CIMB, Vol. 44, Pages 6290-6305: Development of Post-Stroke Cognitive and Depressive Disturbances: Associations with Neurohumoral Indices

Author Contributions

Conceptualization, N.V.G.; methodology, T.A.D., M.Y.Z. and E.E.V.; statistical analysis, M.Y.Z. and A.A.Y.; validation, T.A.D.; formal analysis, M.Y.Z. and T.A.D.; investigation, M.Y.Z., T.A.D., E.E.V. and N.N.E.; resources, A.B.G.; data curation, A.B.G., N.V.G. and S.V.F.; writing—original draft preparation, N.V.G., M.Y.Z., and T.A.D.; writing—review and editing, N.V.G.; supervision, A.B.G. and N.V.G. All authors have read and agreed to the published version of the manuscript.

Abbreviations

ACTH, adrenocorticotropic hormone; ADL, Barthel Index for Activities of Daily Living; BDI, Beck Depression Inventory; HC, healthy control; HPA, hypothalamic-pituitary-adrenal; HAM, Hamilton Rating Scale for Depression; IL-6, interleukin-6; ischemic stroke, IS; HADS, Hospital Anxiety and Depression Scale; MoCA, Montreal Cognitive Assessment; mRS, Modified Rankine Scale; NIHSS, The National Institutes of Health Stroke Scale; PSCI, post-stroke cognitive impairment; PSDD, post-stroke depressive disorder; PSS, Perceived Stress Scale; SAMS, sympathoadrenal medullary system; SRRS, The Holmes and Rahe Stress Inventory, or Social Readjustment Rating Scale.

Figure 1. Time course of salivary cortisol (a), α-amylase (b), and serum IL-6 (c) within one year in IS patients and HC (CONTROL) group. Statistical differences between groups were assessed by Kruskal–Wallis ANOVA followed by post hoc Dunn’s test. # p < 0.1, * p < 0.05, *** p < 0.001, **** p < 0.0001. Kruskal–Wallis ANOVA: (a): p = 0.0002; (b): p = 0.0003, (c): p = 0.0001. HC, n = 32; patients after IS day 1, n = 45; day 30, n = 41; day 180, n = 33; day 365, n = 29.

Figure 1. Time course of salivary cortisol (a), α-amylase (b), and serum IL-6 (c) within one year in IS patients and HC (CONTROL) group. Statistical differences between groups were assessed by Kruskal–Wallis ANOVA followed by post hoc Dunn’s test. # p < 0.1, * p < 0.05, *** p < 0.001, **** p < 0.0001. Kruskal–Wallis ANOVA: (a): p = 0.0002; (b): p = 0.0003, (c): p = 0.0001. HC, n = 32; patients after IS day 1, n = 45; day 30, n = 41; day 180, n = 33; day 365, n = 29.

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Figure 2. Neurological deficit according to the NIHSS scale within one year after IS. Statistical differences between groups were assessed by one-way ANOVA (F (6, 285) =15.53, p = 0.0001) followed by the post hoc Tukey test. **** p < 0.0001. Patients after IS day 1, n = 45; day 30, n = 41, day 180, n = 33; day 365, n = 29.

Figure 2. Neurological deficit according to the NIHSS scale within one year after IS. Statistical differences between groups were assessed by one-way ANOVA (F (6, 285) =15.53, p = 0.0001) followed by the post hoc Tukey test. **** p < 0.0001. Patients after IS day 1, n = 45; day 30, n = 41, day 180, n = 33; day 365, n = 29.

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Figure 3. Time course of salivary cortisol (a), plasma ACTH (b), α-amylase (c), and serum IL-6 (d) within one year after IS. Statistical differences between groups were assessed by RM-ANOVA or by mixed-effects model ANOVA ((a): F (1.476, 36.89) = 5.352, p = 0.02; (b): F (1.919, 34.54) = 2.188, p = 0.13; (c): F (2.102, 48.35) = 7.659, p = 0.001; (d): F (2.393, 56.65) = 4.855, p = 0.008) followed by post hoc Tukey test. * p < 0.05, ** p < 0.01, *** p < 0.001.

Figure 3. Time course of salivary cortisol (a), plasma ACTH (b), α-amylase (c), and serum IL-6 (d) within one year after IS. Statistical differences between groups were assessed by RM-ANOVA or by mixed-effects model ANOVA ((a): F (1.476, 36.89) = 5.352, p = 0.02; (b): F (1.919, 34.54) = 2.188, p = 0.13; (c): F (2.102, 48.35) = 7.659, p = 0.001; (d): F (2.393, 56.65) = 4.855, p = 0.008) followed by post hoc Tukey test. * p < 0.05, ** p < 0.01, *** p < 0.001.

