- Email: [email protected]
Comparison of auditory P300 responses in healthy elderly, people with mild cognitive impairment and people with Alzheimer's disease
Poster Presentations: P1 University, Istanbul, Turkey; 3Dokuz Eylul University, Izmir, Turkey. Contact e-mail: [email protected] Background: The role of beta responses in cognitive load was least understood in comparison to other frequency bands. The aim of the present study is to investigate the role of beta response oscillations upon cognitive load in healthy subjects and in subjects with mild cognitive impairment (MCI). Methods: Seventeen consecutive patients with MCI (mean age 70,76 65,62years) according to Petersen’s criteria and Seventeen age- and education-matched normal elderly controls (mean age 68,49 65,48 years) were included in the study. Visual oddball paradigm was used in the experiments. Oscillatory responses were recorded from F 3, F z, F 4, C 3, C z, C 4, TP 7, TP 8, P 3, P z, P 4, O 1, O z and O 2 scalp electrodes. EEG-evoked power, inter-trial phase synchronization and event related beta responses filtered in 15-20 Hz were obtained in response to target and non-target stimuli for both groups of subjects. Results: EEG-evoked beta power, inter-trial phase synchronization of beta responses and event related filtered beta responses were significantly higher in response target stimulation in comparison to non-target stimulation in healthy subjects (p<0,05). On the other hand, there were no evoked beta power differences between target and non target stimuli in MCI patients. Furthermore, upon presentation of visual oddball paradigm occipital electrodes enhanced higher beta response in comparison to other electrode sites (p< 0,0001). Conclusions: The results of the present study clearly indicated that target stimulation elicited higher event related beta power, event related beta phase locking and event related filtered beta responses than non-target stimulation in all electrode sites in healthy subjects. Event related beta increase could be related to attention and cognitive activity. The increased beta response upon presentation of target stimuli in healthy subjects implies that beta oscillations could shift the system to an attention state and had important function in cognitive activity. This may, in future, open the way to consider the beta activity as universal operator in the brain in cognitive processes. P1-209
COMPARISON OF AUDITORY P300 RESPONSES IN HEALTHY ELDERLY, PEOPLE WITH MILD COGNITIVE IMPAIRMENT AND PEOPLE WITH ALZHEIMER’S DISEASE
ulbalca Cakiroglu2, Meltem Civelek2, Pinar Kurt3, Derya Durusu Emek1, G€ Gorsev Yener2, 1Istanbul Kultur University, Istanbul, Turkey; 2Dokuz Eylul University, Izmir, Turkey; 3Istanbul Arel University, Istanbul, Turkey. Contact e-mail: [email protected] Background: Event-related potentials (ERP) has been widely used as a cognitive measurement tool for diagnosis and prognosis of many neuropsychiatric diseases. In the present study, it is aimed to investigate changing brain dynamics in de novo Alzheimer’s Disease (AD) patients, Mild Cognitive Impairment (MCI) patients and healthy elderly by implying auditory ERPs. Methods: 15 de novo AD patients (mean age 70.53 610.49 years) according to NINCDS-ADRDA criteria, 15 MCI patients (mean age 71.93 67.85 years) according to Petersen’s criteria and 15 healthy elderly (mean age 70.80 67.46 years) were participated to the study. The groups did not differ in terms of age and gender. A classical auditory oddball paradigm was used in the experiments. The EEG was recorded from F 3, F z, F 4, C 3, C z, C 4, P 3, P z, P 4, O 1, O z and O 2 locations. The maximum amplitudes for each subject’s averaged P300 response (0.5-25 Hz) were measured. Independent samples t-test and repeated measures of ANOVA were used for statistical analysis. Results: