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Correlations of magnetic resonance spectroscopy with cognitive Function in remitted late-life major depressive disorder
Poster Presentations P1 lesions in frontal cortical biopsy specimens. Methods: 21 patients (14 women, 14 men; mean age; SD 72.7; 4.6 years, range 62 - 83 years) who had undergone intraventricular pressure monitoring with a right frontal cortical biopsy for suspected normal-pressure hydrocephalus participated in the study. A dynamic 90 min [11C]PiB PET scan was performed. The data was quantified as a region-to-cerebellar cortex ratio from 60-90 min after injection by using an automated region-of interest analysis. Ventricular cerebrospinal fluid (CSF) Aß-, tau- and phophotau-levels were measured. The number of Aß aggregates in the frontal cortical biopsy specimen was evaluated by immunohistochemistry. Results: In patients with Aß aggregates in the frontal cortical biopsy specimen, PET imaging revealed significantly higher [11C]PiB uptake in the right frontal cortex and in the composite neocortical score (an average of uptake in frontal, parietal, lateral temporal, occipital and posterior cingulate cortices). There was a clear association between the number of Aß aggregates in the frontal cortical biopsy specimen and both [11C]PiB uptake in the right frontal cortex (r ¼ 0.91, p < 0.001) and the composite neocortical [11C]PiB uptake score (r ¼ 0.89, p < 0.001). The ventricular CSF Aß-, but not tau and phosphotau levels were associated with both frontal cortical [11C]PiB uptake and the number of Aß aggregates in the biopsy specimen. Conclusions: Our study supports the use of noninvasive [11C]PiB PET in the assessment of Aß deposition in the brain by showing a clear association between in vivo [11C]PiB uptake and the number of Aß aggregates in frontal cortical biopsy specimen. P1-370
DISTINGUISH THE VISUAL TOP-DOWN SPATIAL ATTENTIONAL NEURAL NETWORK BETWEEN NORMAL AND DEMENTIA
Yasuyuki Ohta1, Koji Abe1, Kewei Chen2, Yong Shen3, Jinglong Wu1, 1 Okayama University, Okayama, Japan; 2Banner Alzheimer’s Institute and Banner Good Samaritan PET Center, Phoenix, Arizona, United States; 3 Roskamp Institute, Center for Advanced Therapeutic Strategies for Brain Disorders, Sarasota, Florida, United States. Background: Disturbance of attentional processes represents the first cognitive indicator of neocortical dysfunction in early stage of Dementia of the Alzheimer type (DAT). Our previous tactile angle discrimination task showed that MCI (mild cognitive impairment) and DAT might be caused, at least partially, attentional dysfunction (Yang et al., JAD, 2010). Disconnection between frontal and posterior parietal areas may mediate the selective disruption of attentional functions in DAT. By using Posner task (Posner MI, Q J Exp Psychol, 1980) and fMRI (functional magnetic resonance imaging), we intended to examine the attention related neural network difference between normal and DAT/MCI patients. Methods: Data from 16 normal young (NY), 16 normal elder (NE) and 16 MCI/DAT patients were used. The Posner task used in this study was the spatial attention and the spatial expectation. The target stimulus was used with a width and height both of 2 degrees of eccentricity. For the spatial attention task, participants were constructed to pay attention to the side at which custimulus was presented and to press the reaction key as quickly as possible when the target stimulus was to appear. During the spatial expectation task, cue was presented until the target stimulus appeared. Images were pre-processed using SPM8 and the general linear model determined task vs control condition fMRI signal differences from regions of interest (ROI) (IPL, inferior parietal lobe; MT+, contain both middle temporal (MT) and medial superior temporal (MST); FEF, frontal eye field; IFG, inferior frontal gyrus, all in right hemisphere) and right motor area were further statistically examined using SPSS. Results: Reaction times showed a reaction speed order was in a good agreement with NY (normal younger)> NE (normal elder) > MCI/DAT as the same as the accuracy (p < 0.05 between normal and patient groups). fMRI results found distinct differences among the three groups under the two tasks, respectively, in a number of ROI analyzed. Especially, during the topdown spatial attention task, 4 regions (IPL, MT+, FEF and IFG, all in right hemisphere) were associated with group differences (p ¼ 0.05). During the spatial expectation task, a significant magnitude difference of ROI-based signal change was found within the right motor area (p ¼ 0.05). Conclusions: Using the Posner experimental paradigm, we found the differences among NY, NE and MCI/ DAT patients both from behavioral and brain imaging results. Additional studies with more advanced analytic techniques are needed to confirm our findings.
