Age-stratified analysis of depression onset patterns and treatment response differences following cerebral infarction

Table 1 Comparison of baseline characteristics among different age groups, mean ± SD/n (%)

Item	Young group (n = 68)	Middle-aged group (n = 124)	Elderly group (n = 108)	χ2/F value	P value
Gender				4.126	0.127
Male	45 (66.2)	89 (71.8)	63 (58.3)
Female	23 (33.8)	35 (28.2)	45 (41.7)
BMI (kg/m2)	24.6 ± 3.2	25.3 ± 3.8	23.9 ± 3.5	4.127	0.017
Education level				15.672	0.004
Junior high school or below	18 (26.5)	52 (41.9)	67 (62.0)
High school	28 (41.2)	46 (37.1)	31 (28.7)
College or above	22 (32.3)	26 (21.0)	10 (9.3)
Marital status				12.864	0.002
Married	52 (76.5)	108 (87.1)	83 (76.9)
Single/divorced/widowed	16 (23.5)	16 (12.9)	25 (23.1)
Medical history
Hypertension	28 (41.2)	78 (62.9)	89 (82.4)	24.571	< 0.001
Diabetes	12 (17.6)	35 (28.2)	48 (44.4)	12.398	0.002
Coronary heart disease	5 (7.4)	23 (18.5)	34 (31.5)	13.962	0.001
NIHSS score	8.2 ± 4.6	10.5 ± 5.3	12.1 ± 5.8	19.854	< 0.001
mRS score	2.1 ± 1.2	2.8 ± 1.4	3.2 ± 1.5	21.472	< 0.001
Infarct location				2.185	0.335
Anterior circulation	48 (70.6)	92 (74.2)	84 (77.8)
Posterior circulation	20 (29.4)	32 (25.8)	24 (22.2)

BMI: Body mass index; NIHSS: National Institutes of Health Stroke Scale; mRS: Modified Rankin Scale.

Table 2 Comparison of medication history and clinical characteristics among different age groups, mean ± SD/n (%)

Item	Young group (n = 68)	Middle-aged group (n = 124)	Elderly group (n = 108)	χ2/F value	P value
Medication history
Anticoagulants	8 (11.8)	28 (22.6)	45 (41.7)	17.842	< 0.001
Antihypertensive drugs	26 (38.2)	74 (59.7)	86 (79.6)	24.567	< 0.001
Antidiabetic drugs	10 (14.7)	32 (25.8)	44 (40.7)	12.985	0.002
Lipid-lowering drugs	15 (22.1)	38 (30.6)	42 (38.9)	5.234	0.073
Clinical characteristics
Onset to admission time (hours)	16.8 ± 11.2	20.4 ± 14.9	26.7 ± 18.3	8.254	< 0.001
Initial symptoms				8.942	0.063
Limb weakness	45 (66.2)	89 (71.8)	85 (78.7)
Speech disorders	18 (26.5)	28 (22.6)	18 (16.7)
Others	5 (7.4)	7 (5.6)	5 (4.6)
Imaging characteristics
Large infarct (> 1/3 middle cerebral artery territory)	12 (17.6)	28 (22.6)	35 (32.4)	5.847	0.054
Involvement of key areas	15 (22.1)	35 (28.2)	42 (38.9)	6.234	0.044
TOAST classification				7.865	0.248
Large-artery atherosclerosis	28 (41.2)	56 (45.2)	54 (50.0)
Small-vessel occlusion	24 (35.3)	42 (33.9)	32 (29.6)
Cardioembolism	8 (11.8)	16 (12.9)	18 (16.7)
Other causes	8 (11.8)	10 (8.1)	4 (3.7)

TOAST: Trial of org 10172 in acute stroke treatment.

Table 3 Comparison of laboratory parameters among different age groups, mean ± SD

