Circulating inflammatory biomarkers in relation to brain structural measurements in a non-demented elderly population

Gu, Yian; Vorburger, Robert S.; Scarmeas, Nikolaos; Luchsinger, José A.; Manly, Jennifer J.; Schupf, Nicole; Mayeux, Richard; Brickman, Adam M.

doi:10.1016/j.bbi.2017.04.022

Cited by 71 publications

(47 citation statements)

References 83 publications

(96 reference statements)

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“…These results are in line with Rullmann et al (28) showing no significant association between GM/WM densities or WM diffusivity parameters pre-surgery and changes in CRP post-surgery. Additionally, a recent study reported that circulating CRP and IL-6 levels were not associated with WM integrity parameters or longitudinal change of brain volumes in non-demented elderly participants (54). Even if recent evidence supports the presence of neuroinflammation in the hippocampus, amygdala, cortex and cerebellum in obesity (21), our study revealed no significant association between changes in GM density and postoperative reduction in inflammatory markers.…”

Section: Discussioncontrasting

confidence: 85%

Neuroanatomical Changes in White and Grey Matter after Sleeve Gastrectomy

Michaud

Dadar

Pelletier

et al. 2019

Preprint

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Background: MRI studies show that obese adults have reduced grey (GM) and white matter (WM) tissue density as well as altered WM integrity. It remains to be examined if bariatric surgery induces structural brain changes. The aim of this study is to characterize GM and WM density changes in a longitudinal setting, comparing pre-and post-operation and to determine whether these changes are related to inflammation and cardiometabolic markers. Methods: 29 severely obese participants (age: 45.9±7.8 years) scheduled to undergo sleeve gastrectomy (SG) were recruited. High-resolution T1-weighted anatomical images were acquired 1 month prior to as well as 4 and 12 months after surgery. GM and WM densities were quantified using voxel-based morphometry (VBM). Circulating lipid profile, glucose, insulin and inflammatory markers (interleukin (IL)-6, C-reactive protein (CRP) and lipopolysaccharide-binding protein (LBP) were measured at each time point.A linear mixed effect model was used to compare brain changes before and after SG, controlling for age, gender, initial BMI and diabetic status. To assess the associations between changes in adiposity, metabolism and inflammation and changes in GM or WM density, the mean GM and WM densities were extracted across all the participants using atlas, and linear mixed-effect models were used. Results: As expected, weight, BMI, waist circumference and neck circumference significantly decreased after SG compared with baseline (p<0.001 for all). A widespread increase in WM density was observed after surgery, particularly in the cerebellum, brain stem, cerebellar peduncle, cingulum, corpus callosum and corona radiata (p<0.05, after FDR correction). Significant increases in GM density were observed 4 months after SG compared to baseline in several brain regions such as the bilateral occipital cortex, temporal cortex, precentral gyrus and cerebellum as Michaud et al. 2019, page 3 well as right fusiform gyrus, right hippocampus and right insula. These GM and WM increases were more pronounced and widespread after 12 months and were significantly associated with post-operative weight loss and the improvement of metabolic alterations.Our linear mixed-effect models also showed strong associations between post-operative reductions in LBP, a marker of inflammation, and increased WM density. To confirm our results, we tested whether the peak of each significant region showed BMI-related differences in an independent dataset (Human Connectome Project). We matched a group of severely obese individuals with a group of lean individuals for age, gender and ethnicity.Severe obesity was associated with reduced WM density in the brain stem and cerebellar peduncle as well as reduced GM density in cerebellum, regions that significantly changed after surgery (p<0.01 for all clusters). Conclusions: Bariatric surgery-induced weight loss and improvement in metabolic alterations is associated with widespread increases in WM and GM densities. These post-operative changes overlapped with baseline brain difference...