P1-371
S231 CORRELATIONS OF MAGNETIC RESONANCE SPECTROSCOPY WITH COGNITIVE FUNCTION IN REMITTED LATE-LIFE MAJOR DEPRESSIVE DISORDER
Cheng-Sheng Chen1, 1Kaohsiung Medical University, Kaohsiung, Taiwan, Kaohsiung, Taiwan. Background: Depressive elders with cognitive impairment are at higher risk to develop dementia at follow-up. Understanding of characteristics of brain function of these patients is beneficial to develop preventive strategies. The goal of this study was to examine the biochemical abnormalities of remitted late-life major depression by using 3-T proton magnetic resonance spectroscopy (MRS). Correlations between cognitive function and biochemical abnormalities above these regions will be investigated. Methods: Seventy-four elderly patients with major depressive disorder in remission and 74 age- and sex-match comparison elders received 3-T MRS. MRS spectra were acquired from voxels which were placed in the basal ganglia, dorsolateral prefrontal lobe, and hippocampus. Ratio levels of N-acetylaspartate (NAA), choline, and myo-inositol reference to creatine were calculated. A cognitive battery tapping executive function, memory, and information processing speed were conducted. Bonferroni correction was applied to reduce type I error from multiple testing. Results: Patients with late-life major depressive disorder in remission had a significantly lower NAA/creatine at the basal ganglia and dorsolateral prefrontal lobe, and higher choline/creatine at the basal ganglia, dorsolateral prefrontal lobe and hippocampus as compared to the control subjects. Among all biochemical abnormality at each region, only lower NAA/creatine at basal ganglia associated with poor performance of executive function, delayed recall memory and information processing speed. Conclusions: The elderly with major depressive disorder shows abnormal brain biochemical change even in remitted state. Neuron loss at basal ganglia played a neurobiological basis for the cognitive dysfunction among the depressive elders. P1-372
GREATER IMPACT OF WHITE MATTER HYPERINTENSITIES ON COGNITION IN APOE CARRIERS
Leslie Baxter1, Michael J. Purcell1, Seban Liu1, Kyle steinke1, Richard Caselli2, 1Barrow Neurological Institute, Phoenix, Arizona, United States; 2Mayo Clinic Arizona, Scottsdale, Arizona, United States. Background: White matter hyperintensities (WMH) are commonly observed on magnetic resonance imaging in older individuals, especially with the advent of fluid attenuated inversion recovery (FLAIR). The APOE e4 allele, which confers a greater risk for a steeper decline in some cognitive abilities even before individuals show signs of Alzheimer and cognition in APOE e4 carriers may be more vulnerable to cardiovascular risk. We examined the effect of APOE on the correlation of WMH and cognition in cognitively normal adults. Methods: Subjects from a study of cognitive aging were scanned on the same 3 Tesla GE scanner. A “3D” T2-weighted FLAIR scan and a T1 (MPRAGE) scan were obtained. Subjects with a history of diabetes (n ¼ 5) or no evidence of any WMH (n ¼ 2) were excluded as outliers. A semi-automated method of segmenting WMH was performed based on determining the mean intensity values for WMH and CSF for thresholding. Percentage of WMH were calculated for each region as: (WHM/Total Tissue Voxels)x100 (WMH%). Results: There were no group differences in age, total intracranial volume. Carriers performed worse on verbal memory. There were no group differences in the presence of hypertension. There were no group differences for mean regional WMH%. No correlation was seen with age and WMH% in either groups. Significant correlations of cognitive tests with WMH% occurred only among the APOE e4 carrier group, including Boston Naming Test with left temporal, parietal and periventricular regions. Verbal Comprehension (WAIS-R) correlated with left temporal, left parietal, periventricular, and whole brain WMH%. Trailmaking Test B (executive functioning) correlated with left frontal, left and right parietal, periventricular, right temporal and whole brain WMH%. Conclusions: These data suggest that APOE e4 allele alters the impact of WMH on cognition. This effect was for measures of executive functioning and language rather than memory. These findings are consistent with prior reports of greater vulnerability of apoe e4 carriers to a variety of pathophysiological stresses.
