The prefrontal cortex and episodic memory in dementia syndromes

Episodic memory impairment is commonly reported in neurodegenerative syndromes such as Alzheimer’s disease (AD) and behavioural-variant frontotemporal dementia (bvFTD). These deficits have been attributed predominantly to medial temporal lobe atrophy and poor encoding/retrieval in AD, as opposed to prefrontal cortex (PFC) atrophy and impaired strategic retrieval processes in bvFTD. Evidence suggests, however, that the PFC contributes to episodic memory impairment across both patient groups, although it is unclear whethe rboth lateral and medial subregions of the PFC are involved. This thesis aims to clarify the PFC contributions to episodic memory in AD and bvFTD by comparing performance on both established and novel measures of episodic memory and patterns of PFC atrophy using voxel based morphometry. In a study comparing dysexecutive AD and bvFTD, the two patient groups showed significant overlap on measures of PFC atrophy, performance on standardised neuropsychological episodic memory tests, and correlations between PFC atrophy and memory performance. A second study contrasted the lateral and medial PFC contributions to episodic memory in AD and bvFTD, revealing that performance on standardised neuropsychological episodic memory tests correlated with lateral PFC atrophy across both groups, but correlated with medial PFC atrophy in bvFTD only. The next three studies employed novel experimental tasks to determine the role of the medial PFC in enhancing memory for 1) self-relevant, 2) socially relevant and 3) reward-related information. Collectively, these three studies revealed that value-related memory processes, which are mediated by the medial PFC, are disproportionately disrupted in bvFTD. The main findings of the thesis are that the impact of lateral PFC dysfunction on episodic memory is not specific to bvFTD, and that greater emphasis is needed to try to understand the value-related processes through which the medial PFC augments episodic memory encoding and retrieval. These findings stand to improve differential diagnosis of AD and bvFTD, and improve understanding of the role of the PFC in episodic memory.