Pub Date : 2025-01-21eCollection Date: 2025-01-01DOI: 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.
{"title":"Data-driven discovery of associations between prescribed drugs and dementia risk: A systematic review.","authors":"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","doi":"10.1002/trc2.70037","DOIUrl":"10.1002/trc2.70037","url":null,"abstract":"<p><strong>Abstract: </strong>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.</p><p><strong>Highlights: </strong>·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.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":"e70037"},"PeriodicalIF":4.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015706","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}
Pub Date : 2025-01-20eCollection Date: 2025-01-01DOI: 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。
{"title":"Unraveling the impact of blood RANKL and OPG levels on Alzheimer's disease: Independent of bone mineral density and inflammation.","authors":"Xingzhi Guo, Wenzhi Shi, Juanjuan Lu, Peng Tang, Rui Li","doi":"10.1002/trc2.70044","DOIUrl":"10.1002/trc2.70044","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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, <i>p</i> = 0.004; UKB: OR = 0.85, 95% CI = 0.78-0.91, <i>p</i> < 0.001; FinnGen: OR = 0.83, 95% CI = 0.73-0.94, <i>p</i> = 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.</p><p><strong>Discussion: </strong>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.</p><p><strong>Highlights: </strong>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.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":"e70044"},"PeriodicalIF":4.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11746068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016141","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}
Pub Date : 2025-01-20eCollection Date: 2025-01-01DOI: 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.
{"title":"Dynamic neurocognitive adaptation in aging: Development and validation of a new scale.","authors":"Filippo Cieri, Giulia Di Francesco, Chad Lee Cross, Andrew Bender, Jessica Zoe Kirkland Caldwell","doi":"10.1002/trc2.70049","DOIUrl":"10.1002/trc2.70049","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Discussion: </strong>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.</p><p><strong>Highlights: </strong>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.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":"e70049"},"PeriodicalIF":4.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11746070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016023","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}
Pub Date : 2025-01-20eCollection Date: 2025-01-01DOI: 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.
{"title":"Perspective: Minimally clinically important \"symptomatic\" benefit associated with disease modification resulting from anti-amyloid immunotherapy.","authors":"John Alam, Marwan N Sabbagh","doi":"10.1002/trc2.70035","DOIUrl":"10.1002/trc2.70035","url":null,"abstract":"<p><p>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.</p><p><strong>Highlights: </strong>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.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":"e70035"},"PeriodicalIF":4.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11746071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015974","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}
Pub Date : 2025-01-16eCollection Date: 2025-01-01DOI: 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.
{"title":"Developing, implementing, and evaluating the first national Memory and Cognition Clinic Guidelines in Australia.","authors":"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","doi":"10.1002/trc2.70031","DOIUrl":"10.1002/trc2.70031","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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%).</p><p><strong>Discussion: </strong>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.</p><p><strong>Highlights: </strong>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.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":"e70031"},"PeriodicalIF":4.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016012","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}
Pub Date : 2025-01-16eCollection Date: 2025-01-01DOI: 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。
{"title":"Statin use and dementia risk: A systematic review and updated meta-analysis.","authors":"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","doi":"10.1002/trc2.70039","DOIUrl":"10.1002/trc2.70039","url":null,"abstract":"<p><p>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; <i>p</i> < 0.001). It was also associated with reduced risks of AD (HR 0.82; 95% CI: 0.74 to 0.90; <i>p</i> < 0.001) and VaD (HR 0.89; 95% CI: 0.77 to 1.02; <i>p</i> = 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; <i>p</i> < 0.001), those with exposure to statins for more than 3 years (HR 0.37; 95% CI: 0.30 to 0.46; <i>p</i> < 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.</p><p><strong>Highlights: </strong>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.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":"e70039"},"PeriodicalIF":4.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016006","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}
Pub Date : 2025-01-16eCollection Date: 2025-01-01DOI: 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.
{"title":"Comparison of sample characteristics of Wisconsin Alzheimer's Disease Research Center participants with the Wisconsin state population-An evaluation of the recruitment effort.","authors":"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","doi":"10.1002/trc2.70036","DOIUrl":"10.1002/trc2.70036","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Discussion: </strong>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.</p><p><strong>Highlights: </strong>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.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":"e70036"},"PeriodicalIF":4.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015536","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}
Pub Date : 2025-01-16eCollection Date: 2025-01-01DOI: 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.
{"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}
Pub Date : 2025-01-15eCollection Date: 2025-01-01DOI: 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
{"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":"<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","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}
Pub Date : 2025-01-09eCollection Date: 2025-01-01DOI: 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.<
{"title":"Evaluation of efficiency and effectiveness of different recruitment strategies for the FINGER-NL multidomain lifestyle intervention trial via the Dutch Brain Research Registry.","authors":"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","doi":"10.1002/trc2.70017","DOIUrl":"10.1002/trc2.70017","url":null,"abstract":"<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.<","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":"e70017"},"PeriodicalIF":4.9,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11712179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958835","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}