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Neural basis for cognitive control enhancement in elderly people
Poster Presentations: P1 rivastigmine treatment may be related to the effect of rivastigmine on glutamate uptake.
Figure. Changes in average metabolite ratios (A) and cognitive scores (B) from baseline to four months (Error bars represent 6 1 standard deviation, # represents P<0.1).
P1-167
NEURAL BASIS FOR COGNITIVE CONTROL ENHANCEMENT IN ELDERLY PEOPLE
Jeanyung Chey, Hoyoung Kim, Seoul National University, Seoul, South Korea. Background: Cognitive function is an important aspect of the individual’s functional independence and quality of life especially in the aging population. Cognitive control is a core function for daily adaptation but also an area most vulnerable to aging. This study was intended to develop a training program for older adults to enhance the cognitive control function, and to examine its effects comprehensively. Methods: Twenty seven community-dwelling adults aged 60 and older without diagnosis of significant cognitive impairment participated in this study (training group n ¼ 14; the control group n ¼ 13). A training program targeting cognitive control was developed, which was offered only to the training group. Duration of training was 1 hour per day, 3 days per week, for 8 weeks. We examined the training-related changes in cognitive function and cortical activity with Multisource Interference Task which required cognitive control yet was different from the main training program. More specifically, we compared the regional brain activation utilizing the functional MRI, before and after training. A comprehensive neuropsychological assessment was also completed pre- and post-training. Results: Trained older adults showed overall enhancement in cognitive functions compared with those who were not trained, particularly in the cognitive control measures. In addition, the training effect was also significant in the recognition tasks of working memory and episodic memory tasks, where interference resolution capabilities were required. In addition, general intellectual functioning, as measured with the Korean version of the DRS2, also improved after cognitive control training. The cognitive control trained group showed increased cortical activation in areas of the right fronto-parietal control network, whereas no significant activation change was found between the pre scan and post scan in the control group. Furthermore, cognitive enhancement was significantly correlated to brain activity change in these over-recruited areas in the trained group. Conclusions: We demonstrated the effect of cognitive control training and its neural correlates with functional MRI. The results of this study suggest a compensatory neural process that involves the fronto-parietal control network.
P1-168
A LONGITUDINAL FMRI STUDY OF CHOLINERGIC MODULATION IN NONDEMENTED PATIENTS WITH MILD MEMORY IMPAIRMENT
Judy Pa, Anne Berry, Mariana Compagnone, Jacqueline Boccanfuso, Ian Greenhouse, Michael Rubens, Adam Gazzaley, Julene Johnson, University of California, San Francisco, San Francisco, California, United States.
P167
Background: Cholinesterase inhibitors have been shown to improve or stabilize cognitive functioning in mild-to-moderate Alzheimer’s disease (AD). The increase in acetylcholine (ACh) may aid in synaptic plasticity that facilitates attention and memory. However, the cognitive and neural benefits of enhanced ACh levels in preclinical AD patients have not been well documented. We hypothesized that at-risk, preclinical AD patients would exhibit behavioral and neural benefits with an acetylcholinesterase inhibitor treatment. Methods: We conducted a 3-month, double-blind, placebo-controlled treatment study on the effects of donepezil (brand: Aricept) in twenty-seven non-demented patients with mild objective memory deficits (66.3 6 8 years; range 54-76 years; 12 females). The BOLD signal was measured using functional MRI (fMRI) as a surrogate of neural activity. A face/scene encoding and delayed recognition task was employed. The treatment and placebo groups completed an fMRI scan at baseline prior to treatment and a subsequent 3-month follow-up scan while on a 10mg of donepezil (or placebo) daily regimen. Results: The response time for faces and scenes was significantly faster in the treatment group after 3 months when compared to the placebo group (faces: 175ms gain, scenes: 179ms gain) (P <.05). To control for bottom-up effects due to treatment (e.g., elevated arousal), we used the passive view condition as an internal control. Accuracy for scenes significantly improved in the treatment group when compared to the placebo group (scenes: 6.7% gain; P <.05). The magnitude of change in the univariate BOLD activity was significantly greater in a face-selective region of the fusiform gyrus (FFA) in the treatment group during encoding (P <.05). Using the FFA and parahippocampal place area (PPA) as seeds, we revealed enhanced functional connectivity in prefrontal cognitive control regions and the hippocampus in the treatment group after 3 months (P <.05). Conclusions: These findings suggest that increased cholinergic transmission may improve cognitive and neural processing in patients with mild memory impairment. This mechanism may serve to facilitate the communication of functionally-connected brain networks critical to attention and memory. Longitudinal fMRI may be a useful method for elucidating the neural changes associated with neurochemical modulation and is a potential tool for monitoring treatment efficacy in clinical trials.
