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Associations and Potential Multiple Mechanisms between Subjective Hearing Loss and Cognitive Impairment 主观听力损失与认知障碍之间的关联和潜在多重机制
IF 6.4 Q1 Medicine Pub Date : 2024-03-19 DOI: 10.14283/jpad.2024.62

Abstract

Background

Subjective hearing loss (SHL) refers to an individual’s self-assessment of their hearing loss. The association and underlying mechanisms between SHL and cognitive impairment still necessitate elucidation.

Objectives

To validate potential mechanisms between SHL and cognitive impairment.

Design

Cross-section.

Setting

Shanghai, China.

Participants

A total of 2369 individuals from communities and the cognitive disorder clinic.

Measurements

All participants were subjected to a comprehensive neuropsychological assessment, encompassing the Hearing Handicap Inventory for the Elderly-Screening Version (HHIE-S). The participants’ brain β-amyloid (Aβ) deposition status, plasma biomarkers associated with Alzheimer’s disease (AD), and cardiovascular risk factors were also collected.

Results

In individuals with a heightened SHL, elevated HHIE-S score was linked to diminished cognitive and daily functioning as well as heightened levels of depressed mood. This correlation was observed in auditory memory performance but not in visual memory. The influence of SHL on cognitive function was mediated by depressed mood. SHL was associated with diabetes and smoking, whereas cognitive function was associated with hyperlipidemia and alcohol consumption. In individuals with positive brain Aβ deposition, SHL demonstrated associations with cognitive function independent of plasma Aβ42/40 ratio, P-tau181, neurofilament light chain, and APOE allele status.

Conclusion

SHL has an independent effect on cognitive impairment. The findings do no provide evidence for the common cause mechanism. Instead, the findings support the presence of a cognitive resource mechanism and an impoverished environment mechanism, along with the potential for a pathological interaction mechanism.

摘要 背景 主观听力损失(SHL)是指个人对其听力损失的自我评估。SHL与认知障碍之间的关联和潜在机制仍有待阐明。 目标 验证 SHL 与认知障碍之间的潜在机制。 设计 横断面。 地点 中国上海。 参与者 来自社区和认知障碍诊所的 2369 人。 测量 对所有参与者进行全面的神经心理学评估,包括老年人听力障碍量表筛查版(HHIE-S)。此外,还收集了参与者的大脑β淀粉样蛋白(Aβ)沉积状况、与阿尔茨海默病(AD)相关的血浆生物标志物以及心血管风险因素。 结果 在 SHL 增高的个体中,HHIE-S 评分的升高与认知和日常功能减退以及抑郁情绪水平升高有关。在听觉记忆表现中可以观察到这种相关性,但在视觉记忆中却观察不到。SHL对认知功能的影响是由抑郁情绪介导的。SHL与糖尿病和吸烟有关,而认知功能则与高脂血症和饮酒有关。在脑Aβ沉积阳性的个体中,SHL与认知功能的关系不受血浆Aβ42/40比率、P-tau181、神经丝轻链和APOE等位基因状态的影响。 结论 SHL 对认知障碍有独立影响。研究结果没有为共同病因机制提供证据。相反,研究结果支持认知资源机制和贫困环境机制的存在,以及病理相互作用机制的可能性。
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引用次数: 0
Association of Cognitive Reserve Indicator with Cognitive Decline and Structural Brain Differences in Middle and Older Age: Findings from the UK Biobank 认知储备指标与中老年认知衰退和大脑结构差异的关系:英国生物库的研究结果
IF 6.4 Q1 Medicine Pub Date : 2024-03-19 DOI: 10.14283/jpad.2024.54

Abstract

Background

Cognitive reserve (CR) contributes to preserving cognition when facing brain aging and damage. CR has been linked to dementia risk in late life. However, the association between CR and cognitive changes and brain imaging measures, especially in midlife, is unclear.

Objective

We aimed to explore the association of CR with cognitive decline and structural brain differences in middle and older age.

Design

This longitudinal study was from the UK Biobank project where participants completed baseline surveys between 2006 to 2010 and were followed (mean follow-up: 9 years).

Setting

A population-based study.

Participants

A total of 42,301 dementia-free participants aged 40–70 were followed-up to detect cognitive changes. A subsample (n=34,041) underwent brain magnetic resonance imaging scans.

Measurements

We used latent class analysis to generate a CR indicator (categorized as high, moderate, and low) based on education, occupation, and multiple cognitively stimulating activities. Cognitive tests for global and domain-specific cognition were administrated at baseline and follow-up. Total brain, white matter, grey matter, hippocampal, and white matter hyperintensity volumes (TBV, WMV, GMV, HV, and WMHV) were assessed at the follow-up examination. Data were analyzed using mixed-effects models and analysis of covariance.

