FDG-PET As An Independent Biomarker For Alzheimer's Biological Diagnosis

Objective: Recently,the 2018 National Institute on Aging-Alzheimer's Association(NIA-AA)proposed a research framework of a descriptive classification scheme for biomarkers used in Alzheimer's disease(AD)research.Reduced 18F-fluorodeoxyglucose-positron emission tomography(FDG-PET)brain metabolism was recognized as a biomarker of neurodegeneration in the recently proposed ATN framework for AD's biological definition.However,accumulating evidence suggested that FDG-PET was not only a biomarker of neuronal hypometabolism and neurodegeneration,it might be an independent biomarker of AD,which is denoted as “F” in the very study.Methods: A total of 551 A+T+ individuals from the Alzheimer's Disease Neuroimaging Initiative(ADNI)database were recruited and then further divided into four groups based on the biomarker positivity as 132 A+T+N-F-,102 A+T+N-F+,113 A+T+N+F-,and 204 A+T+N+F+.Frequency distributions of the groups were compared,as well as the clinical progression(measured by the longitudinal changes in cognition and brain structure)between every pair of F+ and F-groups.Kaplan-Meier(KM)analysis and multivariate Cox proportional hazard model to determine the progression from mild cognitive impairment(MCI)to AD dementia was performed.Results: The prevalence of A+T+N+F+ profile was 66.24% in clinically diagnosed AD dementia patients;similarly,the majority of individuals with reduced FDG-PET were AD dementia subjects(N-group: 34.3%,and N+ group: 51.0%).Among the 551 individuals that included,537 had at least one follow-up(varied from 1 to 8 years).Individuals in F+ groups performed worse and dropped faster in Mini-Mental State Examination(MMSE)scale and Rey auditory verbal learning test(RAVLT),and had faster shrinking middle temporal lobe than those in F-groups(all p < 0.05).Moreover,in MCI patients,reduced FDG-PET exerted 2.47 to 4.08-fold risk of AD dementia progression compared with those without significantly impaired FDG-PET;in N-group,the Hazard ratio(HR)=4.08,95% confidence interval(CI)=(1.96-8.48),p < 0.001,and in N+ group: HR = 2.47,95% CI =(1.55-3.93),p < 0.001.Conclusions and Significance: Taken together,the findings,as set forth,from the very study,suggest that A+T+ individuals with reduced brain FDG uptake on PET have worse cognition,accelerated brain atrophy and an increased likelihood of progression from MCI to AD dementia.Based on the analyses,separating FDG-PET from “N” biomarker to build the ATN(F)system is necessary and well-founded.The analysis from this study could be a complement to the original ATN framework for AD's biological definition.