Autoantibodies, Frailty and Cognitive Decline

自身抗体、虚弱和认知能力下降

基本信息

  • 批准号:
    9371387
  • 负责人:
  • 金额:
    $ 24.53万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-07-15 至 2019-04-30
  • 项目状态:
    已结题

项目摘要

Abstract Alzheimer's disease (AD) and frailty are interacting age-related disorders with a high level of morbidity and mortality that both lack biomarkers for prognosis and drugs that can delay and/or prevent disease progression. In older patients, chronic inflammation commonly accompanies frailty and increases risk of cognitive decline and the progression of AD. Autoantibodies (aAbs) angiotensin type 1 receptor (AT1RaAb) are agonistic and increase receptor signaling, which may increase inflammatory burden and thus potentially accelerate the development of AD in frail patients. The presence of circulating AT1RaAbs may facilitate disease development and progression and the levels of these aAbs may be markers of at-risk status. In a study we recently completed of 255 community dwelling adults, Logistic regression analysis of frailty revealed that individuals with AT1RaAb levels above 8.2 µg/ml were 3.9 (95% CI 1.38 - 11.0) times more likely to be frail after controlling for age (p < 0.05). Logistic regression of falls as a function of AT1RaAb levels yielded an odds ratio of 1.33 (95% CI 1.06 to 1.66) for an age, gender, BMI and BP adjusted model. For every 1 µg/ml change in AT1RaAb levels, the odds of falling increased approximately 30%. Regression analysis of the natural logarithm of time to death in a smaller validation group (n=60) yielded a βAT1RaAb of -0.096 (95% CI -0.255 to -0.036) with P < 0.01 after adjusting for age, gender and BMI. For every 1 µg/ml increase in AT1RaAbs, the time to death decreased by 9% after controlling for age, gender, BMI and BP. A case control study of 120 serum samples from subjects with normal cognition on enrollment and later classified as either cognitively normal or diagnosed with AD found baseline AT1RaAb levels were associated with the rate of cognitive decline. We hypothesize that (a) physical frailty is associated with increased levels of AT1RaAb and that, in frail elderly, the highest baseline levels of AT1RaAbs are associated with worsening cognitive status and the development of AD; and (b) ARB treatment would have a positive effect of lessening cognitive decline and delaying the progression to AD in frail subjects. To test these hypotheses we will perform a prospective study assessing the association of baseline aAb levels with longitudinal outcomes (rate of cognitive decline, incidence of frailty and of AD), and determine the capacity of AT1RaAb to predict progression to AD. We will also carry out an exploratory study to investigate the impact of ARB treatment on rate of cognitive decline. The proposed research uses 500 samples from the Rush Alzheimer's Disease Center Repository and core expertise of the Johns Hopkins Biostatistics Center to evaluate a biomarker that could be used to stratify the risk of frail patients for cognitive decline and progression to AD and to identify patients who might benefit from angiotensin receptor blocker treatment.
摘要 阿尔茨海默病(AD)和虚弱是相互作用的年龄相关疾病,具有很高的发病率和 缺乏预后生物标志物和可延缓和/或预防疾病进展的药物的死亡率。 在老年患者中,慢性炎症通常伴随着虚弱,并增加认知能力下降的风险。 以及AD的进展。自身抗体(AABS)血管紧张素1型受体(AT1RaAb)是激动型和 增加受体信号,这可能会增加炎症负担,从而潜在地加速 衰弱患者阿尔茨海默病的发生。循环中AT1RaAbbs的存在可能促进疾病的发展 进展和这些AABS的水平可能是高危状态的标志。在我们最近的一项研究中 完成了255个社区居住成年人的Logistic回归分析,发现个体的脆弱性 当AT1RaAb水平高于8.2微克/毫升时,发生以下疾病的可能性是后者的3.9倍(95%可信区间1.38-11.0 控制年龄(p&lt;0.05)。AT1RaAb水平与跌倒的Logistic回归得出优势比 调整了年龄、性别、BMI和BP的模型为1.33(95%可信区间1.06~1.66)。每改变1微克/毫升 AT1RaAb水平,下降的几率增加约30%。自然对数的回归分析 在较小的验证组(n=60)中,死亡时间的βAT1RaAb为-0.096(95%CI-0.255到-0.036) 经年龄、性别和体重指数调整后的P&lt;0.01。AT1RaAbs每增加1微克/毫升,死亡时间 在控制了年龄、性别、BMI和BP后,下降了9%。120份血清标本的病例对照研究 来自注册时认知正常的受试者,后来被归类为认知正常或确诊的受试者 AD患者AT1RaAb基线水平与认知功能减退率相关。我们假设 (A)身体虚弱与AT1RaAb水平升高有关,在虚弱的老年人中,AT1RaAb水平最高 AT1RaAbbs的基线水平与认知状况恶化和AD的发展有关;以及 (B)ARB治疗将具有减轻认知衰退和延缓病情进展的积极作用 在虚弱的对象中做广告。为了检验这些假设,我们将进行一项前瞻性研究,评估 基线AAB水平与纵向结果(认知减退率、虚弱和AD发生率),以及 确定AT1RaAb预测进展为AD的能力。我们还将进行探索性研究,以 研究ARB治疗对认知功能减退率的影响。拟议中的研究使用了500个样本 来自拉什阿尔茨海默病中心知识库和约翰·霍普金斯生物统计学的核心专业知识 中心评估一种生物标记物,可用于对虚弱患者认知能力下降和 进展到阿尔茨海默病,并确定谁可能受益于血管紧张素受体阻滞剂治疗。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

