- Email: [email protected]
Oxidative Stress Peripheral Biomarkers in Mild Cognitive Impairment and Alzheimer's Disease
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shown that AD patients remember more stimuli with a negative than a positive emotional valence, however, results indicating the opposite have also been found. Methods: A 57 year old male diagnosed with mild probable AD volunteered for this case-study. The spaced-retrieval technique was used to train novel face-name combinations. Face-name combinations of 12 item-pairs were trained in 2 blocks (A and B). Each block consisted of 6 sessions over 3 weeks. Half of the faces expressed a positive emotion (happiness) and half a negative emotion (sadness). Two follow-up measurements were conducted 4 and 8 weeks after the last training session of each block. Results: Results indicated that an initial learning of all novel face-name associations was achieved immediately after training. However, at follow-up, recall for the material became increasingly limited. Two to three days following training a difference in performance on name recall and face recognition was observed, the latter was significantly higher than the former. This difference was also observable in the follow-up measurements. The patient performed quite well on face recognition, which indicates that he had stored the information but was unable to explicitly retrieve the names of the faces. During immediate and delayed face recognition and name recall, no clear difference in performance on negatively vs. positively loaded items was observable. However, during face recognition two months post-training the patient could recognise approximately half of the faces that showed a positive emotional expression but none of the faces that showed a negative emotional expression. Conclusions: Findings in the present case-study indicated that the spaced-retrieval technique can successfully be used for training novel face-name associations in AD. However, a failure to retain the trained face-name associations in explicit memory over longer time periods was observed. An indication of a positive emotional enhancement effect on learning face-name associations was found. P3-482
COGNITIVE PROFILES OF DEMENTIA IN THE UNIFIED DATA SET
David K. Johnson1, Zachary Langford1, Phoung Chow1, Amber Watts1, Jeffrey M. Burns2, 1University of Kansas, Lawrence, KS, USA; 2University of Kansas Medical Center, Kansas City, KS, USA. Contact e-mail: dkj@ku. edu Background: Our objective is to test if a hybrid model of cognitive test performance developed at the Washington University Alzheimer’s Disease Research Center could be generalized to the NACC Unified Data Set. Methods: A reduced hybrid model made up of NACC UDS subtests was compared to four alternate configurations of cognitive test performance using multistep confirmatory factor analysis in individuals with DAT and research participants without clinical dementia. Initial model fitting was conducted with archived data (N ¼ 330) from the Washington University Alzheimer’s Disease Research Center. Models were then cross-validated using an independent sample (N ¼ 137) from the Alzheimer’s and Memory Project at the University of Kansas. Results: After controlling for Alzheimer’s specific changes in episodic memory, performance by people with and without dementia on the NACC Unified Data Set was best represented by a single model of one general factor and two specific factors (verbal memory and working memory). These data provide converging data for the flexibility of the hybrid factor analytic model. Conclusions: The existence of a common set of dimensions of cognition in normal aging and in mild AD simplifies research examining the transition from one state to the other. The presence of a common factor maximizes detection of the disease, whereas the specific factors reveal the heterogeneity of its associated cognitive deficits. P3-483
OXIDATIVE STRESS PERIPHERAL BIOMARKERS IN MILD COGNITIVE IMPAIRMENT AND ALZHEIMER’S DISEASE
Tania Marcourakis, Nathalia B. Quaglio, Larissa H. L. Torres, Gisele T. Souza, Raphael C. T. Garcia, Wallace L. Moreira, Rosana Camarini, Juliana N. Souza-Talarico, Jerusa Smid, Claudia S. Porto, Ricardo Nitrini, University of Sa˜o Paulo, Sa˜o Paulo, Brazil. Contact e-mail: [email protected] Background: It is well established that oxidative stress is associated with aging and neurodegenerative processes, such as Alzheimer’s disease