DISTINGUISH THE VISUAL TOP-DOWN SPATIAL ATTENTIONAL NEURAL NETWORK BETWEEN NORMAL AND DEMENTIA
Yasuyuki Ohta1, Koji Abe1, Kewei Chen2, Yong Shen3, Jinglong Wu1, 1 Okayama University, Okayama, Japan; 2Banner Alzheimer’s Institute and Banner Good Samaritan PET Center, Phoenix, Arizona, United States; 3 Roskamp Institute, Center for Advanced Therapeutic Strategies for Brain Disorders, Sarasota, Florida, United States. Background: Disturbance of attentional processes represents the first cognitive indicator of neocortical dysfunction in early stage of Dementia of the Alzheimer type (DAT). Our previous tactile angle discrimination task showed that MCI (mild cognitive impairment) and DAT might be caused, at least partially, attentional dysfunction (Yang et al., JAD, 2010). Disconnection between frontal and posterior parietal areas may mediate the selective disruption of attentional functions in DAT. By using Posner task (Posner MI, Q J Exp Psychol, 1980) and fMRI (functional magnetic resonance imaging), we intended to examine the attention related neural network difference between normal and DAT/MCI patients. Methods: Data from 16 normal young (NY), 16 normal elder (NE) and 16 MCI/DAT patients were used. The Posner task used in this study was the spatial attention and the spatial expectation. The target stimulus was used with a width and height both of 2 degrees of eccentricity. For the spatial attention task, participants were constructed to pay attention to the side at which custimulus was presented and to press the reaction key as quickly as possible when the target stimulus was to appear. During the spatial expectation task, cue was presented until the target stimulus appeared. Images were pre-processed using SPM8 and the general linear model determined task vs control condition fMRI signal differences from regions of interest (ROI) (IPL, inferior parietal lobe; MT+, contain both middle temporal (MT) and medial superior temporal (MST); FEF, frontal eye field; IFG, inferior frontal gyrus, all in right hemisphere) and right motor area were further statistically examined using SPSS. Results: Reaction times showed a reaction speed order was in a good agreement with NY (normal younger)> NE (normal elder) > MCI/DAT as the same as the accuracy (p < 0.05 between normal and patient groups). fMRI results found distinct differences among the three groups under the two tasks, respectively, in a number of ROI analyzed. Especially, during the topdown spatial attention task, 4 regions (IPL, MT+, FEF and IFG, all in right hemisphere) were associated with group differences (p ¼ 0.05). During the spatial expectation task, a significant magnitude difference of ROI-based signal change was found within the right motor area (p ¼ 0.05). Conclusions: Using the Posner experimental paradigm, we found the differences among NY, NE and MCI/ DAT patients both from behavioral and brain imaging results. Additional studies with more advanced analytic techniques are needed to confirm our findings.
