- Email: [email protected]
Adcs electronic data capture: Collaborative development and management of clinical trial databases
Poster Presentations: P4 Table 2 Validation of proxy-reported cognitive and physical items, n¼300
Neuropsychological test scores General cognitive performance factor Trail Making Test, Part A Trail Making Test, Part B Semantic fluency HVLT-R delayed recall Physical performance measures MLTA Gait speed Grip strength
Sum of most cognitively demanding items
Sum of most physically demanding items
r
r
P value
P value
0.19
.001
0.05
ns
-0.23 -0.15 0.13 0.09
<.001 .013 .021 ns
-0.05 -0.09 -0.02 0.04
ns ns ns ns
0.10
ns
0.36
<.001
0.10 -0.02
ns ns
0.47 0.12
<.001 ns
Cognitive Items selected were Money, Meals, Medications, telephone. Physical Items selected were ADL transfers, ADL walking, SF12 climbing stairs, SF12 moderate activities. Sums of Cognitive and Physical Items: higher scores indicate higher levels of functioning; lower scores indicate dependence; theoretical range 0-4. r ¼ Pearson correlation coefficient. ns ¼ not significant at the .05 confidence level. HVLT-R ¼ Hopkins Verbal Learning Test – Revised. MLTA ¼ Minnesota Leisure Time Activities Questionnaire Score. Trail Making Tests: higher scores reveal greater impairment.
P763
Konyang University Hospital, College of Medicine, Konyang University, Daejeon, South Korea; 2Department of Neurology, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon, South Korea; 3Department of Neurology, Yongin Hyoja Geriatric Hospital, Yongin, South Korea; 4Department of Neurology, Gachon University Gil Medical Center, Incheon, South Korea; 5Department of Neurology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea. Contact e-mail: [email protected] Background: The clinical significance of white matter hyperintensities (WMHs) and lacunes remains unclear in amnestic mild cognitive impairment (aMCI). The purpose of this study is to evaluate the severity and location of WMHs that influence cognition and activities of daily living (ADL) and interactive effects of WMHs on cognition and ADL when accompanied by lacunes or medial temporal atrophy (MTA). Methods: One hundred fifty patients with aMCI underwent MRI, cognitive & functional assessment. WMHs were quantified using a semiautomated volumetric method. Lacune counting and MTA assessment were performed by visual rating. We evaluated the association of each WMHs, lacunes and MTA with cognition and ADL, as well as interactions among these 3 factors. We also analyzed the influence of the location of WMHs on cognition and ADL. Results: The severer WMHs were, the more frontal executive functions declined. The influence on frontal executive functions were greater in periventricular (PV) WMHs than deep WMHs, as well as bigger in anterior, middle, and posterior areas in decreasing order. The instrumental (I) ADL was strongly associated with the anterior and middle area of PVWMHs. WMHs had interactions with lacunes in terms of frontal executive functions and IADL. Conclusions: The location of WMHs as well as total WMHs volume strongly affected executive dysfunctions and poor performance of the IADL, and in particular, the anterior and middle areas of PVWMHs had the strongest effects on them. WMHs and lacunes had synergistic effects on frontal executive functions and the IADL. Therefore, it is important to simultaneously consider WMHs, lacunes and MTA as potential imaging biomarkers for predicting cognition and IADL in aMCI. Special attention should be paid to executive functions and IADL in aMCI patients with coexisting WMHs and lacunes. P4-157
ADCS ELECTRONIC DATA CAPTURE: COLLABORATIVE DEVELOPMENT AND MANAGEMENT OF CLINICAL TRIAL DATABASES
Gustavo Jimenez-Maggiora1, Ronald Thomas1, Stefania Bruschi1, Hongmei Qiu1, Phuoc Hong1, Paul Aisen1, 1UCSD/ADCS, La Jolla, California, United States. Contact e-mail: [email protected]
Figure 1. Difference in Mean Cognitive Ratings and Mean Physical Ratings of Activities. This plot shows the difference between average expert cognitive normalized ratings and physical normalized ratings on each of the 16 items in the expert panel survey. Positive values indicate more cognitive demand. Negative values indicate more physical demand. White triangles indicate four most physically demanding activities chosen as the most physical items. Black triangles indicate four most cognitively demanding activities chosen as the most cognitive items. Legend: AOL ¼ basic Activities of Daily Living. IADL ¼ Instrumental Activities of Daily Living. MOS SF-12 ¼ Medical Outcomes Study 12-ltem Short Form Survey Questionnaire. P4-156
WHITE MATTER HYPERINTENSITIES IN MILD COGNITIVE IMPAIRMENT: CLINICAL IMPACT OF LOCATION AND INTERACTION WITH LACUNES AND MEDIAL TEMPORAL ATROPHY
Bora Yoon1, YongSoo Shim2, Yun-Jeong Hong3, Kee Hyung Park4, YongDuk Kim1, Kee Ook Lee1, Dong Won Yang5, 1Department of Neurology,
