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

Pan Fu, Bihong Zhu, Yangping Huang On behalf of Alzheimer’s Disease Neuroimaging InitiativeDepartment of Neurology, Taizhou First People’s Hospital, Taizhou, Zhejiang, People’s Republic of ChinaCorrespondence: Yangping HuangDepartment of Neurology, Taizhou First People’s Hospital, 218 Hengjie Road, Huangyan District, Taizhou City, Zhejiang Province, People’s Republic of ChinaEmail hypnihao@163.comPurpose: 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: mild cognitive impairment, Alzheimer’s disease, TNF-α, cerebral glucose metabolism, FDG-PET