(AD). Our aim was to determine plasma malondialdehyde (MDA), a lipid peroxidation marker, and to measure the activity of five erythrocytary antioxidant enzymes: catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), and gluthatione S-transferase (GST) on healthy aged subjects and in individuals with mild cognitive impairment (MCI) and AD. MCI is usually seen as an intermediate condition between healthy aging and AD. Methods: Twenty eight healthy subjects (60-81 years), 35 patients with MCI (61-87 years) and 32 with AD (68-90 years) were included in this study. Blood (20 mL) was collected in heparin tubes and centrifuged at 700-1000g (10 min/4 C). Plasma was separated and stored at -80 C. Erythrocytes were washed three times with saline solution and stored at -80 C. Enzymatic colorimetric methods were used to evaluate enzymatic activities. MDA levels were measured by HPLC by UV/Vis detection. Results: No differences in SOD and GST activities were detected among AD, MCI and healthy controls. MDA levels, as well catalase and GPx activities, were similar in MCI and healthy individuals and higher in AD. Finally, GR activity was lower in MCI and AD patients than in healthy aged subjects. Additionally, healthy controls have a significantly higher GR/ GPx ratio, when compared with MCI; the same occurred when the group of MCI individuals was compared with the AD patients. Conclusions: Reduction of GR seems to be a hallmark of cognitive decline, but GR/GPx ratio was more strongly associated with progression of cognitive decline, being higher in healthy subjects, intermediate in MCI and lower in AD subjects. A reduced capacity to restore glutathione (GSH) levels might be the main source of increased oxidative stress status in cognitive decline. Supported by FAPESP P3-484
IS DEPRESSION A PRODROME OF DEMENTIA?
Ge (Gail) Li1, Lucy Y. Wang1, Jane B. Shofer1, MaryLou Thompson1, James D. Bowen2, Wayne McCormick1, Elaine R. Peskind1,3, Paul K. Crane1, Eric B. Larson1,4, 1University of Washington, Seattle, WA, USA; 2Swedish Medical Center, Seattle, WA, USA; 3Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA; 4Group Health Cooperative, Seattle, WA, USA. Contact e-mail: [email protected] Background: Recent studies have shown that depression is associated with increased risk of cognitive decline, mild cognitive impairment and dementia. Whether depression increases risk of dementing illness or whether latelife depression is a prodrome of dementia remains unclear. To address this question, we examined associations between early-life and late-life depression and dementia in participants of the Adult Changes in Thought study, a community-based prospective study. Methods: A combined cohort of 3, 410 cognitively intact participants aged 65 years (60% female and mean age-at-entry 74.9 years) was followed biennially for dementia (diagnosed using DSM-IV criteria). Depression was assessed at baseline using the 11-item version of the Center for Epidemiologic Studies Depression Scale (CESD-11, total score: 0-33), and defined as CESD-11 score > 10. Self-reported history of depression episodes and age-at-onset of these episodes were also collected at baseline interview. Cox proportional hazards regression with delayed entry and age as the time axis was used to assess the impact of baseline depression (CESD-11 > 10), depression history, and their combination, on the hazard for dementia. Results: Over an average of 7.1 [1-15] years follow-up, 657 participants developed dementia. Among participants with dementia, 14% had baseline depression and 21% reported a history of depression (8% reported early-onset [ age 50] and 13% late-onset). Compared with those with no or mild depression (CESD-11 score 10), the hazard ratio (HR) for dementia of baseline depression was 1.71 (1.37, 2.14) after adjusting for age-at-entry ( 80 vs. 50) had an increased hazard of dementia (adjusted HR ¼1.44 [1.14, 1.82]) but not those with early-onset depression (adjusted HR¼1.11 [0.83, 1.47]). Compared to participants with neither baseline depression nor early-onset depression history, those with baseline depression without early-life depression are at highest risk for dementia (adjusted HR¼1.77 [1.39, 2.25]). Conclusions: Late-life depression, but not early-life depression, is associated with subsequent development of dementia, suggesting depression may be a part of the dementia prodrome.