Results

At baseline, 16,032 (37.9%), 10,709 (25.3%), and 15,560 (36.8%) participants had low, moderate, and high levels of CR, respectively. Compared with low CR, high CR was associated with slower declines in global cognition (β [95% confidence interval]: 0.10 [0.08, 0.11]), prospective memory (0.10 [0.06, 0.15]), fluid intelligence (0.07 [0.04, 0.10]), and reaction time (0.04 [0.02, 0.06]). Participants with high CR had lower TBV, WMV, GMV, and WMHV, but higher HV when controlling for global cognition (corrected P <0.01 for all). The significant relationships between CR and cognition and TBV were present among both middle-aged (<60 years) and older (≥60 years) participants. The CR-cognition association remained significant despite reductions in brain structural properties.

Conclusions

Higher CR is associated with slower cognitive decline, higher HV, and lower microvascular burden, especially in middle age. Individuals with high CR could tolerate smaller brain volumes while maintaining cognition. The benefit of CR for cognition is independent of structural brain differences. Our findings highlight the contribution of enhancing CR to helping compensate for neuroimaging alterations and ultimately prevent cognitive decline.

摘要 背景 认知储备(CR)有助于在面临大脑衰老和损伤时保持认知能力。认知储备与晚年痴呆症风险有关。然而,认知储备与认知变化和脑成像测量之间的关系尚不清楚,尤其是在中年时期。 目的 我们旨在探讨 CR 与中老年认知能力下降和大脑结构差异之间的关系。 设计 这项纵向研究来自英国生物库项目,参与者在 2006 年至 2010 年间完成基线调查并接受随访(平均随访时间:9 年)。 环境 基于人口的研究。 参与者 对 42,301 名 40-70 岁未患痴呆症的参与者进行了随访,以检测其认知能力的变化。一个子样本(n=34,041)接受了脑磁共振成像扫描。 测量 我们使用潜类分析法,根据教育、职业和多种刺激认知的活动生成 CR 指标(分为高、中、低三类)。我们在基线和随访期间进行了全面认知和特定领域认知测试。随访检查时评估了大脑总体积、白质体积、灰质体积、海马体积和白质高密度体积(TBV、WMV、GMV、HV 和 WMHV)。数据采用混合效应模型和协方差分析法进行分析。 结果 在基线时,16,032 人(37.9%)、10,709 人(25.3%)和 15,560 人(36.8%)的 CR 水平分别为低、中和高。与低 CR 相比,高 CR 与整体认知(β [95% 置信区间]:0.10 [0.08, 0.11])、前瞻记忆(0.10 [0.06, 0.15])、流体智能(0.07 [0.04, 0.10])和反应时间(0.04 [0.02, 0.06])的下降速度较慢有关。高CR参与者的TBV、WMV、GMV和WMHV较低,但在控制整体认知的情况下,HV较高(校正后的P均为0.01)。在中年(60 岁)和老年(≥60 岁)参与者中,CR 与认知和 TBV 之间均存在重要关系。尽管大脑结构特性有所下降,但 CR 与认知之间的关系仍然显著。 结论 CR 值越高,认知能力衰退越慢,HV 值越高,微血管负担越低,尤其是在中年时期。高CR的人可以忍受较小的脑容量,同时保持认知能力。CR 对认知的益处与大脑结构差异无关。我们的研究结果凸显了提高CR有助于补偿神经影像学改变并最终防止认知能力下降。
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引用次数: 0
Performance of Fully-Automated High-Throughput Plasma Biomarker Assays for Alzheimer’s Disease in Amnestic Mild Cognitive Impairment Subjects 全自动高通量血浆生物标志物测定在失忆性轻度认知障碍受试者中的应用效果
IF 6.4 Q1 Medicine Pub Date : 2024-03-19 DOI: 10.14283/jpad.2024.58

Abstract

Introduction

Novel plasma biomarkers are promising for identifying Alzheimer’s disease (AD) pathological processes in vivo, but most currently employed assays have limitations precluding widespread use.

Methods

CSF and plasma samples were collected from seventy amnestic mild cognitive impairment (aMCI) subjects, stratified as A+ and A−. CSF Aβ40, Aβ42, p-tau181 and t-tau and plasma Aβ40, Aβ42 and p-tau181 quantification were conducted using the Lumipulse G assays (Fujirebio), to evaluate the diagnostic performance of plasma biomarkers and assess their associations with CSF biomarkers.

Results

All plasma biomarkers except Aβ40 showed a very good accuracy in distinguishing A+ aMCI from A− aMCI, Aβ42/p-tau181 ratio being the most accurate (AUC 0.895, sensitivity 95.1%, specificity 82.8%). Plasma biomarkers levels were significantly associated with CSF biomarkers concentration.

Discussion

High-throughput and fully-automated plasma assays could be helpful in discriminating with high accuracy between aMCI in the AD continuum and aMCI unlikely due to AD in clinical settings.

