• Stefan Teipel, Inga Ehlers, Anna Erbe, Carsten Holzmann, Esther Lau, Karlheinz Hauenstein, and Christoph Berger.
• Department of Psychosomatic Medicine, University Medicine Rostock, Rostock, Germany.
• J Neuroimaging. 2015 Jul 1; 25 (4): 634-42.

Background And PurposeWorking memory impairment is among the earliest signs of cognitive decline in Alzheimer's disease (AD) and mild cognitive impairment (MCI). We aimed to study the functional and structural substrate of working memory impairment in early AD dementia and MCI.MethodsWe studied a group of 12 MCI and AD subjects compared to 12 age- and gender-matched healthy elderly controls using diffusion tensor imaging (DTI), and functional magnetic resonance imaging (fMRI) during a 2-back versus 1-back letter recognition task. We performed a three-way image fusion analysis with joint independent component analysis of cortical activation during working memory, and DTI derived measures of fractional anisotropy (FA) and the mode of anisotropy.ResultsWe found significant hypoactivation in posterior brain areas and relative hyperactivation in anterior brain areas during working memory in AD/MCI subjects compared to controls. Corresponding independent components from DTI data revealed reduced FA and reduced mode of anisotropy in intracortical projecting fiber tracts with posterior predominance and increased FA and increased mode along the corticospinal tract in AD/MCI compared to controls.ConclusionsOur findings suggest that impairments of structural fiber tract integrity accompany breakdown of posterior and relatively preserved anterior cortical activation during working memory performance in MCI/AD subjects.Copyright © 2014 by the American Society of Neuroimaging.

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