The maximum amplitudes of auditory P300 for target tones between groups differed significantly on all electrode sites (p¼0.000). Post-hoc comparisons using the independent sample t test revealed that P300 amplitudes of MCI group were significantly lower than in healthy controls and significantly higher than in AD group over the right and left parietal and occipital electrodes [healthy controls and AD patients, respectively, P 3 (p¼0.002; p¼0.018), P 4 (p¼0.000; p¼0.012), O 1 (p¼0.042; p¼0.034) ve O 2 (p¼0.017; p¼0.40)].On all the other electrode sites, P300 amplitudes of MCI subjects were significantly lower than the healthy controls and didn’t differ between AD patients. P300 amplitudes of healthy controls were significantly larger than AD patients in all regions (p¼0.000). Conclusions: A statistically significant dif-
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ference in P300 amplitude is found between the groups. P300 responses are considered to be related to attention and memory processes. Therefore, lower amplitudes of P300 in AD and MCI patients are an electrophysiological reflection of attention and memory deficits. P1-210
CEREBROSPINAL FLUID BIOMARKERS AND PET IMAGING OF CEREBRAL GLUCOSE METABOLISM IN IRAQ AND AFGHANISTAN VETERANS: CONVERGING EVIDENCE OF BRAIN DYSFUNCTION AND NEURODEGENERATION
Elaine Peskind1, Eric Petrie1, Donna Cross2, Gail Li3, Cynthia Mayer1, Satoshi Minoshima2, Jing Zhang4, Thomas Montine2, Murray Raskind1, 1 VA Puget Sound Health Care System, Seattle, Washington, United States; 2 University of Washington, Seattle, Washington, United States; 3University of Washington, Seattle, Washington, United States; 4University of Washington School of Medicine, Seattle, Washington, United States. Contact e-mail: [email protected] Background: Autopsy studies raise concern about possible tauopathy neurodegeneration in military Veterans following repeated blast and/or impact mild traumatic brain injury (mTBI). Here we asked if Iraq and Afghanistan deployed Veterans with mTBI had abnormal brain function or neurodegeneration using FDG-PET brain imaging and measurement of neurodegeneration biomarkers in cerebrospinal fluid (CSF) compared to deployed Veterans without mTBI and civilian controls without mTBI. Methods: Four groups were studied: 34 male Iraq/Afghanistan Veterans with blast concussion mTBI, 16 Veterans deployed to Iraq/Afghanistan with no lifetime history of TBI (Non-blast Veterans), 12 civilian controls with no lifetime TBI (who underwent only FDG-PET), and 55 civilian controls with no lifetime TBI (who underwent only CSF collection). Brain PET images were acquired on a GE Advanced scanner, voxel intensity was normalized to global brain activity, and whole brain voxelwise comparisons were performed using Neurostat/3D-SSP. CSF A b 42, total tau and p-tau 181 were measured using immunobead-based multiplex assays. Results: Both Blast mTBI and Nonblast Veterans had significantly lower CMRglu in the cerebellum, pons, thalamus, and medial temporal cortices bilaterally compared to the 12 civilian community controls, (p values ranging from 0.0007 to 0.038). CMRglu in these brain structures did not differ between Blast mTBI and Non-blast Veterans. The ratio of p-tau 181 to total tau was significantly elevated in both Blast mTBI and Non-blast Veterans compared to civilian controls (p<0.0005). The p-tau 181:total tau ratio did not differ between Blast mTBI and Non-blast Veterans. Conclusions: This study demonstrated regional brain hypometabolism and elevated CSF p-tau 181 to total tau ratio in Iraq and Afghanistan Veterans with or without mTBI. Possible explanations for these findings in the Non-blast Veterans include: selection bias for military service as well as environmental/behavioral exposures during military training and/or deployment to the Iraq and Afghanistan war zones. P1-211