Background: The Alzheimer’s Disease Cooperative Study was founded in 1991 in response to a NIA RFA. The primary aim of the ADCS is to ’advance research in the development of interventions that might be useful for treating, delaying, or preventing AD’. Toward that goal the ADCS has designed, managed, and analyzed over 20 large, multi-site AD clinical trials. The psychometric, clinical, and biological data from these trials have been collected using a locally-developed, web-based electronic data capture (EDC) system. This system serves as a central hub used to coordinate the data management, quality assurance, and monitoring activities of thousands of staff across several continents. Methods: Effective design and management of clinical trials databases rests on active and continued collaboration between clinical, scientific, administrative and regulatory staff, among others, over the course of a study. Historically, however, implementation of the specifications resultant from these activities has been the preserve of IT staff, who work in relative isolation and have limited knowledge of the nuances involved in many design decisions. This disjointed process inevitably leads to delays and misconfiguration of database systems. In designing the ADCS EDC’s administration capabilities, our goal was to eliminate the artificial separation between database design, management, and implementation. We accomplish this by using a set of cloud-based Google Docs spreadsheets to abstract the configuration of the underlying database’s schema, study-event schedule, user privileges, and data quality checks. Results: This poster has the following aims:1. Describe the ADCS EDC’s database administration capabilities.2. Discuss how these
P764
Poster Presentations: P4
capabilities were used to accelerate study startup, facilitate intra-study amendments, and streamline shutdown activities.3. Outline opportunities for future improvement. Conclusions: The ADCS EDC system supports a collaborative design and specification process via an intuitive set of cloud-based spreadsheets which allow multi-disciplinary study teams to manage clinical trial databases without the need for IT staff, thus reducing unnecessary delays and potential errors due to miscommunication. This approach has been used to design and manage databases for more than 20 large, multi-site AD clinical trials as well as several extra-ADCS projects, such as the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the Dominantly Inherited Alzheimer’s Network (DIAN). P4-158
DUAL-TASK GAIT PERFORMANCE IN MILD COGNITIVE IMPAIRMENT MAY PREDICT ALZHEIMER’S DISEASE CONVERSION
Mei Sian Chong1, Laura Tay1, Peng Chew Mark Chan1, Noorhazlina Ali1, Pamela Chew1, Wei Chin Wong1, Wee Shiong Lim1, 1Tan Tock Seng Hospital, Singapore, Singapore. Contact e-mail: Mei_Sian_Chong@ttsh. com.sg Background: By taxing executive resources within a finite working memory capacity, deficits in dual-task performance have been reported to be a potentially useful indicator of early cognitive impairment. However, little is known about the predictive ability of dual-tasking on dementia progression in MCI subjects. Thus we aim to look at dual-task gait performance on predicting AD progression in a cohort of MCI subjects. Methods: We included MCI subjects without underlying central nervous system or systemic disorders that contribute to cognitive impairment. Gait velocity was measured using a 8m walkway under single and dual-task conditions involving either animal category fluency or counting backwards from 100. We compared baseline single and dual-task performance between MCI converters and non-converters over a 1-year period. Results: 17 MCI subjects (mean age 71.4 years, 52.9% male,10.7 years education) were recruited. Mean CMMSE
was 25.4, FAB score 14.7 with CDR-sum-of-boxes (SOB) of 1.0. 3 subjects (17.6%) converted to probable AD. 37.5% females compared to 0% males converted to AD. No other significant demographic or neuroimaging measure (MTA score and ARWMC) differences were found. Gait velocity increased with dual-tasking (1.4m/s single-task versus 1.05m/s and 1.04m/s for single-task versus animal category fluency and subtraction dual-task respectively). Comparing MCI-converters versus non-converters, single and dual-tasking performance were lower in MCI-converters although only dual-task performance on animal naming reached statistical difference (single: 1.07 m/s versus 1.37m/s,p¼0.14, dual-task subtraction 0.8m/s versus 1.0m/s,p¼0.4, dual-task 0.81m/s versus 1.0m/s, p¼0.04 respectively). Conclusions: In older adults with MCI, mean walking speed decreased with dual-tasking (animal-naming), indicating frontal-subcortical dysfunction. These initial findings of impaired dual-task performance in MCIconverters compared to non-converters merits further study in a larger sample.
