¹⁸F-FDG-PET and Multimodal Biomarker Integration: A Powerful Tool for Alzheimer's Disease Diagnosis

An early, biomarker-based diagnosis of Alzheimer's Disease (AD) is crucial, especially with the emerging availability of novel therapeutic options. However, the role of ¹⁸F-FDG-PET and its relationship to other PET and CSF biomarkers remains unclear. Therefore, the aim of this study was the evaluation of the role of ¹⁸F-FDG-PET in AD diagnosis and its relationship to other commonly used fluid and PET biomarkers and their individual and multimodal accuracy in AD diagnosis. We included n = 157 AD patients, n = 603 MCI patients, and n = 380 cognitively normal participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) that underwent PET imaging with ¹⁸F-FDG or ¹⁸F-Florbetapir. Clinical and imaging data including patient characteristics, CSF biomarkers, cognition tests, ¹⁸F-FDG-PET, ¹⁸F-Florbetapir-PET, and ¹⁸F-Flortaucipir-PET were retrospectively analyzed. PET images were quantified in several brain regions. The uptake of ¹⁸F-FDG was inversely correlated with ¹⁸F-Florbetapir and positively correlated with CSF Aβ42 in several brain regions commonly affected by AD. Additionally, ¹⁸F-FDG uptake showed an inverse correlation with both forms of CSF tau, t-tau and p-tau, in various brain regions, but did not correlate with ¹⁸F-Flortaucipir uptake. Moreover, regional ¹⁸F-FDG uptake was positively correlated with cognitive function. Diagnostic accuracies were similarly high for ¹⁸F-FDG uptake in the PCC/Precuneus region, ¹⁸F-Florbetapir uptake, CSF Aβ42, CSF p-tau, and ¹⁸F-Flortaucipir uptake in differentiating AD from cognitively normal individuals. ¹⁸F-FDG-PET and its combination with CSF p-tau/ Aβ42 ratio showed the highest predictive power for disease severity. The study underscores the potential of integrating ¹⁸F-FDG-PET with CSF biomarkers to enhance the diagnosis, prognosis, and monitoring of AD, highlighting the complexity and regional specificity of biomarker interactions in neurodegeneration.

The online version contains supplementary material available at 10.1007/s13139-025-00932-2.