Baseline FDG-PET Brain hypometabolism as a predictive biomarker of cognitive decline and Alzheimer’s disease risk

INTRODUCTION: Brain glucose hypometabolism precedes cognitive decline in Alzheimer's disease, however its role in determining long-term cognitive trajectories remains under studied in current literature in a clear manner. We investigated whether baseline brain glucose metabolism predicts cognitive decline rates and disease conversion risk in a large longitudinal cohort. METHODS: We analyzed 4,732 participants (1,685 with longitudinal cognitive data) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with fluorodeoxyglucose positron emission tomography (FDG-PET), Mini-Mental State Examination (MMSE), and Alzheimer's Disease Assessment Scale (ADAS) measurements over ten years. Mixed-effects models investigated time × brain glucose metabolism interactions on cognitive decline. Cross-validation assessed predictive accuracy for mild cognitive impairment and Alzheimer's disease conversion. RESULTS: Brain glucose metabolism was found to modulate the cognitive decline rates (time × FDG interaction: MMSE β = 0.746, P-value