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Alzheimer''s and Dementia: Translational Research and Clinical Interventions最新文献

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Data-driven discovery of associations between prescribed drugs and dementia risk: A systematic review. 数据驱动的处方药物与痴呆风险之间关联的发现:一项系统综述。
IF 4.9 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-21 eCollection Date: 2025-01-01 DOI: 10.1002/trc2.70037
Benjamin R Underwood, Ilianna Lourida, Jessica Gong, Stefano Tamburin, Eugene Yee Hing Tang, Emad Sidhom, Xin You Tai, Matthew J Betts, Janice M Ranson, Margarita Zachariou, Olajide E Olaleye, Saswati Das, Neil P Oxtoby, Shanquan Chen, David J Llewellyn

Abstract: Recent clinical trials on slowing dementia progression have led to renewed focus on finding safer, more effective treatments. One approach to identify plausible candidates is to assess whether existing medications for other conditions may affect dementia risk. We conducted a systematic review to identify studies adopting a data-driven approach to investigate the association between a wide range of prescribed medications and dementia risk. We included 14 studies using administrative or medical records data for more than 130 million individuals and 1 million dementia cases. Despite inconsistencies in identifying specific drugs that may modify Alzheimer's or dementia risk, some themes emerged for drug classes with biological plausibility. Antimicrobials, vaccinations, and anti-inflammatories were associated with reduced risk, while diabetes drugs, vitamins and supplements, and antipsychotics were associated with increased risk. We found conflicting evidence for antihypertensives and antidepressants. Drug repurposing for use in dementia is an urgent priority. Our findings offer a basis for prioritizing candidates and exploring underlying mechanisms.

Highlights: ·We present a systematic review of studies reporting association between drugs prescribed for other conditions and risk of dementia including 139 million people and 1 million cases of dementia.·Our work supports some previously reported associations, for example, showing decreased risk of dementia with drugs to treat inflammatory disease and increased risk with antipsychotic treatment.·Antimicrobial treatment was perhaps more surprisingly associated with decreased risk, supportive of recent increased interest in this potential therapeutic avenue.·Our work should help prioritize drugs for entry into adaptive platform trials in Alzheimer's disease and will serve as a useful resource for those investigating drugs or classes of drugs and risk of dementia.

摘要:最近关于减缓痴呆症进展的临床试验使人们重新关注寻找更安全、更有效的治疗方法。确定合理的候选药物的一种方法是评估现有的治疗其他疾病的药物是否会影响痴呆症的风险。我们进行了一项系统综述,以确定采用数据驱动方法调查各种处方药与痴呆风险之间关系的研究。我们纳入了14项研究,这些研究使用了超过1.3亿个人和100万痴呆病例的行政或医疗记录数据。尽管在确定可能改变阿尔茨海默病或痴呆症风险的特定药物方面存在不一致,但一些具有生物学合理性的药物类别出现了一些主题。抗微生物药物、疫苗接种和消炎药与风险降低有关,而糖尿病药物、维生素和补充剂以及抗精神病药物与风险增加有关。我们发现关于抗高血压药和抗抑郁药的证据相互矛盾。针对痴呆症的药物再利用是当务之急。我们的发现为确定候选药物的优先级和探索潜在机制提供了基础。·我们对包括1.39亿人和100万例痴呆症患者在内的研究进行了系统回顾,报告了其他疾病处方药物与痴呆症风险之间的关联。·我们的工作支持一些先前报道的关联,例如,显示治疗炎症性疾病的药物降低痴呆风险,抗精神病药物治疗增加风险。·抗菌治疗可能更令人惊讶地与降低风险相关,支持最近对这一潜在治疗途径的兴趣增加。·我们的工作应该有助于优先考虑进入阿尔茨海默病适应性平台试验的药物,并将为那些研究药物或药物类别和痴呆症风险的人提供有用的资源。
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引用次数: 0
Unraveling the impact of blood RANKL and OPG levels on Alzheimer's disease: Independent of bone mineral density and inflammation. 揭示血液RANKL和OPG水平对阿尔茨海默病的影响:独立于骨矿物质密度和炎症。
IF 4.9 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-20 eCollection Date: 2025-01-01 DOI: 10.1002/trc2.70044
Xingzhi Guo, Wenzhi Shi, Juanjuan Lu, Peng Tang, Rui Li

Introduction: Observational studies have revealed a close relationship between reduced bone mineral density (BMD) and Alzheimer's disease (AD) risk. The receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) system, pivotal in regulating bone metabolism, has been implicated in brain function, but the causal impact on AD risk remains unclear.

Methods: We employed bi-directional Mendelian randomization (MR) and multivariable MR (MVMR) approaches to elucidate the effect of blood soluble RANKL (sRANKL) and OPG levels on AD, assessing whether this influence was independent of BMD and inflammation. Three distinct AD genome-wide association study (GWAS) data sets from the International Genomics of Alzheimer's Project (IGAP), UK Biobank (UKB), and FinnGen were utilized. Summary-level data on blood sRANKL and OPG were sourced from deCODE Genetics.

Results: Genetically predicted per standard deviation (SD) increase in blood sRANKL levels was significantly associated with a reduced risk of AD across all three AD GWAS data sets (IGAP: odds ratio [OR] = 0.82, 95% confidence interval [CI] = 0.72-0.94, p = 0.004; UKB: OR = 0.85, 95% CI = 0.78-0.91, p < 0.001; FinnGen: OR = 0.83, 95% CI = 0.73-0.94, p = 0.004). No significant causal relationship was observed between OPG levels and AD. In addition, there was no causal impact of AD on the blood levels of sRANKL and OPG. MVMR results showed that the inverse association between sRANKL and AD risk persisted after adjusting for BMD and interleukin-1α and chemoattractant protein-1.

Discussion: Our study provides evidence that elevated sRANKL levels are causally linked to a reduced risk of AD, independent of BMD and inflammation. These findings enhance our understanding of the complex interactions between bone metabolism and AD.

