Cognitive Function in SLE (COGNITION)

SLE 的认知功能 (COGNITION)

• 批准号: 7222712
• 负责人: ROBIN L BREY
• 金额: $ 87.64万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-14 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7222712
• 关键词: African American; Age; American; Antibodies; Biological Assay; Biological Markers; Biological Process; Body mass index; Brain; Clinical; Cognitive; Cohort Studies; Complement; Computers; Condition; Data; Development; Diabetes Mellitus; Diamond; Diffuse; Disease; Disease Outcome; Doctor of Medicine; Education; Enrollment; Ethnic Origin; Ethnic group; Etiology; Flare; Gelatinase B; Gender; Glutamate Receptor; Goals; Health Sciences; Hispanic Americans; Hispanics; Hyperlipidemia; Hypertension; Impaired cognition; Institution; Lead; Matched Group; Matrix Metalloproteinases; Measures; Medical; Mental Depression; Metric; Monitor; Morbidity - disease rate; Neuropsychiatric Systemic Lupus Erythematosus; Neuropsychological Tests; Newly Diagnosed; Not Hispanic or Latino; Numbers; Operative Surgical Procedures; Pathogenesis; Patients; Pattern; Performance; Pharmaceutical Preparations; Play; Population Study; Prevalence; Preventive; Public Health; Race; Research Personnel; Respondent; Rheumatology; Risk Factors; Robin bird; Role; Serological; Serum; Severities; Smoking Status; Social Security; Socioeconomic Status; Special Hospitals; Study Subject; Syndrome; Systemic Lupus Erythematosus; Testing; Texas; Therapeutic; Time; Tissues; Trustees; Universities; Work; cerebral atrophy; cognitive function; cohort; college; computerized; ethnic difference; illness length; inhibitor/antagonist; medical schools; neuropsychological; prospective; response; success; therapy design

DESCRIPTION (provided by applicant): This is a revised application to study cognitive function over time in subjects with Systemic Lupus Erythematosus (SLE) versus a matched group of normal healthy controls. Our prior work demonstrates that the persistent presence of antiphospholipid (aPL), and anti-nbosomal P (anti-P) antibodies are associated with cognitive dysfunction in SLE. Also, Hispanic (HA) ethnicity appears to be a separate risk factor for cognitive dysfunction. This finding is consistent with the more severe disease course overall that has been observed in African American (AA) and HA SLE patients in other studies. In this application we propose to enroll a total of 200 SLE subjects in 3 ethnic groups (HA, AA, and non-Hispanic White [n-HW]) and 200 matched controls from the University of Texas HSC at San Antonio (UTHSCSA), Johns Hopkins Medical Institutions (JHMI) and the Hospital for Special Surgery (HSS). We will test the following Hypotheses: 1a-cognitive functioning over time will be worse in SLE subjects compared to normal controls adjusting for non-SLE related co-morbid conditions associated with cognitive dysfunction (e.g. depression, hypertension, etc.);1b-cognitive function will be worse in both AA and HA SLE subjects compared with n-HW SLE subjects adjusting for age, education, SES, and co-morbid conditions associated with cognitive dysfunction in people with (disease duration, cumulative SLE-related damage, disease activity, medication use) and without SLE (depression, hypertension, etc.); 2a-persistently positive levels of several biomarkers in SLE subjects (aPL, anti-P and anti-glutamate receptor [anti-glutamate receptor [antiNR2] antibodies and matrix metalloproteinase-9 [MMP-9] and its tissue inhibitor [TIMP] will be independently associated with poorer cognitive function after adjusting for age, education, SES, and co-morbid conditions; 2b - cognitive dysfunction will be increased in SLE subjects with abnormal MMP-9/TIMP levels and persistently abnormal levels of some or all of the auto-antibodies. The JHMI Cohort contains equal numbers of AA and n-HW SLE subjects, and HSS has a mixture of HA, AA and n-HW SLE subjects, complementing the primarily HA population at UTHSCSA. Dr. Betty Diamond at The Trustees of Columbia University will collaborate on this project by performing the antibody assays for the anti-NR2 antibodies. A computerized neuropsychological battery (ANAM) will be the primary measure pf cognitive functioning. It is possible that combinations of biomarkers and co-morbidities are needed to lead to the clinical expression of cognitive dysfunction in SLE and that these factors are modified by ethnicity. The information that will be gained from this study is essential for the successful discovery of biological processes that impact on cognitive function in SLE that could be potentially amenable to disease-reversing therapies.

DESCRIPTION (provided by applicant): This is a revised application to study cognitive function over time in subjects with Systemic Lupus Erythematosus (SLE) versus a matched group of normal healthy controls. Our prior work demonstrates that the persistent presence of antiphospholipid (aPL), and anti-nbosomal P (anti-P) antibodies are associated with cognitive dysfunction in SLE. Also, Hispanic (HA) ethnicity appears to be a separate risk factor for cognitive dysfunction. This finding is consistent with the more severe disease course overall that has been observed in African American (AA) and HA SLE patients in other studies. In this application we propose to enroll a total of 200 SLE subjects in 3 ethnic groups (HA, AA, and non-Hispanic White [n-HW]) and 200 matched controls from the University of Texas HSC at San Antonio (UTHSCSA), Johns Hopkins Medical Institutions (JHMI) and the Hospital for Special Surgery (HSS). We will test the following Hypotheses: 1a-cognitive functioning over time will be worse in SLE subjects compared to normal controls adjusting for non-SLE related co-morbid conditions associated with cognitive dysfunction (e.g. depression, hypertension, etc.);1b-cognitive function will be worse in both AA and HA SLE subjects compared with n-HW SLE subjects adjusting for age, education, SES, and co-morbid conditions associated with cognitive dysfunction in people with (disease duration, cumulative SLE-related damage, disease activity, medication use) and without SLE (depression, hypertension, etc.); 2a-persistently positive levels of several biomarkers in SLE subjects (aPL, anti-P and anti-glutamate receptor [anti-glutamate receptor [antiNR2] antibodies and matrix metalloproteinase-9 [MMP-9] and its tissue inhibitor [TIMP] will be independently associated with poorer cognitive function after adjusting for age, education, SES, and co-morbid conditions; 2b - cognitive dysfunction will be increased in SLE subjects with abnormal MMP-9/TIMP levels and persistently abnormal levels of some or all of the auto-antibodies. The JHMI Cohort contains equal numbers of AA and n-HW SLE subjects, and HSS has a mixture of HA, AA and n-HW SLE subjects, complementing the primarily HA population at UTHSCSA. Dr. Betty Diamond at The Trustees of Columbia University will collaborate on this project by performing the antibody assays for the anti-NR2 antibodies. A computerized neuropsychological battery (ANAM) will be the primary measure pf cognitive functioning. It is possible that combinations of biomarkers and co-morbidities are needed to lead to the clinical expression of cognitive dysfunction in SLE and that these factors are modified by ethnicity. The information that will be gained from this study is essential for the successful discovery of biological processes that impact on cognitive function in SLE that could be potentially amenable to disease-reversing therapies.