Retrospective analysis cognitive function changes in elderly depressive patients after gastrointestinal tumor surgery and exploration of cholinergic mechanism

Table 1 Univariate analysis of post-operative cognitive dysfunction in older patients with depression after surgery for a gastrointestinal tumor, n (%)

Variable	POCD group (n = 35)	Non-POCD group (n = 60)	t/χ2/Z	P value
Age (years)	75.2 ± 4.9	70.8 ± 5.6	-3.892	< 0.001
Male sex	18 (51.4)	34 (56.7)	0.256	0.613
BMI (kg/m2)	22.8 ± 3.5	23.3 ± 3.0	0.734	0.465
Education (year)	7.6 ± 3.5	9.0 ± 3.9	1.822	0.072
ASA grade (II/III)	20/15	43/17	1.438	0.230
Pre-operative HAMD score	21.1 ± 3.8	17.0 ± 3.9	-5.063	< 0.001
Pre-operative MMSE score	26.5 ± 1.6	27.0 ± 1.4	1.583	0.117
Pre-operative MoCA score	23.8 ± 2.3	24.5 ± 1.9	1.621	0.108
Hypertension	24 (68.6)	34 (56.7)	1.359	0.244
Diabetes	14 (40.0)	17 (28.3)	1.441	0.230
Tumor site (gastric/colorectal)	17/18	24/36	0.383	0.536
TNM stage (I-II/III)	19/16	40/20	1.186	0.276
Laparoscopic approach	22 (62.9)	45 (75.0)	1.655	0.198
Duration of surgery (minute)	205.7 ± 48.1	169.2 ± 38.5	-4.052	< 0.001
Intra-operative blood loss (mL)	200 (150, 250)	120 (80, 180)	-4.125	< 0.001
Intra-operative anticholinergic use	17 (48.6)	11 (18.3)	9.952	0.002
24-hour post-operative VAS score	5.1 ± 1.1	4.2 ± 1.1	-3.852	< 0.001
Post-operative infection	9 (25.7)	6 (10.0)	4.183	0.041
Pre-operative IL-6 (pg/mL)	5.6 [4.1, 7.8]	4.3 [2.9, 5.7]	-2.891	0.004
Post-operative IL-6 (pg/mL)	42.3 [31.5, 55.2]	20.1 [15.3, 28.4]	-5.234	< 0.001
Pre-operative TNF-α (pg/mL)	7.1 [5.6, 9.3]	5.7 [4.3, 7.2]	-2.456	0.014
Post-operative TNF-α (pg/mL)	26.8 [19.4, 35.7]	13.8 [9.6, 19.2]	-4.987	< 0.001
Pre-operative CHE (U/L)	6 450 ± 1 380	7 080 ± 1 150	2.345	0.021
Post-operative CHE (U/L)	4 520 ± 1 280	5 820 ± 1 360	4.892	< 0.001
IL-6 change (%)	655.4 ± 189.3	367.4 ± 120.6	-8.123	< 0.001
TNF-α change (%)	277.6 ± 95.8	142.1 ± 63.5	-7.856	< 0.001
CHE change (%)	-29.8 ± 10.2	-17.8 ± 6.9	-6.234	< 0.001

POCD: Post-operative cognitive dysfunction; BMI: Body mass index; ASA: American Society of Anesthesiologists; HAMD: Hamilton Depression Rating Scale; MMSE: Mini-Mental State Examination; MoCA: Montreal Cognitive Assessment; VAS: Visual Analog Scale; IL-6: Interleukin-6; TNF-α: Tumor necrosis factor-alpha; CHE: Cholinesterase.