EFFECTS OF MS4A VARIANTS ON CEREBROSPINAL FLUID BETA-AMYLOID 1-42
Lyzel Elias-Sonnenschein1, F. R. J. Verhey2, Pieter Jelle Visser3, Maastricht University, Maastricht, Netherlands; 2Maastricht University, Maastricht, Netherlands; 3VUMC, Maastricht, Netherlands. Contact e-mail: [email protected] 1
Background: Single nucleotide polymorphisms (SNPs) in the membranespanning 4-domains, subfamily A (MS4A) gene cluster have been identified in genome-wide association studies (GWAS) to be associated with Alzheimer’s disease (AD). We recently reported that MS4A4A rs2304933, but not MS4A4E rs670139 and MS4A6A rs2304933, significantly reduced cerebrospinal fluid (CSF) amyloid beta 1-42 isoform (A b 1-42) in a Finnish AD population. We aim to replicate these findings in an independent cohort composed of various diagnostic groups. Methods: We included 243 participants (78 AD, 93 mild cognitive impairment, 48 other type of dementia, 24 cognitively healthy control subjects) from the European multicentre EDAR study. Genomic DNA was extracted from EDTA anticoagulated blood and was amplified by polymerase chain reaction (PCR). We genotyped MS4A4E rs670139, MS4A6A rs610932 and MS4A4A rs2304933 on the
COMPARISON OF AUDITORY P300 RESPONSES IN HEALTHY ELDERLY, PEOPLE WITH MILD COGNITIVE IMPAIRMENT AND PEOPLE WITH ALZHEIMER’S DISEASE
ulbalca Cakiroglu2, Meltem Civelek2, Pinar Kurt3, Derya Durusu Emek1, G€ Gorsev Yener2, 1Istanbul Kultur University, Istanbul, Turkey; 2Dokuz Eylul University, Izmir, Turkey; 3Istanbul Arel University, Istanbul, Turkey. Contact e-mail: [email protected] Background: Event-related potentials (ERP) has been widely used as a cognitive measurement tool for diagnosis and prognosis of many neuropsychiatric diseases. In the present study, it is aimed to investigate changing brain dynamics in de novo Alzheimer’s Disease (AD) patients, Mild Cognitive Impairment (MCI) patients and healthy elderly by implying auditory ERPs. Methods: 15 de novo AD patients (mean age 70.53 610.49 years) according to NINCDS-ADRDA criteria, 15 MCI patients (mean age 71.93 67.85 years) according to Petersen’s criteria and 15 healthy elderly (mean age 70.80 67.46 years) were participated to the study. The groups did not differ in terms of age and gender. A classical auditory oddball paradigm was used in the experiments. The EEG was recorded from F 3, F z, F 4, C 3, C z, C 4, P 3, P z, P 4, O 1, O z and O 2 locations. The maximum amplitudes for each subject’s averaged P300 response (0.5-25 Hz) were measured. Independent samples t-test and repeated measures of ANOVA were used for statistical analysis. Results: The maximum amplitudes of auditory P300 for target tones between groups differed significantly on all electrode sites (p¼0.000). Post-hoc comparisons using the independent sample t test revealed that P300 amplitudes of MCI group were significantly lower than in healthy controls and significantly higher than in AD group over the right and left parietal and occipital electrodes [healthy controls and AD patients, respectively, P 3 (p¼0.002; p¼0.018), P 4 (p¼0.000; p¼0.012), O 1 (p¼0.042; p¼0.034) ve O 2 (p¼0.017; p¼0.40)].On all the other electrode sites, P300 amplitudes of MCI subjects were significantly lower than the healthy controls and didn’t differ between AD patients. P300 amplitudes of healthy controls were significantly larger than AD patients in all regions (p¼0.000). Conclusions: A statistically significant dif-
P229
ference in P300 amplitude is found between the groups. P300 responses are considered to be related to attention and memory processes. Therefore, lower amplitudes of P300 in AD and MCI patients are an electrophysiological reflection of attention and memory deficits. P1-210