P4-159
DEVELOPMENT OF DEMENTIA IN A COHORT OF ELDERLY WHO FREQUENTLY USE AMBULATORY HEALTH SERVICES
Daniel Seinhart1, Luis Camera2, Maria Carolina Majo Bellagamba3, Patricia Riccio2, Edith Labos4, Diego Giunta5, 1Hospital Italiano de Buenos Aires, Buenos Aires, Argentina; 2Hospital Italiano Buenos Aires, Buenos Aires, Argentina; 3Hospital Italiano, Buenos Aires, Argentina; 4Faculta de Medicina UBA, Buenos Aires, Argentina; 5Hospital Italiano, Buenos Aires, Argentina. Contact e-mail: [email protected] Background: Some patients show a behavior characterized by frequent assistance requeriments from health services without an evident reason. These patients are mentioned as “frequent attenders” (FA). FA often generate in physicians a feeling that the consultation is unnecessary and frequently are evaluated with extensive testing with negative findings. The behavior of FA patients is associated with anxiety, depression and somatoform disorder. However, psychiatric symptoms frequently aren‘t mentioned by the patients during visits. Altered behavior and psychiatric disorders (PD) (depression, apathy, agresivity, sleep disorders) in adults have been associated with dementia development. Our objective was to evaluate if FA behavior in elderly is associate with further dementia development. Methods: Prospective cohort study. Between July2000/July 2001 we enrolled a cohort of outpatients older than 65 years affiliated to our HMO with 4 monthly visits to the health system during the previous year and without dementia diagnosis at enrolment. This subjects were considered FA. A matched control group with <2 montlhy visits during the previous year was also enroled (Non FA). All subject were evaluated at baseline with geriatric assesment and with PRIME MD test for PD. C ohort was followed for 10 years. Dementia diagnosis was formulated by the assistant geriatricians during follow up and was retrieved through electronic medical record revision.The risk of dementia development was evaluated with a Cox model of proportional risk. Crudes and adjusted Hazard ratios with 95% CI are presented. Results: 78 FA and 98 Non FA subjects were enrolled. Baseline characteristics and PD of subjects are presented (tables 1-2-3). 31/78 (42,5%) FA Subjects and 11/ 98 Non FA developed dementia (12,6%) HR 3,73 (1,73-8,05) p 0,001 HR adjusted for depression, age and somatoform disorders was 3,53 (1,49842) P< 0,004 (table 4). Other baseline PDs didn’t correlated with dementia development and weren‘t adjusted (table4). Conclusions: FA behavioral pattern was associated with development of dementia in our cohort during follow up. The relationship was independent of baseline psychiatric diagnosis. We hypothesize that FA behavior in elderly could be a dementia predictor, or it could be an early symptom of a dementing illness. We discuss about a possible pathogenesis of this behavior. Table 1 Demographics
Ref: Sexo (gender), Edad (Age) Somatizacion (Somatomorf disorder) Ansiedad (Anxiety) Depresion (Depression) Policonsultadores crudo (Frequent attender crude) Policonsultadores ajustado (Adjusted Frequent attender).