Highlights: Blood soluble receptor activator of nuclear factor kappa-B ligand (sRANKL) levels are linked to a reduced risk of Alzheimer's disease (AD).The association between sRANKL levels and AD is independent of bone mineral density (BMD) and inflammation.No causal link exists between blood osteoprotegerin levels and AD.AD does not affect blood levels of sRANKL or osteoprotegerin.

观察性研究揭示了骨密度(BMD)降低与阿尔茨海默病(AD)风险之间的密切关系。核因子κ b配体受体激活剂(RANKL)和骨保护素(OPG)系统在调节骨代谢中起关键作用,已被认为与脑功能有关,但其对AD风险的因果影响尚不清楚。方法:我们采用双向孟德尔随机化(MR)和多变量MR (MVMR)方法来阐明血溶性RANKL (sRANKL)和OPG水平对AD的影响,评估这种影响是否独立于BMD和炎症。三个不同的AD全基因组关联研究(GWAS)数据集分别来自国际阿尔茨海默氏症基因组计划(IGAP)、英国生物银行(UKB)和FinnGen。血液sRANKL和OPG的汇总数据来自deCODE Genetics。结果:在所有三个AD GWAS数据集中,遗传预测的每标准差(SD)血中sRANKL水平升高与AD风险降低显著相关(IGAP:优势比[OR] = 0.82, 95%可信区间[CI] = 0.72-0.94, p = 0.004;UKB: OR = 0.85, 95% CI = 0.78-0.91, p < 0.001;FinnGen:或= 0.83,95% CI -0.94 = 0.73, p = 0.004)。OPG水平与AD之间没有明显的因果关系。此外,AD对血液中sRANKL和OPG水平没有因果影响。MVMR结果显示,在调整BMD、白细胞介素-1α和趋化蛋白-1后,sRANKL与AD风险的负相关关系仍然存在。讨论:我们的研究提供了证据,表明升高的sRANKL水平与AD风险降低有因果关系,与BMD和炎症无关。这些发现增强了我们对骨代谢和AD之间复杂相互作用的理解。重点:血溶性受体激活物核因子κ b配体(sRANKL)水平与阿尔茨海默病(AD)风险降低有关。sRANKL水平与AD之间的关联与骨密度(BMD)和炎症无关。血液中骨保护素水平与AD之间不存在因果关系。AD不影响血液中sRANKL或骨保护素的水平。
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引用次数: 0
Dynamic neurocognitive adaptation in aging: Development and validation of a new scale. 衰老中的动态神经认知适应:新量表的开发和验证。
IF 4.9 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-20 eCollection Date: 2025-01-01 DOI: 10.1002/trc2.70049
Filippo Cieri, Giulia Di Francesco, Chad Lee Cross, Andrew Bender, Jessica Zoe Kirkland Caldwell

Introduction: Forty-five percent of Alzheimer's disease (AD) cases may have been preventable through protective factors. Reserve, resilience, and resistance share common neurocognitive adaptive processes, acting through protective mechanisms. In this article we propose the development and validation of a new scale, called dynamic Neurocognitive Adaptation, developed in this direction.

Methods: We included 815 participants (50% women; 65+ years inclusive of age), divided into two subsamples for exploratory and confirmatory factor analysis. Our initial scale was composed of 30 items, investigating seven dimensions, explored by a 5-point Likert scale reflecting the frequency of activities, for seven time windows.

Results: Our final scale had 20 items divided among four dimensions: physical, cognitive, creative, and social. There were no issues related to multi-collinearity or non-collinearity. Kaiser-Meyer-Olkin (KMO) = 0.80 and Bartlett's test of sphericity indicated all values ≤0.01; Cronbach's alpha = 0.83.

Discussion: We have validated a reliable, novel, easy to complete, and comprehensive scale to assess lifetime behaviors, which can be applied in research on AD risk reduction, mild cognitive impairment, and in clinical practice.

Highlights: Reserve, resistance, and resilience share similar adaptive mechanisms.Dynamic Neurocognitive Adaptation is a new scale to assess lifetime protective factors.Dynamic Neurocognitive Adaptation is a reliable, novel, and easy to complete scale.This approach can characterize specific life stages that are ripe for risk-reduction interventions.Our scale can be used to personalize health recommendations in aging.

导语:45%的阿尔茨海默病(AD)病例可以通过保护因素来预防。储备、恢复力和抵抗具有共同的神经认知适应过程,通过保护机制起作用。在这篇文章中,我们提出了一个新的尺度的发展和验证,称为动态神经认知适应,在这个方向上发展。方法:我们纳入815名参与者(50%为女性;65岁以上(含年龄),分为两个子样本进行探索性和验证性因素分析。我们最初的量表由30个项目组成,调查了7个维度,通过5点李克特量表反映了7个时间窗口的活动频率。结果:我们的最终量表有20个项目,分为四个维度:身体、认知、创造力和社交。不存在多重共线性或非共线性的问题。Kaiser-Meyer-Olkin (KMO) = 0.80, Bartlett球度检验结果均≤0.01;Cronbach’s alpha = 0.83。讨论:我们验证了一种可靠、新颖、易于完成、全面的终身行为评估量表,可用于阿尔茨海默病风险降低、轻度认知障碍的研究和临床实践。重点:储备、抵抗和恢复具有相似的适应机制。动态神经认知适应是一种评价终身保护因素的新量表。动态神经认知适应量表是一种可靠、新颖、易于完成的量表。这种方法可以描述适合采取降低风险干预措施的特定生命阶段。我们的量表可以用来为老年人提供个性化的健康建议。
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引用次数: 0
Perspective: Minimally clinically important "symptomatic" benefit associated with disease modification resulting from anti-amyloid immunotherapy. 观点:抗淀粉样蛋白免疫治疗与疾病改善相关的最低临床重要“症状性”获益。
IF 4.9 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-20 eCollection Date: 2025-01-01 DOI: 10.1002/trc2.70035
John Alam, Marwan N Sabbagh

Despite some skepticism regarding the amyloid hypothesis, there is growing evidence that clearing amyloid by targeting specific species of amyloid (plaque, oligomers, fibrils, and protofibrils) for removal has therapeutic benefits. Specifically, there is growing evidence that, in mild cognitive impairment and mild dementia due to Alzheimer's disease (AD), robust and aggressive removal of amyloid can slow cognitive decline as measured by global instruments, composite measures, and cognitive testing. Furthermore, clinical efficacy signals coupled with clear biomarker changes provide the first evidence of disease modification. This effect seems to be in addition to symptomatic treatments and opens speculation that the effect of anti-amyloid monoclonal antibodies might be clinically meaningful through symptomatic amelioration that is a result of disease modification.