摘要 引言 新型血浆生物标记物有望确定阿尔茨海默病(AD)的体内病理过程,但目前使用的大多数检测方法都存在局限性,无法广泛使用。 方法 收集了 70 名轻度认知障碍(aMCI)患者的脑脊液和血浆样本,将其分为 A+ 和 A-。使用Lumipulse G测定法(Fujirebio)对脑脊液中的Aβ40、Aβ42、p-tau181和t-tau以及血浆中的Aβ40、Aβ42和p-tau181进行定量分析,以评估血浆生物标志物的诊断性能及其与脑脊液生物标志物的关联。 结果 除 Aβ40 外,所有血浆生物标志物在区分 A+ aMCI 和 A- aMCI 方面都表现出很高的准确性,其中 Aβ42/p-tau181 比值最为准确(AUC 0.895,灵敏度 95.1%,特异性 82.8%)。血浆生物标志物水平与脑脊液生物标志物浓度明显相关。 讨论 高通量和全自动血浆检测有助于在临床环境中高精度地区分AD连续性AMCI和不可能由AD引起的AMCI。
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引用次数: 0
Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU): Trial Satisfaction and Attitudes towards Future Clinical Trials 显性遗传性阿尔茨海默病网络试验单位(DIAN-TU):试验满意度和对未来临床试验的态度
IF 6.4 Q1 Medicine Pub Date : 2024-03-19 DOI: 10.14283/jpad.2024.61
Haiyan Liu, J. Li, E. Ziegemeier, S. Adams, E. McDade, D. B. Clifford, Y. Cao, G. Wang, Y. Li, S. L. Mills, A. M. Santacruz, S. Belyew, J. D. Grill, B. J. Snider, C. J. Mummery, G. Surti, D. Hannequin, D. Wallon, S. B. Berman, I. Z. Jimenez-Velazquez, E. D. Roberson, C. H. van Dyck, L. S. Honig, R. Sanchez-Valle, W. S. Brooks, S. Gauthier, D. Galasko, C. L. Masters, J. Brosch, G.-Y. R. Hsiung, S. Jayadev, M. Formaglio, M. Masellis, R. Clarnette, J. Pariente, B. Dubois, F. Pasquier, R. J. Bateman, Jorge J. Llibre-Guerra

Background

Clinical trial satisfaction is increasingly important for future trial designs and is associated with treatment adherence and willingness to enroll in future research studies or to recommend trial participation. In this post-trial survey, we examined participant satisfaction and attitudes toward future clinical trials in the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU).

Methods

We developed an anonymous, participant satisfaction survey tailored to participants enrolled in the DIAN-TU-001 double-blind clinical trial of solanezumab or gantenerumab and requested that all study sites share the survey with their trial participants. A total of 194 participants enrolled in the trial at 24 study sites. We utilized regression analysis to explore the link between participants’ clinical trial experiences, their satisfaction, and their willingness to participate in upcoming trials.

Results

Survey responses were received over a sixteen-month window during 2020–2021 from 58 participants representing 15 study sites. Notably, 96.5% of the survey respondents expressed high levels of satisfaction with the trial, 91.4% would recommend trial participation, and 96.5% were willing to enroll again. Age, gender, and education did not influence satisfaction levels. Participants reported enhanced medical care (70.7%) and pride in contributing to the DIAN-TU trial (84.5%). Satisfaction with personnel and procedures was high (98.3%). Respondents had a mean age of 48.7 years, with most being from North America and Western Europe, matching the trial’s demographic distribution. Participants’ decisions to learn their genetic status increased during the trial, and most participants endorsed considering future trial participation regardless of the DIAN-TU-001 trial outcome.

Conclusion

Results suggest that DIAN-TU-001 participants who responded to the survey exhibited high motivation to participate in research, overall satisfaction with the clinical trial, and willingness to participate in research in the future, despite a long trial duration of 4–7 years with detailed annual clinical, cognitive, PET, MRI, and lumbar puncture assessments. Implementation of features that alleviate barriers and challenges to trial participation is like to have a high impact on trial satisfaction and reduce participant burden.

