Increase in Core Body Temperature of Alzheimer’s Disease Patients as a Possible Indicator of Chronic Neuroinflammation: A Meta-Analysis

Abstract

Background: Neuroinflammation contributes to the pathogenesis of Alzheimer’s disease (AD). Increased pro-inflammatory cytokine levels have been reported in the brain and cerebro-spinal fluid of individuals affected by this neurodegenerative disorder. These same cytokines, including interleukin -1, interleukin-6 and tumor necrosis factor-α, are also believed to be involved in thermoregulation. Furthermore, their effects are thought to be mediated through the induction of cyclooxygenases resulting in increased production of inflammatory prostaglandins. Such increases have been observed in AD brains. We hypothesized that these increased levels of inflammatory mediators could lead to an increase in core body temperature in AD patients. Objective: To determine whether clinical signs of AD are accompanied by an increase in core body temperature. Methods: Analysis of the scientific literature identified six studies that used continuous rectal measurements of core body temperature in AD and control patients. Meta-analysis was performed on these published data. Results: Meta-analysis showed that the mean core body temperature in AD patients was significantly increased by 0.10°C when compared to healthy elderly subjects. The two-sided p value was 0.0355, and the 95% confidence interval was 0.0068–0.1950. The severity of AD pathology did not appear to contribute significantly (p = 0.235) to the heterogeneity in the core body temperature among different groups of AD patients. Conclusion: The significant increase in core body temperature in AD patients could be a direct consequence of local inflammatory reactions in the brain. Although the changes observed are probably too small to be of any diagnostic value, these observations lend further support to the neuroinflammatory hypothesis of AD pathology.