Age (years) Female gender
FA (n¼78)
No FA (n¼98)
p
74,2 (SD 5,1) 83,3%
74,9 (SD 5) 67,3%
0,369 0,016
Neuropsychological test scores General cognitive performance factor Trail Making Test, Part A Trail Making Test, Part B Semantic fluency HVLT-R delayed recall Physical performance measures MLTA Gait speed Grip strength
Sum of most cognitively demanding items
Sum of most physically demanding items
r
r
P value
P value
0.19
.001
0.05
ns
-0.23 -0.15 0.13 0.09
<.001 .013 .021 ns
-0.05 -0.09 -0.02 0.04
ns ns ns ns
0.10
ns
0.36
<.001
0.10 -0.02
ns ns
0.47 0.12
<.001 ns
Cognitive Items selected were Money, Meals, Medications, telephone. Physical Items selected were ADL transfers, ADL walking, SF12 climbing stairs, SF12 moderate activities. Sums of Cognitive and Physical Items: higher scores indicate higher levels of functioning; lower scores indicate dependence; theoretical range 0-4. r ¼ Pearson correlation coefficient. ns ¼ not significant at the .05 confidence level. HVLT-R ¼ Hopkins Verbal Learning Test – Revised. MLTA ¼ Minnesota Leisure Time Activities Questionnaire Score. Trail Making Tests: higher scores reveal greater impairment.
P763
Konyang University Hospital, College of Medicine, Konyang University, Daejeon, South Korea; 2Department of Neurology, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon, South Korea; 3Department of Neurology, Yongin Hyoja Geriatric Hospital, Yongin, South Korea; 4Department of Neurology, Gachon University Gil Medical Center, Incheon, South Korea; 5Department of Neurology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea. Contact e-mail: [email protected] Background: The clinical significance of white matter hyperintensities (WMHs) and lacunes remains unclear in amnestic mild cognitive impairment (aMCI). The purpose of this study is to evaluate the severity and location of WMHs that influence cognition and activities of daily living (ADL) and interactive effects of WMHs on cognition and ADL when accompanied by lacunes or medial temporal atrophy (MTA). Methods: One hundred fifty patients with aMCI underwent MRI, cognitive & functional assessment. WMHs were quantified using a semiautomated volumetric method. Lacune counting and MTA assessment were performed by visual rating. We evaluated the association of each WMHs, lacunes and MTA with cognition and ADL, as well as interactions among these 3 factors. We also analyzed the influence of the location of WMHs on cognition and ADL. Results: The severer WMHs were, the more frontal executive functions declined. The influence on frontal executive functions were greater in periventricular (PV) WMHs than deep WMHs, as well as bigger in anterior, middle, and posterior areas in decreasing order. The instrumental (I) ADL was strongly associated with the anterior and middle area of PVWMHs. WMHs had interactions with lacunes in terms of frontal executive functions and IADL. Conclusions: The location of WMHs as well as total WMHs volume strongly affected executive dysfunctions and poor performance of the IADL, and in particular, the anterior and middle areas of PVWMHs had the strongest effects on them. WMHs and lacunes had synergistic effects on frontal executive functions and the IADL. Therefore, it is important to simultaneously consider WMHs, lacunes and MTA as potential imaging biomarkers for predicting cognition and IADL in aMCI. Special attention should be paid to executive functions and IADL in aMCI patients with coexisting WMHs and lacunes. P4-157
ADCS ELECTRONIC DATA CAPTURE: COLLABORATIVE DEVELOPMENT AND MANAGEMENT OF CLINICAL TRIAL DATABASES
Gustavo Jimenez-Maggiora1, Ronald Thomas1, Stefania Bruschi1, Hongmei Qiu1, Phuoc Hong1, Paul Aisen1, 1UCSD/ADCS, La Jolla, California, United States. Contact e-mail: [email protected]
Figure 1. Difference in Mean Cognitive Ratings and Mean Physical Ratings of Activities. This plot shows the difference between average expert cognitive normalized ratings and physical normalized ratings on each of the 16 items in the expert panel survey. Positive values indicate more cognitive demand. Negative values indicate more physical demand. White triangles indicate four most physically demanding activities chosen as the most physical items. Black triangles indicate four most cognitively demanding activities chosen as the most cognitive items. Legend: AOL ¼ basic Activities of Daily Living. IADL ¼ Instrumental Activities of Daily Living. MOS SF-12 ¼ Medical Outcomes Study 12-ltem Short Form Survey Questionnaire. P4-156
WHITE MATTER HYPERINTENSITIES IN MILD COGNITIVE IMPAIRMENT: CLINICAL IMPACT OF LOCATION AND INTERACTION WITH LACUNES AND MEDIAL TEMPORAL ATROPHY
Bora Yoon1, YongSoo Shim2, Yun-Jeong Hong3, Kee Hyung Park4, YongDuk Kim1, Kee Ook Lee1, Dong Won Yang5, 1Department of Neurology,