P1-169
CHANGES OF CAROTID DUPLEX SONOGRAPHIC FINDINGS BEFORE AND AFTER CAROTID ARTERY STENTING IN A POST-STROKE DEMENTIA
Jun Hong Lee1, Soo Jeong Shin2, 1National Health Insurance Corporation Ilsan Hospital, Department of Neurology, Goyang-si, South Korea; 2Yonsei University Medical Center, Seoul, South Korea. Background: Carotid arterial stenosis becomes more common and important risk factor for stroke patients in Asian area. We reviewed stroke database to investigate changes of carotid duplex sonographic findings, which reflects hemodynamic changes before and after carotid stenting in post-stroke dementia patients. Methods: Post-stroke dementia patients of which carotid stenting have been done when admitted at the National Health Insurance Corporation Ilsan Hospital from January 2005 to December 2010 with available carotid ultrasound study that was done before and after carotid stenting formed the analysis cohorts. Retrospective review was performed. Results: A total of 26 patients were included during that period. By duplex ultrasound, common, internal and external carotid arteries were examined and the degree of stenosis was graded by five groups;<50%, >50% and<75%, >75% and<95% stenosis, subtotal occlusion and occlusion. Average follow-up period between before and after stenting was 18 months. 16 patients among 26 patients showed no change of adjacent carotid stenosis degrees between before and after stenting. 5 patients among 26 patients showed changes in the stenosis degree of ipsilateral adjacent carotid and another 5 patients showed changes in the stenosis degree of contralateral adjacent carotid arteries. Conclusions: Between before and after carotid stenting, the flow of adjacent carotid arteries were changed in patients of about one third and another two thirds showed no change. The hemodynamic changes of carotid flow can be
Figure. Changes in average metabolite ratios (A) and cognitive scores (B) from baseline to four months (Error bars represent 6 1 standard deviation, # represents P<0.1).
P1-167
NEURAL BASIS FOR COGNITIVE CONTROL ENHANCEMENT IN ELDERLY PEOPLE
Jeanyung Chey, Hoyoung Kim, Seoul National University, Seoul, South Korea. Background: Cognitive function is an important aspect of the individual’s functional independence and quality of life especially in the aging population. Cognitive control is a core function for daily adaptation but also an area most vulnerable to aging. This study was intended to develop a training program for older adults to enhance the cognitive control function, and to examine its effects comprehensively. Methods: Twenty seven community-dwelling adults aged 60 and older without diagnosis of significant cognitive impairment participated in this study (training group n ¼ 14; the control group n ¼ 13). A training program targeting cognitive control was developed, which was offered only to the training group. Duration of training was 1 hour per day, 3 days per week, for 8 weeks. We examined the training-related changes in cognitive function and cortical activity with Multisource Interference Task which required cognitive control yet was different from the main training program. More specifically, we compared the regional brain activation utilizing the functional MRI, before and after training. A comprehensive neuropsychological assessment was also completed pre- and post-training. Results: Trained older adults showed overall enhancement in cognitive functions compared with those who were not trained, particularly in the cognitive control measures. In addition, the training effect was also significant in the recognition tasks of working memory and episodic memory tasks, where interference resolution capabilities were required. In addition, general intellectual functioning, as measured with the Korean version of the DRS2, also improved after cognitive control training. The cognitive control trained group showed increased cortical activation in areas of the right fronto-parietal control network, whereas no significant activation change was found between the pre scan and post scan in the control group. Furthermore, cognitive enhancement was significantly correlated to brain activity change in these over-recruited areas in the trained group. Conclusions: We demonstrated the effect of cognitive control training and its neural correlates with functional MRI. The results of this study suggest a compensatory neural process that involves the fronto-parietal control network.
