title: Preservation of episodic memory in semantic dementia: The importance of regions beyond the medial temporal lobes.
abstract: Episodic memory impairment represents one of the hallmark clinical features of patients with Alzheimer's disease (AD) attributable to the degeneration of medial temporal and parietal regions of the brain. In contrast, a somewhat paradoxical profile of relatively intact episodic memory, particularly for non-verbal material, is observed in semantic dementia (SD), despite marked atrophy of the hippocampus. This retrospective study investigated the neural substrates of episodic memory retrieval in 20 patients with a diagnosis of SD and 21 disease-matched cases of AD and compared their performance to that of 35 age- and education-matched healthy older Controls. Participants completed the Rey Complex Figure and the memory subscale of the Addenbrooke's Cognitive Examination-Revised as indices of visual and verbal episodic recall, respectively. Relative to Controls, AD patients showed compromised memory performance on both visual and verbal memory tasks. In contrast, memory deficits in SD were modality-specific occurring exclusively on the verbal task. Controlling for semantic processing ameliorated these deficits in SD, while memory impairments persisted in AD. Voxel-based morphometry analyses revealed significant overlap in the neural correlates of verbal episodic memory in AD and SD with predominantly anteromedial regions, including the bilateral hippocampus, strongly implicated. Controlling for semantic processing negated this effect in SD, however, a distributed network of frontal, medial temporal, and parietal regions was implicated in AD. Our study corroborates the view that episodic memory deficits in SD arise very largely as a consequence of the conceptual loading of traditional tasks. We propose that the functional integrity of frontal and parietal regions enables new learning to occur in SD in the face of significant hippocampal and anteromedial temporal lobe pathology, underscoring the inherent complexity of the episodic memory circuitry.
authors.affiliation: School of Psychology, The University of New South Wales, Sydney, Australia; Neuroscience Research Australia, Randwick, Sydney, Australia; Australian Research Council Centre of Excellence in Cognition and its Disorders, Sydney, Australia. Electronic address: m.irish@neura.edu.au.
authors.forename: Muireann
authors.initials: M
authors.lastname: Irish
authors.affiliation: Neuroscience Research Australia, Randwick, Sydney, Australia.
authors.forename: Steffie
authors.initials: S
authors.lastname: Bunk
authors.affiliation: Neuroscience Research Australia, Randwick, Sydney, Australia; Australian Research Council Centre of Excellence in Cognition and its Disorders, Sydney, Australia; School of Medical Sciences, The University of New South Wales, Sydney, Australia.
authors.forename: Sicong
authors.initials: S
authors.lastname: Tu
authors.affiliation: Neuroscience Research Australia, Randwick, Sydney, Australia.
authors.forename: Jody
authors.initials: J
authors.lastname: Kamminga
authors.affiliation: Neuroscience Research Australia, Randwick, Sydney, Australia; Australian Research Council Centre of Excellence in Cognition and its Disorders, Sydney, Australia; School of Medical Sciences, The University of New South Wales, Sydney, Australia.
authors.forename: John R
authors.initials: JR
authors.lastname: Hodges
authors.affiliation: Australian Research Council Centre of Excellence in Cognition and its Disorders, Sydney, Australia; Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Hornberger
authors.affiliation: Neuroscience Research Australia, Randwick, Sydney, Australia; Australian Research Council Centre of Excellence in Cognition and its Disorders, Sydney, Australia; School of Medical Sciences, The University of New South Wales, Sydney, Australia.
authors.forename: Olivier
authors.initials: O
authors.lastname: Piguet
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D001284:Atrophy / Q000473:pathology; D001931:Brain Mapping; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D057180:Frontotemporal Dementia / Q000150:complications* / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016014:Linear Models; D008297:Male; D008569:Memory Disorders / Q000209:etiology*; D061212:Memory, Episodic; D011939:Mental Recall / Q000502:physiology; D008875:Middle Aged; D009483:Neuropsychological Tests; D010296:Parietal Lobe / Q000473:pathology*; D010775:Photic Stimulation; D012189:Retrospective Studies; D013702:Temporal Lobe / Q000473:pathology*; D014706:Verbal Learning / Q000502:physiology
keywords: Alzheimer's disease; Angular gyrus; Hippocampus; Posterior cingulate cortex; Prefrontal cortex; Semantic memory