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Utility of Centrally Acting Angiotensin Converting Enzyme Inhibitors to slow the progression of Dementia

中枢作用血管紧张素转换酶抑制剂减缓痴呆进展的效用

基本信息

批准号：
10259832
负责人：
Claudene George
金额：
$ 16万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-15 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10259832
关键词：
Acetylcholine Address Affect Aging Alzheimer&apos s Disease Alzheimer&apos s disease risk Angiotensin II Angiotensin-Converting Enzyme Inhibitors Attention Award Biological Biometry Blood - brain barrier anatomy Blood Pressure Blood Vessels Brain Cerebrovascular Circulation Clinical Clinical Markers Cognition Cognitive Consumption Coupled Data Databases Dementia Detection Development Diabetes Mellitus Disease Drug Prescriptions Early identification Elderly Epidemiologic Methods Gait Goals Grant Harm Reduction Health and Retirement Study Heart failure Hypertension Impaired cognition Incidence Individual Inflammatory Investigation Kidney Kidney Diseases Knowledge Lacunar Infarctions Learning Link Memory Memory impairment Mentored Patient-Oriented Research Career Development Award Microvascular Dysfunction Modality Motor Nerve Degeneration Neurobiology Neurons Neuropsychological Tests Observational Study Outcome Participant Pathologic Pathology Pathway interactions Peripheral Pharmaceutical Preparations Physical Performance Physicians Population Prevalence Prevention Registries Renin-Angiotensin System Research Research Personnel Research Training Risk Role Structure System Techniques Testing Time Training White Matter Disease Work base career career development clinically relevant cognitive development cohort cytokine dementia risk design evidence base executive function experience falls functional decline hippocampal atrophy improved longitudinal analysis memory consolidation memory retrieval mild cognitive impairment neural correlate neuroimaging neuropathology rate of change skills targeted treatment

项目摘要

Abstract My prior training, background, and experiences are very relevant to my specific plans as described in the grant. My overall career development goal is to develop the skills necessary to pursue a career as an independent clinical researcher, able to conduct investigations that will broaden our understanding of the relationship between functional decline in aging and medication use. My specific research training objectives during the 5-year award period are: 1. To enhance my knowledge of neural correlates of gait and cognitive dysfunction. 2. Advance my knowledge of the brain Renin Angiotensin System (RAS) and connected pathways as a biological pathway that may link cognitive and motoric declines in aging. 3. Learn neuroimaging modalities and analytic techniques to identify and quantify structural findings related to cognitive and functional decline in aging. 4. Improve my knowledge of epidemiological methods and biostatistics for observational studies and longitudinal analysis. 5. Apply for an ROI grant at the end of this K23 award to extend this line of research into additional cohorts that will allow for more detailed investigations into the use of CACE-I and related agents in protecting against declines in gait and cognition in older adults at risk for Alzheimer’s disease and related disorders. My research aims will add to our knowledge of the clinical and neurobiological consequences of medication use in aging by focusing on medications with less of a negative impact on functional decline than similar medication counterparts. Angiotensin Converting Enzyme Inhibitors (ACEI) are widely used for a number of conditions beyond hypertension. They can be categorized as centrally or peripherally acting based upon their ability to cross the blood brain barrier. Available data suggests that centrally acting ACEI decrease the rate of cognitive and functional decline among those with Alzheimer’s Disease and related disorders. My specific aims focus on older individuals without Alzheimer’s disease and related disorders and are to 1) To quantify motoric consequences (gait velocity) of CACE-I versus PACE-I use in older adults using the nationally representative Health and Retirement Study (HRS) database. 2) To determine cognitive consequences of CACE-I versus PACE-I use in older adults using the HRS. 3) To examine the relation of CACE-I and PACE-I use with neurodegenerative and vascular pathologies linked to dementia using the Alzheimer’s disease Neuroimaging Initiative (ADNI) database. Early identification of older adults at risk for the development of cognitive impairment and decline in physical performance, coupled with a better understanding of how ACEI subtypes affect cortical regions associated with dementia, is of paramount importance as a prelude to identification of targeted therapies to slow the progression of cognitive impairment in aging and Alzheimer’s Disease. There is a knowledge gap regarding clinical consequences of different classes of ACEI that limits evidence based prescribing. This proposal will produce clinically relevant data that will form the basis of an R01 designed to extend this line of research into additional cohorts, to allow for more detailed investigations into the use of CACE-I and related agents in protecting against declines in gait and cognition in older adults at risk for Alzheimer’s disease and related disorders.

摘要