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Figure 4. Time course of MoCA scores (a) and NIHSS (b) in IS patients with and without PSCI. Differences between groups were assessed by RM-ANOVA or by mixed-effects model ANOVA ((a): F (3, 87) = 5.807, p = 0.001; (b): F (6, 177) = 0.9638, p = 0.45) followed by the post hoc Sidak test. MoCA scores for groups without (n = 17) and with PSCI (n = 16), p = 0.0012. NIHSS for groups without (n = 17) and with PSCI (n = 16), p = 0.5. * p < 0.05, **** p < 0.0001.

Figure 4. Time course of MoCA scores (a) and NIHSS (b) in IS patients with and without PSCI. Differences between groups were assessed by RM-ANOVA or by mixed-effects model ANOVA ((a): F (3, 87) = 5.807, p = 0.001; (b): F (6, 177) = 0.9638, p = 0.45) followed by the post hoc Sidak test. MoCA scores for groups without (n = 17) and with PSCI (n = 16), p = 0.0012. NIHSS for groups without (n = 17) and with PSCI (n = 16), p = 0.5. * p < 0.05, **** p < 0.0001.

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Figure 5. Changes in cortisol levels in blood serum (a) and saliva (b) in the groups of patients with and without cognitive impairment. Statistical differences between groups were assessed by RM-ANOVA or by mixed-effects model ANOVA ((a): F (3, 60) = 3.876, p = 0.013; (b): F (3, 71) = 2.464, p = 0.07) followed by post hoc analysis (Tukey test). # p < 0.1, * p < 0.05, ** p < 0.01. Group without cognitive decline (n = 11); group with cognitive decline (n = 11).

Figure 5. Changes in cortisol levels in blood serum (a) and saliva (b) in the groups of patients with and without cognitive impairment. Statistical differences between groups were assessed by RM-ANOVA or by mixed-effects model ANOVA ((a): F (3, 60) = 3.876, p = 0.013; (b): F (3, 71) = 2.464, p = 0.07) followed by post hoc analysis (Tukey test). # p < 0.1, * p < 0.05, ** p < 0.01. Group without cognitive decline (n = 11); group with cognitive decline (n = 11).

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Figure 6. Time course of NIHSS (a) and HADS scores (b) in patient groups with and without PSDD. NIHSS scale for groups without depressive disorder (n = 23) and with depressive disorder (n = 10) p = 0.6; HADS scale for the group without depressive disorder (n = 23) and with depressive disorder (n = 10) p = 0.04. Statistical differences between groups were assessed by RM-ANOVA or by mixed-effects model ANOVA ((a): F (6, 177) = 0.8, p = 0.57; (b): F (3, 87) = 2.844, p = 0.04) followed by post hoc analysis (Sidak test). ** p < 0.01, *** p < 0.001.

Figure 6. Time course of NIHSS (a) and HADS scores (b) in patient groups with and without PSDD. NIHSS scale for groups without depressive disorder (n = 23) and with depressive disorder (n = 10) p = 0.6; HADS scale for the group without depressive disorder (n = 23) and with depressive disorder (n = 10) p = 0.04. Statistical differences between groups were assessed by RM-ANOVA or by mixed-effects model ANOVA ((a): F (6, 177) = 0.8, p = 0.57; (b): F (3, 87) = 2.844, p = 0.04) followed by post hoc analysis (Sidak test). ** p < 0.01, *** p < 0.001.

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Figure 7. Time course of α-amylase in saliva (a) and IL-6 in blood serum (b) in groups of patients with and without PSDD. Statistical differences between groups were assessed by RM-ANOVA or mixed-effects model ANOVA ((a): F (3, 64) = 4.087, p = 0.01; (b): F (3, 62) = 3.789, p = 0.02) followed by post hoc analysis (Tukey test). * p < 0.05, ** p < 0.01,*** p < 0.001, **** p < 0.0001. Group with PSDD disorder (n = 9); group without PSDD (n = 21).

Figure 7. Time course of α-amylase in saliva (a) and IL-6 in blood serum (b) in groups of patients with and without PSDD. Statistical differences between groups were assessed by RM-ANOVA or mixed-effects model ANOVA ((a): F (3, 64) = 4.087, p = 0.01; (b): F (3, 62) = 3.789, p = 0.02) followed by post hoc analysis (Tukey test). * p < 0.05, ** p < 0.01,*** p < 0.001, **** p < 0.0001. Group with PSDD disorder (n = 9); group without PSDD (n = 21).

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