Effect of Acetylcholinesterase inhibitors on Bone Metabolism and Fracture Risk Factors among older adults with mild to moderate Alzheimer's Disease

乙酰胆碱酯酶抑制剂对患有轻至中度阿尔茨海默病的老年人骨代谢和骨折危险因素的影响

• 批准号: 10739853
• 负责人: Richard Hsang-Yang Lee
• 金额: $ 23.94万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10739853
• 关键词: Acetylcholinesterase Inhibitors; Ache; Address; Adult; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease related dementia; Apoptosis; Area; Biological Markers; Bone Density; Bone Resorption; C-telopeptide; Capsicum; Caring; Cholinergic Receptors; Clinic; Clinical; Cognitive; Diagnosis; Dose; Elderly; Epidemiology; Fracture; Goals; Harm Reduction; Intervention; Knowledge; Measures; Memory Disorders; Morbidity - disease rate; Muscarinics; N-terminal; Newly Diagnosed; Osteoblasts; Osteoclasts; Osteogenesis; Pathway interactions; Patients; Pharmaceutical Preparations; Pharmacologic Actions; Physical Function; Pilot Projects; Placebos; Prevention program; Probability; Procollagen; Public Health; Publishing; Quality of life; Randomized; Regimen; Resources; Risk Factors; Roentgen Rays; Side; Trabecular Bone Score; Work; aged; bone; bone metabolism; bone quality; bone turnover; clinical risk; clinically significant; cohort; comorbidity; design; donepezil; fracture risk; hip bone; improved; innovation; mortality; older men; osteoblast proliferation; pharmacologic; preclinical study; prevent; programs; prospective; rational design; recruit; Acetylcholinesterase Inhibitors; Ache; Address; Adult; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease related dementia; Apoptosis; Area; Biological Markers; Bone Density; Bone Resorption; C-telopeptide; Capsicum; Caring; Cholinergic Receptors; Clinic; Clinical; Cognitive; Diagnosis; Dose; Elderly; Epidemiology; Fracture; Goals; Harm Reduction; Intervention; Knowledge; Measures; Memory Disorders; Morbidity - disease rate; Muscarinics; N-terminal; Newly Diagnosed; Osteoblasts; Osteoclasts; Osteogenesis; Pathway interactions; Patients; Pharmaceutical Preparations; Pharmacologic Actions; Physical Function; Pilot Projects; Placebos; Prevention program; Probability; Procollagen; Public Health; Publishing; Quality of life; Randomized; Regimen; Resources; Risk Factors; Roentgen Rays; Side; Trabecular Bone Score; Work; aged; bone; bone metabolism; bone quality; bone turnover; clinical risk; clinically significant; cohort; comorbidity; design; donepezil; fracture risk; hip bone; improved; innovation; mortality; older men; osteoblast proliferation; pharmacologic; preclinical study; prevent; programs; prospective; rational design; recruit

Project Abstract Older adults with Alzheimer's disease and related dementias (ADRD) have a 2-fold increased risk of clinical bone fracture, and 33% higher rate of morbidity and mortality following fracture. Our prior study showed clinical fractures were reduced by 18% among those prescribed an acetylcholinesterase inhibitor (AchEI). With both cognitive and non-cognitive benefits, AchEIs such as donepezil would be valuable in a fracture prevention program, for older adults with ADRD, with multiple complementary and synergistic components. However, the pathways by which AchEIs reduce fracture risk represent a significant gap in knowledge. Before incorporating AchEIs into a multicomponent program, the specific effects of AchEIs on bone metabolism must be understood. The objective of this application is to measure the effect of ADRD treatment with AchEIs on fracture risk factors including bone mineral density (BMD), bone turnover markers, and bone quality. Our central hypothesis is that AchEIs reduce fracture risk through direct effects on bone metabolism via stimulation of osteoblastic bone formation and reduction in osteoclastic bone resorption. We will recruit adults aged >50 years from the Memory Disorders Clinic with mild to moderate ADRD (N = 45) who will be randomized 2:1 to either the AchEI donepezil 10 mg daily or placebo, respectively. From this biomarker-diagnosed cohort of older adults with mild to moderate ADRD, we will address the following Specific Aims: 1) Determine change over 12-months in Bone Mineral Density measured by dual x-ray absorptiometry associated with the initiation of donepezil; 2) Determine change over 6- and 12-months in Bone Turnover measured by (A) the Bone Resorption Marker C-telopeptide (CTX) and (B) the Bone Formation Marker Procollagen 1 intact N-terminal Pro-peptide (P1NP) associated with the initiation of donepezil; 3) Determine change over 12-months in Bone Quality measured by Trabecular Bone Score associated with the initiation of donepezil. In addressing this significant area, the current application focuses on several NIA priorities including multiple comorbidities and care for adults with ADRD. The proposed study is innovative in its comprehensive, prospective assessment of bone metabolism among adults with biomarker- based diagnosis of ADRD initiating AchE.

项目摘要 老年人患有阿尔茨海默氏病和相关痴呆症（ADRD）的老年人的临床风险增加了2倍 骨折，骨折后发病率和死亡率提高33％。我们先前的研究表明临床 在处方乙酰胆碱酯酶抑制剂（ACHEI）的那些处方中，骨折减少了18％。两者 认知和非认知益处，诸如多奈奈齐的ACHEI在预防裂缝中很有价值 计划，适用于ADRD的老年人，具有多个互补和协同成分。但是， ACHEI降低断裂风险的途径代表了知识的显着差距。在合并之前 ACHEI成为一个多组分程序，必须了解ACHEI对骨代谢的特定影响。 该应用的目的是衡量ACHEI治疗ADRD治疗对裂缝风险因素的影响 包括骨矿物质密度（BMD），骨转换标记和骨质质量。我们的中心假设是 ACHEI通过刺激成骨细胞骨而直接影响骨骼代谢，从而降低了骨折的风险 破骨骨吸收的形成和减少。我们将从记忆中招募> 50岁的成年人 疾病诊所的轻度至中度ADRD（n = 45）将被随机2：1与Achei Donepezil一起。 每天10毫克或安慰剂。从这个生物标志物诊断为轻度至中度的老年人的队列 ADRD，我们将解决以下特定目的：1）确定骨矿物12个月以上的变化 通过与多奈哌齐的启动相关的双X射线吸收法测量的密度； 2）确定变化 通过（a）骨吸收标记C-塞肽（CTX）和 （b）与起始相关的骨形成标志物procollagen 1完整的N末端促肽（P1NP） 多奈替齐; 3）确定通过小梁骨评分测量的骨质质量超过12个月的变化 与多奈哌齐的启动有关。在解决这一重要领域时，当前的申请将重点 在几个NIA优先事项上，包括多种合并症和针对ADRD的成年人的护理。拟议的研究是 在具有生物标志物的成年人中对骨代谢的全面，前瞻性评估的创新性 基于ADRD的诊断启动ACHE。