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Section: Discussioncontrasting

confidence: 85%

Neuroanatomical Changes in White and Grey Matter after Sleeve Gastrectomy

Michaud

Dadar

Pelletier

et al. 2019

Preprint

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“…have linked systemic inflammatory responses to the vulnerability of the aging brain. 9,10,49,50 Several lines of evidence suggest that CRP plays a critical role in these interactions. Epidemiological studies in elderly population cohorts show that higher serum CRP levels are positively associated with white matter hyperintensities on neuroimaging and progression of cerebral small-vessel disease.…”

Section: Discussionmentioning

confidence: 99%

The trajectory of C‐reactive protein serum levels in older hip fracture patients with postoperative delirium

Slor

Witlox

Adamis

et al. 2019

Int J Geriat Psychiatry

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Objectives Important precipitating risk factors for delirium such as infections, vascular disorders, and surgery are accompanied by a systemic inflammatory response. Systemic inflammatory mediators can induce delirium in susceptible individuals. Little is known about the trajectory of systemic inflammatory markers and their role in the development and outcome of delirium. Methods This is a prospective cohort study of older patients undergoing acute surgery for hip fracture. Baseline characteristics were assessed preoperatively. During hospital admission, presence of delirium was assessed daily according to the Confusion Assessment Method criteria. This study compared the trajectory of serum levels of the C‐reactive protein (CRP) between people with and without postoperative delirium. Blood samples were taken at baseline and at postoperative day 1 through postoperative day 5. Results Forty‐one out of 121 patients developed postoperative delirium after hip fracture surgery. Longitudinal analysis of the trajectory of serum CRP levels using the Generalized Estimating Equations (GEE) method identified that higher CRP levels were associated with postoperative delirium. CRP levels were higher from postoperative day 2 through postoperative day 5. No significant differences in serum CRP levels were found when we compared patients with short (1‐2 days) and more prolonged delirium (3 days or more). Conclusions Delirium is associated with an increased systemic inflammatory response, and our results suggest that CRP plays a role in the underlying (inflammatory‐vascular) pathological pathway of postoperative delirium.

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“…We aimed to capture inflammation that has been well documented in AD states (Table ). Our analytes relate to inflammasome formation (IL1β) and systemic inflammation (IL‐6, TNFα, IP‐10, IL‐17A) . To capture neuroinflammation, we quantified a marker of astrocytic activation (GFAP) .…”

Section: Introductionmentioning

confidence: 99%

Plasma biomarkers of astrocytic and neuronal dysfunction in early‐ and late‐onset Alzheimer's disease

Elahi

Casaletto

Joie

et al. 2020

Alzheimer's & Dementia

158

107

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Introduction We investigated plasma proteomic markers of astrocytopathy, brain degeneration, plasticity, and inflammation in sporadic early‐onset versus late‐onset Alzheimer's disease (EOAD and LOAD). Methods Plasma was analyzed using ultra‐sensitive immuno‐based assays from 33 EOAD, 30 LOAD, and 36 functionally normal older adults. Results Principle component analyses identified 3 factors: trophic (BDNF, VEGF, TGFβ), degenerative (GFAP, NfL), and inflammatory (TNFα, IL‐6, IP‐10, IL‐10). Trophic factor was elevated in both AD groups and associated with cognition and gray matter volumes. Degenerative factor was elevated in EOAD, with higher levels associated with worse functioning in this group. Biomarkers of inflammation were not significantly different between groups and were only associated with age. Disucssion Plasma proteomic biomarkers provide novel means of investigating molecular processes in vivo and their contributions to clinical outcomes. We present initial investigations of several of these fluid biomarkers, capturing aspects of astrocytopathy, neuronal injury, cellular plasticity, and inflammation in EOAD versus LOAD.

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Circulating inflammatory biomarkers in relation to brain structural measurements in a non-demented elderly population

Cited by 71 publications

References 83 publications

Neuroanatomical Changes in White and Grey Matter after Sleeve Gastrectomy

Neuroanatomical Changes in White and Grey Matter after Sleeve Gastrectomy

The trajectory of C‐reactive protein serum levels in older hip fracture patients with postoperative delirium

Plasma biomarkers of astrocytic and neuronal dysfunction in early‐ and late‐onset Alzheimer's disease

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