Prediction of cognitive decline in normal elderly subjects with 2-[F-18]fluoro-2-deoxy-D-glucose/positron-emission tomography (FDG/PET)

Neuropathology studies show that patients with mild cognitive impairment (M Cl) and Alzheimer's disease typically have lesions of the entorhinal cortex (EC), hippocampus (Hip), and temporal neocortex., Related observations wit h in vivo imaging have enabled the prediction of dementia from MCl. Althoug h individuals with normal cognition may have focal EC lesions, this anatomy has not been studied,as a predictor of cognitive decline and brain change. The objective of this MRI-guided 2-[F-18]fluoro-2-deoxy-D-glucose/ positro n-emission tomography (FDG/PET) study was to examine the hypothesis that am ong normal elderly subjects, EC METglu reductions predict decline and the i nvolvement of the Hip and neocortex. In a 3-year longitudinal study of 48 h ealthy normal elderly, 12 individuals (mean age 72) demonstrated cognitive decline (11 to MCl and 1 to Alzheimer's disease). Nondeclining controls wer e matched on apolipoprotein E genotype, age, education, and gender. At base line, metabolic reductions in the EC accurately predicted the conversion fr om normal to MCl. Among those who declined, the baseline EC predicted longi tudinal memory and temporal neocortex metabolic reductions. At follow-up, t hose who declined showed memory impairment and hypometabolism in temporal l obe neocortex and Hip. Among those subjects who declined, apolipoprotein E E4 carriers showed marked longitudinal temporal neocortex reductions. In su mmary, these data suggest that an EC stage of brain involvement can be dete cted in normal elderly that predicts future cognitive and brain metabolism reductions. Progressive E4-related hypometabolism may underlie the known in creased susceptibility for dementia. Further study is required to estimate individual risks and to determine the physiologic basis for METglu changes detected while cognition is normal.