- Email: [email protected]
ADCS electronic data capture: Integrated image management
Poster Presentations: P4 associated was hypertension, which was higher in group C. p¼ 0.002 OR 3,6 IC 95% 1,64-8,3 p ¼ 0.002 OR 3.6 95% CI 1.64 to 8.3. Conclusions: Our results show that aging is associated with a higher frequency in amnestic MCI component linked to a higher rate of conversion to dementia mainly mixed with a vascular component and influenced by hypertension. P4-184
ADCS ELECTRONIC DATA CAPTURE: INTEGRATED IMAGE MANAGEMENT
Gustavo Jimenez-Maggiora1, Ronald Thomas1, Jim Brewer1, Stefania Bruschi1, Phuoc Hong1, Paul Aisen1, 1UCSD/ADCS, La Jolla, California, United States. Contact e-mail: [email protected] 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 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: The management of medical images collected in the course of a clinical trial usually involves the use of a specialized repository which combines acquisition, de-identification, sharing, processing, and analysis capabilities. These monolithic repositories tend to be complex, inflexible, and resource-intensive. Furthermore, they contribute to the more general problem of “data sprawl”, a state of highly fragmented datasets that are difficult to manage and analyze. In the most extreme cases, the sprawl extends beyond institutional boundaries. As an alternative, we have chosen to extend the ADCS EDC to accommodate the collection, de-identification, and management of medical images while allowing analysis workflows to be handled flexibly via a standard set of APIs (application programming interfaces). This integrated approach ensures that timely access to a well structured and comprehensive trial data set can be easily provided. Results: This poster has the following aims:1. Provide a description of the ADCS EDC system’s image management capabilities.2. Discuss how these capabilities are used to support ongoing ADCS clinical trials.3. Outline opportunities for future improvement. Conclusions: The ADCS EDC system supports integrated image management that mitigates the need for specialized image management systems thereby avoiding the issues associated with dispersed datasets or “data sprawl”. P4-185
RAPID COGNITIVE SCREEN: SENSITIVITY AND SPECIFICITY FOR COGNITIVE DYSFUNCTION AND PREDICTIVE VALIDITY FOR POOR HEALTH OUTCOMES
Theodore Malmstrom1, Dulce Cruz-Oliver2, Lenise Cummings-Vaughn3, George Grossberg2, Nina Tumosa4, John Morley2, 1Saint Louis University, Saint Louis, Missouri, United States; 2Saint Louis University School of Medicine, St. Louis, Missouri, United States; 3St. Louis VA Medical Center/St. Louis University, Saint Louis, Missouri, United States; 4Saint Louis VA Medical Center/ St. Louis Univeristy, Saint Louis, Missouri, United States. Contact e-mail: [email protected] Background: The Rapid Cognitive Screen (RCS) is a very brief screening tool for the detection of cognitive impairment. The RCS includes 3-items from the Veterans Affairs Saint Louis University Mental Status (SLUMS) Exam: recall, clock drawing, and insight. RCS scores range from 0-10 (0¼worst to 10¼best). The objectives for this retrospective study were to 1) examine the RCS sensitivity and specificity to detect MCI and dementia, and 2) evaluate the RCS predictive validity for health outcomes. Methods: Participants (N¼702; ages 65-92) from the St. Louis, MO Geriatric Research Education and Clinical Center (GRECC), Veterans’ Affairs Medical Center (VAMC) hospitals completed cognitive screening and clinical diagnosis evaluations during a clinic visit in 2003. DSM-IV criteria were used to make the diagnosis of MCI or dementia. Nursing home placement and mortality were examined for N¼533/702 (76%; ages 65-92) participants based on chart review (2003-2010). Receiver operator characteristic (ROC) curves
P773