背景临床试验满意度对于未来的试验设计越来越重要,它与治疗依从性、参加未来研究或推荐参加试验的意愿有关。在这项试验后调查中,我们研究了参与者对显性遗传性阿尔茨海默病网络试验单位(DIAN-TU)未来临床试验的满意度和态度。方法我们为参加 DIAN-TU-001 索拉尼珠单抗或甘特纳单抗双盲临床试验的参与者量身定制了一份匿名参与者满意度调查表,并要求所有研究机构与他们的试验参与者分享这份调查表。共有 194 名参与者参加了 24 个研究机构的试验。我们利用回归分析法探讨了参与者的临床试验经历、满意度和参与未来试验的意愿之间的联系。结果在2020-2021年的16个月时间里,我们收到了来自15个研究机构的58名参与者的调查回复。值得注意的是,96.5%的受访者对试验表示高度满意,91.4%的受访者会推荐参加试验,96.5%的受访者愿意再次参加试验。年龄、性别和教育程度并不影响满意度。参与者表示医疗服务得到了改善(70.7%),并对参与 DIAN-TU 试验感到自豪(84.5%)。对人员和程序的满意度很高(98.3%)。受访者的平均年龄为 48.7 岁,大部分来自北美和西欧,与试验的人口分布相吻合。结论结果表明,尽管试验持续时间长达 4-7 年,而且每年都要进行详细的临床、认知、正电子发射计算机断层扫描、核磁共振成像和腰椎穿刺评估,但对调查做出回应的 DIAN-TU-001 参与者表现出很高的参与研究的积极性、对临床试验的总体满意度以及未来参与研究的意愿。减轻试验参与障碍和挑战的功能将对试验满意度和减轻参与者负担产生很大影响。
{"title":"Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU): Trial Satisfaction and Attitudes towards Future Clinical Trials","authors":"Haiyan Liu, J. Li, E. Ziegemeier, S. Adams, E. McDade, D. B. Clifford, Y. Cao, G. Wang, Y. Li, S. L. Mills, A. M. Santacruz, S. Belyew, J. D. Grill, B. J. Snider, C. J. Mummery, G. Surti, D. Hannequin, D. Wallon, S. B. Berman, I. Z. Jimenez-Velazquez, E. D. Roberson, C. H. van Dyck, L. S. Honig, R. Sanchez-Valle, W. S. Brooks, S. Gauthier, D. Galasko, C. L. Masters, J. Brosch, G.-Y. R. Hsiung, S. Jayadev, M. Formaglio, M. Masellis, R. Clarnette, J. Pariente, B. Dubois, F. Pasquier, R. J. Bateman, Jorge J. Llibre-Guerra","doi":"10.14283/jpad.2024.61","DOIUrl":"https://doi.org/10.14283/jpad.2024.61","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Clinical trial satisfaction is increasingly important for future trial designs and is associated with treatment adherence and willingness to enroll in future research studies or to recommend trial participation. In this post-trial survey, we examined participant satisfaction and attitudes toward future clinical trials in the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU).</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We developed an anonymous, participant satisfaction survey tailored to participants enrolled in the DIAN-TU-001 double-blind clinical trial of solanezumab or gantenerumab and requested that all study sites share the survey with their trial participants. A total of 194 participants enrolled in the trial at 24 study sites. We utilized regression analysis to explore the link between participants’ clinical trial experiences, their satisfaction, and their willingness to participate in upcoming trials.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Survey responses were received over a sixteen-month window during 2020–2021 from 58 participants representing 15 study sites. Notably, 96.5% of the survey respondents expressed high levels of satisfaction with the trial, 91.4% would recommend trial participation, and 96.5% were willing to enroll again. Age, gender, and education did not influence satisfaction levels. Participants reported enhanced medical care (70.7%) and pride in contributing to the DIAN-TU trial (84.5%). Satisfaction with personnel and procedures was high (98.3%). Respondents had a mean age of 48.7 years, with most being from North America and Western Europe, matching the trial’s demographic distribution. Participants’ decisions to learn their genetic status increased during the trial, and most participants endorsed considering future trial participation regardless of the DIAN-TU-001 trial outcome.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Results suggest that DIAN-TU-001 participants who responded to the survey exhibited high motivation to participate in research, overall satisfaction with the clinical trial, and willingness to participate in research in the future, despite a long trial duration of 4–7 years with detailed annual clinical, cognitive, PET, MRI, and lumbar puncture assessments. Implementation of features that alleviate barriers and challenges to trial participation is like to have a high impact on trial satisfaction and reduce participant burden.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140147013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sex Difference in the Association between Prior Fracture and Subsequent Risk of Incident Dementia: A Longitudinal Cohort Study 既往骨折与后续痴呆症发病风险之间的性别差异:纵向队列研究
IF 6.4 Q1 Medicine Pub Date : 2024-03-13 DOI: 10.14283/jpad.2024.56
D. Gao, W. Rong, C. Li, J. Liang, Y. Wang, Y. Pan, W. Zhang, Fanfan Zheng, Wuxiang Xie

Background

A history of fracture has been associated with increased risk of dementia; however, it is uncertain whether sex difference exists in the association between prior fracture and subsequent risk of incident dementia.

Objectives

To investigate whether sex modified the relationship between prior fracture and subsequent risk of dementia.

Design

Prospective cohort study.

Setting

UK Biobank.

Participants

496,331 participants (54.6% women) free of dementia at baseline.

Measurements

History of fracture was self-reported via touchscreen questionnaires at baseline. The primary outcome was all-cause dementia.

Results

Both any fracture and fragility fracture were significantly associated with an increased risk of subsequent all-cause dementia in men (adjusted hazard ratio (HR): 1.28; 95% confidence interval (CI): 1.14–1.43; adjusted HR: 1.48; 95% CI: 1.18–1.87, respectively), but not in women (adjusted HR: 1.04; 95% CI 0.95–1.15; adjusted HR: 1.01; 95% CI: 0.87–1.18, respectively); and these sex-differences were significant (P interaction = 0.006; P interaction = 0.007, respectively). The sex differences in the impacts of different fracture sites (including upper limb, lower limb, spine, and multiple sites) were consistent on all-cause dementia.

