Development of Chinese Card Sorting Test and its Validity Assessment

Development of Chinese Card Sorting Test and its Validity Assessment

Alzheimer’s Imaging Consortium IC-P: Imaging Posters (M.W. 1500, DD.90%) against Cu(II)-induced neurotoxicity in primary cultured rat cortical neurons...

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Alzheimer’s Imaging Consortium IC-P: Imaging Posters (M.W. 1500, DD.90%) against Cu(II)-induced neurotoxicity in primary cultured rat cortical neurons. Methods: Cortical neurons were cultured at 37  C for 7days then incubated more for 12 hours in culture medium without or with 0.4, 0.2, and 0.1mg/ml COSs, respectively. After removed the culture medium and the cultured cortical neurons were added fresh culture medium containing 50mM CuCl2, incubated for 48 hours at 37  C in a humidified incubator. Cell viability were assayed by MTT, Hoechst 33342 assay and lactate dehydrogenase (LDH) assay, and the reactive oxygen species(ROS) levels were detected byROS assay based on the ROS-mediated conversion of nonfluorescent 2’,7’-DCFH-DA into fluorescent DCFH. Results: The toxicity of Cu(II) to cortical neurons was obviously attenuated in a concentration-dependent manner by COSs. The data derived from the LDH and Hoechst 33342 assay support the results from MTT assay well. The following ROS assay indicated that COSs prevent Cu(II)-induced the elevation of intracellular ROS. Conclusions: These findings suggest that COSs protect against Cu(II) induced neurotoxicity in primary cortical neurons by interfering with an increase in intracellular ROS. It will be helpful to further develop the usages of COSs in AD treatment. IC-P-044

LONGITUDINAL IMAGING CHANGES AND VASCULAR RISK FACTORS: A 10-YEAR STUDY

David S. Knopman1, Alan D. Penman2, Laura H. Coker3, Diane J. Catellier4, Dean Shibata5, Thomas H. Mosley2, 1Mayo Clinic, Rochester, MN, USA; 2University of Mississippi Medical Center, Jackson, MS, USA; 3Wake Forest University School of Medicine, Winston-Salem, NC, USA; 4University of North Carolina, Chapel Hill, NC, USA; 5University of Washington, Seattle, WA, USA. Contact e-mail: [email protected] Background: Vascular risk factors are associated with late life cognitive impairment and dementia, but the mechanisms are not well understood. Using longitudinal imaging data from participants in the Atherosclerosis Risk in Communities (ARIC) study, we determined associations between APOE genotype, vascular risk factors and changes on MR imaging over a 10 year period. Methods: MR scans, APOE genotype and assessments of diabetes, hypertension and other cardiovascular risk factors were initially obtained in 1812 participants in 1994-5. In 2004-6, 1084 of those participants underwent repeat MR scans. MR scans were rated semiquantitatively on a validated 9-point scale for ventricular size (VS) and white matter hyperintensity lesion (WML) burden. The presence of infarcts (INF) was noted. Ordinal logistic regression analysis was used to assess associations between vascular risk factors at baseline and change in VS, WML (on a 4 point ordinal scale: no change, worsening by 1, 2 or 3 grades) or incident INF (unchanged or additional new), controlling for age, sex and race. Hypertension and diabetes were defined by composite of historical and laboratory measures. Results: At the baseline visit, the 1084 participants (378 black women, 195 black men, 295 white women, 216 white men) had a mean age 61.7 6 4.3 yrs. A majority of subjects experienced increases in VS (76.1%) and WML burden (62.1%). New INF were observed in 20.1%. Hypertension was associated with incident INF (OR ¼ 1.72, 95% CI 1.22 - 2.43), increasing VS (OR ¼ 1.28, 95% CI 1.01 - 1.64) and WML (OR ¼ 1.33, 95% CI 1.04 1.70). Similarly, diabetes was associated with incident INF (OR ¼ 1.91, 95% CI 1.26 - 2.91), increasing VS (OR ¼ 1.45, 95% CI 1.04 - 2.02) and WML (OR ¼ 1.48, 95% CI 1.07 - 2.06). APOE e4 genotype was associated with only increasing VS (OR ¼ 1.39, 95% CI 1.06 - 1.81). Conclusions: Diabetes and hypertension were both associated with the appearance of new INF, increasing VS and WML. These observations support the contention that diabetes and hypertension exert deleterious effects on the aging brain via vascular mechanisms, although they cannot refute the possibility that they also have direct effects on Alzheimer pathology. Supported by R01-HL70825, N01-HC-55015 through 55022. IC-P-045

