Early Onset Alzheimer's Disease and Related Dementias: A Population-Based Approach to Identify Characteristics and Risk Factors
早发性阿尔茨海默氏病和相关痴呆症:基于人群的特征和危险因素识别方法
基本信息
- 批准号:10659338
- 负责人:
- 金额:$ 76.87万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-06-15 至 2027-02-28
- 项目状态:未结题
- 来源:
- 关键词:AdultAffectAgeAge YearsAge of OnsetAlcohol consumptionAlzheimer&aposs DiseaseAlzheimer&aposs disease related dementiaBehavioralBlood PressureBlood VesselsBody mass indexCardiovascular systemCharacteristicsClinicalCognitiveCohort StudiesCraniocerebral TraumaDataDevelopmentDiabetes MellitusDiagnosisDiseaseDisease ProgressionDistressEarly DiagnosisEarly Onset Alzheimer DiseaseEducationEligibility DeterminationEpidemiologyEvaluationEventFrontotemporal DementiaGeneral PopulationGenesGeneticGenetic Predisposition to DiseaseGenetic RiskHealth behaviorHeart DiseasesHigh PrevalenceHypertensionIncidenceIndividualInfrastructureInternationalInterventionLate Onset Alzheimer DiseaseLewy Body DementiaLife StyleLightLipidsMeasuresMedicalMental DepressionNatureParticipantPatientsPersonsPhysical activityPhysiologicalPopulationPopulation StudyPredisposing FactorPredispositionPrevalencePreventionPrevention strategyPrimary PreventionProspective StudiesQuality of lifeRaceRenal functionReportingRiskRisk FactorsRoleSample SizeSecondary PreventionSmokingSocial isolationStrokeSymptomsSyndromeTestingTimeVariantVascular DementiaVulnerable PopulationsWomanbiobankburden of illnesscardiovascular healthcardiovascular risk factorcohortdata harmonizationdementia riskdemographicsearly onsetgenetic varianthigh riskhuman old age (65+)insightlifestyle factorsmiddle agemulti-ethnicnon-geneticpolygenic risk scorepopulation basedpresenilin-1presenilin-2protective factorsrare variantscreeningsexstroke incidencetertiary preventiontrendyoung adult
项目摘要
Summary
Alzheimer's Disease and Related Dementias (ADRD) is an overwhelming medical condition at any age, but
ADRD in younger adulthood is particularly devastating, affecting quality of life and independence of individuals
in their prime years. Early onset ADRD (EOD) is defined as an ADRD diagnosis before age 65. While it is
commonly perceived that EOD occurs primarily as a rare genetic syndrome, the known genetic variants account
for less than 5% of cases. Despite the distressing course and unclear nature of the disease in the majority of
cases, EOD is widely understudied. Current data on the prevalence and incidence of EOD seem to
underestimate the magnitude of the problem and there is no information available regarding predisposing and/or
protective factors for EOD.
Using the infrastructure of an international Dementia Risk Pooling Project (DRPP), we propose a prospective
study of EOD development which comprises individuals from five large multi-ethnic population-based cohort
studies (ARIC, MESA, FHS, Whitehall II and, UK Biobank). This study provides the opportunity to (1) refine
estimates of incident EOD, (2) investigate the role of cardiovascular, lifestyle and behavioral risk factors in the
onset of EOD and (3) study whether a favorable midlife risk profile in the presence of genetic predisposition
delays EOD age of onset. This evaluation will be the first study to pool multiple international population-based
cohorts to prospectively study ADRD before the age of 65 in young and middle-aged adults. The current notion
that EOD is merely driven by genetic syndromes has shadowed efforts to identify distinct predisposing and/or
protective factors for EOD and targeting vulnerable populations for early detection and prevention. The findings
will shed much needed light on the vulnerability and unique risk factors for EOD and may lead to development
of more effective targets for prevention to delay onset and progression of disease. EOD is relatively rare and
thus primordial and primary prevention may be more efficient than screening and secondary or tertiary
prevention. Our data on EOD risk factors will strengthen targeted intervention strategies with focus on primordial
and primary prevention.
总结
阿尔茨海默病和相关痴呆症(ADRD)是一种压倒性的医疗条件,在任何年龄,但
ADRD在年轻的成年人中特别具有破坏性,影响生活质量和个人的独立性
在他们的黄金岁月。早发性ADRD(EOD)定义为65岁之前诊断出ADRD。虽然
通常认为EOD主要是一种罕见的遗传综合征,已知的遗传变异解释了
不到5%的病例。尽管大多数人的病程令人痛苦,而且疾病的性质尚不清楚,
在这些案件中,爆炸物处理问题普遍未得到充分研究。目前关于爆炸物处理流行率和发生率的数据似乎
低估了问题的严重性,并且没有关于诱发和/或
爆炸物处理的保护因素。
利用国际痴呆风险汇集项目(DRPP)的基础设施,我们提出了一个前瞻性的
EOD发展研究,包括来自五个大型多种族人群队列的个人
研究(ARIC、梅萨、FHS、Whitehall II和UK Biobank)。这项研究提供了机会,以(1)完善
事件EOD的估计,(2)调查心血管,生活方式和行为危险因素在EOD中的作用。
EOD的发病和(3)研究是否在存在遗传易感性的有利中年风险概况
延迟爆炸物处理的发病年龄。这项评估将是第一项汇集多个国际人口为基础的研究,
队列前瞻性研究65岁之前的年轻和中年成人ADRD。目前的概念
爆炸物处理仅仅是由遗传综合征驱动的,这给确定不同的诱发因素和/或
爆炸物处理的保护因素,并针对易受伤害的人群进行早期发现和预防。这些发现
将揭示爆炸物处理的脆弱性和独特风险因素,
更有效的预防目标,以延缓疾病的发作和进展。爆炸物处理相对罕见,
因此,原始和初级预防可能比筛查和二级或三级预防更有效。
预防我们关于爆炸物处理风险因素的数据将加强有针对性的干预战略,重点是原始的
一级预防。
项目成果
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