were computed to determine the RCS sensitivity and specificity for MCI (n¼180) and dementia (n¼82). Logistic regressions were computed to investigate the RCS predictive validity for nursing home placement (n¼31) and mortality (n¼176). In a separate pilot study (N¼118), a ROC curve was computed to determine the RCS sensitivity and specificity for cognitive dysfunction (n¼81) on the Montreal Cognitive Assessment (MoCA). Results: The RCS predicted MCI (area under the curve [AUC]¼0.86, 95% confidence interval [CI]: 0.83-0.89) and dementia (AUC¼0.98, 95% CI: 0.95-1.00). RCS optimal cutoff scores were < 7 for MCI (sensitivity¼0.87, specificity¼0.70) and < 5 for dementia (sensitivity¼0.89, specificity¼0.94). Higher RCS scores were protective against nursing home placement (odds ratio [OR]¼0.85, 95% CI: 0.73-0.98) and mortality (OR¼0.84, 95% CI: 0.77-0.91) up to 7.5 years later. The RCS predicted cognitive dysfunction on the MOCA (AUC¼0.80, 95% CI: 0.71-0.88; RCS scores < 7: sensitivity¼0.70, specificity¼0.76). Conclusions: The 3-item RCS exhibits good sensitivity and specificity for the detection of MCI and dementia, and high cognitive function on the RCS is protective against nursing home placement and mortality. Unlike the Mini-Cog the RCS identifies MCI as well as dementia. The RCS may be a useful, very brief screening instrument for the detection of cognitive dysfunction in a clinical setting. P4-186
CLINICAL CORRELATES OF HIPPOCAMPAL SCLEROSIS OF AGING: THE UNIVERSITY OF KENTUCKY EXPERIENCE
Peter Nelson1, Erin Abner2, Charles Smith3, Gregory Jicha2, Richard Kryscio4, David Fardo5, Janna Neltner2, Linda Van Eldik2, Frederick Schmitt2, 1University of Kentucky, Lexington, Kentucky, United States; 2University of Kentucky, Lexington, Kentucky, United States; 3UK MRISC, Lexington, Kentucky, United States; 4University of Kentucky, Lexington, Kentucky, United States Minor Outlying Islands; 5College of Public Health, Lexington, Kentucky, United States. Contact e-mail: [email protected] Background: Here we describe the clinical correlates of hippocampal sclerosis of aging (HS-Aging) using data from the University of Kentucky Alzheimer’s Disease Center. HS-Aging is characterized by cell loss and gliosis in the hippocampus and subiculum that does not appear to be explained by Alzheimer’s disease (AD) pathology. Almost no one is diagnosed during life with HS-Aging although approximately 20% of patients over 85 years of age have this pathology. Because this disease adversely affects the hippocampal formation, HS-Aging is an important potential confounder for AD diagnostically and in relation to clinical trials and therapeutic strategies. We previously found that category verbal fluency (CVF) is relatively preserved relative to episodic memory (word list) delayed recall (EMD) in patients with eventual pathologic diagnosis of HS-Aging. Methods: We first assessed a subset of participants who had neuroimaging data (MRI), longitudinal cognitive data, and subsequent autopsy confirmation of HS-Aging pathology. This series includes 4 patients who had concomitant AD and HS-Aging pathology, and 4 patients with relatively pure HS-Aging pathology. We compared these patients’ radiographical, neurocognitive, and other clinical aspects with controls. We also assessed whether there was evidence in the living cohort (N¼1,013) for a subset of patients with relatively preserved verbal fluency, but diminished word list delay performance (CVF/ EMD); these subjects would be predicted to be at higher risk for HS-Aging. Results: As expected, the trajectory of cognitive impairment followed a steeper decline in patients where HS-Aging was combined with AD pathology. By contrast, some patients with “pure” HS-Aging pathology have severe word list delay for years without showing clinical features analogous to CDR¼3; this confirms our prior published work. Further, there is a cohort among our living subjects with relatively high verbal fluency despite impairments in word list delayed recall. This cohort is at increased risk for HS-Aging pathology. Conclusions: We identify the clinical profile of patients at risk for HS-Aging pathology, as opposed to AD pathology, despite memory problems and MRI-proven hippocampal shrinkage. This CVF to EMD cognitive profile is directly relevant to clinical trials and to neuroimaging studies where the prevalence of HS-Aging seems to generally be under-appreciated.
