Evidence for a pervasive autobiographical memory impairment in Logopenic Progressive Aphasia: clinical and neural correlates

Abstract

Logopenic Progressive Aphasia is a rare language disorder characterised by repetition and naming difficulties, reflecting the progressive degeneration of left-lateralized peri-sylvian temporal and inferior parietal regions. Mounting evidence suggests that cognitive impairments in this syndrome extend beyond the language domain to include episodic encoding and retrieval disturbances. To date, it remains unknown whether autobiographical memories from across the lifespan are also subject to decline, yet this information is critical to arrive at a comprehensive understanding of the Logopenic syndrome. The objective of this study was to provide the first in depth examination of autobiographical memory function in Logopenic Progressive Aphasia using the Autobiographical Interview, a validated semi-structured interview which assesses recollection of the past under free and probed recall conditions. Autobiographical memory performance in 10 well-characterised Logopenic Progressive Aphasia patients was contrasted with that of 18 typical amnestic Alzheimers disease and 16 healthy Control participants. Relative to Controls, Logopenic Progressive Aphasia cases showed marked impairment in the free recall of episodic details, scoring comparably to disease-matched cases of Alzheimers disease. This impairment was evident across all time periods and persisted even when formal structured probing was provided. Importantly, controlling for overall level of language disruption failed to ameliorate the autobiographical memory impairment in the Logopenic Progressive Aphasia group, suggesting a genuine amnesia spanning recent and remote memories. Whole-brain voxel-based morphometry analyses revealed that total episodic information retrieved in Logopenic Progressive Aphasia was associated with decreased grey matter intensity predominantly in a bilateral posterior parietal network. Taken together, our findings reveal for the first time the presence of marked remote and recent autobiographical memory impairments in Logopenic Progressive Aphasia, that cannot be explained solely due to their language difficulties or disease staging. Our findings hold important clinical implications for the accurate characterization of Logopenic Progressive Aphasia, and suggest that episodic memory difficulties should be considered as one of the core clinical features of this syndrome.

Establishing two principal dimensions of cognitive variation in logopenic progressive aphasia

“…Significant socioemotional dysfunction including loss of empathy and impaired emotion detection abilities has also been documented ( Hazelton et al , 2017 ; Multani et al , 2017 ; Fittipaldi et al , 2019 ). Finally, LPA patients demonstrate significant verbal episodic and autobiographical memory difficulties ( Butts et al , 2015 ; Casaletto et al , 2017 ; Win et al , 2017 ; Eikelboom et al , 2018 ; Ramanan et al , 2020 a ) comparable to that observed in typical Alzheimer’s disease ( Ramanan et al , 2016 ; Ramanan et al , 2020 a , b ). While such deficits could manifest simply as a by-product of language and lexical retrieval difficulties in LPA, compromised performance on tasks with minimal language demands suggests otherwise.…”

The Box Task: A novel tool to differentiate the primary progressive aphasias

“…With increasing task difficulty, however, higher‐level visuospatial attentional demands are likely to be subserved by dorsolateral prefrontal structures [32,34]—regions potentially more compromised in lv‐PPA, nfv‐PPA and AD than in sv‐PPA [4]. We note, however, that no single region modulates visuospatial working memory performance [33] and frontotemporoparietal white matter dysconnectivity likely also contribute to the attentional, memory and high‐level visuospatial deficits of PPA and AD [29,38].…”