Highlights: Clearance of brain amyloid plaques may lead to a clinical benefit in patients with early AD.Aggregated Aβ may play a role in both disease expression and progression.Anti-amyloid monoclonal antibodies might be clinically meaningful through symptomatic amelioration resulting from disease modification.

尽管一些人对淀粉样蛋白假说持怀疑态度,但越来越多的证据表明,通过针对特定种类的淀粉样蛋白(斑块、低聚物、原纤维和原纤维)清除淀粉样蛋白具有治疗益处。具体来说,越来越多的证据表明,在阿尔茨海默病(AD)引起的轻度认知障碍和轻度痴呆中,通过全球仪器、综合测量和认知测试,强有力和积极地去除淀粉样蛋白可以减缓认知衰退。此外,临床疗效信号加上明确的生物标志物变化提供了疾病改变的第一个证据。这种效果似乎是对症治疗的补充,并开启了一种推测,即抗淀粉样蛋白单克隆抗体的作用可能通过疾病改变导致的症状改善而具有临床意义。重点:清除脑淀粉样斑块可能对早期AD患者有临床益处。聚集的a β可能在疾病表达和进展中发挥作用。抗淀粉样蛋白单克隆抗体可能通过疾病修饰引起的症状改善而具有临床意义。
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引用次数: 0
Developing, implementing, and evaluating the first national Memory and Cognition Clinic Guidelines in Australia. 制定,实施和评估澳大利亚第一个国家记忆和认知临床指南。
IF 4.9 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-16 eCollection Date: 2025-01-01 DOI: 10.1002/trc2.70031
Inga Mehrani, Matthew Paradise, Lee-Fay Low, Sue Kurrle, Valerie Arsenova, Gemma Jahn, Katrina Fyfe, Johannes C Michaelian, Katharine Salmon, Jane Alty, Sharon L Naismith, Perminder S Sachdev

Introduction: A lack of national consensus on the roles and responsibilities of Australian memory and cognition clinics contributes to the large variability seen across services. The introduction of guidelines and a quality assessment framework could facilitate greater harmonization and quality improvements.

Methods: We used a modified Delphi process to develop the guidelines. Pilot clinics completed a self-assessment, case-note audit, and review meeting to evaluate their service against the guidelines.

Results: The final guidelines included 160 standards on 14 different topics. Standards around maximum waiting times for an assessment and minimum post-diagnostic care responsibilities were particularly controversial. Seven clinics participated in the pilot. On average, clinics achieved 56% of standards (range of 18% to 87%).

Discussion: The Memory and Cognition Clinic Guidelines form the first step toward greater harmonization and quality improvements. Key learnings from the clinics' feedback included reducing the number of secondary standards and streamlining data collection with the national dementia clinical quality registry.

Highlights: We developed and implemented the first national consensus-based best-practice guidelines for memory and cognition clinics in Australia.The guidelines are based on consultation with 125 Australian health professionals and 89 Australians living with dementia and care partners.First-time national agreement on standards around maximum waiting times for an assessment and minimum post-diagnostic care requirements is presented in the guidelines.The guidelines were implemented in seven memory and cognition clinics from five different states.Clinicians' feedback included: reducing the number of secondary standards to increase conciseness and practicability should be considered for future iterations.

简介:澳大利亚记忆和认知诊所的角色和责任缺乏全国共识,导致各服务机构的差异很大。采用准则和质量评估框架可以促进更大程度的协调和质量改进。方法:采用改进的德尔菲法制定指南。试点诊所完成了自我评估、病例记录审计和审查会议,以根据指南评估其服务。结果:最终指南包括14个不同主题的160个标准。关于评估的最长等待时间和最低诊断后护理责任的标准尤其有争议。七家诊所参与了试点。平均而言,诊所达到了56%的标准(范围为18%至87%)。讨论:记忆与认知临床指南是迈向更大协调和质量改进的第一步。从这些诊所的反馈中得到的主要教训包括减少二级标准的数量,以及通过国家痴呆症临床质量登记处简化数据收集。重点:我们为澳大利亚的记忆和认知诊所制定并实施了第一个基于全国共识的最佳实践指南。该指南是在咨询了125名澳大利亚卫生专业人员和89名患有痴呆症的澳大利亚人及其护理伙伴之后制定的。指南中首次提出了关于评估的最长等待时间和最低诊断后护理要求的标准的国家协议。该指南在来自五个不同州的七个记忆和认知诊所实施。临床医生的反馈包括:应考虑减少二级标准的数量以增加简洁性和实用性。
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引用次数: 0
Statin use and dementia risk: A systematic review and updated meta-analysis. 他汀类药物使用与痴呆风险:一项系统综述和最新荟萃分析。
IF 4.9 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-16 eCollection Date: 2025-01-01 DOI: 10.1002/trc2.70039
Fernando Luiz Westphal Filho, Paulo Roberto Moss Lopes, Artur Menegaz de Almeida, Vitor Kendi Tsuchiya Sano, Fernanda Moraes Tamashiro, Ocílio Ribeiro Gonçalves, Francisco Cezar Aquino de Moraes, Michele Kreuz, Francinny Alves Kelly, Pablo Vinícius Silveira Feitoza