COGNITION DECLINE OF ALZHEIMER’S DISEASE PATIENTS IN A MEMORY CLINIC SETTING, SHANGHAI, CHINA

Zhen Hong1, Bin Zhou2, Qianhua Zhao1, Satoshi Teramukai2, Ding Ding1, Qihao Guo1, Masanori Fukushima2, 1Institution of Neurology, Fudan

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University, Shanghai, China; 2Translational Research Informatics Center, Kobe, Japan. Contact e-mail: [email protected] Background: The high prevalence of dementia with the rapid increase of the older population and the lack of effective therapy raise the global issues of human life with aging. Methods: All the cases diagnosed as Alzheimer’s Disease (AD) in the memory clinic of Huashan Hospital Shanghai, China from Jan. 1st 2003 through Dec.31th 2006 were included in this study. The participants were followed via face-to-face clinical and neuropsychological reassessment during September 1, 2007 and July 31, 2008. Those who could not come to the hospital were followed by telephone. Demographic information, the change of cognitive function, behavior, ability of daily life, neurological symptoms, comorbid conditions (aspiration pneumonia, urinary tract infections and decubitus ulcers) were collected. Correlation analysis and logistic regression analysis were conducted to identify the predictors associated with the deterioration of cognitive function. Results: Among the 624 initially clinical diagnosed AD patients, 16 were excluded after diagnosis verification. 608 confirmed AD cases were enrolled in final analysis. 400 cases were followed (163 came to our hospital to receive the whole neuropsychological battery which included auditory verbal fluency test (AVLT), logic memory test, Stroop color word test, Rey-Osterrich complex figure test (CFT), category verbal fluency test (VFT), trail making test (TMT), clock drawing test (CDT), five point test. 237 received telephone follow-up), 69 cases died and the rest 139 lost contact. For the 163 reassessed cases, MMSE total score (p ¼ 0.000), AVLT short delayed recall (p ¼ 0.019), Stroop C correct score (p ¼ 0.002), CFT-copy (p ¼ 0.000), VFT (p ¼ 0.001-0.017), TMT B time(p ¼ 0.030), CDT score(p ¼ 0.013) decreased significantly over time. Among demographic information, previous medical history, family history and comorbid/complications no factor had significant regression with the change of cognition. Conclusions: Memory may be the main affected domain in the early stage of AD. When the disease progressed to the moderate to severe stage, it tended to affect across all cognitive field with no exception.

IC-P-046

DEVELOPMENT OF CHINESE CARD SORTING TEST AND ITS VALIDITY ASSESSMENT

Qihao Guo, Qianhua Zhao, Xinyi Cao, Yan Zhou, Zhen Hong, Institution of Neurology, Fudan University, Shanghai, China. Contact e-mail: dr. [email protected] Background: To develop Chinese Card Sorting Test as an efficient, brief test for evaluating executive function in Chinese elderly. Methods: 35 mild Alzheimer disease (AD), 69 Mild cognitive impairment (MCI) (aMCI-s, 25; aMCI-m, 19; naMCI, 20) and 124 cognitively normal controls (NC) were administered a battery of neuropsychological tests including Chinese Card Sorting Test (CCST). Three sets (including figures, words and numbers) of cards were adopted. Each set had 6 cards. Subjected were asked to sort cards according to shape, number, color and meaning. Full mark is 4 for each set and 12 for totally three sets. Results: Comparison among NC, MCI and AD: in NC group, set II was most difficult while set I was easiest. However, in MCI and AD group, patients scored similar among three sets, indicating same discriminative efficacy. Set I and III sorting started with ‘‘color’’ and followed with ‘‘meaning’’. Set II sorting started with ‘‘meaning’’. The accuracy score for Set II was the lowest which may due to the inhibition effect of ‘‘meaning’’ to other sorting strategy (similar as Stroop effect). ‘‘Number’’ is the most difficult and least used sorting dimension. There were few misclassification which indicated test design produced few misunderstanding. When CCST full mark scored below 6 the sensitivity and specificity for recognizing AD is 94.3% and 74.2%, respectively. When CCST scored below 5, the sensitivity and specificity for recognizing AD is 74.3%, 89.5%, respectively. For those poor educated, optimal cut-off score is 5. Optimal cut-off score should be set as 6 in high educated subjects. Comparison among three MCI subgroups: naMCI-s subgroup scored lowest while aMCI-s scored highest. CCST can distinguish amnestic and non-amnestic MCI. There are significant difference between aMCI-s and naMCI-s for all 3 sets of cards. Significant difference only existed for Set II between aMCI-m and naMCI-s. There was significant difference among 3 subgroups in ‘‘color’’. No difference existed in

