(18F)FDG-PET as a Biomarker for Early Alzheimer's Disease

Fluorine)fluorodeoxiglucose-Positron Emission Tomgraphy ( 18 F FDG-PET) has gained a leading role in the diagnostic assessment of patients with cognitive complaints, notably Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD). Together with morphological Magnetic Resonance Imaging (MRI) and cerebrospinal fluid biomarker assays it allows early identification of subjects with neurodegeneration of the AD-type, which is crucial in view of effective disease-modifying drugs. (18F)FDG-PET identifies hypometabolic regions in posterior cingulate-precuneus, posterior lateral and medial temporal-parietal association cortex, and in lateral frontal cortex. Hypometabolism in posterior cingulate-precuneus may be found even in MCI patients not yet converted to AD after a reasonable follow-up time and thus it might be a marker of memory deficit rather than of AD conversion. As (18F)FDG-PET is sensitive to synaptic dysfunction and depletion, hypometabolic areas can be detected before atrophy is highlighted by MRI in the same regions. The interpretation of the pathophysiological meaning of hypometabolism is discussed also in view of the most recent theory on the brain 'default mode network'. In longitudinal 1-year studies, (18F)FDG-PET has been shown an adequate tool to detect metabolic deterioration in AD patients better than amyloid-PET. It has been proposed as a surrogate biomarker to evaluate the effect of disease-modifying drugs in AD with a five times higher power than the commonly used neuropsychological scales. A flow-chart on the clinical use of (18F)FDG-PET is proposed, in which it is strongly recommended in MCI patients with suspected neurodegeneration.