FDG-PET as an independent biomarker for Alzheimer's biological diagnosis: a longitudinal study

BackgroundReduced F-18-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.MethodsA 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.ResultsThe 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 8years). 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).ConclusionsBased 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.