Dementia affects 55 million people globally, with the number projected to triple by 2050. Statins, widely prescribed for cardiovascular benefits, may also have neuroprotective effects, although studies on their impact on dementia risk have shown contradictory results. In this systematic review and meta-analysis, we searched PubMed, Embase, and Cochrane following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We assessed the risk of dementia, Alzheimer's disease (AD), and vascular dementia (VaD), with subgroup analyses by gender, statin type, and diabetes status. Fifty-five observational studies including over 7 million patients were analyzed. Statin use significantly reduced the risk of dementia compared to nonusers (hazard ratio [HR] 0.86; 95% confidence interval [CI]: 0.82 to 0.91; p < 0.001). It was also associated with reduced risks of AD (HR 0.82; 95% CI: 0.74 to 0.90; p < 0.001) and VaD (HR 0.89; 95% CI: 0.77 to 1.02; p = 0.093). Subgroup analyses revealed significant dementia risk reductions among patients with type 2 diabetes mellitus (HR 0.87; 95% CI: 0.85 to 0.89; p < 0.001), those with exposure to statins for more than 3 years (HR 0.37; 95% CI: 0.30 to 0.46; p < 0.001), and populations from Asia, where the greatest protective effect was observed (HR 0.84; 95% CI: 0.80 to 0.88). Additionally, rosuvastatin demonstrated the most pronounced protective effect for all-cause dementia among specific statins (HR 0.72; 95% CI: 0.60 to 0.88). Our findings underscore the neuroprotective potential of statins in dementia prevention. Despite the inherent limitations of observational studies, the large dataset and detailed subgroup analyses enhance the reliability of our results. Future randomized clinical trials are necessary to confirm these findings and enlighten clinical guidelines.

Highlights: Largest meta-analysis to date on statins and dementia risk, including 55 studies and more than 7 million patients.Statin use linked to lower risks of all-dementia, AD, and VaD.Numerous significant subgroup results highlight statins' diverse neuroprotective effects.Findings support statins as a public health tool, especially in low-income countries.Future research should explore the impact of statins across diverse patient populations.

全球有5500万人患有痴呆症,预计到2050年这一数字将增加两倍。他汀类药物广泛用于治疗心血管疾病,也可能具有神经保护作用,尽管有关其对痴呆风险影响的研究显示出相互矛盾的结果。在本系统评价和荟萃分析中,我们按照系统评价和荟萃分析(PRISMA)指南的首选报告项目检索了PubMed、Embase和Cochrane。我们评估了痴呆、阿尔茨海默病(AD)和血管性痴呆(VaD)的风险,并根据性别、他汀类药物类型和糖尿病状况进行了亚组分析。共分析了55项观察性研究,包括700多万患者。与未使用他汀类药物的患者相比,使用他汀类药物可显著降低痴呆风险(风险比[HR] 0.86;95%置信区间[CI]: 0.82 ~ 0.91;p p p = 0.093)。亚组分析显示,2型糖尿病患者痴呆风险显著降低(HR 0.87;95% CI: 0.85 ~ 0.89;亮点:迄今为止最大的关于他汀类药物与痴呆风险的荟萃分析,包括55项研究和700多万患者。他汀类药物的使用与全痴呆、AD和VaD的风险降低有关。许多重要的亚组结果突出了他汀类药物不同的神经保护作用。研究结果支持他汀类药物作为公共卫生工具,特别是在低收入国家。未来的研究应该探索他汀类药物对不同患者群体的影响。
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引用次数: 0
Comparison of sample characteristics of Wisconsin Alzheimer's Disease Research Center participants with the Wisconsin state population-An evaluation of the recruitment effort. 威斯康星州阿尔茨海默病研究中心参与者的样本特征与威斯康星州人口的比较——对招募工作的评估
IF 4.9 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-16 eCollection Date: 2025-01-01 DOI: 10.1002/trc2.70036
Yue Ma, Maria C Mora Pinzon, William R Buckingham, Andrew J Bersch, W Ryan Powell, Tamara J LeCaire, Gilda E Ennis, Yuetiva Deming, Erin M Jonaitis, Nathaniel A Chin, Lindsay R Clark, Dorothy F Edwards, Art Walaszek, Ozioma C Okonkwo, Megan Zuelsdorff, Richard J Chappell, Sterling C Johnson, Sanjay Asthana, Carey E Gleason, Amy J Kind, Barbara B Bendlin, Cynthia M Carlsson

Introduction: Understanding how a research sample compares to the population from which it is drawn can help inform future recruitment planning. We compared the Wisconsin Alzheimer's Disease Research Center (WADRC) participant sample to the Wisconsin state population (WI-pop) on key demographic, social exposome, and vascular risk measures.

Methods: The WADRC sample included 930 participants. Population statistics were estimated using several national and state data sources. We compared WADRC to WI-pop for two age groups, 45-64 years and ≥65 years, separately.

Results: Compared to WI-pop, WADRC participants were older and included more women, more Black and American Indian individuals, and fewer Hispanic and Asian individuals. WADRC participants had higher levels of educational attainment, consisted of smaller proportions living in rural areas and disadvantaged neighborhoods, and showed lower vascular risks. Greater differences between WADRC and WI-pop were found for most metrics in the ≥65 group compared to the 45-64 group.

Discussion: The findings revealed opportunities to increase enrollment from the Hispanic/Latino and Asian American populations, to include participants from a broader range of educational backgrounds, and to enroll more residents from rural areas and disadvantaged neighborhoods, which may lead to a broader distribution of cardiovascular risk factors. Expanding sociodemographic and health profiles represented in the participant candidate pool for study selection and including those who are underrepresented in research may potentially reduce selection bias but not eliminate it. Statistical approaches can be applied to address bias and generalize findings from a study sample to its target population by adjusting for their differences in the joint distribution of covariates. Although research centers have different regional populations and specific recruitment focuses for scientific reasons, evaluating their participant characteristics may help plan engagement efforts to improve the inclusion of underrepresented groups and collaboratively support generalizable research nationwide.

Highlights: We compared the characteristics of Wisconsin Alzheimer's Disease Research Center (WADRC) participants with the Wisconsin population.Metrics of comparison included demographics, social exposomes, and vascular risks.WADRC participants are different from the Wisconsin population.We explored the implications and causes of the differences.We discussed strategies for engaging and recruiting underrepresented groups.