Conclusions

This study demonstrated that prior fracture was associated with an increased risk of dementia in men but not in women, and the sex difference was significant. Previous fracture may be an important marker for identifying subsequent dementia in middle-aged and older men.

背景骨折史与痴呆症风险增加有关;但是,目前还不确定在既往骨折史与随后的痴呆症发病风险之间是否存在性别差异。研究目的探讨性别是否会改变既往骨折史与随后的痴呆症风险之间的关系。结果任何骨折和脆性骨折均与男性后续全因痴呆风险的增加显著相关(调整后危险比 (HR):1.28;95% 置信区间 (CI):1.14-1.43;调整后危险比 (HR):1.28;95% 置信区间 (CI):1.14-1.43)。43;调整HR:1.48;95% CI:1.18-1.87),而女性则不然(调整HR:1.04;95% CI:0.95-1.15;调整HR:1.01;95% CI:0.87-1.18);这些性别差异具有显著性(P交互作用=0.006;P交互作用=0.007)。不同骨折部位(包括上肢、下肢、脊柱和多个部位)的性别差异对全因痴呆症的影响是一致的。结论这项研究表明,既往骨折与男性痴呆症风险增加有关,但与女性无关,且性别差异显著。既往骨折可能是识别中老年男性继发性痴呆的重要标志。
{"title":"Sex Difference in the Association between Prior Fracture and Subsequent Risk of Incident Dementia: A Longitudinal Cohort Study","authors":"D. Gao, W. Rong, C. Li, J. Liang, Y. Wang, Y. Pan, W. Zhang, Fanfan Zheng, Wuxiang Xie","doi":"10.14283/jpad.2024.56","DOIUrl":"https://doi.org/10.14283/jpad.2024.56","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>A history of fracture has been associated with increased risk of dementia; however, it is uncertain whether sex difference exists in the association between prior fracture and subsequent risk of incident dementia.</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>To investigate whether sex modified the relationship between prior fracture and subsequent risk of dementia.</p><h3 data-test=\"abstract-sub-heading\">Design</h3><p>Prospective cohort study.</p><h3 data-test=\"abstract-sub-heading\">Setting</h3><p>UK Biobank.</p><h3 data-test=\"abstract-sub-heading\">Participants</h3><p>496,331 participants (54.6% women) free of dementia at baseline.</p><h3 data-test=\"abstract-sub-heading\">Measurements</h3><p>History of fracture was self-reported via touchscreen questionnaires at baseline. The primary outcome was all-cause dementia.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Both any fracture and fragility fracture were significantly associated with an increased risk of subsequent all-cause dementia in men (adjusted hazard ratio (HR): 1.28; 95% confidence interval (CI): 1.14–1.43; adjusted HR: 1.48; 95% CI: 1.18–1.87, respectively), but not in women (adjusted HR: 1.04; 95% CI 0.95–1.15; adjusted HR: 1.01; 95% CI: 0.87–1.18, respectively); and these sex-differences were significant (P interaction = 0.006; P interaction = 0.007, respectively). The sex differences in the impacts of different fracture sites (including upper limb, lower limb, spine, and multiple sites) were consistent on all-cause dementia.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>This study demonstrated that prior fracture was associated with an increased risk of dementia in men but not in women, and the sex difference was significant. Previous fracture may be an important marker for identifying subsequent dementia in middle-aged and older men.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140072600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evaluation of Clinical Meaningfulness of Fortasyn Connect in Terms of “Time Saved” 从 "节省的时间 "角度评估 Fortasyn Connect 的临床意义
IF 6.4 Q1 Medicine Pub Date : 2024-03-13 DOI: 10.14283/jpad.2024.55
Samuel Dickson, A. Solomon, M. Kivipelto, T. Hartmann, A. M. J. van Hees, A. Brownlee, B. Haaland, C. H. Mallinckrodt, S. B. Hendrix

Assessment of meaningfulness in randomized clinical trials (RCTs) in Alzheimer’s disease (AD) is challenging, particularly in early disease. Converting clinical outcomes to disease progression time allows assessment of treatment effects using a metric that is understandable and meaningful: time. We demonstrate time savings assessments using meta time component tests (TCTs) in the LipiDiDiet multinutrient RCT. Dietary patterns are important for dementia prevention, likely due to individual cumulative nutrient effects. LipiDiDiet used a multinutrient (Fortasyn Connect) formulation in patients with prodromal AD, benefitting cognition (5-item composite NTB, effect 0.089), cognition and function (CDR-SB, −0.605), and slowing hippocampal atrophy (0.122 cm3). Meaningfulness of point differences is unclear. However, a combination TCT showed 9-month disease time savings at 24 months (38% slowing of disease time): 9.0, 10.5, and 7.2 months for NTB, CDR-SB, and hippocampal volume, underscoring the value of TCTs in AD RCTs and the need for continued validation of this approach.

