Altered Verbal Working Memory Process in Patients with Alzheimer’s Disease

Impaired working memory processing is one of the broad range of cognitive deficits in patients with Alzheimer’s disease (AD). We aimed to elucidate the differences in brain activities involved in the process of working memory between AD patients and healthy comparison subjects. Twelve patients with AD were recruited along with 12 healthy volunteers as a comparison group. Functional magnetic resonance imaging was employed to assess cortical activities during the performance of a 1-back working memory paradigm using the Korean alphabet as mnemonic content. Subsequently, the difference in neural activities between the 2 groups was analyzed. The AD group performed the tasks with reduced accuracy. Group comparison analysis revealed that the AD group showed decreased brain activity in the left frontal pole (Brodmann area, BA, 10), the left ventrolateral prefrontal cortex (BA47), the left insula (BA13) and the right premotor cortex (BA6) compared to the control group. The AD group showed increased activation in the left precuneus (BA7) compared to the control group. A decreased level of activation in the prefrontal cortex and an increased level of activation in the parietal neural networks from the patient group may document an altered verbal working memory process in the patients with AD.

[1]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[2]  Karl J. Friston,et al.  Multisubject fMRI Studies and Conjunction Analyses , 1999, NeuroImage.

[3]  Charles D. Smith,et al.  Women at risk for AD show increased parietal activation during a fluency task , 2002, Neurology.

[4]  Edward E. Smith,et al.  The Role of Parietal Cortex in Verbal Working Memory , 1998, The Journal of Neuroscience.

[5]  Edward E. Smith,et al.  A parametric study of prefrontal cortex involvement in human working memory , 1996, NeuroImage.

[6]  Andrew J Saykin,et al.  Mild cognitive impairment: conceptual issues and structural and functional brain correlates. , 2003, Seminars in clinical neuropsychiatry.

[7]  Adrian M. Owen,et al.  The role of the lateral frontal cortex in mnemonic processing: the contribution of functional neuroimaging , 2000, Experimental Brain Research.

[8]  M. D’Esposito,et al.  Functional MRI studies of spatial and nonspatial working memory. , 1998, Brain research. Cognitive brain research.

[9]  Richard S. J. Frackowiak,et al.  The neural correlates of the verbal component of working memory , 1993, Nature.

[10]  Seung-Schik Yoo,et al.  NEURAL SUBSTRATES ASSOCIATED WITH THE CONCURRENT PERFORMANCE OF DUAL WORKING MEMORY TASKS , 2004, The International journal of neuroscience.

[11]  F. Collette,et al.  Alzheimer' Disease as a Disconnection Syndrome? , 2003, Neuropsychology Review.

[12]  Stephen M. Rao,et al.  Functional magnetic resonance imaging response to increased verbal working memory demands among patients with multiple sclerosis , 2006, Human brain mapping.

[13]  N Butters,et al.  Episodic memory changes are associated with the APOE- epsilon 4 allele in nondemented older adults , 1995, Neurology.

[14]  M. Torrens.  Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268 , 1990 .

[15]  S. Rombouts,et al.  Altered resting state networks in mild cognitive impairment and mild Alzheimer's disease: An fMRI study , 2005, Human brain mapping.

[16]  D. Siegmund,et al.  Testing for a Signal with Unknown Location and Scale in a Stationary Gaussian Random Field , 1995 .

[17]  Edward E. Smith,et al.  Working Memory: A View from Neuroimaging , 1997, Cognitive Psychology.

[18]  S E Petersen,et al.  A positron emission tomography study of the short-term maintenance of verbal information , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[19]  Kathryn M. McMillan,et al.  N‐back working memory paradigm: A meta‐analysis of normative functional neuroimaging studies , 2005, Human brain mapping.

[20]  Sara Rosenblum,et al.  Neuropsychological prediction of conversion to Alzheimer disease in patients with mild cognitive impairment. , 2006, Archives of general psychiatry.

[21]  F Barkhof,et al.  Alterations in brain activation during cholinergic enhancement with rivastigmine in Alzheimer’s disease , 2002, Journal of neurology, neurosurgery, and psychiatry.

[22]  J. Desmond,et al.  Load-Dependent Roles of Frontal Brain Regions in the Maintenance of Working Memory , 1999, NeuroImage.

[23]  Jong‐Han Park,et al.  Modification of the mini‐mental state examination for use in the elderly in a non‐western society. Part 1. Development of korean version of mini‐mental state examination , 1990 .

[24]  F. Collette,et al.  Phonological loop and central executive functioningin Alzheimers disease , 1999, Neuropsychologia.

[25]  Andrew J Saykin,et al.  Cholinergic enhancement of frontal lobe activity in mild cognitive impairment. , 2004, Brain : a journal of neurology.

[26]  S. Corkin,et al.  Working memory in mild Alzheimer's disease and early Parkinson's disease. , 2003, Neuropsychology.

[27]  James K. Kroger,et al.  Rostrolateral Prefrontal Cortex Involvement in Relational Integration during Reasoning , 2001, NeuroImage.