引言:了解一个研究样本如何与人口进行比较,可以帮助告知未来的招聘计划。我们比较了威斯康星州阿尔茨海默病研究中心(WADRC)的参与者样本和威斯康星州人口(WI-pop)的关键人口统计、社会暴露和血管风险措施。方法:WADRC样本共930人。人口统计数据是利用几个国家和州的数据来源估计的。我们将WADRC和WI-pop分别用于45-64岁和≥65岁两个年龄组进行比较。结果:与WI-pop相比,WADRC参与者年龄更大,包括更多的女性,更多的黑人和美洲印第安人,更少的西班牙裔和亚洲人。WADRC参与者受教育程度较高,居住在农村地区和弱势社区的比例较小,血管风险较低。与45-64岁组相比,≥65岁组的WADRC和WI-pop在大多数指标上存在较大差异。讨论:研究结果表明,有机会增加西班牙裔/拉丁裔和亚裔美国人的入组,包括来自更广泛教育背景的参与者,并招收更多来自农村地区和弱势社区的居民,这可能导致心血管危险因素的更广泛分布。扩大研究选择的参与者候选池中所代表的社会人口学和健康概况,并包括那些在研究中代表性不足的人,可能会减少选择偏差,但不能消除它。统计方法可以通过调整协变量联合分布中的差异来解决偏差,并将研究样本的发现推广到目标人群。尽管由于科学原因,研究中心有不同的区域人口和特定的招聘重点,但评估其参与者特征可能有助于计划参与工作,以改善代表性不足群体的包容性,并协同支持全国范围内的可推广研究。重点:我们比较了威斯康星州阿尔茨海默病研究中心(WADRC)参与者与威斯康星州人群的特征。比较指标包括人口统计、社会暴露和血管风险。WADRC的参与者与威斯康星州的人口不同。我们探讨了这些差异的含义和原因。我们讨论了参与和招募代表性不足群体的策略。
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引用次数: 0
LD-informed deep learning for Alzheimer's gene loci detection using WGS data. 基于ld的深度学习用于WGS数据的阿尔茨海默病基因位点检测。
IF 4.9 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-16 eCollection Date: 2025-01-01 DOI: 10.1002/trc2.70041
Taeho Jo, Paula Bice, Kwangsik Nho, Andrew J Saykin

Introduction: The exponential growth of genomic datasets necessitates advanced analytical tools to effectively identify genetic loci from large-scale high throughput sequencing data. This study presents Deep-Block, a multi-stage deep learning framework that incorporates biological knowledge into its AI architecture to identify genetic regions as significantly associated with Alzheimer's disease (AD). The framework employs a three-stage approach: (1) genome segmentation based on linkage disequilibrium (LD) patterns, (2) selection of relevant LD blocks using sparse attention mechanisms, and (3) application of TabNet and Random Forest algorithms to quantify single nucleotide polymorphism (SNP) feature importance, thereby identifying genetic factors contributing to AD risk.

Methods: The Deep-Block was applied to a large-scale whole genome sequencing (WGS) dataset from the Alzheimer's Disease Sequencing Project (ADSP), comprising 7416 non-Hispanic white (NHW) participants (3150 cognitively normal older adults (CN), 4266 AD).

Results: 30,218 LD blocks were identified and then ranked based on their relevance with Alzheimer's disease. Subsequently, the Deep-Block identified novel SNPs within the top 1500 LD blocks and confirmed previously known variants, including APOE rs429358 and rs769449. Expression Quantitative Trait Loci (eQTL) analysis across 13 brain regions provided functional evidence for the identified variants. The results were cross-validated against established AD-associated loci from the European Alzheimer's and Dementia Biobank (EADB) and the GWAS catalog.

Discussion: The Deep-Block framework effectively processes large-scale high throughput sequencing data while preserving SNP interactions during dimensionality reduction, minimizing bias and information loss. The framework's findings are supported by tissue-specific eQTL evidence across brain regions, indicating the functional relevance of the identified variants. Additionally, the Deep-Block approach has identified both known and novel genetic variants, enhancing our understanding of the genetic architecture and demonstrating its potential for application in large-scale sequencing studies.

Highlights: Growing genomic datasets require advanced tools to identify genetic loci in sequencing.Deep-Block, a novel AI framework, was used to process large-scale ADSP WGS data.Deep-Block identified both known and novel AD-associated genetic loci.rs429358 (APOE) was key; rs11556505 (TOMM40), rs34342646 (NECTIN2) were significant.The AI framework uses biological knowledge to enhance detection of Alzheimer's loci.