阿尔茨海默病(AD)随机临床试验(RCT)的意义评估具有挑战性,尤其是在疾病早期。将临床结果转换为疾病进展时间,可以使用一种易于理解且有意义的指标(时间)来评估治疗效果。我们在 LipiDiDiet 多营养素临床试验中展示了使用元时间成分测试(TCT)进行的时间节省评估。膳食模式对预防痴呆症非常重要,这可能是由于个别营养素的累积效应。LipiDiDiet 采用多营养素(Fortasyn Connect)配方,对阿兹海默症前驱期患者的认知(5 项复合 NTB,效应 0.089)、认知和功能(CDR-SB,-0.605)均有益处,并能减缓海马萎缩(0.122 cm3)。点差异的意义尚不明确。不过,综合 TCT 显示,在 24 个月时可节省 9 个月的患病时间(患病时间减缓 38%):在NTB、CDR-SB和海马体积方面,分别节省了9.0、10.5和7.2个月的时间,这凸显了TCT在AD RCT中的价值以及继续验证这种方法的必要性。
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引用次数: 0
Fish and Shellfish Consumption, Cognitive Health and Mortality from Alzheimer’s Disease among US Adults Aged 60 and Older 美国 60 岁及以上成年人的鱼类和贝类摄入量、认知健康和阿尔茨海默病死亡率
IF 6.4 Q1 Medicine Pub Date : 2024-03-11 DOI: 10.14283/jpad.2024.57

Abstract

Background

Relationships of fish-shellfish consumption, cognitive health and mortality from Alzheimer’s disease (AD) among US adults aged 60 years and older have not been adequately studied.

Objectives

To determine the relationship of fish-shellfish consumption, cognitive health and mortality from AD in US adults aged 60 years and older.

Design, Setting and Participants

The data of this cross-sectional study of US adults aged 60 years and older were from the National Nutrition and Health Examination Survey (NHANES) datasets. Frequency of fish-shellfish consumption, its association with subjective cognitive decline (SCD) and AD mortality of these participants between 1999 and 2018 and cognitive assessment scores between 2011 and 2014 were analyzed.

Measurements and Results

US adults aged 60 years and older consumed fish-shellfish 1.2 times/week and had a blood Hg of 1.63 ug/L on average between 1999 and 2018. Participants aged 60 years and older in the highest quartile of fish-shellfish consumption (∼3 times/week) had significantly higher cognitive assessment scores than those in the lowest quartile (rare or no fish-shellfish consumption). Adults in the highest quartile of fish-shellfish consumption had a 30% lower risk (odds ratio 0.7, 95%CI 0.57–0.87) of SCD, and 44% lower risk (hazard ratio 0.56, 95%CI 0.35–0.9) of AD mortality than those in the lowest quartile.

Conclusion

Increased fish-shellfish consumption was associated with improved scores of cognitive assessment and reduced risks of SCD and AD mortality.

摘要 背景 尚未对美国 60 岁及以上成年人食用鱼类贝类、认知健康和阿尔茨海默病(AD)死亡率之间的关系进行充分研究。 目的 确定美国 60 岁及以上成年人食用鱼类贝类、认知健康和阿尔茨海默病死亡率之间的关系。 设计、地点和参与者 这项横断面研究的数据来自美国国家营养与健康调查(NHANES)数据集,研究对象为美国 60 岁及以上的成年人。研究分析了这些参与者在 1999 年至 2018 年期间食用鱼类-贝类的频率、其与主观认知能力下降(SCD)和注意力缺失症死亡率的关系,以及 2011 年至 2014 年期间的认知评估得分。 测量和结果 美国 60 岁及以上的成年人在 1999 年至 2018 年间平均每周食用 1.2 次鱼介贝类,血液中的汞含量为 1.63 微克/升。鱼贝类摄入量最高四分位数(∼3 次/周)的 60 岁及以上参与者的认知评估得分显著高于最低四分位数(很少或未摄入鱼贝类)的参与者。与最低四分位数的人相比,鱼贝类摄入量最高四分位数的成年人患 SCD 的风险降低了 30%(几率比 0.7,95%CI 0.57-0.87),患 AD 的风险降低了 44%(危险比 0.56,95%CI 0.35-0.9)。 结论 鱼类-贝类食用量的增加与认知评估得分的提高以及SCD和AD死亡风险的降低有关。
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引用次数: 0
Association between Comorbidity Indices and Functional Autonomy in Individuals with Cognitive Impairment: A Systematic Review 认知障碍患者的合并症指数与功能自主性之间的关系:系统回顾
IF 6.4 Q1 Medicine Pub Date : 2024-03-06 DOI: 10.14283/jpad.2024.51
M. N. Temedda, A. Garnier-Crussard, C. Mouchoux, Virginie Dauphinot