ADCS ELECTRONIC DATA CAPTURE: INTEGRATED IMAGE MANAGEMENT
Gustavo Jimenez-Maggiora1, Ronald Thomas1, Jim Brewer1, Stefania Bruschi1, Phuoc Hong1, Paul Aisen1, 1UCSD/ADCS, La Jolla, California, United States. Contact e-mail: [email protected] 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 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: The management of medical images collected in the course of a clinical trial usually involves the use of a specialized repository which combines acquisition, de-identification, sharing, processing, and analysis capabilities. These monolithic repositories tend to be complex, inflexible, and resource-intensive. Furthermore, they contribute to the more general problem of “data sprawl”, a state of highly fragmented datasets that are difficult to manage and analyze. In the most extreme cases, the sprawl extends beyond institutional boundaries. As an alternative, we have chosen to extend the ADCS EDC to accommodate the collection, de-identification, and management of medical images while allowing analysis workflows to be handled flexibly via a standard set of APIs (application programming interfaces). This integrated approach ensures that timely access to a well structured and comprehensive trial data set can be easily provided. Results: This poster has the following aims:1. Provide a description of the ADCS EDC system’s image management capabilities.2. Discuss how these capabilities are used to support ongoing ADCS clinical trials.3. Outline opportunities for future improvement. Conclusions: The ADCS EDC system supports integrated image management that mitigates the need for specialized image management systems thereby avoiding the issues associated with dispersed datasets or “data sprawl”. P4-185
RAPID COGNITIVE SCREEN: SENSITIVITY AND SPECIFICITY FOR COGNITIVE DYSFUNCTION AND PREDICTIVE VALIDITY FOR POOR HEALTH OUTCOMES
Theodore Malmstrom1, Dulce Cruz-Oliver2, Lenise Cummings-Vaughn3, George Grossberg2, Nina Tumosa4, John Morley2, 1Saint Louis University, Saint Louis, Missouri, United States; 2Saint Louis University School of Medicine, St. Louis, Missouri, United States; 3St. Louis VA Medical Center/St. Louis University, Saint Louis, Missouri, United States; 4Saint Louis VA Medical Center/ St. Louis Univeristy, Saint Louis, Missouri, United States. Contact e-mail: [email protected] Background: The Rapid Cognitive Screen (RCS) is a very brief screening tool for the detection of cognitive impairment. The RCS includes 3-items from the Veterans Affairs Saint Louis University Mental Status (SLUMS) Exam: recall, clock drawing, and insight. RCS scores range from 0-10 (0¼worst to 10¼best). The objectives for this retrospective study were to 1) examine the RCS sensitivity and specificity to detect MCI and dementia, and 2) evaluate the RCS predictive validity for health outcomes. Methods: Participants (N¼702; ages 65-92) from the St. Louis, MO Geriatric Research Education and Clinical Center (GRECC), Veterans’ Affairs Medical Center (VAMC) hospitals completed cognitive screening and clinical diagnosis evaluations during a clinic visit in 2003. DSM-IV criteria were used to make the diagnosis of MCI or dementia. Nursing home placement and mortality were examined for N¼533/702 (76%; ages 65-92) participants based on chart review (2003-2010). Receiver operator characteristic (ROC) curves
P773