Background: The Alzheimer’s Disease Cooperative Study was founded in 1991 in response to a NIA RFA. The primary aim of the ADCS is to ’advance research in the development of interventions that might be useful for treating, delaying, or preventing AD’. Toward that goal the ADCS has designed, managed, and analyzed over 20 large, multi-site AD clinical trials. The psychometric, clinical, and biological data from these trials have been collected using a locally-developed, web-based electronic data capture (EDC) system. This system serves as a central hub used to coordinate the data management, quality assurance, and monitoring activities of thousands of staff across several continents. Methods: Effective design and management of clinical trials databases rests on active and continued collaboration between clinical, scientific, administrative and regulatory staff, among others, over the course of a study. Historically, however, implementation of the specifications resultant from these activities has been the preserve of IT staff, who work in relative isolation and have limited knowledge of the nuances involved in many design decisions. This disjointed process inevitably leads to delays and misconfiguration of database systems. In designing the ADCS EDC’s administration capabilities, our goal was to eliminate the artificial separation between database design, management, and implementation. We accomplish this by using a set of cloud-based Google Docs spreadsheets to abstract the configuration of the underlying database’s schema, study-event schedule, user privileges, and data quality checks. Results: This poster has the following aims:1. Describe the ADCS EDC’s database administration capabilities.2. Discuss how these
P764
Poster Presentations: P4
capabilities were used to accelerate study startup, facilitate intra-study amendments, and streamline shutdown activities.3. Outline opportunities for future improvement. Conclusions: The ADCS EDC system supports a collaborative design and specification process via an intuitive set of cloud-based spreadsheets which allow multi-disciplinary study teams to manage clinical trial databases without the need for IT staff, thus reducing unnecessary delays and potential errors due to miscommunication. This approach has been used to design and manage databases for more than 20 large, multi-site AD clinical trials as well as several extra-ADCS projects, such as the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the Dominantly Inherited Alzheimer’s Network (DIAN). P4-158
DUAL-TASK GAIT PERFORMANCE IN MILD COGNITIVE IMPAIRMENT MAY PREDICT ALZHEIMER’S DISEASE CONVERSION
Mei Sian Chong1, Laura Tay1, Peng Chew Mark Chan1, Noorhazlina Ali1, Pamela Chew1, Wei Chin Wong1, Wee Shiong Lim1, 1Tan Tock Seng Hospital, Singapore, Singapore. Contact e-mail: Mei_Sian_Chong@ttsh. com.sg Background: By taxing executive resources within a finite working memory capacity, deficits in dual-task performance have been reported to be a potentially useful indicator of early cognitive impairment. However, little is known about the predictive ability of dual-tasking on dementia progression in MCI subjects. Thus we aim to look at dual-task gait performance on predicting AD progression in a cohort of MCI subjects. Methods: We included MCI subjects without underlying central nervous system or systemic disorders that contribute to cognitive impairment. Gait velocity was measured using a 8m walkway under single and dual-task conditions involving either animal category fluency or counting backwards from 100. We compared baseline single and dual-task performance between MCI converters and non-converters over a 1-year period. Results: 17 MCI subjects (mean age 71.4 years, 52.9% male,10.7 years education) were recruited. Mean CMMSE
was 25.4, FAB score 14.7 with CDR-sum-of-boxes (SOB) of 1.0. 3 subjects (17.6%) converted to probable AD. 37.5% females compared to 0% males converted to AD. No other significant demographic or neuroimaging measure (MTA score and ARWMC) differences were found. Gait velocity increased with dual-tasking (1.4m/s single-task versus 1.05m/s and 1.04m/s for single-task versus animal category fluency and subtraction dual-task respectively). Comparing MCI-converters versus non-converters, single and dual-tasking performance were lower in MCI-converters although only dual-task performance on animal naming reached statistical difference (single: 1.07 m/s versus 1.37m/s,p¼0.14, dual-task subtraction 0.8m/s versus 1.0m/s,p¼0.4, dual-task 0.81m/s versus 1.0m/s, p¼0.04 respectively). Conclusions: In older adults with MCI, mean walking speed decreased with dual-tasking (animal-naming), indicating frontal-subcortical dysfunction. These initial findings of impaired dual-task performance in MCIconverters compared to non-converters merits further study in a larger sample.