P1-168
A LONGITUDINAL FMRI STUDY OF CHOLINERGIC MODULATION IN NONDEMENTED PATIENTS WITH MILD MEMORY IMPAIRMENT
Judy Pa, Anne Berry, Mariana Compagnone, Jacqueline Boccanfuso, Ian Greenhouse, Michael Rubens, Adam Gazzaley, Julene Johnson, University of California, San Francisco, San Francisco, California, United States.
P167
Background: Cholinesterase inhibitors have been shown to improve or stabilize cognitive functioning in mild-to-moderate Alzheimer’s disease (AD). The increase in acetylcholine (ACh) may aid in synaptic plasticity that facilitates attention and memory. However, the cognitive and neural benefits of enhanced ACh levels in preclinical AD patients have not been well documented. We hypothesized that at-risk, preclinical AD patients would exhibit behavioral and neural benefits with an acetylcholinesterase inhibitor treatment. Methods: We conducted a 3-month, double-blind, placebo-controlled treatment study on the effects of donepezil (brand: Aricept) in twenty-seven non-demented patients with mild objective memory deficits (66.3 6 8 years; range 54-76 years; 12 females). The BOLD signal was measured using functional MRI (fMRI) as a surrogate of neural activity. A face/scene encoding and delayed recognition task was employed. The treatment and placebo groups completed an fMRI scan at baseline prior to treatment and a subsequent 3-month follow-up scan while on a 10mg of donepezil (or placebo) daily regimen. Results: The response time for faces and scenes was significantly faster in the treatment group after 3 months when compared to the placebo group (faces: 175ms gain, scenes: 179ms gain) (P <.05). To control for bottom-up effects due to treatment (e.g., elevated arousal), we used the passive view condition as an internal control. Accuracy for scenes significantly improved in the treatment group when compared to the placebo group (scenes: 6.7% gain; P <.05). The magnitude of change in the univariate BOLD activity was significantly greater in a face-selective region of the fusiform gyrus (FFA) in the treatment group during encoding (P <.05). Using the FFA and parahippocampal place area (PPA) as seeds, we revealed enhanced functional connectivity in prefrontal cognitive control regions and the hippocampus in the treatment group after 3 months (P <.05). Conclusions: These findings suggest that increased cholinergic transmission may improve cognitive and neural processing in patients with mild memory impairment. This mechanism may serve to facilitate the communication of functionally-connected brain networks critical to attention and memory. Longitudinal fMRI may be a useful method for elucidating the neural changes associated with neurochemical modulation and is a potential tool for monitoring treatment efficacy in clinical trials.
P1-169
CHANGES OF CAROTID DUPLEX SONOGRAPHIC FINDINGS BEFORE AND AFTER CAROTID ARTERY STENTING IN A POST-STROKE DEMENTIA
Jun Hong Lee1, Soo Jeong Shin2, 1National Health Insurance Corporation Ilsan Hospital, Department of Neurology, Goyang-si, South Korea; 2Yonsei University Medical Center, Seoul, South Korea. Background: Carotid arterial stenosis becomes more common and important risk factor for stroke patients in Asian area. We reviewed stroke database to investigate changes of carotid duplex sonographic findings, which reflects hemodynamic changes before and after carotid stenting in post-stroke dementia patients. Methods: Post-stroke dementia patients of which carotid stenting have been done when admitted at the National Health Insurance Corporation Ilsan Hospital from January 2005 to December 2010 with available carotid ultrasound study that was done before and after carotid stenting formed the analysis cohorts. Retrospective review was performed. Results: A total of 26 patients were included during that period. By duplex ultrasound, common, internal and external carotid arteries were examined and the degree of stenosis was graded by five groups;<50%, >50% and<75%, >75% and<95% stenosis, subtotal occlusion and occlusion. Average follow-up period between before and after stenting was 18 months. 16 patients among 26 patients showed no change of adjacent carotid stenosis degrees between before and after stenting. 5 patients among 26 patients showed changes in the stenosis degree of ipsilateral adjacent carotid and another 5 patients showed changes in the stenosis degree of contralateral adjacent carotid arteries. Conclusions: Between before and after carotid stenting, the flow of adjacent carotid arteries were changed in patients of about one third and another two thirds showed no change. The hemodynamic changes of carotid flow can be