Reduced F-fluorodeoxyglucose-positron emission tomography (FDG-PET) brain metabolism was recognized as a biomarker of neurodegeneration in the recently proposed ATN framework for Alzheimer's disease (AD) biological definition. However, accumulating evidence suggested it is an independent biomarker, which is denoted as "F" in the very study. A total of 551 A+T+ individuals from the Alzheimer's Disease Neuroimaging Initiative 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, and mild cognitive impairment (MCI) to AD dementia conversion between every pair of F+ and F- groups. 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. 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 scale 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 (both p < 0.001). 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.