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

From previous studies in healthy volunteers the prefrontal regions are deeply involved in prospective memory (PM), although little is known about the functional neural basis of PM in prodromal Alzheimer's disease (AD). To this end, we retrospectively recruited 18 patients with mild cognitive impairment caused by AD and 23 matched healthy control subjects who had undergone 18F-fluorodeoxyglucose positron emission tomography and the PM-specific paradigm test. Brain metabolism was correlated with the PM score in the 2 groups separately to find those brain areas correlated with PM performance, which were then used as a hub for an inter-regional metabolic connectivity analyses (inter-regional correlation analysis). Of note, in mild cognitive impairment caused by AD, but not in healthy control subjects, PM score positively correlated with metabolic levels in the right anterior prefrontal cortex (middle and inferior frontal gyri), which disclosed a loss of interhemispheric connectivity in the inter-regional correlation analysis. According to our findings, the functioning of the right anterior prefrontal cortex and its interhemispheric metabolic connectivity is crucial in early AD to sustain PM performance, which deteriorates along with progressive metabolic failure of the interconnected areas.