P1-371
S231 CORRELATIONS OF MAGNETIC RESONANCE SPECTROSCOPY WITH COGNITIVE FUNCTION IN REMITTED LATE-LIFE MAJOR DEPRESSIVE DISORDER
Cheng-Sheng Chen1, 1Kaohsiung Medical University, Kaohsiung, Taiwan, Kaohsiung, Taiwan. Background: Depressive elders with cognitive impairment are at higher risk to develop dementia at follow-up. Understanding of characteristics of brain function of these patients is beneficial to develop preventive strategies. The goal of this study was to examine the biochemical abnormalities of remitted late-life major depression by using 3-T proton magnetic resonance spectroscopy (MRS). Correlations between cognitive function and biochemical abnormalities above these regions will be investigated. Methods: Seventy-four elderly patients with major depressive disorder in remission and 74 age- and sex-match comparison elders received 3-T MRS. MRS spectra were acquired from voxels which were placed in the basal ganglia, dorsolateral prefrontal lobe, and hippocampus. Ratio levels of N-acetylaspartate (NAA), choline, and myo-inositol reference to creatine were calculated. A cognitive battery tapping executive function, memory, and information processing speed were conducted. Bonferroni correction was applied to reduce type I error from multiple testing. Results: Patients with late-life major depressive disorder in remission had a significantly lower NAA/creatine at the basal ganglia and dorsolateral prefrontal lobe, and higher choline/creatine at the basal ganglia, dorsolateral prefrontal lobe and hippocampus as compared to the control subjects. Among all biochemical abnormality at each region, only lower NAA/creatine at basal ganglia associated with poor performance of executive function, delayed recall memory and information processing speed. Conclusions: The elderly with major depressive disorder shows abnormal brain biochemical change even in remitted state. Neuron loss at basal ganglia played a neurobiological basis for the cognitive dysfunction among the depressive elders. P1-372
GREATER IMPACT OF WHITE MATTER HYPERINTENSITIES ON COGNITION IN APOE CARRIERS
Leslie Baxter1, Michael J. Purcell1, Seban Liu1, Kyle steinke1, Richard Caselli2, 1Barrow Neurological Institute, Phoenix, Arizona, United States; 2Mayo Clinic Arizona, Scottsdale, Arizona, United States. Background: White matter hyperintensities (WMH) are commonly observed on magnetic resonance imaging in older individuals, especially with the advent of fluid attenuated inversion recovery (FLAIR). The APOE e4 allele, which confers a greater risk for a steeper decline in some cognitive abilities even before individuals show signs of Alzheimer and cognition in APOE e4 carriers may be more vulnerable to cardiovascular risk. We examined the effect of APOE on the correlation of WMH and cognition in cognitively normal adults. Methods: Subjects from a study of cognitive aging were scanned on the same 3 Tesla GE scanner. A “3D” T2-weighted FLAIR scan and a T1 (MPRAGE) scan were obtained. Subjects with a history of diabetes (n ¼ 5) or no evidence of any WMH (n ¼ 2) were excluded as outliers. A semi-automated method of segmenting WMH was performed based on determining the mean intensity values for WMH and CSF for thresholding. Percentage of WMH were calculated for each region as: (WHM/Total Tissue Voxels)x100 (WMH%). Results: There were no group differences in age, total intracranial volume. Carriers performed worse on verbal memory. There were no group differences in the presence of hypertension. There were no group differences for mean regional WMH%. No correlation was seen with age and WMH% in either groups. Significant correlations of cognitive tests with WMH% occurred only among the APOE e4 carrier group, including Boston Naming Test with left temporal, parietal and periventricular regions. Verbal Comprehension (WAIS-R) correlated with left temporal, left parietal, periventricular, and whole brain WMH%. Trailmaking Test B (executive functioning) correlated with left frontal, left and right parietal, periventricular, right temporal and whole brain WMH%. Conclusions: These data suggest that APOE e4 allele alters the impact of WMH on cognition. This effect was for measures of executive functioning and language rather than memory. These findings are consistent with prior reports of greater vulnerability of apoe e4 carriers to a variety of pathophysiological stresses.