基因组数据集的指数级增长需要先进的分析工具来有效地从大规模高通量测序数据中识别遗传位点。本研究提出了deep - block,这是一个多阶段深度学习框架,将生物学知识纳入其人工智能架构,以识别与阿尔茨海默病(AD)显著相关的遗传区域。该框架采用三阶段方法:(1)基于连锁不平衡(LD)模式的基因组分割,(2)利用稀疏注意机制选择相关LD块,以及(3)应用TabNet和Random Forest算法量化单核苷酸多态性(SNP)特征重要性,从而确定导致AD风险的遗传因素。方法:Deep-Block应用于来自阿尔茨海默病测序项目(ADSP)的大规模全基因组测序(WGS)数据集,包括7416名非西班牙裔白人(NHW)参与者(3150名认知正常的老年人(CN), 4266名AD)。结果:30,218个LD块被确定,然后根据它们与阿尔茨海默病的相关性进行排名。随后,Deep-Block在前1500个LD块中发现了新的snp,并确认了以前已知的变体,包括APOE rs429358和rs769449。跨13个脑区的表达数量性状位点(eQTL)分析为鉴定的变异提供了功能证据。将结果与欧洲阿尔茨海默病和痴呆症生物银行(EADB)和GWAS目录中已建立的ad相关基因座进行交叉验证。讨论:Deep-Block框架有效地处理大规模高通量测序数据,同时在降维过程中保留SNP相互作用,最大限度地减少偏差和信息损失。该框架的发现得到了跨大脑区域的组织特异性eQTL证据的支持,表明了已识别变体的功能相关性。此外,Deep-Block方法已经确定了已知和新的遗传变异,增强了我们对遗传结构的理解,并展示了其在大规模测序研究中的应用潜力。亮点:不断增长的基因组数据集需要先进的工具来识别测序中的遗传位点。采用一种新的人工智能框架Deep-Block对大规模ADSP WGS数据进行处理。Deep-Block发现了已知的和新的ad相关基因位点。rs429358 (APOE)是关键;rs11556505 (TOMM40)、rs34342646 (NECTIN2)具有显著性。人工智能框架利用生物学知识来加强对阿尔茨海默氏症基因位点的检测。
{"title":"LD-informed deep learning for Alzheimer's gene loci detection using WGS data.","authors":"Taeho Jo, Paula Bice, Kwangsik Nho, Andrew J Saykin","doi":"10.1002/trc2.70041","DOIUrl":"10.1002/trc2.70041","url":null,"abstract":"<p><strong>Introduction: </strong>The exponential growth of genomic datasets necessitates advanced analytical tools to effectively identify genetic loci from large-scale high throughput sequencing data. This study presents Deep-Block, a multi-stage deep learning framework that incorporates biological knowledge into its AI architecture to identify genetic regions as significantly associated with Alzheimer's disease (AD). The framework employs a three-stage approach: (1) genome segmentation based on linkage disequilibrium (LD) patterns, (2) selection of relevant LD blocks using sparse attention mechanisms, and (3) application of TabNet and Random Forest algorithms to quantify single nucleotide polymorphism (SNP) feature importance, thereby identifying genetic factors contributing to AD risk.</p><p><strong>Methods: </strong>The Deep-Block was applied to a large-scale whole genome sequencing (WGS) dataset from the Alzheimer's Disease Sequencing Project (ADSP), comprising 7416 non-Hispanic white (NHW) participants (3150 cognitively normal older adults (CN), 4266 AD).</p><p><strong>Results: </strong>30,218 LD blocks were identified and then ranked based on their relevance with Alzheimer's disease. Subsequently, the Deep-Block identified novel SNPs within the top 1500 LD blocks and confirmed previously known variants, including <i>APOE</i> rs429358 and rs769449. Expression Quantitative Trait Loci (eQTL) analysis across 13 brain regions provided functional evidence for the identified variants. The results were cross-validated against established AD-associated loci from the European Alzheimer's and Dementia Biobank (EADB) and the GWAS catalog.</p><p><strong>Discussion: </strong>The Deep-Block framework effectively processes large-scale high throughput sequencing data while preserving SNP interactions during dimensionality reduction, minimizing bias and information loss. The framework's findings are supported by tissue-specific eQTL evidence across brain regions, indicating the functional relevance of the identified variants. Additionally, the Deep-Block approach has identified both known and novel genetic variants, enhancing our understanding of the genetic architecture and demonstrating its potential for application in large-scale sequencing studies.</p><p><strong>Highlights: </strong>Growing genomic datasets require advanced tools to identify genetic loci in sequencing.Deep-Block, a novel AI framework, was used to process large-scale ADSP WGS data.Deep-Block identified both known and novel AD-associated genetic loci.rs429358 (<i>APOE</i>) was key; rs11556505 (<i>TOMM40</i>), rs34342646 (<i>NECTIN2</i>) were significant.The AI framework uses biological knowledge to enhance detection of Alzheimer's loci.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":"e70041"},"PeriodicalIF":4.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cognitive and Alzheimer's disease biomarker effects of oral nicotinamide riboside (NR) supplementation in older adults with subjective cognitive decline and mild cognitive impairment. 口服烟酰胺核苷(NR)补充剂对主观认知能力下降和轻度认知障碍的老年人的认知和阿尔茨海默病生物标志物的影响
IF 4.9 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-15 eCollection Date: 2025-01-01 DOI: 10.1002/trc2.70023
Chao-Yi Wu, Ashley C Kupferschmid, Liu Chen, Alison J McManus, Pia Kivisäkk, Jake A Galler, Nadine A Schwab, Libby A DesRuisseaux, Victoria J Williams, Jessica Gerber, Misha Riley, Cathrine Young, Edmarie Guzmán-Vélez, Hiroko H Dodge, Rudolph E Tanzi, Clifford M Singer, Steven E Arnold
<p><strong>Introduction: </strong>Age-associated depletion in nicotinamide adenine dinucleotide (NAD+) concentrations has been implicated in metabolic, cardiovascular, and neurodegenerative disorders. Supplementation with NAD+ precursors, such as nicotinamide riboside (NR), offers a potential therapeutic avenue against neurodegenerative pathologies in aging, Alzheimer's disease, and related dementias. A crossover, double-blind, randomized placebo (PBO) controlled trial was conducted to test the safety and efficacy of 8 weeks' active treatment with NR (1 g/day) on cognition and plasma AD biomarkers in older adults with subjective cognitive decline and mild cognitive impairment.</p><p><strong>Methods: </strong>The primary efficacy outcome was the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Secondary outcomes included plasma phosphorylated tau 217 (pTau<sup>217</sup>), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL). Exploratory outcomes included Lumosity gameplay (<i>z</i>-scores) for cognition and step counts from wearables. Mixed model for repeated measures was used for between-group comparisons; paired <i>t</i>-tests were used for within-individual comparisons.