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Alzheimer’s Imaging Consortium IC-P: Imaging Posters

‘‘number’’ and ‘‘meaning’’ . There was significant difference between aMCI and naMCI in ‘‘color’’ and ‘‘number’’. There were no difference between aMCI and naMCI in ‘‘shape’’ and ‘‘meaning’’ . Conclusions: Chinese Card Sorting Test is an effective, efficient, feasible executive assessing test. IC-P-047

THE EFFECT OF AGE, GENDER AND EDUCATION IN COGNITIVELY NORMAL ELDERLY ON THE STRATEGY OF TWO DIFFERENT CATEGORY VERBAL FLUENCY TESTS

Qianhua Zhao, Qihao Guo, Ding Ding, Zhen Hong, Institution of Neurology, Fudan University, Shanghai, China. Contact e-mail: applenasa@ hotmail.com Background: Clustering and switching strategy had not been extensively studied in cognitively normal elderly in China. Few studies compared the two semantic verbal fluency tests according to different defined categories. Methods: We recruited cognitively normal subjects and administered neuropsychological tests to them including mini-mental status examination (MMSE), auditory verbal learning test (AVLT), trail making test (TMT), complex figure test (CFT), semantic verbal fluency test (VFT), five point test (FPT), etc. We adopted ‘‘supermarket’’ and ‘‘animal’’ as the two defined categories. Two components_clustering (generating words within subcategories) and switching (shifting between subcategories) were examined. Results: Three hundred and seventy four subjects were enrolled which comprise of 156 men and 218 women with the age as 66.26 6 7.16, education year as 12.72 6 2.79. For the supermarket VFT, the mean score of total correct score, subcategory, cluster size, subcategory switch are 20.19 6 5.83, 4.04 6 1.27, 4.80 6 2.48, 5.94 6 2.91, respectively. With regard to the animal VFT, the scores are 16.79 6 4.56, 2.94 6 1.03, 4.29 6 2.48, 4.64 6 2.49. The zodiac animal score is 6.37 6 2.41. Co-variance analysis showed that: subcategory score was the main significant difference between men and women (supermarket VFT, men, 4.13 6 1.30, women, 3.97 6 1.25, p ¼ 0.035; animal VFT, men 3.11 6 1.07, women, 2.82 6 0.99, p ¼ 0.038). The cluster size decreased significantly in supermarket VFT with aging (p ¼ 0.001), but not in animal VFT. Education level correlated significantly with cluster size (educational year12, 4.58 6 2.25, educational year >12, 5.11 6 2,73, p ¼ 0.007 for supermarket VFT, 3.90 6 2.13, 4.81 6 2.81, p ¼ 0.001 for animal VFT, respectively). Conclusions: Women generate fewer subcategories in verbal fluency test than men. Older groups or poor educated population produce fewer words due to smaller cluster size. These results support a dual processing model in verbal fluency and different strategy in each demographic subgroup. IC-P-048

APPLICATION STUDY OF QUICK COGNITIVE SCREENING TEST IN IDENTIFYING MILD COGNITIVE IMPAIRMENT

Qihao Guo, Xinyi Cao, Yan Zhou, Qianhua Zhao, Ding Ding, Zhen Hong, Institution of Neurology, Fudan University, Shanghai, China. Contact e-mail: [email protected] Background: There are few screening neuropsychological tools for detecting mild cognitive impairment. We developed the Quick Cognitive Screening Test (QCST) and assessed whether it could quickly identify mild cognitive impairment (MCI). Methods: QCST and a full set of standardized neuropsychological tests, including mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA) were performed. A total number of 121 cases of MCI [41 cases of amnestic MCI-single domain (aMCIs); 44 of amnestic MCI-multiple domain (aMCI-m); 36 of nonamnestic MCI-single domain (naMCI)], 79 cases of mild Alzheimer’s disease (AD) and 186 healthy elderly volunteers were employed in the present study. All the participants (55-85 years old) had an education level no less than 5 years. QCST subtests included word list recall, naming test, animal fluency test, similarity test, color trail-1min, clock drawing test, finger construction test, and digit span test. The total score of QCST was 90 points, 10 points for each index of subtests. Results: The total scores of QCST in the MCI, AD and the control groups were (58.13 6 8.18), (44.53 6 10.54) and (72.92 6 6.85) points, respectively. According to the education

level, the cut-off scores of participants with an education of 5-8 years, 9-12 years and more than 13 years were  63, 65 and 68 points, respectively. The sensitivity and specificity of QCST in detection of MCI were 87.6% (, 85.7% for aMCI-s, 90.1% for aMCI-m and 89.5% for naMCI) and 84.3%, respectively. The area under the curve was 0.923 (95% CI: 0.8920.953). Delayed memory, color trails-1min and similarity test could help distinguish between aMCI and naMCI. Conclusions: QCST may have a good sensitivity and specificity for MCI detection, which warrants its further clinical application. IC-P-049