This systematic review aimed to examine whether higher comorbidity burden, as assessed by comorbidity indices, was associated with a functional autonomy decline in individuals with cognitive impairment. The search was conducted in the following databases: PubMed/MEDLINE, ScienceDirect, Cochrane, and Embase. Both cross-sectional and longitudinal studies that examined the relationship between comorbidity indices and scales measuring activities of daily living (ADL) in individuals with cognitive impairment were included. The quality assessment tool for observational cohort and cross-sectional studies of the National Institutes of Health (NIH) was used. Overall, 12 studies were included, among which three were longitudinal. Significant association was frequently reported by cross-sectional designs (n=7 studies) and only one study reported a significant longitudinal association. This longitudinal study repeatedly assessed both comorbidity burden and functional autonomy, and considered comorbidity burden as a time-varying covariate. Considering comorbidity burden as a time varying covariate may deal with the dynamic nature of comorbidity burden over time, and conducting repeated assessments during the follow-up using both comorbidity index and ADL scales may increase their sensitivity to reliably measure comorbidity burden and functional autonomy decline over time. In conclusion, a higher comorbidity index was associated with a lower level of functional autonomy in people with cognitive impairment. This relationship seems to be dynamic over time and using comorbidity indices and ADL scales only once may not deal with the fluctuation of both comorbidity burden and functional autonomy decline. To cope with complexity of this relationship this review highlights some methodological approaches to be considered.

本系统性综述旨在研究以合并症指数评估的较高合并症负担是否与认知障碍患者功能自主性下降有关。检索在以下数据库中进行:PubMed/MEDLINE、ScienceDirect、Cochrane 和 Embase。纳入了研究认知障碍患者合并症指数与日常生活活动量表(ADL)之间关系的横断面研究和纵向研究。研究采用了美国国立卫生研究院(NIH)的观察性队列研究和横断面研究质量评估工具。总共纳入了 12 项研究,其中 3 项为纵向研究。横断面设计(7 项研究)经常报告了显著的关联性,只有一项研究报告了显著的纵向关联性。这项纵向研究反复评估了合并症负担和功能自主性,并将合并症负担视为时变协变量。将合并症负担视为随时间变化的协变量可能会处理合并症负担随时间变化的动态性质,而在随访期间使用合并症指数和ADL量表进行重复评估可能会提高其灵敏度,从而可靠地测量合并症负担和功能自主性随时间下降的情况。总之,合并症指数越高,认知障碍患者的功能自主性越低。这种关系似乎随着时间的推移而不断变化,仅使用一次合并症指数和 ADL 量表可能无法应对合并症负担和功能自主性下降的波动。为了应对这种关系的复杂性,本综述强调了一些需要考虑的方法。
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引用次数: 0
Prediction of Alzheimer’s Disease Based on 3D Genome Selected circRNA 基于三维基因组选择的 circRNA 预测阿尔茨海默病
IF 6.4 Q1 Medicine Pub Date : 2024-03-06 DOI: 10.14283/jpad.2024.52

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease and there is by far no effective treatment for it, especially in its late stage. Circular RNAs (circRNAs), known as a class of non-coding RNAs are widely observed in eukaryotic transcriptomes, and are reported to play an important role in neurodegenerative diseases including AD. circRNAs usually act as microRNA (miRNA) inhibitors or «sponges» to regulate the function of miRNAs, leading to subsequent changes in protein activities and functions. Accumulating evidence indicates that circRNAs can serve as potential biomarker in AD early prediction. The functional roles of circRNAs are very versatile including miRNAs binding - thus affecting downstream gene expression, generating abnormally translated protein peptides, and affecting epigenetic modifications which subsequently affect AD related gene expressions. Therefore, identifying AD-related circRNAs can contribute to AD early diagnosis and intervention. In this work, we collected and curated an AD-related circRNA dataset; by exploring the circRNAs’ corresponding DNA loci distribution in chromatin 3D conformation (3D genome) and utilize the such 3D genome information, we were able to selected a concise yet predictively effective circRNA panel, based on which, significantly better AD prediction machine learning models were achieved.

摘要 阿尔茨海默病(AD)是一种神经退行性疾病,目前尚无有效的治疗方法,尤其是在晚期。环状 RNAs(circRNAs)被称为一类非编码 RNAs,广泛存在于真核生物转录组中,据报道在包括阿兹海默病在内的神经退行性疾病中发挥着重要作用。越来越多的证据表明,circRNAs 可作为潜在的生物标志物,用于早期预测老年痴呆症。circRNAs的功能作用非常广泛,包括与miRNAs结合--从而影响下游基因的表达、产生翻译异常的蛋白肽,以及影响表观遗传修饰,进而影响AD相关基因的表达。因此,识别与AD相关的circRNA有助于AD的早期诊断和干预。在这项工作中,我们收集并整理了一个与AD相关的circRNA数据集;通过探索circRNA对应的DNA位点在染色质三维构象(三维基因组)中的分布,并利用这些三维基因组信息,我们得以筛选出一个简洁而又能有效预测的circRNA面板,并在此基础上建立了明显更好的AD预测机器学习模型。
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引用次数: 0
Value of Knowing: Health-Related Behavior Changes following Amyloid PET Results Disclosure in Mild Cognitive Impairment 了解的价值:轻度认知障碍患者淀粉样蛋白正电子发射计算机断层扫描结果披露后与健康相关的行为变化
IF 6.4 Q1 Medicine Pub Date : 2024-03-06 DOI: 10.14283/jpad.2024.50
Y. Wang, D. Ren, J. S. Roberts, L. K. Tamres, J. H. Lingler

Background

Growing evidence supports the clinical utility of amyloid PET, however, whether patients at risk for dementia use knowledge of their brain amyloid status to alter their health behaviors remains unclear.