were computed to determine the RCS sensitivity and specificity for MCI (n¼180) and dementia (n¼82). Logistic regressions were computed to investigate the RCS predictive validity for nursing home placement (n¼31) and mortality (n¼176). In a separate pilot study (N¼118), a ROC curve was computed to determine the RCS sensitivity and specificity for cognitive dysfunction (n¼81) on the Montreal Cognitive Assessment (MoCA). Results: The RCS predicted MCI (area under the curve [AUC]¼0.86, 95% confidence interval [CI]: 0.83-0.89) and dementia (AUC¼0.98, 95% CI: 0.95-1.00). RCS optimal cutoff scores were < 7 for MCI (sensitivity¼0.87, specificity¼0.70) and < 5 for dementia (sensitivity¼0.89, specificity¼0.94). Higher RCS scores were protective against nursing home placement (odds ratio [OR]¼0.85, 95% CI: 0.73-0.98) and mortality (OR¼0.84, 95% CI: 0.77-0.91) up to 7.5 years later. The RCS predicted cognitive dysfunction on the MOCA (AUC¼0.80, 95% CI: 0.71-0.88; RCS scores < 7: sensitivity¼0.70, specificity¼0.76). Conclusions: The 3-item RCS exhibits good sensitivity and specificity for the detection of MCI and dementia, and high cognitive function on the RCS is protective against nursing home placement and mortality. Unlike the Mini-Cog the RCS identifies MCI as well as dementia. The RCS may be a useful, very brief screening instrument for the detection of cognitive dysfunction in a clinical setting. P4-186
CLINICAL CORRELATES OF HIPPOCAMPAL SCLEROSIS OF AGING: THE UNIVERSITY OF KENTUCKY EXPERIENCE
Peter Nelson1, Erin Abner2, Charles Smith3, Gregory Jicha2, Richard Kryscio4, David Fardo5, Janna Neltner2, Linda Van Eldik2, Frederick Schmitt2, 1University of Kentucky, Lexington, Kentucky, United States; 2University of Kentucky, Lexington, Kentucky, United States; 3UK MRISC, Lexington, Kentucky, United States; 4University of Kentucky, Lexington, Kentucky, United States Minor Outlying Islands; 5College of Public Health, Lexington, Kentucky, United States. Contact e-mail: [email protected] Background: Here we describe the clinical correlates of hippocampal sclerosis of aging (HS-Aging) using data from the University of Kentucky Alzheimer’s Disease Center. HS-Aging is characterized by cell loss and gliosis in the hippocampus and subiculum that does not appear to be explained by Alzheimer’s disease (AD) pathology. Almost no one is diagnosed during life with HS-Aging although approximately 20% of patients over 85 years of age have this pathology. Because this disease adversely affects the hippocampal formation, HS-Aging is an important potential confounder for AD diagnostically and in relation to clinical trials and therapeutic strategies. We previously found that category verbal fluency (CVF) is relatively preserved relative to episodic memory (word list) delayed recall (EMD) in patients with eventual pathologic diagnosis of HS-Aging. Methods: We first assessed a subset of participants who had neuroimaging data (MRI), longitudinal cognitive data, and subsequent autopsy confirmation of HS-Aging pathology. This series includes 4 patients who had concomitant AD and HS-Aging pathology, and 4 patients with relatively pure HS-Aging pathology. We compared these patients’ radiographical, neurocognitive, and other clinical aspects with controls. We also assessed whether there was evidence in the living cohort (N¼1,013) for a subset of patients with relatively preserved verbal fluency, but diminished word list delay performance (CVF/ EMD); these subjects would be predicted to be at higher risk for HS-Aging. Results: As expected, the trajectory of cognitive impairment followed a steeper decline in patients where HS-Aging was combined with AD pathology. By contrast, some patients with “pure” HS-Aging pathology have severe word list delay for years without showing clinical features analogous to CDR¼3; this confirms our prior published work. Further, there is a cohort among our living subjects with relatively high verbal fluency despite impairments in word list delayed recall. This cohort is at increased risk for HS-Aging pathology. Conclusions: We identify the clinical profile of patients at risk for HS-Aging pathology, as opposed to AD pathology, despite memory problems and MRI-proven hippocampal shrinkage. This CVF to EMD cognitive profile is directly relevant to clinical trials and to neuroimaging studies where the prevalence of HS-Aging seems to generally be under-appreciated.