Neural Correlates of Verbal Episodic Memory and Lexical Retrieval in Logopenic Variant Primary Progressive Aphasia

Abstract

Objective: Logopenic variant primary progressive aphasia (lvPPA) is commonly associated with Alzheimer's disease (AD) pathology. But lvPPA patients display different cognitive and anatomical profile from the common clinical AD patients, whose verbal episodic memory is primarily affected. Reports of verbal episodic memory difficulty in lvPPA are inconsistent, and we hypothesized that their lexical retrieval impairment contributes to verbal episodic memory performance and is associated with left middle temporal gyrus atrophy.Methods: We evaluated patients with lvPPA (n = 12) displaying prominent word-finding and repetition difficulties, and a demographically-matched cohort of clinical Alzheimer's disease (AD, n = 26), and healthy seniors (n = 16). We assessed lexical retrieval with confrontation naming and verbal episodic memory with delayed free recall. Whole-brain regressions related naming and delayed free recall to gray matter atrophy. Medial temporal lobe (MTL) subfields were examined using high in-plane resolution imaging.Results: lvPPA patients had naming and delayed free recall impairments, but intact recognition memory. In lvPPA, delayed free recall was related to naming; both were associated with left middle temporal gyrus atrophy but not MTL atrophy. Despite cerebrospinal fluid evidence consistent with AD pathology, examination of MTL subfields revealed no atrophy in lvPPA. While AD patients displayed impaired delayed free recall, this deficit did not correlate with naming. Regression analyses related delayed free recall deficits in clinical AD patients to MTL subfield atrophy, and naming to left middle temporal gyrus atrophy.Conclusion: Unlike amnestic AD patients, MTL subfields were not affected in lvPPA patients. Verbal episodic memory deficit observed in lvPPA was unlikely to be due to a hippocampal-mediated mechanism but appeared to be due to poor lexical retrieval. Relative sparing of MTL volume and intact recognition memory are consistent with previous reports of hippocampal-sparing variant cases of AD pathology, where neurofibrillary tangles are disproportionately distributed in cortical areas with relative sparing of the hippocampus. This suggests that AD neuropathology in lvPPA may originate in neuronal networks outside of the MTL, which deviates from the typical Braak staging pattern of spreading pathology in clinical AD.

Neuropsychological differentiation of progressive aphasic disorders

“…It is possible that at an earlier stage of disease greater differences might have been elicited between the two groups. However, the average number of years since disease onset was relatively low in the lvPPA group (mean 3.82 years) and in line with that cited in other studies of lvPPA (Foxe et al ., ; Krishnan et al ., ; Whitwell et al ., ; Win et al ., ). Moreover, the majority of patients were assessed within a year of their medical referral, so were still at a relatively early stage of illness.…”

“…Cognitive domains were chosen owing to their theoretical importance in a study of progressive aphasia; yet, there are some notable omissions. One such factor is episodic memory, which has been found to be significantly impaired in AD relative to lvPPA (Win et al ., ) and in lvPPA relative to nfvPPA (Piguet, Leyton, Gleeson, Hoon, & Hodges, ). In this study, standard episodic memory measures were omitted on the grounds that performance may be compromised secondarily by problems in language and working memory.…”

Linguistic Aspects of Primary Progressive Aphasia

“…However, this group included a mixture of PPA variants (including agrammatic, logopenic, and semantic). Another study associated lexical retrieval difficulty during verbal episodic memory recall with mid-temporal atrophy in the left hemisphere, that is, the same area implicated in the confrontation naming difficulty of these patients (Win et al 2017). A detailed examination indicated that these patients had no evidence of disease affecting parts of the brain important for episodic memory.…”

Caracterización del lenguaje en las variantes lingüísticas de la Afasia Progresiva Primaria

“…Otros autores refieren que el solapamiento entre ambos puede provenir de dificultades en la evaluación de la memoria episódica verbal. Esta memoria, deteriorada en la EA, en los casos de APP-L sería una manifestación de las dificultades de recuperación léxica y no de alteraciones mnésicas propiamente dichas (Win, Pluta, Yushkevich, Irwin, McMillan, Rascovsky, Wolk & Grossman, 2017). Finalmente, el equipo de Giannini et al (2017) propone utilizar el concepto de 'espectro logopénico', para englobar a tres subsíndromes diferentes, en función del cumplimiento de los criterios diagnósticos nucleares y específicos propuestos por Gorno-Tempini et al (2011).…”