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.

Episodic memory refers to a complex and multifaceted process which enables the retrieval of richly detailed evocative memories from the past. In contrast, semantic memory is conceptualized as the retrieval of general conceptual knowledge divested of a specific spatiotemporal context. The neural substrates of the episodic and semantic memory systems have been dissociated in healthy individuals during functional imaging studies, and in clinical cohorts, leading to the prevailing view that episodic and semantic memory represent functionally distinct systems subtended by discrete neurobiological substrates. Importantly, however, converging evidence focusing on widespread neural networks now points to significant overlap between those regions essential for retrieval of autobiographical memories, episodic learning, and semantic processing. Here we review recent advances in episodic memory research focusing on neurodegenerative populations which has proved revelatory for our understanding of the complex interplay between episodic and semantic memory. Whereas episodic memory research has traditionally focused on retrieval of autobiographical events from the past, we also include evidence from the recent paradigm shift in which episodic memory is viewed as an adaptive and constructive process which facilitates the imagining of possible events in the future. We examine the available evidence which converges to highlight the pivotal role of semantic memory in providing schemas and meaning whether one is engaged in autobiographical retrieval for the past, or indeed, is endeavoring to construct a plausible scenario of an event in the future. It therefore seems plausible to contend that semantic processing may underlie most, if not all, forms of episodic memory, irrespective of temporal condition.

The enhancing effect of music on autobiographical memory recall in mild Alzheimer’s disease individuals (n = 10; Mini-Mental State Examination score >17/30) and healthy elderly matched individuals (n = 10; Mini-Mental State Examination score 25–30) was investigated. Using a repeated-measures design, each participant was seen on two occasions: once in music condition (Vivaldi’s ‘Spring’ movement from ‘The Four Seasons’) and once in silence condition, with order counterbalanced. Considerable improvement was found for Alzheimer individuals’ recall on the Autobiographical Memory Interview in the music condition, with an interaction for condition by group (p < 0.005). There were no differences in terms of overall arousal using galvanic skin response recordings or attentional errors during the Sustained Attention to Response Task. A significant reduction in state anxiety was found on the State Trait Anxiety Inventory in the music condition (p < 0.001), suggesting anxiety reduction as a potential mechanism underlying the enhancing effect of music on autobiographical memory recall.

Semantic dementia is a progressive neurodegenerative disorder characterized by the amodal and profound loss of semantic knowledge attributable to the degeneration of the left anterior temporal lobe. Although traditionally conceptualized as a language disorder, patients with semantic dementia display significant alterations in behaviour and socioemotional functioning. Recent evidence points to an impaired capacity for theory of mind in predominantly left-lateralized cases of semantic dementia; however, it remains unclear to what extent semantic impairments contribute to these deficits. Further the neuroanatomical signature of such disturbance remains unknown. Here, we sought to determine the neural correlates of theory of mind performance in patients with left predominant semantic dementia (n = 11), in contrast with disease-matched cases with behavioural-variant frontotemporal dementia (n = 10) and Alzheimer’s disease (n = 10), and healthy older individuals (n = 14) as control participants. Participants completed a simple cartoons task, in which they were required to describe physical and theory of mind scenarios. Irrespective of subscale, patients with semantic dementia exhibited marked impairments relative to control subjects; however, only theory of mind deficits persisted when we covaried for semantic comprehension. Voxel-based morphometry analyses revealed that atrophy in right anterior temporal lobe structures, including the right temporal fusiform cortex, right inferior temporal gyrus, bilateral temporal poles and amygdalae, correlated significantly with theory of mind impairments in the semantic dementia group. Our results point to the marked disruption of cognitive functions beyond the language domain in semantic dementia, not exclusively attributable to semantic processing impairments. The significant involvement of right anterior temporal structures suggests that with disease evolution, the encroachment of pathology into the contralateral hemisphere heralds the onset of social cognitive deficits in this syndrome.