Contrasting prefrontal cortex contributions to episodic memory dysfunction in behavioural variant frontotemporal dementia and Alzheimer's disease

Stephanie Wong; Emma Flanagan; Greg Savage; John R Hodges; Michael Hornberger

doi:10.1371/journal.pone.0087778

Contrasting prefrontal cortex contributions to episodic memory dysfunction in behavioural variant frontotemporal dementia and Alzheimer's disease

PLoS One. 2014 Feb 4;9(2):e87778. doi: 10.1371/journal.pone.0087778. eCollection 2014.

Authors

Stephanie Wong¹, Emma Flanagan², Greg Savage³, John R Hodges⁴, Michael Hornberger⁴

Affiliations

¹ Neuroscience Research Australia, Randwick, Sydney, New South Wales, Australia ; Department of Psychology, Macquarie University, Sydney, New South Wales, Australia ; Australian Research Council Centre of Excellence in Cognition and its Disorders, Sydney, New South Wales, Australia.
² Neuroscience Research Australia, Randwick, Sydney, New South Wales, Australia.
³ Department of Psychology, Macquarie University, Sydney, New South Wales, Australia ; Australian Research Council Centre of Excellence in Cognition and its Disorders, Sydney, New South Wales, Australia.
⁴ Neuroscience Research Australia, Randwick, Sydney, New South Wales, Australia ; Australian Research Council Centre of Excellence in Cognition and its Disorders, Sydney, New South Wales, Australia ; School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.

Abstract

Recent evidence has questioned the integrity of episodic memory in behavioural variant frontotemporal dementia (bvFTD), where recall performance is impaired to the same extent as in Alzheimer's disease (AD). While these deficits appear to be mediated by divergent patterns of brain atrophy, there is evidence to suggest that certain prefrontal regions are implicated across both patient groups. In this study we sought to further elucidate the dorsolateral (DLPFC) and ventromedial (VMPFC) prefrontal contributions to episodic memory impairment in bvFTD and AD. Performance on episodic memory tasks and neuropsychological measures typically tapping into either DLPFC or VMPFC functions was assessed in 22 bvFTD, 32 AD patients and 35 age- and education-matched controls. Behaviourally, patient groups did not differ on measures of episodic memory recall or DLPFC-mediated executive functions. BvFTD patients were significantly more impaired on measures of VMPFC-mediated executive functions. Composite measures of the recall, DLPFC and VMPFC task scores were covaried against the T1 MRI scans of all participants to identify regions of atrophy correlating with performance on these tasks. Imaging analysis showed that impaired recall performance is associated with divergent patterns of PFC atrophy in bvFTD and AD. Whereas in bvFTD, PFC atrophy covariates for recall encompassed both DLPFC and VMPFC regions, only the DLPFC was implicated in AD. Our results suggest that episodic memory deficits in bvFTD and AD are underpinned by divergent prefrontal mechanisms. Moreover, we argue that these differences are not adequately captured by existing neuropsychological measures.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Alzheimer Disease / diagnosis
Alzheimer Disease / physiopathology*
Atrophy
Behavior*
Cognition
Female
Frontotemporal Dementia / diagnosis
Frontotemporal Dementia / physiopathology*
Humans
Magnetic Resonance Imaging / methods
Male
Memory, Episodic*
Mental Recall
Middle Aged
Neuropsychological Tests
Prefrontal Cortex / pathology
Prefrontal Cortex / physiopathology*
Risk Factors

Grants and funding

This work was supported by the Australian Research Council (ARC) Centre of Excellence for Cognition and its Disorders; the National Health and Medical Research Council (NHMRC) of Australia; and an Australian Postgraduate Award Scholarship (to SW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.