P4-159
DEVELOPMENT OF DEMENTIA IN A COHORT OF ELDERLY WHO FREQUENTLY USE AMBULATORY HEALTH SERVICES
Daniel Seinhart1, Luis Camera2, Maria Carolina Majo Bellagamba3, Patricia Riccio2, Edith Labos4, Diego Giunta5, 1Hospital Italiano de Buenos Aires, Buenos Aires, Argentina; 2Hospital Italiano Buenos Aires, Buenos Aires, Argentina; 3Hospital Italiano, Buenos Aires, Argentina; 4Faculta de Medicina UBA, Buenos Aires, Argentina; 5Hospital Italiano, Buenos Aires, Argentina. Contact e-mail: [email protected] Background: Some patients show a behavior characterized by frequent assistance requeriments from health services without an evident reason. These patients are mentioned as “frequent attenders” (FA). FA often generate in physicians a feeling that the consultation is unnecessary and frequently are evaluated with extensive testing with negative findings. The behavior of FA patients is associated with anxiety, depression and somatoform disorder. However, psychiatric symptoms frequently aren‘t mentioned by the patients during visits. Altered behavior and psychiatric disorders (PD) (depression, apathy, agresivity, sleep disorders) in adults have been associated with dementia development. Our objective was to evaluate if FA behavior in elderly is associate with further dementia development. Methods: Prospective cohort study. Between July2000/July 2001 we enrolled a cohort of outpatients older than 65 years affiliated to our HMO with 4 monthly visits to the health system during the previous year and without dementia diagnosis at enrolment. This subjects were considered FA. A matched control group with <2 montlhy visits during the previous year was also enroled (Non FA). All subject were evaluated at baseline with geriatric assesment and with PRIME MD test for PD. C ohort was followed for 10 years. Dementia diagnosis was formulated by the assistant geriatricians during follow up and was retrieved through electronic medical record revision.The risk of dementia development was evaluated with a Cox model of proportional risk. Crudes and adjusted Hazard ratios with 95% CI are presented. Results: 78 FA and 98 Non FA subjects were enrolled. Baseline characteristics and PD of subjects are presented (tables 1-2-3). 31/78 (42,5%) FA Subjects and 11/ 98 Non FA developed dementia (12,6%) HR 3,73 (1,73-8,05) p 0,001 HR adjusted for depression, age and somatoform disorders was 3,53 (1,49842) P< 0,004 (table 4). Other baseline PDs didn’t correlated with dementia development and weren‘t adjusted (table4). Conclusions: FA behavioral pattern was associated with development of dementia in our cohort during follow up. The relationship was independent of baseline psychiatric diagnosis. We hypothesize that FA behavior in elderly could be a dementia predictor, or it could be an early symptom of a dementing illness. We discuss about a possible pathogenesis of this behavior. Table 1 Demographics
Ref: Sexo (gender), Edad (Age) Somatizacion (Somatomorf disorder) Ansiedad (Anxiety) Depresion (Depression) Policonsultadores crudo (Frequent attender crude) Policonsultadores ajustado (Adjusted Frequent attender).
Age (years) Female gender
FA (n¼78)
No FA (n¼98)
p
74,2 (SD 5,1) 83,3%
74,9 (SD 5) 67,3%
0,369 0,016