Table 4.

Meta-analyses examining associations of cortisol and immune markers with cognitive function in clinical populations.

Author	Population	Measure	Findings
Morrens et al. (2022)	Psychotic and mood disorders	Immune markers and cognitive dysfunction	In analysis including all psychotic and mood disorders patients, proinflammatory markers were negatively correlated with global cognitive performance (k = 53, r = −0.076 (95% CI: −0.126 to −0.027) p = 0.003), verbal memory (k = 36, r = −0.089 (95% CI: −0.148 to −0.029) p = 0.004), visual memory (k = 15, r = −0.036 (95% CI: −0.049 to −0.023) p = <0.001), working memory (k = 23, r = −0.065 (95% CI: −0.118 to −0.011) p = 0.018), and processing speed (k = 20, r = −0.082 (95% CI: −0.151 to −0.012) p = 0.022) but were not significantly associated with attention (k = 27, r = −0.027 (95% CI: −0.091 to 0.037) p = 0.412), reasoning (k = 37, r = −0.025 (95% CI: −0.096 to 0.045) p = 0.378), or language (k = 21, r = −0.052 (95% CI: −0.144 to 0.041) p = 0.271). Anti-inflammatory markers were not significantly associated with global cognitive performance (k = 5, r = 0.067 (95% CI: −0.069 to 0.201) p = 0.334), verbal memory (k = 3, r = −0.074 (95% CI: −0.240 to 0.097) p = 0.398), processing speed (k = 4, r = 0.125 (95% CI: −0.030 to 0.275) p = 0.113), or reasoning (k = 4, r = −0.002 (95% CI: −0.245 to 0.241) p = 0.985). In analyses restricted to patients with schizophrenia, proinflammatory markers were negatively correlated with visual memory (k = 9, r = −0.142 (95% CI: −0.241 to −0.040) p = 0.006) with no significant associations observed with global cognitive performance (k = 27, r = −0.036 (95% CI: −0.113 to 0.042) p = 0.370), verbal memory (k = 22, r = −0.072 (95% CI: −0.172 to 0.030) p = 0.168), working memory (k = 16, r = 0.002 (95% CI: −0.071 to 0.076) p = 0.947), attention (k = 16, r = −0.071 (95% CI: −0.164 to 0.022) p = 0.135) Processing speed (k = 12, r = −0.080 (95% CI: −0.171 to 0.013) p = 0.090), reasoning (k = 18, r = −0.026 (95% CI: −0.096 to 0.045) p = 0.476), or language (k = 16, r = −0.033 (95% CI: −0.137 to 0.072) p = 0.538).
Redddi Patlola et al. (2023)	Schizophrenia	Inflammatory biomarkers and cognitive dysfunction	IL-6 was significantly associated with attention and processing speed (k = 7, μ = -0.173, (95% CI: -0.302 to -0.045) p = 0.008), executive functioning (k = 8, μ = -0.181, (95% CI: -0.266 to -0.097) p < 0.001), verbal learning and memory (k = 7, μ = -0.169, (95% CI: -0.307 to -0.032) p = 0.016), and working memory (k = 6, μ = -0.136, (95% CI: -0.270 to -0.003) p = 0.046), but not with visual learning and memory (k = 4, μ = -0.08, (95% CI: -0.227 to 0.065) p = 0.279). TNF-α levels were significantly associated with attention and processing speed (k = 9, μ = -0.198, (95% CI: -0.341 to -0.055) p = 0.007), executive functioning (k = 9, μ = -0.188, (95% CI: -0.324 to -0.052) p = 0.007), and visual learning and memory (k = 4, μ = -0.38, (95% CI: -0.538 to -0.222) p < 0.001) but not with verbal learning and memory (k = 7, μ = -0.118, (95% CI: -0.324 to 0.089) p = 0.610) or working memory (k = 6, μ = -0.15, (95%CI:-0.367 to 0.067) p = 0.175). IL-1β levels significantly associated with attention and processing speed (k = 4, μ = -0.372, (95% CI: -0.619 to -0.125) p = 0.003), visual learning and memory (k = 3, μ = -0.454, (95% CI: -0.627 to -0.282) p < 0.001), and working memory (k = 3, μ = -0.476, (95% CI: -0.649 to -0.303) p < 0.001). CRP levels significantly associated with attention and processing speed (k = 9, μ = -0.299, (95% CI:-0.494 to -0.103) p = 0.003), verbal learning and memory (k = 7, μ = -0.278, (95% CI: -0.356 to -0.20) p < 0.001), visual learning and memory (k = 5, μ = -0.311, (95% CI: -0.538 to -0.084) p = 0.007), working memory (k = 6, μ = -0.168, (95% CI: -0.315 to -0.022) p = 0.024), but not executive functioning (k = 5, μ = -0.159, (95% CI: -0.502 to 0.184) p = 0.364).
Zheng et al. (2020)	Alzheimer’s disease and controls	Cortisol secretion and cognitive decline	Compared to cognitively-normal controls, Alzheimer’s disease patients showed significantly increased morning cortisol levels when measured in blood (k = 38, g = 0.422 (95% CI: CI: 0.289 to 0.556) p < 0.001), saliva (k = 5, g = 0.540, (95% CI: 0.276 to 0.804) p < 0.001) and CSF (k = 5, g = 0.565 (95% CI: 0.198 to 0.931) p = 0.003). In contrast, MCI patients showed no differences in cortisol levels when measured in blood (k = 5, g = 0.002 (95% CI: -0.162 to 0.167) p = 0.978) or saliva (k = 10, g = 0.106 (95% CI: -0.047 to 0.258) p = 0.174) when compared to cognitively-normal controls but showed elevations in CSF cortisol (k = 4, g = 0.309 (95% CI: 0.125 to 0.492) p = 0.001).

Abbreviations: k: number of effect sizes included in analysis; g: Hedges g effect size; SMD: standardised mean difference; CI: confidence interval; CRP: C-reactive protein; IL: interleukin; IFN: interferon; TNF: tumour necrosis factor; CSF: cerebrospinal fluid; MCI: mild cognitive impairment.