</p><p><strong>Results: </strong>Forty-six participants aged over 55 were randomized to NR-PBO or PBO-NR groups; 41 completed baseline visits, and 37 completed the trial. NR supplementation was safe and well tolerated with no differences in adverse events reported between NR and PBO treatment phases. For the between-group comparison, there was a 7% reduction in pTau<sup>217</sup> concentrations after taking NR, while an 18% increase with PBO (<i>p</i> = 0.02). No significant between-group differences were observed for RBANS, other plasma biomarkers(GFAP and NfL), Lumosity gameplay scores or step counts. For the within-individual comparison, pTau<sup>217</sup> concentrations significantly decreased during the NR phase compared to the PBO (<i>p</i> = 0.02), while step counts significantly increased during the NR phase than PBO (<i>p</i> = 0.04).</p><p><strong>Discussion: </strong>Eight weeks NR supplementation is safe and lowered pTau<sup>217</sup> concentrations but did not alter cognition as measured by conventional or novel digital assessments. Further research is warranted to validate NR's efficacy in altering pathological brain aging processes.</p><p><strong>Highlights: </strong>The integrated study design combines a two-arm parallel trial with a crossover phase, offering the opportunity to enhance sample size for within-individual analysis and assess carryover effects.NR is safe but did not alter cognition as measured by multi-modal assessments in SCD/MCI.For between-group comparison, pTau<sup>217</sup> levels decreased with NR and increased with PBO at 8-week follow-up.For within-individual comparison, step counts increased after NR and decreased after PBO.A larger, longer study with pharmacodynamic and pathophysiological bio
年龄相关的烟酰胺腺嘌呤二核苷酸(NAD+)浓度的减少与代谢、心血管和神经退行性疾病有关。补充NAD+前体,如烟酰胺核苷(NR),为对抗衰老、阿尔茨海默病和相关痴呆的神经退行性病变提供了一种潜在的治疗途径。本研究进行了一项交叉、双盲、随机安慰剂(PBO)对照试验,以检验NR (1 g/天)积极治疗8周对主观认知能力下降和轻度认知障碍的老年人认知和血浆AD生物标志物的安全性和有效性。方法:主要疗效指标为神经心理状态评估可重复测试(RBANS)。次要结局包括血浆磷酸化tau 217 (pTau217)、胶质纤维酸性蛋白(GFAP)和神经丝轻链(NfL)。探索性结果包括Lumosity游戏玩法(z分数)的认知和可穿戴设备的步数。组间比较采用重复测量混合模型;配对t检验用于个体内比较。结果:46名55岁以上的参与者随机分为NR-PBO组或PBO-NR组;41人完成基线访问,37人完成试验。NR补充是安全且耐受性良好的,在NR和PBO治疗阶段之间报告的不良事件没有差异。在组间比较中,服用NR后pTau217浓度降低7%,而服用PBO后pTau217浓度升高18% (p = 0.02)。rban、其他血浆生物标志物(GFAP和NfL)、Lumosity游戏得分或步数在组间无显著差异。在个体内比较中,pTau217浓度在NR期显著低于PBO (p = 0.02),步数在NR期显著高于PBO (p = 0.04)。讨论:8周NR补充是安全的,并且降低了pTau217浓度,但通过传统或新型数字评估测量没有改变认知。需要进一步的研究来验证NR在改变病理性脑老化过程中的功效。重点:综合研究设计结合了双臂平行试验和交叉阶段,为个体内分析和评估结转效应提供了增加样本量的机会。在SCD/MCI的多模式评估中,NR是安全的,但不会改变认知。在8周的随访中,pTau217水平随NR降低,随PBO升高。在个体内比较中,NR后步数增加,PBO后步数减少。需要更大规模、更长期的药效学和病理生理生物标志物研究来评估NR的疾病改善作用。
{"title":"Cognitive and Alzheimer's disease biomarker effects of oral nicotinamide riboside (NR) supplementation in older adults with subjective cognitive decline and mild cognitive impairment.","authors":"Chao-Yi Wu, Ashley C Kupferschmid, Liu Chen, Alison J McManus, Pia Kivisäkk, Jake A Galler, Nadine A Schwab, Libby A DesRuisseaux, Victoria J Williams, Jessica Gerber, Misha Riley, Cathrine Young, Edmarie Guzmán-Vélez, Hiroko H Dodge, Rudolph E Tanzi, Clifford M Singer, Steven E Arnold","doi":"10.1002/trc2.70023","DOIUrl":"10.1002/trc2.70023","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Age-associated depletion in nicotinamide adenine dinucleotide (NAD+) concentrations has been implicated in metabolic, cardiovascular, and neurodegenerative disorders. Supplementation with NAD+ precursors, such as nicotinamide riboside (NR), offers a potential therapeutic avenue against neurodegenerative pathologies in aging, Alzheimer's disease, and related dementias. A crossover, double-blind, randomized placebo (PBO) controlled trial was conducted to test the safety and efficacy of 8 weeks' active treatment with NR (1 g/day) on cognition and plasma AD biomarkers in older adults with subjective cognitive decline and mild cognitive impairment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The primary efficacy outcome was the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Secondary outcomes included plasma phosphorylated tau 217 (pTau&lt;sup&gt;217&lt;/sup&gt;), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL). Exploratory outcomes included Lumosity gameplay (&lt;i&gt;z&lt;/i&gt;-scores) for cognition and step counts from wearables. Mixed model for repeated measures was used for between-group comparisons; paired &lt;i&gt;t&lt;/i&gt;-tests were used for within-individual comparisons.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Forty-six participants aged over 55 were randomized to NR-PBO or PBO-NR groups; 41 completed baseline visits, and 37 completed the trial. NR supplementation was safe and well tolerated with no differences in adverse events reported between NR and PBO treatment phases. For the between-group comparison, there was a 7% reduction in pTau&lt;sup&gt;217&lt;/sup&gt; concentrations after taking NR, while an 18% increase with PBO (&lt;i&gt;p&lt;/i&gt; = 0.02). No significant between-group differences were observed for RBANS, other plasma biomarkers(GFAP and NfL), Lumosity gameplay scores or step counts. For the within-individual comparison, pTau&lt;sup&gt;217&lt;/sup&gt; concentrations significantly decreased during the NR phase compared to the PBO (&lt;i&gt;p&lt;/i&gt; = 0.02), while step counts significantly increased during the NR phase than PBO (&lt;i&gt;p&lt;/i&gt; = 0.04).