Objectives

To explore the effect of amyloid PET results disclosure on self-reported health behaviors in patients with mild cognitive impairment.

Design

Self-reported health behaviors were a secondary outcome of the Return of Amyloid Imaging Scan Results (RAISR) randomized clinical trial of amyloid PET results disclosure for individuals with mild cognitive impairment.

Setting

Academic medical center.

Participants

RAISR study participants included 82 patients with mild cognitive impairment who were 92% non-Hispanic white, 59% male, and, on average, 73 ± 8.61 years old with 16.25 ± 2.49 years of education.

Intervention

Participants were assigned to a scan group with the opportunity to have an amyloid PET scan and learn their results or to a control group consisting only of a mild cognitive impairment education session and no opportunity for an amyloid PET scan.

Measurements

A 14-item health behavior questionnaire supplemented with qualitative data from the open-ended text entries to describe “other” health behaviors and follow-up semi-structured interviews. Baseline assessments were conducted prior to group assignment. For the present analysis, 71 participants had available data and scan group participants were divided by amyloid status, creating three groups for comparison: amyloid positive, amyloid negative, and control (no scan).

Results

Over 12 months of follow-up, no significant differences were observed in lifestyle, vitamin/supplement use, stress reduction activities, cognitive stimulation, or advance directive completion. Amyloid-negative participants were less likely than controls to consider long-term care insurance (63.6% vs. 89.2%; P =.025), and to endorse behaviors classified as “other” (36.4% vs. 64.9%; P = 0.037). After adjusting for education level, gender, and Mini-Mental State Exam score, logistic regression showed that amyloid-negative patients were 74% less likely than controls to report “other” behaviors (OR = 0.26, 95% CI [0.08, 0.85], P = 0.025), and 78% less likely to consider long-term care insurance (OR= 0.22, 95% CI [0.06, 0.86], P = 0.03). Qualitative analysis of open-ended questionnaire data and supplemental interviews with scan group participants revealed “other” activities to include changes in areas like employment, driving, and residential status, and engagement in other non-medical activities (e.g., pursuing bucket lists).

背景越来越多的证据支持淀粉样蛋白PET的临床应用,然而,痴呆症高危患者是否会利用大脑淀粉样蛋白状态的知识来改变自己的健康行为仍不清楚。目的探讨淀粉样蛋白PET结果公开对轻度认知障碍患者自我报告的健康行为的影响。设计自我报告的健康行为是淀粉样蛋白成像扫描结果回报(RAISR)随机临床试验的次要结果,该试验针对轻度认知障碍患者进行淀粉样蛋白 PET 结果披露。参与者RAISR研究参与者包括82名轻度认知障碍患者,其中92%为非西班牙裔白人,59%为男性,平均年龄为(73±8.61)岁,受教育年限为(16.25±2.49)年。干预措施参与者被分配到扫描组,该组有机会进行淀粉样蛋白 PET 扫描并了解扫描结果;或者被分配到对照组,该组只有轻度认知障碍教育课程,没有机会进行淀粉样蛋白 PET 扫描。在分组前进行了基线评估。结果在 12 个月的随访中,在生活方式、维生素/补充剂使用、减压活动、认知刺激或预先指示完成情况方面没有观察到显著差异。与对照组相比,淀粉样蛋白阴性的参与者不太可能考虑长期护理保险(63.6% 对 89.2%;P =0.025),也不太可能赞同被归类为 "其他 "的行为(36.4% 对 64.9%;P =0.037)。调整教育水平、性别和迷你精神状态检查得分后,逻辑回归显示淀粉样蛋白阴性患者报告 "其他 "行为的可能性比对照组低 74%(OR=0.26,95% CI [0.08,0.85],P=0.025),考虑长期护理保险的可能性低 78%(OR=0.22,95% CI [0.06,0.86],P=0.03)。对开放式问卷数据的定性分析以及对扫描组参与者的补充访谈显示,"其他 "活动包括就业、驾驶和居住状况等方面的变化,以及参与其他非医疗活动(如追求遗愿清单)。结论这项对淀粉样蛋白PET披露后健康相关行为变化的探索性分析表明,了解一个人大脑淀粉样蛋白状态的价值可能因扫描结果而异,并包括更注重最大限度提高生活质量而非促进认知健康的行动。
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引用次数: 0
期刊
The Journal of Prevention of Alzheimer's Disease
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