Table 2 Multivariate logistic regression analysis variable assignment

Independent variable	Coding instruction	Variable type	Reference group/unit
Age	Actual value (years)	Continuous	Per 1-year increase
Pre-operative HAMD score	Actual value (points)	Continuous	Per 1-point increase
Operative time	Actual value (minute)	Continuous	Per 10-minute increase
Intra-operative blood loss	Actual value (mL)	Continuous	Per 50-mL increase
Intra-operative anticholinergic use	0 = no, 1 = yes	Binary	Reference: No use (0)
24-hour post-operative VAS score	Actual value (points)	Continuous	Per 1-point increase
Post-operative infection	0 = no, 1 = yes	Binary	Reference: No infection (0)
Pre-operative IL-6	Actual value (pg/mL)	Continuous	Per 1 pg/mL increase
Post-operative IL-6	Actual value (pg/mL)	Continuous	Per 1 pg/mL increase
IL-6 change rate	(Post-operative - pre-operative)/pre-operative × 100%	Continuous	Per 10% increase
Pre-operative TNF-α	Actual value (pg/mL)	Continuous	Per 1 pg/mL increase
Post-operative TNF-α	Actual value (pg/mL)	Continuous	Per 1 pg/mL increase
TNF-α change rate	(Post-operative - pre-operative)/pre-operative × 100%	Continuous	Per 10% increase
Pre-operative CHE activity	Actual value (U/L)	Continuous	Per 100 U/L increase
Post-operative CHE activity	Actual value (U/L)	Continuous	Per 100 U/L increase
CHE change rate	(Post-operative - pre-operative)/pre-operative × 100%	Continuous	Per 1% increase

HAMD: Hamilton Depression Rating Scale; VAS: Visual Analog Scale; IL-6: Interleukin-6; TNF-α: Tumor necrosis factor-alpha; CHE: Cholinesterase.

Table 3 Multivariate logistic regression analysis of post-operative cognitive dysfunction in older patients with depression after surgery for a gastrointestinal tumor

Variable (unit increment)	β	SE	Wald χ2	P value	OR	95%CI
Age (per 1 year)	0.13	0.05	6.76	0.009	1.14	1.03-1.26
Pre-operative HAMD score (per 1 point)	0.18	0.06	9.00	0.003	1.20	1.07-1.35
Duration of surgery (per 10 minutes)	0.09	0.03	9.00	0.003	1.01	1.00-1.02
Intra-operative anticholinergic use (yes vs no)	1.18	0.42	7.88	0.005	3.25	1.43-7.38
Post-operative IL-6 changes rate (per 10%)	0.05	0.02	6.25	0.012	1.05	1.01-1.09
Intra-operative blood loss (per 50 mL)	0.08	0.05	2.56	0.110	1.08	0.98-1.19
24-hour post-operative VAS score (per 1 point)	0.12	0.08	2.25	0.134	1.13	0.96-1.32
Post-operative infection (yes vs no)	0.65	0.48	1.83	0.176	1.92	0.75-4.91
Pre-operative IL-6 (per 1 pg/mL)	0.04	0.03	1.78	0.182	1.04	0.98-1.10
Post-operative TNF-α change rate (per 10%)	0.02	0.02	1.00	0.317	1.02	0.98-1.06
Pre-operative CHE (per 100 U/L)	-0.01	0.01	1.00	0.317	0.99	0.97-1.01
Post-operative CHE activity (per 100 U/L)	-0.02	0.02	1.00	0.317	0.98	0.94-1.02
Post-operative TNF-α (per 1 pg/mL)	0.01	0.02	0.25	0.617	1.01	0.97-1.05
Pre-operative TNF-α (per 1 pg/mL)	0.01	0.03	0.11	0.740	1.01	0.96-1.06
CHE change rate (per 1%)	-0.01	0.03	0.11	0.740	0.99	0.94-1.04
Constant	-20.85	5.23	15.89	< 0.001	0.00	-

HAMD: Hamilton Depression Rating Scale; VAS: Visual Analog Scale; IL-6: Interleukin-6; TNF-α: Tumor necrosis factor-alpha; CHE: Cholinesterase.

Table 4 Mediation effect analysis of the inflammatory mediation model and the cholinergic mediation model

Model	Pathway	Effect estimates	Boot SE	Boot 95%LLCI	Boot 95%ULCI	Percentage mediated (%)
Inflammatory mediator	HAMD to IL-6 to MoCA	-0.098	0.040	-0.188	-0.032	19.7
Cholinergic mediator	HAMD to CHE to MoCA	-0.085	0.036	-0.169	-0.025	17.2

95%LLCI: 95% low limit confidence interval; 95%ULCI: 95% upper limit confidence interval; HAMD: Hamilton Depression Rating Scale; IL-6: Interleukin-6; MoCA: Montreal Cognitive Assessment; CHE: Cholinesterase.