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;Eight weeks NR supplementation is safe and lowered pTau&lt;sup&gt;217&lt;/sup&gt; concentrations but did not alter cognition as measured by conventional or novel digital assessments. Further research is warranted to validate NR's efficacy in altering pathological brain aging processes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Highlights: &lt;/strong&gt;The integrated study design combines a two-arm parallel trial with a crossover phase, offering the opportunity to enhance sample size for within-individual analysis and assess carryover effects.NR is safe but did not alter cognition as measured by multi-modal assessments in SCD/MCI.For between-group comparison, pTau&lt;sup&gt;217&lt;/sup&gt; levels decreased with NR and increased with PBO at 8-week follow-up.For within-individual comparison, step counts increased after NR and decreased after PBO.A larger, longer study with pharmacodynamic and pathophysiological bio","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":"e70023"},"PeriodicalIF":4.9,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evaluation of efficiency and effectiveness of different recruitment strategies for the FINGER-NL multidomain lifestyle intervention trial via the Dutch Brain Research Registry. 通过荷兰脑研究注册中心评估FINGER-NL多域生活方式干预试验的不同招募策略的效率和有效性。
IF 4.9 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-09 eCollection Date: 2025-01-01 DOI: 10.1002/trc2.70017
Lisa Waterink, Sietske A M Sikkes, Lion M Soons, Sonja Beers, Yvonne Meijer-Krommenhoek, Ondine van de Rest, Smidt Nynke, Joukje M Oosterman, Erik Scherder, Kay Deckers, Yannick Vermeiren, Rianne A A de Heus, Sebastian Köhler, Wiesje M van der Flier, Marissa D Zwan
<p><strong>Introduction: </strong>Recruitment of participants for intervention studies is challenging. We evaluated the effectiveness and efficiency of a participant recruitment campaign through an online registry for the FINGER-NL study, a multi-domain lifestyle intervention trial targeting cognitively healthy individuals aged 60-79 with dementia prevention potential. Additionally, we explored which recruitment strategy successfully reached individuals from underrepresented groups in research.</p><p><strong>Methods: </strong>The campaign entailed seven recruitment strategies referring to The Dutch Brain Research Registry (DBRR): (1) Facebook advertisements, (2) appearance on national television, (3) newspaper articles, (4) researcher outreach, (5) patient organizations, (6) search engines, and (7) other. For each strategy, we describe the number of individuals (a) registered, (b) potentially eligible, and (c) included in FINGER-NL. Subsequently, the efficiency, defined by the eligibility ratio (eligible/registered), and effectiveness, defined by the inclusion ratio (included/registered) were calculated. Associations between recruitment strategies and sociodemographic factors of underrepresented groups were tested with binomial logistic regressions.</p><p><strong>Results: </strong>The campaign resulted in 13,795 new DBRR registrants, of which <i>n</i> = 3475 were eligible (eligibility ratio = 0.25) and <i>n</i> = 1008 were included (inclusion ratio = 0.07). The Facebook advertisements and television appearance resulted in the highest numbers of registrants (<i>n</i> = 4678 and <i>n</i> = 2182) which translated to the highest number of inclusions (<i>n</i> = 288 and <i>n</i> = 262). The appearance on national television (eligibility ratio = 0.35), newspaper articles (0.26), and Facebook campaigns (0.26) were the most efficient strategies. The national television appearance (inclusion ratio = 0.13) was the most effective strategy. The Facebook campaign and appearance on national television performed relatively better in recruiting individuals from underrepresented groups.</p><p><strong>Discussion: </strong>A multipronged recruitment campaign via a national online recruitment registry is efficient and effective in recruiting and prescreening an adequate number of individuals aged 60-79 years with prevention potential for a multi-site intervention trial within a limited time frame of 15 months. Social media advertisements and television are preferred strategies to recruit individuals from underrepresented groups.</p><p><strong>Highlights: </strong>An online brain research registry recruited eligible participants successfully.Mass media recruitment strategies are efficient for reaching large numbers.Direct recruitment through researchers and patient organizations seems more effective.Online registries offer automated prescreening and alternatives for screen-failures.Tailored strategies are needed to reach underrepresented groups to improve diversity.<
引言:干预研究的参与者招募是具有挑战性的。我们通过FINGER-NL研究的在线注册评估了参与者招募活动的有效性和效率,FINGER-NL研究是一项多领域生活方式干预试验,针对60-79岁具有痴呆症预防潜力的认知健康个体。此外,我们探索了哪种招聘策略能成功地吸引到研究中代表性不足的群体的个人。方法:该活动涉及荷兰脑研究登记处(DBRR)的七种招募策略:(1)Facebook广告,(2)在国家电视上露面,(3)报纸文章,(4)研究人员外展,(5)患者组织,(6)搜索引擎,以及(7)其他。对于每个策略,我们描述了(a)已注册的个体数量,(b)潜在合格的个体数量,以及(c)包括在FINGER-NL中的个体数量。随后,计算以合格比(合格/注册)定义的效率和以纳入比(纳入/注册)定义的有效性。用二项logistic回归检验了代表性不足群体的招聘策略与社会人口学因素之间的关系。结果:本次活动共获得13795名DBRR新注册人,其中n = 3475名(合格比= 0.25),n = 1008名(纳入比= 0.07)。Facebook广告和电视露面导致注册人数最多(n = 4678和n = 2182),这转化为最多的包含数(n = 288和n = 262)。在全国电视上露面(合格率为0.35)、在报纸上发表文章(合格率为0.26)、在Facebook上进行宣传(合格率为0.26)是最有效的策略。全国电视亮相(纳入比= 0.13)是最有效的策略。Facebook的竞选活动和在全国电视上的露面在从代表性不足的群体中招募个人方面表现相对较好。讨论:在15个月的有限时间框架内,通过国家在线招募注册进行多管齐下的招募活动,在招募和预筛选足够数量的60-79岁具有预防潜力的个体进行多站点干预试验方面是高效和有效的。社交媒体广告和电视是从代表性不足的群体中招募个人的首选策略。亮点:一个在线脑研究注册成功招募了合格的参与者。大众媒体的招聘策略对于接触到大量的人是有效的。通过研究人员和患者组织直接招募似乎更有效。在线注册提供自动预筛选和屏幕故障的替代方案。需要有针对性的战略来接触代表性不足的群体,以改善多样性。
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Alzheimer''s and Dementia: Translational Research and Clinical Interventions
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