Adiposity, Inflammation and Neurocognitive Decline in African Americans

非裔美国人的肥胖、炎症和神经认知能力下降

• 批准号: 8696123
• 负责人: Beverly Gwen Windham
• 金额: $ 64.28万
• 依托单位: UNIVERSITY OF MISSISSIPPI MED CTR
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-15 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8696123
• 关键词: Accounting; Affect; African American; Age; Aging; Alzheimer' s Disease; American; Arterial Disorder; Atrophic; Biological Assay; Biological Markers; Blood; Blood Pressure; Blood Vessels; Body mass index; Brain; Brain imaging; Caucasians; Caucasoid Race; Clinical; Cognitive; Data; Dementia; Diagnosis; Disease; Early identification; Early treatment; Essential Hypertension; Ethnic group; European; Family; Fatty acid glycerol esters; Female; Hormones; Impaired cognition; Individual; Inflammation; Intervention; Knowledge; Magnetic Resonance Imaging; Measures; Mediating; Neurocognitive; Obesity; Participant; Pathway interactions; Persons; Phenotype; Population; Prevention; Reporting; Resources; Risk; Risk Factors; Sampling; Siblings; Stratification; Structure; System; Testing; Vascular Diseases; Ventricular; Visit; White Matter Hyperintensity; X-Ray Computed Tomography; abdominal fat; adipokines; aging brain; brain volume; cardiovascular risk factor; cerebral atrophy; clinical risk; cognitive function; cohort; disorder risk; effective therapy; follow-up; genetic epidemiology; high risk; hypertension control; improved; insight; member; modifiable risk; novel; prevent; programs; public health relevance; tool; vascular risk factor; waist circumference

DESCRIPTION (provided by applicant): Alzheimer Disease (AD) and dementia affect an estimated 5.4 million people in the US with a new case diagnosed every 68 seconds. Obesity is a proposed modifiable risk factor for dementia and cognitive dysfunction. Obesity and dementia disproportionately affect African Americans (AA), yet AAs are underrepresented in studies of adiposity and cognitive function and mechanisms through which obesity increases dementia risk are poorly understood. In addition, risk scores to aid clinicians in identifying AA at risk of cognitive dysfunction are lacking. We will examine vascular and non-vascular mechanisms through which adiposity may affect brain structure, cognitive function (cross-sectional) and cognitive decline (longitudinal) using the GENOA study, a cohort of AA sibships. Adiposity measures, traditional and novel biomarkers, and vascular risk factors will be used to develop a cognitive dysfunction clinical risk tool for AA. We hypothesize a cascade of adiposity effects occurring through inflammation, adipokine, and vascular risk factor pathways which contribute deleteriously to cognitive function/decline. The specific aims of this study are: (1) Quantify cross-sectional adiposity and brain structure relationships, and cross-sectional and longitudinal relationships between adiposity and cognitive function, accounting for brain structure. We hypothesize that: 1.1) Greater central and overall adiposity will be associated with more brain atrophy, white matter hyperintensities, increased ventricular and decreased total brain volume across age. We also hypothesize that, accounting for brain structure, cardiovascular risk factors and clinical disease: 1.2) Greater adiposity will be associated with poorer cross-sectional cognitive function; and 1.3) Greater increases in adiposity will be associated with greater cognitive decline; and 1.4) Cross-sectional associations of CT-imaged abdominal adiposity will have stronger associations with cognitive function than waist circumference or body mass index. (2) Contrast the mediating effects of brain structure, inflammation, adipokines and vascular disease/risk factors in explaining relationships of adiposity to cognitive function/decline. We hypothesize that: Inflammation, adipokines and vascular contributors will explain 2.1) cross-sectional associations of adiposity to cognitive function and 2.2) associations of adiposity to cognitive decline, more so than brain structure. (3) Develop a clinical risk score to predict 3.1) cognitive dysfunction and 3.2) decline in AA. We hypothesize that an inflammation biomarker profile and adiposity measures will improve existing cardiovascular risk scores to predict 3.1) cognitive dysfunction and 3.2) cognitive decline. The proposed analyses will fill salient gaps in knowledge regarding prevalent and modifiable risk factors for cognitive impairment and will improve clinicians' ability to identify AA at high risk of cognitive dysfunction and decline for targeted interventions.

DESCRIPTION (provided by applicant): Alzheimer Disease (AD) and dementia affect an estimated 5.4 million people in the US with a new case diagnosed every 68 seconds. Obesity is a proposed modifiable risk factor for dementia and cognitive dysfunction. Obesity and dementia disproportionately affect African Americans (AA), yet AAs are underrepresented in studies of adiposity and cognitive function and mechanisms through which obesity increases dementia risk are poorly understood. In addition, risk scores to aid clinicians in identifying AA at risk of cognitive dysfunction are lacking. We will examine vascular and non-vascular mechanisms through which adiposity may affect brain structure, cognitive function (cross-sectional) and cognitive decline (longitudinal) using the GENOA study, a cohort of AA sibships. Adiposity measures, traditional and novel biomarkers, and vascular risk factors will be used to develop a cognitive dysfunction clinical risk tool for AA. We hypothesize a cascade of adiposity effects occurring through inflammation, adipokine, and vascular risk factor pathways which contribute deleteriously to cognitive function/decline. The specific aims of this study are: (1) Quantify cross-sectional adiposity and brain structure relationships, and cross-sectional and longitudinal relationships between adiposity and cognitive function, accounting for brain structure. We hypothesize that: 1.1) Greater central and overall adiposity will be associated with more brain atrophy, white matter hyperintensities, increased ventricular and decreased total brain volume across age. We also hypothesize that, accounting for brain structure, cardiovascular risk factors and clinical disease: 1.2) Greater adiposity will be associated with poorer cross-sectional cognitive function; and 1.3) Greater increases in adiposity will be associated with greater cognitive decline; and 1.4) Cross-sectional associations of CT-imaged abdominal adiposity will have stronger associations with cognitive function than waist circumference or body mass index. (2) Contrast the mediating effects of brain structure, inflammation, adipokines and vascular disease/risk factors in explaining relationships of adiposity to cognitive function/decline. We hypothesize that: Inflammation, adipokines and vascular contributors will explain 2.1) cross-sectional associations of adiposity to cognitive function and 2.2) associations of adiposity to cognitive decline, more so than brain structure. (3) Develop a clinical risk score to predict 3.1) cognitive dysfunction and 3.2) decline in AA. We hypothesize that an inflammation biomarker profile and adiposity measures will improve existing cardiovascular risk scores to predict 3.1) cognitive dysfunction and 3.2) cognitive decline. The proposed analyses will fill salient gaps in knowledge regarding prevalent and modifiable risk factors for cognitive impairment and will improve clinicians' ability to identify AA at high risk of cognitive dysfunction and decline for targeted interventions.