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

Abstract

Neuropathology studies show that patients with mild cognitive impairment (MCI) and Alzheimer's disease typically have lesions of the entorhinal cortex (EC), hippocampus (Hip), and temporal neocortex. Related observations with in vivo imaging have enabled the prediction of dementia from MCI. Although 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-[ 18 F]fluoro-2-deoxy-D-glucose͞ positron-emission tomography (FDG͞PET) study was to examine the hypothesis that among normal elderly subjects, EC METglu reductions predict decline and the involvement of the Hip and neocortex. In a 3-year longitudinal study of 48 healthy normal elderly, 12 individuals (mean age 72) demonstrated cognitive decline (11 to MCI and 1 to Alzheimer's disease). Nondeclining controls were matched on apolipoprotein E genotype, age, education, and gender. At baseline, metabolic reductions in the EC accurately predicted the conversion from normal to MCI. Among those who declined, the baseline EC predicted longitudinal memory and temporal neocortex metabolic reductions. At follow-up, those who declined showed memory impairment and hypometabolism in temporal lobe neocortex and Hip. Among those subjects who declined, apolipoprotein E E4 carriers showed marked longitudinal temporal neocortex reductions. In summary, these data suggest that an EC stage of brain involvement can be detected in normal elderly that predicts future cognitive and brain metabolism reductions. Progressive E4-related hypometabolism may underlie the known increased 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.W ith increasing age, there is an increased risk for memory impairment (1); however, the affected anatomy predicting future impairment has not been well characterized. Although many conditions result in memory loss, Alzheimer's disease (AD) may be the most common cause (2). Neuropathology studies of normal elderly and subjects with clinically recognizable mild cognitive impairments (MCI) show that both the entorhinal cortex (EC) and hippocampus (Hip), structures important for memory function, are particularly vulnerable to neurofibrillary tangle (NFT) pathology (3, 4) and neuronal loss (5). Braak and Braak (3) proposed a staging model for brain AD where the NFT distribution expands from an EC locus to involve the Hip and then the neocortex. Carriers of an apolipoprotein E (apoE) E4 allele show at younger ages increased neocortical beta amyloid deposits (6) and EC NFTs (7). These changes may contribute to their increased risk for AD.In vivo, little is known of the regional anatomical changes marking the transitions between normal cognition and dementia. Although cross-sectional MRI and positron-emission tomography (PET) studies support an in vivo adaptation of the Braak staging model (8, 9), longitudinal imaging s...

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