 2 Distribution of psychiatric and cognitive outcomes after stroke

Characteristics	Overall cohort (n = 160)
HAMD-17 score, median (IQR)	5 (3.14)
PSD (HAMD-17 ≥ 7), n (%)	45 (28.13)
HAMA score, median (IQR)	5 (3.11)
PSA (HAMA ≥ 7), n (%)	41 (25.63)
MoCA score, median (IQR)	26 (20.28)
PSCI (MoCA < 26), n (%)	65 (40.63)

HAMD-17: 17-item Hamilton Depression Rating Scale; PSD: Post-stroke depression; HAMA: Hamilton Anxiety Rating Scale; PSA: Post-stroke anxiety; MoCA: Montreal Cognitive Assessment; PSCI: Post-stroke cognitive impairment; IQR: Interquartile range.

Table 3 Comparison of demographic and clinical characteristics in patients with stroke who have sleep disturbances vs those who do not, n (%)

Characteristics	Sleep disturbance (PSQI > 5, n = 96)	Non-sleep disturbance (PSQI ≤ 5, n = 64)	t/χ2/Z	P value
Age, years, mean ± SD	61.00 ± 9.77	64.09 ± 10.93	-1.871	0.063
Sex			0.317	0.573
Male	35 (36.46)	27 (42.19)
Female	61 (63.54)	37 (57.81)
Stroke type			0.709	0.400
Ischemic stroke	76 (79.17)	47 (73.44)
Hemorrhagic stroke	20 (20.83)	17 (26.56)
NIHSS score, median (IQR)	5 (4, 7)	4 (3, 6)	-1.905	0.057
Comorbidities
Hypertension	60 (62.50)	37 (57.81)	0.353	0.552
Diabetes mellitus	27 (28.13)	20 (31.25)	0.181	0.671
Cardiovascular disease	25 (26.04)	17 (26.56)	0.005	0.942
Acute-phase inflammatory markers, median (IQR)
CRP, mg/L	8.44 (6.77, 13.51)	8.49 (6.57, 14.92)	-0.233	0.815
IL-6, pg/mL	8.67 (7.09, 10.23)	7.87 (6.26, 10.59)	-1.118	0.264
TNF-α, pg/mL	9.85 (8.51, 11.27)	9.19 (7.16, 11.19)	-1.027	0.304
NLR	2.67 (2.30, 3.94)	2.65 (2.15, 3.52)	-0.998	0.318
PSD (HAMD-17 ≥ 7)	33 (34.38)	12 (18.75)	4.638	0.031
PSA (HAMA ≥ 7)	30 (31.25)	11 (17.19)	3.984	0.046
PSCI (MoCA < 26)	46 (47.92)	19 (29.69)	5.290	0.021

NIHSS: National Institutes of Health Stroke Scale; IQR: Interquartile range; CRP: C-reactive protein; IL-6: Interleukin-6; TNF-α: Tumor necrosis factor-α; NLR: Neutrophil-to-lymphocyte ratio; PSD: Post-stroke depression; PSA: Post-stroke anxiety; PSCI: Post-stroke cognitive impairment; PSQI: Pittsburgh Sleep Quality Index; HAMD-17: 17-item Hamilton Depression Rating Scale; HAMA: Hamilton Anxiety Rating Scale; MoCA: Montreal Cognitive Assessment.

Table 4 Univariate analysis of factors associated with post-stroke depression, post-stroke anxiety, and post-stroke cognitive impairment

Variables	PSD		PSA		PSCI
	t/χ2/Z	P value	t/χ2/Z	P value	t/χ2/Z	P value
Age	-0.965	0.336	0.284	0.777	0.320	0.750
Sex	0.855	0.355	0.492	0.483	1.109	0.292
Stroke type	0.442	0.506	0.050	0.824	3.690	0.055
NIHSS score	-0.703	0.482	-1.861	0.063	-1.600	0.110
CRP	-2.150	0.032	-2.253	0.024	-0.215	0.829
IL-6	-2.118	0.034	-2.017	0.044	-2.486	0.013
TNF-α	-1.133	0.257	-1.477	0.140	-3.676	0.000
NLR	-3.355	0.001	-2.322	0.020	-2.785	0.005
Hypertension	0.010	0.919	0.003	0.958	0.038	0.845
Diabetes mellitus	0.734	0.392	0.605	0.437	2.093	0.148
Cardiovascular disease	2.321	0.128	1.775	0.183	0.502	0.478
Sleep disturbance	4.638	0.031	3.984	0.046	5.290	0.021

PSD: Post-stroke depression; PSA: Post-stroke anxiety; PSCI: Post-stroke cognitive impairment; NIHSS: National Institutes of Health Stroke Scale; CRP: C-reactive protein; IL-6: Interleukin-6; TNF-α: Tumor necrosis factor-α; NLR: Neutrophil-to-lymphocyte ratio.

Table 5 Multivariable logistic regression analysis of factors associated with post-stroke outcomes

Outcome	Variables	β	SE	χ2	P value	OR (95%CI)
PSD	Sleep disturbance	0.849	0.394	4.65	0.031	2.34 (1.08-5.06)
	Inflammatory burden	0.387	0.177	4.79	0.029	1.47 (1.04-2.08)
PSA	Sleep disturbance	0.825	0.409	4.08	0.043	2.28 (1.03-5.08)
	Inflammatory burden	0.443	0.181	6.01	0.014	1.56 (1.09-2.22)
PSCI	Sleep disturbance	0.799	0.349	5.20	0.023	2.22 (1.12-4.40)
	Inflammatory burden	0.374	0.167	5.01	0.025	1.45 (1.05-2.02)

PSD: Post-stroke depression; PSA: Post-stroke anxiety; PSCI: Post-stroke cognitive impairment; OR: Odds ratio; CI: Confidence interval.