NEAL S FEDARKO其他文献

NEAL S FEDARKO的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('NEAL S FEDARKO', 18)}}的其他基金

Multiplexed enzyme-linked immunosorbent assay workstation for clinical research
用于临床研究的多重酶联免疫吸附测定工作站
  • 批准号:
    10413539
  • 财政年份:
    2022
  • 资助金额:
    $ 24.53万
  • 项目类别:
Small Integrin-binding Glycophosphoproteins as Biomarkers for Prostate Cancer
小整合素结合糖磷蛋白作为前列腺癌的生物标志物
  • 批准号:
    8277907
  • 财政年份:
    2011
  • 资助金额:
    $ 24.53万
  • 项目类别:
Small Integrin-binding Glycophosphoproteins as Biomarkers for Prostate Cancer
小整合素结合糖磷蛋白作为前列腺癌的生物标志物
  • 批准号:
    8474712
  • 财政年份:
    2011
  • 资助金额:
    $ 24.53万
  • 项目类别:
Small Integrin-binding Glycophosphoproteins as Biomarkers for Prostate Cancer
小整合素结合糖磷蛋白作为前列腺癌的生物标志物
  • 批准号:
    8108168
  • 财政年份:
    2011
  • 资助金额:
    $ 24.53万
  • 项目类别:
FASEB Summer Research Conference on Osteopontin Biology
FASEB 骨桥蛋白生物学夏季研究会议
  • 批准号:
    8004256
  • 财政年份:
    2010
  • 资助金额:
    $ 24.53万
  • 项目类别:
2007 Small Intergin Binding Proteins Gordon Research Conference
2007 年小整合素结合蛋白戈登研究会议
  • 批准号:
    7329283
  • 财政年份:
    2007
  • 资助金额:
    $ 24.53万
  • 项目类别:
Small integrin-binding proteins and tumor progression
小整合素结合蛋白与肿瘤进展
  • 批准号:
    7147389
  • 财政年份:
    2006
  • 资助金额:
    $ 24.53万
  • 项目类别:
Small integrin-binding proteins and tumor progression
小整合素结合蛋白与肿瘤进展
  • 批准号:
    7425047
  • 财政年份:
    2006
  • 资助金额:
    $ 24.53万
  • 项目类别:
Small integrin-binding proteins and tumor progression
小整合素结合蛋白与肿瘤进展
  • 批准号:
    7259482
  • 财政年份:
    2006
  • 资助金额:
    $ 24.53万
  • 项目类别:
Pilot/Exploratory Studies Core
试点/探索性研究核心
  • 批准号:
    10201469
  • 财政年份:
    2003
  • 资助金额:
    $ 24.53万
  • 项目类别:

相似海外基金

Developing a Young Adult-Mediated Intervention to Increase Colorectal Cancer Screening among Rural Screening Age-Eligible Adults
制定年轻人介导的干预措施,以增加农村符合筛查年龄的成年人的结直肠癌筛查
  • 批准号:
    10653464
  • 财政年份:
    2023
  • 资助金额:
    $ 24.53万
  • 项目类别:
Doctoral Dissertation Research: Estimating adult age-at-death from the pelvis
博士论文研究:从骨盆估算成人死亡年龄
  • 批准号:
    2316108
  • 财政年份:
    2023
  • 资助金额:
    $ 24.53万
  • 项目类别:
    Standard Grant
Determining age dependent factors driving COVID-19 disease severity using experimental human paediatric and adult models of SARS-CoV-2 infection
使用 SARS-CoV-2 感染的实验性人类儿童和成人模型确定导致 COVID-19 疾病严重程度的年龄依赖因素
  • 批准号:
    BB/V006738/1
  • 财政年份:
    2020
  • 资助金额:
    $ 24.53万
  • 项目类别:
    Research Grant
Transplantation of Adult, Tissue-Specific RPE Stem Cells for Non-exudative Age-related macular degeneration (AMD)
成人组织特异性 RPE 干细胞移植治疗非渗出性年龄相关性黄斑变性 (AMD)
  • 批准号:
    10294664
  • 财政年份:
    2020
  • 资助金额:
    $ 24.53万
  • 项目类别:
Sex differences in the effect of age on episodic memory-related brain function across the adult lifespan
年龄对成人一生中情景记忆相关脑功能影响的性别差异
  • 批准号:
    422882
  • 财政年份:
    2019
  • 资助金额:
    $ 24.53万
  • 项目类别:
    Operating Grants
Modelling Age- and Sex-related Changes in Gait Coordination Strategies in a Healthy Adult Population Using Principal Component Analysis
使用主成分分析对健康成年人群步态协调策略中与年龄和性别相关的变化进行建模
  • 批准号:
    430871
  • 财政年份:
    2019
  • 资助金额:
    $ 24.53万
  • 项目类别:
    Studentship Programs
Transplantation of Adult, Tissue-Specific RPE Stem Cells as Therapy for Non-exudative Age-Related Macular Degeneration AMD
成人组织特异性 RPE 干细胞移植治疗非渗出性年龄相关性黄斑变性 AMD
  • 批准号:
    9811094
  • 财政年份:
    2019
  • 资助金额:
    $ 24.53万
  • 项目类别:
Study of pathogenic mechanism of age-dependent chromosome translocation in adult acute lymphoblastic leukemia
成人急性淋巴细胞白血病年龄依赖性染色体易位发病机制研究
  • 批准号:
    18K16103
  • 财政年份:
    2018
  • 资助金额:
    $ 24.53万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Doctoral Dissertation Research: Literacy Effects on Language Acquisition and Sentence Processing in Adult L1 and School-Age Heritage Speakers of Spanish
博士论文研究:识字对西班牙语成人母语和学龄传统使用者语言习得和句子处理的影响
  • 批准号:
    1823881
  • 财政年份:
    2018
  • 资助金额:
    $ 24.53万
  • 项目类别:
    Standard Grant
Adult Age-differences in Auditory Selective Attention: The Interplay of Norepinephrine and Rhythmic Neural Activity
成人听觉选择性注意的年龄差异:去甲肾上腺素与节律神经活动的相互作用
  • 批准号:
    369385245
  • 财政年份:
    2017
  • 资助金额:
    $ 24.53万
  • 项目类别:
    Research Grants
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了