Perioperative levels of IL8 and IL18, but not IL6, are associated with nucleus basalis magnocellularis atrophy three months after surgery

Medical Laboratory Science Geriatrics Rheumatology and Immunology Neurology Basic Medical Sciences Medical Imaging Medicine
nucleus basalis magnocellularis acetylcholine interleukins surgery atrophy neurodegeneration

Association Study of Perioperative IL8 and IL18 Levels with Brain Basal Ganglia Atrophy Three Months After Surgery

Background

In recent years, an increasing number of studies have shown that surgical procedures may accelerate brain atrophy. Meanwhile, the relationship between systemic inflammation and neurodegenerative diseases has also received considerable attention. This study hypothesizes that postoperative interleukin (IL) levels and perioperative changes in IL levels may be associated with postoperative atrophy of the Nucleus Basalis Magnocellularis (NBM). NBM is the main source of acetylcholine for the cerebral cortex. Previous studies have observed that cortical thickness may decrease, ventricles may enlarge, and hippocampal atrophy may accelerate after surgery, but these studies did not provide specific data on perioperative inflammatory parameters.

Paper Source

This research is from the Journal of Neuroimmune Pharmacology, Volume 19, Issue 10, 2024. The main authors include Maria Heinrich, Claudia Spies, Friedrich Borchers, Insa Feinkohl, and others, mostly from renowned European medical research institutions such as Charité-Universitätsmedizin Berlin. The study was received on March 26, 2023, and accepted on February 18, 2024.

Research Design and Methods

This study is a sub-project of the Biocog study, which aims to develop biomarker-based algorithms to predict postoperative delirium and cognitive dysfunction. The research was conducted in two major European medical centers, including European Caucasian patients aged ≥65 years with surgery duration ≥60 minutes. The research procedure is as follows:

Research Process

  1. Patient Selection and Inclusion: Included patients aged 65 and above, scheduled for major surgery with a Mini-Mental State Examination (MMSE) score above 23.

  2. Baseline Assessment: Including MRI scans, blood sample collection, cognitive tests, etc.

  3. Postoperative Assessment: Blood sample collection on the first day after surgery.

  4. Three-month Follow-up: Including repeated MRI scans and cognitive tests.

  5. Data Selection and Processing: Selected patients with follow-up MRI data and IL6, IL8, or IL18 measurement data.

Experimental Methods

  • Interleukin Measurement: Used commercial kits from companies such as BioVendor to measure IL levels in blood samples. Samples were stored at -80°C, and all measurements were performed according to standard operating procedures.

  • MRI Analysis: Used high-field MRI scanners for two 60-minute scans before surgery and three months after surgery, data processing used SPM12 software.

  • Cognitive Tests: Included a series of computerized tests such as CANTAB, Grooved Pegboard Test (GPT), and Trail Making Test (TMT).

  • Statistical Analysis: Used linear regression models to analyze the relationship between perioperative IL levels and NBM atrophy, and performed logistic regression analysis to predict potential markers of NBM atrophy.

Main Results

  1. Relationship between IL levels and NBM atrophy:

    • IL8 and IL18 levels on the first day after surgery were significantly associated with NBM atrophy, while IL6 showed no significant correlation.
    • For IL8 and IL18, every 2.72-fold increase in postoperative IL levels was associated with a 0.79% and 1.21% decrease in NBM volume, respectively.

  2. Relationship between preoperative IL levels and NBM atrophy:

    • Preoperative IL8 and IL18 levels were significantly associated with NBM atrophy, with a 2.72-fold increase in preoperative IL levels leading to a 2.3% and 1.6% decrease in NBM volume, respectively.
    • Perioperative changes in IL levels did not significantly affect NBM atrophy.

  3. Relationship between cognitive function and NBM volume:

    • NBM volume three months after surgery was significantly associated with better cognitive function performance, but NBM atrophy did not significantly affect perioperative changes in cognitive function.

  4. IL as a potential marker for predicting NBM atrophy:

    • Preoperative IL8 and IL18 levels showed weak discriminative ability in predicting NBM atrophy.

Research Conclusions and Significance

Scientific Value

This study reveals a significant relationship between postoperative IL8 and IL18 levels and NBM atrophy, and indicates that this relationship is mainly driven by preoperative chronic inflammation rather than acute perioperative inflammatory responses. The study is the first to link perioperative inflammation with postoperative brain atrophy, providing a possible pathological mechanism for postoperative neurocognitive disorders.

Application Value

The results suggest that patients with high preoperative inflammation levels may require special management to reduce the risk of postoperative neurodegenerative changes. Additionally, the association between postoperative NBM atrophy and cognitive function suggests potential clinical intervention pathways, such as regulating inflammatory responses to protect the brain.

Research Highlights

  • First systematic analysis of the relationship between perioperative inflammation and NBM atrophy.
  • Comprehensive analysis using multiple biomarkers and imaging data.
  • Identification of the contribution of preoperative chronic low-grade inflammation to postoperative brain atrophy.