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shown that AD patients remember more stimuli with a negative than a positive emotional valence, however, results indicating the opposite have also been found. Methods: A 57 year old male diagnosed with mild probable AD volunteered for this case-study. The spaced-retrieval technique was used to train novel face-name combinations. Face-name combinations of 12 item-pairs were trained in 2 blocks (A and B). Each block consisted of 6 sessions over 3 weeks. Half of the faces expressed a positive emotion (happiness) and half a negative emotion (sadness). Two follow-up measurements were conducted 4 and 8 weeks after the last training session of each block. Results: Results indicated that an initial learning of all novel face-name associations was achieved immediately after training. However, at follow-up, recall for the material became increasingly limited. Two to three days following training a difference in performance on name recall and face recognition was observed, the latter was significantly higher than the former. This difference was also observable in the follow-up measurements. The patient performed quite well on face recognition, which indicates that he had stored the information but was unable to explicitly retrieve the names of the faces. During immediate and delayed face recognition and name recall, no clear difference in performance on negatively vs. positively loaded items was observable. However, during face recognition two months post-training the patient could recognise approximately half of the faces that showed a positive emotional expression but none of the faces that showed a negative emotional expression. Conclusions: Findings in the present case-study indicated that the spaced-retrieval technique can successfully be used for training novel face-name associations in AD. However, a failure to retain the trained face-name associations in explicit memory over longer time periods was observed. An indication of a positive emotional enhancement effect on learning face-name associations was found. P3-482
COGNITIVE PROFILES OF DEMENTIA IN THE UNIFIED DATA SET
David K. Johnson1, Zachary Langford1, Phoung Chow1, Amber Watts1, Jeffrey M. Burns2, 1University of Kansas, Lawrence, KS, USA; 2University of Kansas Medical Center, Kansas City, KS, USA. Contact e-mail: dkj@ku. edu Background: Our objective is to test if a hybrid model of cognitive test performance developed at the Washington University Alzheimer’s Disease Research Center could be generalized to the NACC Unified Data Set. Methods: A reduced hybrid model made up of NACC UDS subtests was compared to four alternate configurations of cognitive test performance using multistep confirmatory factor analysis in individuals with DAT and research participants without clinical dementia. Initial model fitting was conducted with archived data (N ¼ 330) from the Washington University Alzheimer’s Disease Research Center. Models were then cross-validated using an independent sample (N ¼ 137) from the Alzheimer’s and Memory Project at the University of Kansas. Results: After controlling for Alzheimer’s specific changes in episodic memory, performance by people with and without dementia on the NACC Unified Data Set was best represented by a single model of one general factor and two specific factors (verbal memory and working memory). These data provide converging data for the flexibility of the hybrid factor analytic model. Conclusions: The existence of a common set of dimensions of cognition in normal aging and in mild AD simplifies research examining the transition from one state to the other. The presence of a common factor maximizes detection of the disease, whereas the specific factors reveal the heterogeneity of its associated cognitive deficits. P3-483
OXIDATIVE STRESS PERIPHERAL BIOMARKERS IN MILD COGNITIVE IMPAIRMENT AND ALZHEIMER’S DISEASE
Tania Marcourakis, Nathalia B. Quaglio, Larissa H. L. Torres, Gisele T. Souza, Raphael C. T. Garcia, Wallace L. Moreira, Rosana Camarini, Juliana N. Souza-Talarico, Jerusa Smid, Claudia S. Porto, Ricardo Nitrini, University of Sa˜o Paulo, Sa˜o Paulo, Brazil. Contact e-mail: [email protected] Background: It is well established that oxidative stress is associated with aging and neurodegenerative processes, such as Alzheimer’s disease
