Specific and disease stage-dependent episodic memory-related brain activation patterns in Alzheimer’s disease: a coordinate-based meta-analysis
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Episodic memory is typically affected during the course of Alzheimer’s disease (AD). Due to the pronounced heterogeneity of functional neuroimaging studies on episodic memory impairments in mild cognitive impairment (MCI) and AD regarding their methodology and findings, we aimed to delineate consistent episodic memory-related brain activation patterns. We performed a systematic, quantitative, coordinate-based whole-brain activation likelihood estimation meta-analysis of 28 functional magnetic resonance imaging (fMRI) studies comprising 292 MCI and 102 AD patients contrasted to 409 age-matched control subjects. We included episodic encoding and/or retrieval phases, investigated the effects of group, verbal or image stimuli and correlated mean Mini-Mental-Status-Examination (MMSE) scores with the modelled activation estimates. MCI patients presented increased right hippocampal activation during memory encoding, decreased activation in the left hippocampus and fusiform gyrus during retrieval tasks, as well as attenuated activation in the right anterior insula/inferior frontal gyrus during verbal retrieval. In AD patients, however, stronger activation within the precuneus during encoding tasks was accompanied by attenuated right hippocampal activation during retrieval tasks. Low cognitive performance (MMSE scores) was associated with stronger activation of the precuneus and reduced activation of the right (para)hippocampus and anterior insula/inferior frontal gyrus. This meta-analysis provides evidence for a specific and probably disease stage-dependent brain activation pattern related to the pathognomonic AD characteristic of episodic memory loss.
KeywordsAlzheimer’s disease Mild cognitive impairment Episodic memory Functional neuroimaging Meta-analysis Hippocampus
We would like to thank B. Hampstead for sharing additional data which lead to the inclusion of one further study (Hampstead et al. 2011). We would like to furthermore thank Imis Dogan for her invaluable input during our data investigation, Ana Costa for providing knowledge and relevant literature about the different human memory systems and Melissa Chung for proofreading the manuscript. NJS and JBS are in part funded by the Helmholtz Alliance ICEMED - Imaging and Curing Environmental Metabolic Diseases, through the Initiative and Network Fund of the Helmholtz Association. SBE was funded by the Human Brain Project (R01-MH074457-01A1) and acknowledges funding by the Initiative and Networking Fund of the Helmholtz Association within the Helmholtz Alliance on Systems Biology (Human Brain Model) and the IRTG 1328. SBE and KR were funded by the Excellence Initiative of the German federal and state governments.
Conflict of interest
The authors declare that they have no conflict of interest.
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