ABSTRACT
BACKGROUND AND PURPOSE: Working 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. METHODS: We 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. RESULTS: We 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. CONCLUSIONS: Our 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.
Subject(s)
Cognitive Dysfunction/pathology , Connectome/methods , Memory Disorders/pathology , Memory, Short-Term , Multimodal Imaging/methods , Nerve Net/pathology , Aged , Aged, 80 and over , Cognitive Dysfunction/complications , Cognitive Dysfunction/physiopathology , Diffusion Tensor Imaging/methods , Female , Humans , Magnetic Resonance Imaging/methods , Male , Memory Disorders/etiology , Memory Disorders/physiopathology , Nerve Net/physiopathology , White Matter/physiologyABSTRACT
BACKGROUND: Research suggests generally impaired cognitive control functions in working memory (WM) processes in amnestic mild cognitive impairment (MCI) and incipient Alzheimer's disease (AD). Little is known how emotional salience of task-irrelevant stimuli may modulate cognitive control of WM performance and neurofunctional activation in MCI and AD individuals. OBJECTIVE: We investigated the impact of emotional task-irrelevant visual stimuli on cortical activation during verbal WM. METHODS: Twelve AD/MCI individuals and 12 age-matched healthy individuals performed a verbal WM (nback-) task with task-irrelevant emotionally neutral and emotionally negative background pictures during fMRI measurement. RESULTS: AD/MCI individuals showed decreased WM performance compared with controls; both AD/MCI and control groups reacted slower during presentation of negative pictures, regardless of WM difficulty. The AD/MCI group showed increased activation in the left hemispheric prefrontal network, higher amygdala and less cerebellar activation with increasing WM task difficulty compared to healthy controls. Correlation analysis between neurofunctional activation and WM performance revealed a negative correlation between task sensitivity and activation in the dorsal anterior cingulum for the healthy controls but not for the AD/MCI group. CONCLUSION: Our data suggest compensatory activation in prefrontal cortex and amygdala, but also dysfunctional inhibition of distracting information in the AD/MCI group during higher WM task difficulty. Additionally, attentional processes affecting the correlation between WM performance and neurofunctional activation seem to be different between incipient AD and healthy aging.
