The role of anterior prefrontal cortex in prospective memory: an exploratory FDG-PET study in early Alzheimer's disease

Introduction. Prospective memory (PM) is the ability of forming and maintaining an intention in memory over time while performing another task. From previous studies in healthy volunteers the prefrontal regions are deeply involved in PM, although little is known in early Alzheimer's disease (AD). Hence, we investigated the functional neural basis of PM in patients with mild cognitive impairment due to AD (MCI-AD) by assessing brain metabolism (18F-FDG PET). Methods. Eighteen patients (10 males, age:74±4.9; MMSE score:27.7±1.6) with intermediate or high likelihood of MCI-AD and a control group (HC) of 23 healthy subjects (11 males, age:71.5±5.7) underwent FDG-PET, neuropsychological evaluation and the PM-specific Shum and Ungvari paradigm test. Brain metabolism was correlated with the PM score in the two groups separately to find those brain areas correlated with PM performance ('PM cluster'), which were then used as central hub for the subsequent interregional metabolic connectivity analyses (IRCA). Results. In MCI-AD patients PM score positively correlated with metabolic levels in the right anterior prefrontal cortex (aPFC, middle and inferior frontal gyri); no correlation was found in HC. The IRCA showed in MCI-AD patients a loss of the interhemispheric connectivity of the PM cluster. Conclusion. The functioning of the right aPFC and its metabolic interhemispheric connectivity is crucial in early AD to sustain PM performance which deteriorates along with progressive metabolic failure in these regions.