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

Abstract

Purpose: Emerging studies have suggested that tumor necrosis factor-alpha (TNF-α) 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-α 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-α 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- α 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-α was negatively associated with MMSE scores, but not verbal memory or FDG-PET. In the longitudinal study, higher CSF TNF- α 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-α levels were associated with a steeper decline in cerebral glucose metabolism among non-demented older people.

Keywords: Alzheimer’s disease; FDG-PET; TNF-α; cerebral glucose metabolism; mild cognitive impairment.

Figure 1

Associations of CSF TNF- α with change in AD-related markers over time. Higher CSF TNF-α levels were associated with a faster decline in FDG SUVR (estimate = −0.0089, se= 0.0043, p value = 0.0385, (C) but not MMSE scores (estimate = −0.1246, se= 0.1592, p value = 0.4341, (A) or RAVLT total learning scores (estimate = 0.0105, se= 0.2333, p value = 0.9641, (B).

Figure 2

Associations of CSF TNF- α with change in FDG SUVR over time in the amyloid negative MCI subjects and amyloid positive MCI subjects. In the amyloid-positive group, CSF TNF-α was not associated with change in FDG over time in MCI (p > 0.05, A). However, higher CSF TNF-α levels were associated with a steeper decline in FDG SUVR in the amyloid-negative group (p < 0.05, B).