Semantic dementia is a progressive neurodegenerative condition characterized by the profound and amodal loss of semantic memory in the context of relatively preserved episodic memory. In contrast, patients with Alzheimer's disease typically display impairments in episodic memory, but with semantic deficits of a much lesser magnitude than in semantic dementia. Our understanding of episodic memory retrieval in these cohorts has greatly increased over the last decade, however, we know relatively little regarding the ability of these patients to imagine and describe possible future events, and whether episodic future thinking is mediated by divergent neural substrates contingent on dementia subtype. Here, we explored episodic future thinking in patients with semantic dementia (n=11) and Alzheimer's disease (n=11), in comparison with healthy control participants (n=10). Participants completed a battery of tests designed to probe episodic and semantic thinking across past and future conditions, as well as standardized tests of episodic and semantic memory. Further, all participants underwent magnetic resonance imaging. Despite their relatively intact episodic retrieval for recent past events, the semantic dementia cohort showed significant impairments for episodic future thinking. In contrast, the group with Alzheimer's disease showed parallel deficits across past and future episodic conditions. Voxel-based morphometry analyses confirmed that atrophy in the left inferior temporal gyrus and bilateral temporal poles, regions strongly implicated in semantic memory, correlated significantly with deficits in episodic future thinking in semantic dementia. Conversely, episodic future thinking performance in Alzheimer's disease correlated with atrophy in regions associated with episodic memory, namely the posterior cingulate, parahippocampal gyrus and frontal pole. These distinct neuroanatomical substrates contingent on dementia group were further qualified by correlational analyses that confirmed the relation between semantic memory deficits and episodic future thinking in semantic dementia, in contrast with the role of episodic memory deficits and episodic future thinking in Alzheimer's disease. Our findings demonstrate that semantic knowledge is critical for the construction of novel future events, providing the necessary scaffolding into which episodic details can be integrated. Further research is necessary to elucidate the precise contribution of semantic memory to future thinking, and to explore how deficits in self-projection manifest on behavioural and social levels in different dementia subtypes.
