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

项目摘要 患有阿尔茨海默病和相关痴呆(ADRD)的老年人临床风险增加2倍 骨折后的发病率和死亡率要高出33%。我们先前的研究显示临床 在服用乙酰胆碱酯酶抑制剂(AchEI)的患者中，骨折减少了18%。两者都有 认知和非认知的益处，AchEIs如多奈哌齐在骨折预防中将是有价值的 该方案针对患有ADRD的老年人，具有多种互补和协同作用的组成部分。然而， AchEI降低骨折风险的途径在知识上存在重大差距。在合并之前 AchEis是一个多组分的计划，必须了解AchEis对骨代谢的具体影响。 本应用的目的是测量AchEIs的ADRD治疗对骨折危险因素的影响 包括骨密度(BMD)、骨转换标志物和骨质量。我们的中心假设是 AchEIs通过刺激成骨细胞骨直接影响骨代谢，从而降低骨折风险 破骨细胞性骨吸收的形成和减少。我们将从记忆中招募50岁的成年人 轻至中度ADRD患者的临床研究(N=45)，患者将以2：1的比例随机分为两组：一组服用阿奇多奈哌齐 每日服用10毫克，或服用安慰剂。从这个生物标记物诊断的轻度到中度老年人队列中 ADRD，我们将解决以下具体目标：1)确定12个月内骨矿物质的变化 与多奈哌齐的启动有关的双x射线吸收法测量的密度；2)确定变化 6个月和12个月以上的骨转换：(A)骨吸收标志物C-端肽(CTX)和 (B)与启动相关的骨形成标志物前胶原1完整N末端前肽(P1NP) 3)通过骨小梁评分确定12个月内骨质量的变化 与多奈哌齐的启动有关。为了解决这一重要领域，当前的应用程序将重点放在 关于NIA的几个优先事项，包括多种合并症和成人ADRD的护理。建议的研究是 在使用生物标记物对成年人骨代谢进行全面、前瞻性评估方面的创新- 根据ADRD引发疼痛的诊断。

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.