Compensatory reallocation of brain resources supporting verbal episodic memory in Alzheimer's disease

Alzheimer's disease (AD) is a progressive neurodegenerative disease that has as its primary symptom early in its course a profound memory loss. ^[1] Neuropsychological studies demonstrate that secondary memory is particularly affected, whilst aspects of primary or working memory can remain relatively normal. ^[2-5] Neuropathologic studies are consistent with these symptoms, with mesial temporal, temporal cortical, and diencephalic structures, which are known to be involved in normal memory functions, showing the neuritic plaques, neurofibrillary tangles, and neuronal loss characteristic of the disease. ^[6]

The tight coupling of local neural activity to regional cerebral blood flow (rCBF) and the ease with which multiple whole brain images of rCBF can be obtained with¹⁵ O-water using PET has allowed the development of a powerful human brain functional mapping technique. ^[7-9] With use of cognitive and sensory tasks, this technique has been successfully applied in normal subjects, and although there have been a variety of studies of resting rCBF in AD patients, ^[10-14] few studies have examined rCBF in AD patients using activation paradigms. ^[15-18] The results of cross-sectional studies using PET ^[19,20] and SPECT ^[21-23] show decreases in blood flow in the temporal and parietal cortices early in AD, consistent with the pattern of neurodegenerative changes in these regions, although the reliability of these findings has been recently questioned. ^[24] Furthermore, longitudinal PET studies have shown that these changes may parallel or precede measurable change in cognitive function. ^[25]

More recent PET studies of young, healthy normal volunteers have revealed distinct patterns of functional activity as the subjects engage in tasks related to auditory verbal short-term memory. ^[26-31] These studies are of particular relevance because the procedures have the potential to reveal specific functional defects related to specific information-processing deficits prior to any observable structural abnormalities. We report the results of a …