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Associative and Semantic Memory Deficits in Amnestic Mild Cognitive Impairment as Revealed by Functional Magnetic Resonance Imaging

van der Meulen, Marian PhD*,†; Lederrey, Cécile; Rieger, Sebastian W. PhD*; van Assche, Mitsouko PhD*,†; Schwartz, Sophie PhD*,†; Vuilleumier, Patrik MD, PhD*,†; Assal, Frédéric MD, PhD

Cognitive and Behavioral Neurology: December 2012 - Volume 25 - Issue 4 - p 195–215
doi: 10.1097/WNN.0b013e31827de67f
Original Studies

Objective: To identify the neural underpinnings of cognitive deficits associated with memory problems in amnestic mild cognitive impairment (aMCI).

Background: Functional magnetic resonance imaging (fMRI) is increasingly used to assess patients with aMCI and could potentially help predict conversion to Alzheimer disease, but imaging results so far have been inconsistent in identifying brain activation patterns in aMCI. There is an immediate need to identify the neural substrates of different memory components that are affected by aMCI.

Methods: We used fMRI to study 13 patients with aMCI and 15 healthy age-matched controls during an associative memory encoding and recognition task. The picture-pair memory task encompassed different types of recognition trials to investigate recollection versus familiarity, and manipulated the relationship between paired pictures to investigate semantic processing.

Results: Brain activation during both encoding and recognition was lower in patients than controls, with greatest implications in the medial temporal lobe during encoding. Patients also had much greater impairment of associative recollection than recognition based on familiarity, along with a failure to recruit regions that normally respond to violations of learned associations. Finally, patients’ impaired semantic encoding was reflected by deficient activation of a left frontotemporal network responsible for elaborate semantic processes.

Conclusions: We show that a simple fMRI task may be sensitive to deficits in different memory components in aMCI and could thus prove useful in the development of an fMRI tool to assess and monitor patients.

*Laboratory for Neurology and Imaging of Cognition, University of Geneva, Switzerland

Department of Neurology, Geneva University Hospital, Switzerland

Supported by the Société Académique de Genève (Fonds Cognitive Memory, NAC 08-025 to F.A., Fonds Foremane to P.V.) and the Fonds National Suisse (grant 320030_138163/1 and grant SPUM 33CM30-124115 to F.A.).

The authors declare no conflicts of interest.

Reprints: Marian van der Meulen, PhD, Laboratory of Psychobiology and Neurophysiology at the University of Luxembourg, 162a, Avenue de la Faïencerie, L-1511 Luxembourg, Luxembourg (e-mail:

Received January 5, 2012

Accepted August 28, 2012

© 2012 Lippincott Williams & Wilkins, Inc.