CSF TNF-α Levels Were Associated with Longitudinal Change in Brain Glucose Metabolism Among Non-Demented Older People

Purpose: Emerging studies have suggested that tumor necrosis factor-alpha (TNF-alpha) is implicated in the pathogenesis of Alzheimer's disease (AD), and that cerebral glucose hypometabolism is a key feature of AD. However, the association of CSF TNF-alpha levels with changes in cerebral glucose metabolism has not been studied among non-demented older people. Patients and Methods: At baseline, there were a total of 214 non-demented older people from Alzheimer's Disease Neuroimaging Initiative (ADNI) study. We examined the cross-sectional and longitudinal associations of CSF TNF-alpha with global cognition (as assessed by mini-mental state examination), verbal memory (as assessed by Rey Auditory Verbal Learning Test-total learning score), and cerebral glucose metabolism (as measured by FDF-PET). Linear mixed-effects models were used to examine the longitudinal association of CSF TNF-alpha with change in each outcome over time with adjustment of age, educational level, gender, and APOE4 status. Results: In the cross-sectional study, CSF TNF-alpha was negatively associated with MMSE scores, but not verbal memory or FDG-PET. In the longitudinal study, higher CSF TNF-alpha at baseline was associated with a faster decline in cerebral glucose metabolism, but not MMSE scores or RAVLT total learning scores. Conclusion: Higher CSF TNF-alpha levels were associated with a steeper decline in cerebral glucose metabolism among non-demented older people.

Automated summary

This study found that higher levels of TNF-alpha in cerebrospinal fluid were associated with a faster decline in cerebral glucose metabolism among non-demented older individuals, suggesting a potential role of TNF-alpha in the pathogenesis of Alzheimer's disease.