Item familiarity and controlled associative retrieval in Alzheimer's disease: an fMRI study.

Typical Alzheimer's disease (AD) is characterized by an impaired form of associative memory, recollection, that includes the controlled retrieval of associations. In contrast, familiarity-based memory for individual items may sometimes be preserved in the early stages of the disease. This is the first study that directly examines whole-brain regional activity during one core aspect of the recollection function: associative controlled episodic retrieval (CER), contrasted to item familiarity in AD patients. Cerebral activity related to associative CER and item familiarity in AD patients and healthy controls (HCs) was measured with functional magnetic resonance imaging during a word-pair recognition task to which the process dissociation procedure was applied. Some patients had null CER estimates (AD-), whereas others did show some CER abilities (AD+), although significantly less than HC. In contrast, familiarity estimates were equivalent in the three groups. In AD+, as in controls, associative CER activated the inferior precuneus/posterior cingulate cortex (PCC). When performing group comparisons, no region was found to be significantly more activated during CER in HC than AD+ and vice versa. However, during associative CER, functional connectivity between this region and the hippocampus, the inferior parietal and dorsolateral prefrontal cortex (DLPFC) was significantly higher in HC than in AD+. In all three groups, item familiarity was related to activation along the intraparietal sulcus (IPS). In conclusion, whereas the preserved automatic detection of an old item (without retrieval of accurate word association) is related to parietal activation centred on the IPS, the inferior precuneus/PCC supports associative CER ability in AD patients, as in HC. However, AD patients have deficient functional connectivity during associative CER, suggesting that the residual recollection function in these patients might be impoverished by the lack of some recollection-related aspects such as autonoetic quality, episodic details and verification.