Item	Young group (n = 68)	Middle-aged group (n = 124)	Elderly group (n = 108)	F value	P value
Blood routine
White blood cells (× 109/L)	8.2 ± 2.4	8.8 ± 2.9	9.1 ± 3.2	2.847	0.059
Neutrophil percentage (%)	69.2 ± 8.5	71.8 ± 9.3	73.5 ± 10.1	6.124	0.002
Hemoglobin (g/L)	132 ± 18	128 ± 19	124 ± 21	4.258	0.015
Platelets (× 109/L)	248 ± 67	265 ± 82	278 ± 94	3.156	0.044
Biochemical indicators
Blood glucose (mmol/L)	6.5 ± 1.8	7.2 ± 2.4	8.1 ± 2.9	11.567	< 0.001
Creatinine (μmol/L)	76 ± 16	84 ± 21	92 ± 28	12.483	< 0.001
Blood urea nitrogen (mmol/L)	5.1 ± 1.6	5.8 ± 2.1	6.8 ± 2.5	15.234	< 0.001
Alanine aminotransferase (U/L)	28 ± 12	32 ± 16	35 ± 19	3.924	0.021
Aspartate aminotransferase (U/L)	31 ± 14	36 ± 18	42 ± 23	6.785	0.001
Total cholesterol (mmol/L)	4.8 ± 1.1	4.6 ± 1.0	4.4 ± 1.2	3.154	0.044
Triglycerides (mmol/L)	1.9 ± 1.0	2.2 ± 1.3	2.0 ± 1.1	2.687	0.070
Electrolytes
Serum sodium (mmol/L)	139.2 ± 2.8	139.1 ± 3.2	138.8 ± 3.8	0.326	0.722
Serum potassium (mmol/L)	4.1 ± 0.4	4.0 ± 0.5	4.0 ± 0.6	0.847	0.430
Serum chloride (mmol/L)	102.5 ± 3.8	101.9 ± 4.1	100.7 ± 4.9	4.126	0.017
Serum calcium (mmol/L)	2.38 ± 0.15	2.35 ± 0.18	2.29 ± 0.21	5.687	0.004
Serum phosphorus (mmol/L)	1.18 ± 0.24	1.22 ± 0.28	1.28 ± 0.32	2.845	0.060
Cardiac enzymes
Creatine kinase (U/L)	142 ± 52	156 ± 68	168 ± 75	3.847	0.022
Creatine kinase-MB (U/L)	16 ± 7	19 ± 9	22 ± 11	4.124	0.017
Lactate dehydrogenase (U/L)	198 ± 45	218 ± 58	235 ± 67	8.562	< 0.001
Other indicators
Prothrombin time (second)	12.8 ± 1.4	13.2 ± 1.8	14.1 ± 2.3	9.234	< 0.001
Activated partial thromboplastin time (second)	31.5 ± 4.2	33.1 ± 5.6	36.8 ± 7.1	15.647	< 0.001
Troponin I (ng/mL)	0.03 ± 0.04	0.06 ± 0.09	0.09 ± 0.15	6.147	0.002
HbA1c (%)	6.2 ± 1.1	6.8 ± 1.4	7.5 ± 1.8	15.832	< 0.001
hs-CRP (mg/L)	3.2 ± 2.1	5.8 ± 3.4	8.9 ± 4.7	42.578	< 0.001
Homocysteine (μmol/L)	12.4 ± 3.8	15.7 ± 4.9	19.3 ± 6.2	36.124	< 0.001
BNP (pg/mL)	156 ± 89	234 ± 156	387 ± 234	28.964	< 0.001

BNP: B-type natriuretic peptide; HbA1c: Glycated hemoglobin; hs-CRP: High-sensitivity C-reactive protein.

Table 4 Changes in depression assessment scale scores over time among different age groups, mean ± SD

Time point	Young group (n = 68)	Middle-aged group (n = 124)	Elderly group (n = 108)	F value	P value
HAMD-17 total score
At discharge	9.2 ± 4.5	9.8 ± 5.1	10.4 ± 5.6	1.247	0.289
1-month post-discharge	12.8 ± 5.2	13.5 ± 6.1	12.9 ± 5.8	1.156	0.316
3-month post-discharge	10.4 ± 4.8	14.2 ± 6.3	16.1 ± 7.2	18.542	< 0.001
6-month post-discharge	10.1 ± 4.3	12.5 ± 5.9	15.8 ± 7.1	21.643	< 0.001
PHQ-9 total score
At discharge	6.1 ± 3.4	6.5 ± 3.8	6.9 ± 4.1	0.987	0.374
1-month post-discharge	8.5 ± 4.1	9.0 ± 4.8	8.6 ± 4.5	0.542	0.582
3-month post-discharge	6.9 ± 3.7	9.5 ± 5.2	10.8 ± 5.9	12.847	< 0.001
6-month post-discharge	6.8 ± 3.6	8.4 ± 4.7	10.6 ± 5.8	14.256	< 0.001

Repeated measures analysis of variance results: (1) Hamilton Depression Rating Scale-17 items total score: Time effect F = 28.452, P < 0.001; between-group effect F = 24.183, P < 0.001; time × group interaction effect F = 12.847, P < 0.001; and (2) Patient Health Questionnaire-9 items total score: Time effect F = 22.156, P < 0.001; between-group effect F = 19.247, P < 0.001; time × group interaction effect F = 9.156, P < 0.001. HAMD-17: Hamilton Depression Rating Scale-17 items; PHQ-9: Patient Health Questionnaire-9 items.