CEREBROSPINAL FLUID BIOMARKERS AND PET IMAGING OF CEREBRAL GLUCOSE METABOLISM IN IRAQ AND AFGHANISTAN VETERANS: CONVERGING EVIDENCE OF BRAIN DYSFUNCTION AND NEURODEGENERATION
Elaine Peskind1, Eric Petrie1, Donna Cross2, Gail Li3, Cynthia Mayer1, Satoshi Minoshima2, Jing Zhang4, Thomas Montine2, Murray Raskind1, 1 VA Puget Sound Health Care System, Seattle, Washington, United States; 2 University of Washington, Seattle, Washington, United States; 3University of Washington, Seattle, Washington, United States; 4University of Washington School of Medicine, Seattle, Washington, United States. Contact e-mail: [email protected] Background: Autopsy studies raise concern about possible tauopathy neurodegeneration in military Veterans following repeated blast and/or impact mild traumatic brain injury (mTBI). Here we asked if Iraq and Afghanistan deployed Veterans with mTBI had abnormal brain function or neurodegeneration using FDG-PET brain imaging and measurement of neurodegeneration biomarkers in cerebrospinal fluid (CSF) compared to deployed Veterans without mTBI and civilian controls without mTBI. Methods: Four groups were studied: 34 male Iraq/Afghanistan Veterans with blast concussion mTBI, 16 Veterans deployed to Iraq/Afghanistan with no lifetime history of TBI (Non-blast Veterans), 12 civilian controls with no lifetime TBI (who underwent only FDG-PET), and 55 civilian controls with no lifetime TBI (who underwent only CSF collection). Brain PET images were acquired on a GE Advanced scanner, voxel intensity was normalized to global brain activity, and whole brain voxelwise comparisons were performed using Neurostat/3D-SSP. CSF A b 42, total tau and p-tau 181 were measured using immunobead-based multiplex assays. Results: Both Blast mTBI and Nonblast Veterans had significantly lower CMRglu in the cerebellum, pons, thalamus, and medial temporal cortices bilaterally compared to the 12 civilian community controls, (p values ranging from 0.0007 to 0.038). CMRglu in these brain structures did not differ between Blast mTBI and Non-blast Veterans. The ratio of p-tau 181 to total tau was significantly elevated in both Blast mTBI and Non-blast Veterans compared to civilian controls (p<0.0005). The p-tau 181:total tau ratio did not differ between Blast mTBI and Non-blast Veterans. Conclusions: This study demonstrated regional brain hypometabolism and elevated CSF p-tau 181 to total tau ratio in Iraq and Afghanistan Veterans with or without mTBI. Possible explanations for these findings in the Non-blast Veterans include: selection bias for military service as well as environmental/behavioral exposures during military training and/or deployment to the Iraq and Afghanistan war zones. P1-211
EFFECTS OF MS4A VARIANTS ON CEREBROSPINAL FLUID BETA-AMYLOID 1-42
Lyzel Elias-Sonnenschein1, F. R. J. Verhey2, Pieter Jelle Visser3, Maastricht University, Maastricht, Netherlands; 2Maastricht University, Maastricht, Netherlands; 3VUMC, Maastricht, Netherlands. Contact e-mail: [email protected] 1
Background: Single nucleotide polymorphisms (SNPs) in the membranespanning 4-domains, subfamily A (MS4A) gene cluster have been identified in genome-wide association studies (GWAS) to be associated with Alzheimer’s disease (AD). We recently reported that MS4A4A rs2304933, but not MS4A4E rs670139 and MS4A6A rs2304933, significantly reduced cerebrospinal fluid (CSF) amyloid beta 1-42 isoform (A b 1-42) in a Finnish AD population. We aim to replicate these findings in an independent cohort composed of various diagnostic groups. Methods: We included 243 participants (78 AD, 93 mild cognitive impairment, 48 other type of dementia, 24 cognitively healthy control subjects) from the European multicentre EDAR study. Genomic DNA was extracted from EDTA anticoagulated blood and was amplified by polymerase chain reaction (PCR). We genotyped MS4A4E rs670139, MS4A6A rs610932 and MS4A4A rs2304933 on the