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Worsening cognitive performance is associated with increases in systemic inflammation following hematopoietic cell transplantation.

ABSTRACT: BACKGROUND:Cognitive decline is a frequently cited concern among patients receiving hematopoietic cell transplantation (HCT), and patients often experience neurocognitive deficits (i.e., stable or worsening neurocognitive performance) throughout the transplant course. Deficits can be most severe during the acute transplant period (i.e., 90?days after transplantation), when patients also typically experience elevated systemic levels of inflammation. Previous studies have identified inflammation as a likely mechanism underlying neurocognitive deficits, primarily in women with breast cancer; however, longitudinal studies have been limited. In this study, our aim was to evaluate the relationship between changes in systemic inflammation and changes in cognition from pre- to post-transplant in patients receiving allogeneic HCT. METHODS:Patients scheduled for allogeneic HCT (n?=?85) were assessed prior to HCT and 90?days after HCT. Biomarkers of inflammation included IL-6, sTNF-RII, CRP, and IL-1ra, which have been previously associated with neurocognitive deficits in cancer patients. Patients completed neuropsychological testing and self-report questionnaires. RESULTS:Mixed models demonstrated that from pre- to post-HCT, increases in IL-6 and sTNF-RII were associated with neurocognitive deficits, and decreases in CRP were associated with better neurocognitive performance. There were no significant associations between changes in inflammation and self-reported cognitive performance. CONCLUSIONS:Our findings are the first to our knowledge to report a robust relationship between increasing inflammation and neurocognitive deficits from pre- to post-HCT. Additional studies are needed to confirm these findings in a larger sample.

SUBMITTER: Hoogland AI

PROVIDER: S-EPMC6660393 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Worsening cognitive performance is associated with increases in systemic inflammation following hematopoietic cell transplantation.

Hoogland Aasha I AI Nelson Ashley M AM Gonzalez Brian D BD Small Brent J BJ Breen Elizabeth C EC Sutton Steve K SK Syrjala Karen L KL Bower Julienne E JE Pidala Joseph J Booth-Jones Margaret M Jacobsen Paul B PB Jim Heather S L HSL

Brain, behavior, and immunity 20190403

<h4>Background</h4>Cognitive decline is a frequently cited concern among patients receiving hematopoietic cell transplantation (HCT), and patients often experience neurocognitive deficits (i.e., stable or worsening neurocognitive performance) throughout the transplant course. Deficits can be most severe during the acute transplant period (i.e., 90 days after transplantation), when patients also typically experience elevated systemic levels of inflammation. Previous studies have identified inflam ...[more]

PMID: 30953767

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Project description:Objectives/Background: Systemic inflammation can affect cognitive performance over time. The current study examined associations between systemic inflammation and cognitive performance among African Americans and Whites urban adults, stratifying by sex, and age group and by race. Patients/Methods: Among 1,555-1,719 White and African-American urban adults [Agebase: 30-64y, 2004-2013, mean±SD follow-up time(y): 4.64 ± 0.93y], conducted linear mixed-effects regression models were conducted to test associations of inflammatory markers [C-reactive protein, Erythrocyte Sedimentation Rate (ESR), albumin, iron, and an inflammation composite score (ICS)] with longitudinal cognitive performance. Results: Among key findings, CRP was linked to poorer baseline mental status among younger women (≤50y, γ01 = -0.03 ± 0.01, p = 0.002) and poorer attention in older women (>50y, γ01 = -0.024 ± 0.007, p < 0.004) and African-Americans (γ01 = -0.029 ± 0.008, p < 0.001). ESR was related to faster decline on verbal memory among older men (>50y, γ11 = -0.008 ± 0.003, P = 0.009); with poorer performance on attention tests overall (γ01 = -0.010 ± 0.003, P = 0.003) and among African-Americans (γ01 = -0.013 ± 0.004, P = 0.002); on verbal fluency among older women (>50y,γ01 = -0.037 ± 0.013, P = 0.004) and on executive function: overall (γ01 = +0.62 ± 0.21, P = 0.004), older men (>50y, γ01 = +1.69 ± 0.53, P = 0.001) and African-Americans (γ01 = +0.84 ± 0.28, P = 0.002). Albumin was linked to slower attention decline among older men (>50y, γ11 = +0.329 ± 0.103, P = 0.009), over-time improvement in executive function overall (γ11 = -6.00 ± 2.26, P = 0.008), and better baseline psychomotor speed among African-Americans (γ01 = +0.56 ± 0.19, P = 0.003). Finally, ICS predicted faster decline on visual memory/visuo-constructive abilities among older men (>50y, γ11 = +0.17 ± 0.06, p = 0.003). Conclusion: In sum, strong associations between systemic inflammation and longitudinal cognitive performance were detected, largely among older individuals (>50y) and African-Americans. Randomized trials targeting inflammation are warranted.

Project description:PurposeHematopoietic stem cell transplant (HSCT) recipients are at risk for cognitive decline. Cross-sectional studies show patients' complaints of cognitive decline do not correlate well with concurrently measured objective neuropsychological performance, but rather with emotional variables and health-related quality of life. This longitudinal study investigated whether patient self-report of cognitive status would be concordant with objectively measured neuropsychological performance after accounting for change from their own pre-transplant objective baseline.MethodsPre-HSCT and at 30 and 100 days post-HSCT, 46 patients underwent computerized neuropsychological testing (CogState) and completed surveys assessing patient-reported cognitive complaints, emotional symptoms (depression, anxiety), sleep quality, daytime sleepiness, and physical and functional well-being. Correlations were calculated between cognitive complaints and neuropsychological performance (at each time-point and across time-points), as well as all other patient-reported variables.ResultsPatient-reported cognitive complaints were largely independent of concurrently assessed objective neuropsychological performance. Uniquely, our longitudinal data demonstrated significant medium to large effect size associations between subjective cognitive complaints post-HSCT with objectively measured change from pre-HSCT in attention, visual learning, and working memory (p < .05-.01). Subjective cognitive complaints post-HSCT were also associated with depression, anxiety, daytime sleepiness and physical well-being (p < .05-.001).ConclusionsPatients appear better able to assess their cognitive functioning relative to their own baseline and changes across time rather than relative to community norms. Thus, patient complaints of cognitive compromise justify further in-depth neuropsychological, emotional, and functional assessment. Future research into relationships between cognitive complaints and neuropsychological performance should account for changes in performance over time.

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Worsening cognitive performance is associated with increases in systemic inflammation following hematopoietic cell transplantation.

Publications

Worsening cognitive performance is associated with increases in systemic inflammation following hematopoietic cell transplantation.

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