Table 5 Changes in Mini-Mental State Examination scores over time among different age groups, mean ± SD

Time point	Young group (n = 68)	Middle-aged group (n = 124)	Elderly group (n = 108)	F value	P value
At discharge	26.8 ± 2.4	25.1 ± 3.2	22.6 ± 4.1	32.847	< 0.001
1-month post-discharge	25.9 ± 2.7	24.2 ± 3.5	21.3 ± 4.4	28.156	< 0.001
3-month post-discharge	27.2 ± 2.3	25.8 ± 3.1	22.8 ± 4.0	35.742	< 0.001
6-month post-discharge	27.6 ± 2.1	26.3 ± 2.9	23.5 ± 3.8	38.924	< 0.001

Repeated measures analysis of variance results: Time effect F = 18.432, P < 0.001; between-group effect F = 45.628, P < 0.001; time × group interaction effect F = 5.247, P = 0.002.

Table 6 Functional status assessment results among different age groups, mean ± SD

Time point	Young group (n = 68)	Middle-aged group (n = 124)	Elderly group (n = 108)	F value	P value
Barthel index
At discharge	65.8 ± 19.2	58.4 ± 21.5	48.6 ± 24.1	14.273	< 0.001
1-month post-discharge	76.2 ± 17.4	67.8 ± 20.1	54.9 ± 23.8	21.847	< 0.001
3-month post-discharge	84.5 ± 15.8	74.2 ± 18.6	61.3 ± 22.4	31.526	< 0.001
6-month post-discharge	88.7 ± 13.2	78.9 ± 17.1	65.8 ± 21.6	36.841	< 0.001
mRS score
At discharge	2.6 ± 1.4	3.1 ± 1.5	3.4 ± 1.6	6.847	0.001
1-month post-discharge	2.2 ± 1.3	2.9 ± 1.4	3.1 ± 1.5	9.184	< 0.001
3-month post-discharge	1.8 ± 1.1	2.5 ± 1.3	2.8 ± 1.4	15.657	< 0.001
6-month post-discharge	1.6 ± 1.0	2.3 ± 1.2	2.6 ± 1.3	18.294	< 0.001

Repeated measures analysis of variance results: (1) Barthel index: Time effect F = 124.367, P < 0.001; between-group effect F = 38.156, P < 0.001; time × group interaction effect F = 9.584, P < 0.001; and (2) Modified Rankin Scale score: Time effect F = 67.429, P < 0.001; between-group effect F = 41.283, P < 0.001; time × group interaction effect F = 6.847, P < 0.001. mRS: Modified Rankin Scale.

Table 7 Multiple linear regression analysis of factors influencing Hamilton Depression Rating Scale-17 items scores at 6 months

Variable	Regression coefficient (β)	SE	Standardized coefficient	t value	P value	95%CI
Age	0.124	0.028	0.234	4.429	< 0.001	0.069-0.179
NIHSS score	0.346	0.075	0.287	4.613	< 0.001	0.198-0.494
hs-CRP	0.187	0.068	0.142	2.750	0.006	0.053-0.321
MMSE score	-0.308	0.098	-0.176	-3.143	0.002	-0.501 to -0.115
Infarct size (large)	1.426	0.634	0.108	2.249	0.025	0.179-2.673
Onset to admission time	0.048	0.023	0.087	2.087	0.038	0.003-0.093
Baseline depression score	0.285	0.098	0.156	2.908	0.004	0.092-0.478
Social support score	-0.142	0.067	-0.089	-2.119	0.035	-0.274 to 0.010

R² = 0.428, adjusted R² = 0.408, F = 19.267, P < 0.001, model passed collinearity diagnosis, all variance inflation factor values < 2.5. CI: Confidence interval; NIHSS: National Institutes of Health Stroke Scale; hs-CRP: High-sensitivity C-reactive protein; MMSE: Mini-Mental State Examination.

Table 8 Generalized estimating equation analysis of depression symptom treatment response among different age groups

Effect	Wald χ2	df	P value
Time	42.158	3	< 0.001
Age group	28.347	2	< 0.001
Time × age group	16.842	6	0.010
NIHSS score	12.546	1	< 0.001
MMSE score	9.327	1	0.002
hs-CRP	6.184	1	0.013
Infarct size	4.832	1	0.028
Baseline depression score	8.746	1	0.003

Contrast estimates (reference: Young group): (1) Middle-aged vs young group: β = 1.74, SE = 0.48, P < 0.001; (2) Elderly vs young group: β = 3.21, SE = 0.67, P < 0.001; and (3) Middle-aged vs elderly group: β = -1.47, SE = 0.56, P = 0.009. NIHSS: National Institutes of Health Stroke Scale; hs-CRP: High-sensitivity C-reactive protein; MMSE: Mini-Mental State Examination.