AMYLOID IMAGING WITH [11C]SB-13 PET: A TESTRETEST RELIABILITY STUDY

Nicolaas P. L. G. Verhoeff1,2, Kie Honjo3,4, Edward D. Kaye1,5, Ana Petrovic-Poljak6, Alan A. Wilson7,2, Pablo Rusjan7, Sylvain Houle7, Robert van Reekum2, Morris Freedman8,4, Sandra Black3,4, 1Kunin-Lunenfeld Applied Research Unit and Department of Psychiatry, Baycrest, Toronto, ON, Canada; 2Department of Psychiatry, University of Toronto, Toronto, ON, Canada; 3Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; 4Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON, Canada; 5Institute of Medical Science, University of Toronto, Toronto, ON, Canada; 6Baycrest Mood Clinic, Toronto, ON, Canada; 7PET Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada; 8Rotman Research Institute and Division of Neurology, Department of Medicine, Baycrest, Toronto, ON, Canada. Contact e-mail: pverhoeff@klaru-baycrest. on.ca Background: The purpose of this study is to assess the reliability of in-vivo beta-amyloid imaging with [11C]SB-13 positron emission tomography (PET). The validity had been previously assessed by comparison with [11C]PIB PET (Am J Geriatr Psychiatry 2004;12:584-595). Methods: Ten mild AD patients (7 males, 3 females; age 72 6 13 years; MMSE scores 22.3 6 2.9) and 10 matched healthy controls ((7 males, 3 females; age 70 6 15 years; MMSE scores 29.6 6 0.7; MOCA scores 27.4 6 2.4) each underwent a magnetic resonance imaging (MRI) scan and two 90-minute PET scans following about 10 mCi intravenous administration of [11C]SB-13. The test-retest intervals for the PET scans were 42 6 17 days for the mild AD patients and 32 6 26 days for the controls. Regions of interest were created using a semi-automated brain region extraction from the MRI images, which were then coregistered with the PET images. Standardized uptake values (SUVs) were calculated by normalizing tissue concentration (nCi/mL) by injected dose per body mass (nCi/g) 40-90 minutes post injection. Standardized uptake value ratios (SUVRs) of the region of interest divided by the cerebellum (reference region) were calculated. Coefficients of variation (COVs: [standard deviation / average] * 100%) for the SUVs and SUVRs were calculated. Results: One 88-year-old male outlier control (average SUV 3.04, SUVR 1.67) was omitted from the comparison. Average 6 standard deviation of the [11C]SB-13 PET SUVs for all brain regions combined were 1.99 6 0.42 for the 10 mild AD patients and 1.35 6 0.22 for the 9 controls (effect size 1.98). The SUVRs for all brain regions combined were 1.26 6 0.21 for the 10 mild AD patients and 0.99 6 0.06 for the 9 controls (effect size 2.01). The COVs for the SUVs in all regions combined were 8.49 6 5.61% for the 10 mild AD patients and 8.76 6 5.46% for the 10 controls. The COVs for the SUVRs in all regions combined were 1.37 6 1.12% for the 10 mild AD patients and 1.81 6 0.82% for the 10 controls. Conclusions: Our preliminary data suggest that [11C]SB-13 PET SUVRs and SUVs are reliable in mild AD patients and controls. Additional semi-quantification methods, such as binding potential estimates, could provide superior effect sizes reflecting the ability to distinguish AD patients from controls. IC-P-050

AUTOMATED VOLUMETRIC MEASUREMENT OF BRAIN STRUCTURES AND WHITE MATTER LESIONS IN ALZHEIMER’S DISEASE AND MILD COGNITIVE IMPAIRMENT

Huali Wang1,2, Frithjof Kruggel3, Daniel Chang4, Min-Ying Su4, Xin Yu1,2, Peking University Institute of Mental Health, Beijing, China; 2Key

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