(AD). Our aim was to determine plasma malondialdehyde (MDA), a lipid peroxidation marker, and to measure the activity of five erythrocytary antioxidant enzymes: catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), and gluthatione S-transferase (GST) on healthy aged subjects and in individuals with mild cognitive impairment (MCI) and AD. MCI is usually seen as an intermediate condition between healthy aging and AD. Methods: Twenty eight healthy subjects (60-81 years), 35 patients with MCI (61-87 years) and 32 with AD (68-90 years) were included in this study. Blood (20 mL) was collected in heparin tubes and centrifuged at 700-1000g (10 min/4 C). Plasma was separated and stored at -80 C. Erythrocytes were washed three times with saline solution and stored at -80 C. Enzymatic colorimetric methods were used to evaluate enzymatic activities. MDA levels were measured by HPLC by UV/Vis detection. Results: No differences in SOD and GST activities were detected among AD, MCI and healthy controls. MDA levels, as well catalase and GPx activities, were similar in MCI and healthy individuals and higher in AD. Finally, GR activity was lower in MCI and AD patients than in healthy aged subjects. Additionally, healthy controls have a significantly higher GR/ GPx ratio, when compared with MCI; the same occurred when the group of MCI individuals was compared with the AD patients. Conclusions: Reduction of GR seems to be a hallmark of cognitive decline, but GR/GPx ratio was more strongly associated with progression of cognitive decline, being higher in healthy subjects, intermediate in MCI and lower in AD subjects. A reduced capacity to restore glutathione (GSH) levels might be the main source of increased oxidative stress status in cognitive decline. Supported by FAPESP P3-484
IS DEPRESSION A PRODROME OF DEMENTIA?
Ge (Gail) Li1, Lucy Y. Wang1, Jane B. Shofer1, MaryLou Thompson1, James D. Bowen2, Wayne McCormick1, Elaine R. Peskind1,3, Paul K. Crane1, Eric B. Larson1,4, 1University of Washington, Seattle, WA, USA; 2Swedish Medical Center, Seattle, WA, USA; 3Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA; 4Group Health Cooperative, Seattle, WA, USA. Contact e-mail: [email protected] Background: Recent studies have shown that depression is associated with increased risk of cognitive decline, mild cognitive impairment and dementia. Whether depression increases risk of dementing illness or whether latelife depression is a prodrome of dementia remains unclear. To address this question, we examined associations between early-life and late-life depression and dementia in participants of the Adult Changes in Thought study, a community-based prospective study. Methods: A combined cohort of 3, 410 cognitively intact participants aged 65 years (60% female and mean age-at-entry 74.9 years) was followed biennially for dementia (diagnosed using DSM-IV criteria). Depression was assessed at baseline using the 11-item version of the Center for Epidemiologic Studies Depression Scale (CESD-11, total score: 0-33), and defined as CESD-11 score > 10. Self-reported history of depression episodes and age-at-onset of these episodes were also collected at baseline interview. Cox proportional hazards regression with delayed entry and age as the time axis was used to assess the impact of baseline depression (CESD-11 > 10), depression history, and their combination, on the hazard for dementia. Results: Over an average of 7.1 [1-15] years follow-up, 657 participants developed dementia. Among participants with dementia, 14% had baseline depression and 21% reported a history of depression (8% reported early-onset [ age 50] and 13% late-onset). Compared with those with no or mild depression (CESD-11 score 10), the hazard ratio (HR) for dementia of baseline depression was 1.71 (1.37, 2.14) after adjusting for age-at-entry ( 80 vs. 50) had an increased hazard of dementia (adjusted HR ¼1.44 [1.14, 1.82]) but not those with early-onset depression (adjusted HR¼1.11 [0.83, 1.47]). Compared to participants with neither baseline depression nor early-onset depression history, those with baseline depression without early-life depression are at highest risk for dementia (adjusted HR¼1.77 [1.39, 2.25]). Conclusions: Late-life depression, but not early-life depression, is associated with subsequent development of dementia, suggesting depression may be a part of the dementia prodrome.