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Economic Impact of Progression from Mild Cognitive Impairment to Alzheimer Disease in the United States 美国从轻度认知障碍发展到阿尔茨海默病的经济影响
IF 6.4 Q1 Medicine Pub Date : 2024-04-02 DOI: 10.14283/jpad.2024.68
Feride H. Frech, G. Li, T. Juday, Y. Ding, S. Mattke, A. Khachaturian, A. S. Rosenberg, C. Ndiba-Markey, A. Rava, R. Batrla, S. De Santi, H. Hampel

Background

Limited evidence exists on the economic burden of individuals who progress from mild cognitive impairment (MCI) to Alzheimer disease and related dementia disorders (ADRD).

Objectives

To assess the all-cause health care resource utilization and costs for individuals who develop ADRD following an MCI diagnosis compared to those with stable MCI.

Design

This was a retrospective cohort study from January 01, 2014, to December 31, 2019.

Setting

The Merative MarketScan Commercial and Medicare Databases were used.

Participants

Individuals were included if they: (1) were aged 50 years or older; (2) had ≥1 claim with an MCI diagnosis based on the International Classification of Diseases, Ninth Revision (ICD-9) code of 331.83 or the Tenth Revision (ICD-10) code of G31.84; and had continuous enrollment. Individuals were excluded if they had a diagnosis of Parkinson’s disease or ADRD or prescription of ADRD medication.

Measurements

Outcomes included all-cause utilization and costs per patient per year in the first 12 months following MCI diagnosis, in total and by care setting: inpatient admissions, emergency department (ED) visits, outpatient visits, and pharmacy claims.

Results

Out of the total of 5185 included individuals, 1962 (37.8%) progressed to ADRD (MCI-to-ADRD subgroup) and 3223 (62.2%) did not (Stable MCI subgroup). Adjusted all-cause utilization was higher for all care settings in the MCI-to-ADRD subgroup compared with the Stable MCI subgroup. Adjusted all-cause mean total costs ($34599 vs $24541; mean ratio [MR], 1.41 [95% CI, 1.31–1.51]; P<.001), inpatient costs ($47463 vs $38004; MR, 1.25 [95% CI, 1.08–1.44]; P=.002), ED costs ($4875 vs $3863; MR, 1.26 [95% CI, 1.11–1.43]; P<.001), and outpatient costs ($16652 vs $13015; MR, 1.28 [95% CI, 1.20–1.37]; P<.001) were all significantly higher for the MCI-to-ADRD subgroup compared with the Stable MCI subgroup.

Conclusions

Individuals who progressed from MCI to ADRD had significantly higher health care costs than individuals with stable MCI. Early identification of MCI and delaying its progression is important to improve patient and economic outcomes.

背景关于从轻度认知功能障碍(MCI)发展为阿尔茨海默病和相关痴呆症(ADRD)的个人经济负担的证据有限.目的评估与稳定型MCI患者相比,确诊MCI后发展为ADRD的个人的全因医疗资源利用率和成本.设计这是一项回顾性队列研究,研究时间为2014年1月1日至2019年12月31日.研究使用Merative MarketScan商业数据库和医疗保险数据库.参与者只要符合以下条件即可纳入研究:(1)年龄在50岁或以上;(2)根据国际疾病分类第九版(ICD-9)代码,有≥1项MCI诊断索赔:(1) 年龄在 50 岁或以上;(2) 根据《国际疾病分类》第九版(ICD-9)代码 331.83 或《国际疾病分类》第十版(ICD-10)代码 G31.84 诊断为 MCI 的索赔次数≥1 次;且连续参保。测量结果包括MCI确诊后头12个月内每位患者每年的全因使用率和费用,包括住院、急诊科就诊、门诊就诊和药房报销等方面的总费用和护理费用。结果在纳入的 5185 人中,1962 人(37.8%)发展为 ADRD(MCI-to-ADRD 亚组),3223 人(62.2%)没有发展为 ADRD(稳定 MCI 亚组)。与稳定型 MCI 亚组相比,MCI-ADRD 亚组所有护理机构的调整后全因使用率更高。调整后的全因平均总费用(34599 美元 vs 24541 美元;平均比率 [MR],1.41 [95% CI,1.31-1.51];P< .001)、住院费用(47463 美元 vs 38004 美元;MR,1.25 [95% CI, 1.08-1.44]; P=.002)、急诊室费用(4875 美元 vs 3863 美元;MR, 1.26 [95% CI, 1.11-1.43]; P<.001)和门诊费用(16652 美元 vs 13015 美元;MR, 1.结论 从 MCI 发展为 ADRD 的个体的医疗费用显著高于稳定 MCI 的个体。早期识别MCI并延缓其进展对改善患者和经济效益非常重要。
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引用次数: 0
Evaluating the Performance of Different Criteria in Diagnosing AD and Preclinical AD with the Bayesian Latent Class Model 用贝叶斯潜类模型评估诊断注意力缺失症和临床前注意力缺失症的不同标准的性能
IF 6.4 Q1 Medicine Pub Date : 2024-04-02 DOI: 10.14283/jpad.2024.71
X. Wang, G. Niu, J. Zhao, H. Zhu, F. Li, J. Tian, Z. Zhang, G. Chen, Y. He, Qi Gao

Background

The diagnostic criteria for Alzheimer’s disease (AD) should be highly sensitive and specific. Clinicians have varying opinions on the different criteria, including the International Working Group-1 (IWG-1), International Working Group-2 (IWG-2), and AT(N) criteria. Few studies had evaluated the performance of these criteria in diagnosing AD and preclinical AD when the gold standard was absent.

Methods

We estimated and compared the performance of these criteria in diagnosing AD using data from 908 subjects in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Additionally, 622 subjects were selected to evaluate and compare the performance of IWG-2 and AT(N) criteria in diagnosing preclinical AD. A novel approach, Bayesian latent class models with fixed effect dependent, was utilized to estimate the diagnostic accuracy of these criteria in detecting different AD statuses simultaneously.

Results

The sensitivity of the IWG-1, IWG-2, and AT(N) criteria in diagnosing AD was 0.850, 0.836, and 0.665. The specificity of these criteria was 0.788, 0.746, and 0.747. The IWG-1 criteria had the highest Youden Index in detecting AD. When diagnosing preclinical AD, the sensitivity of the IWG-2 and AT(N) criteria was 0.797 and 0.955. The specificity of these criteria was 0.922 and 0.720. The IWG-2 criteria had the highest Youden Index.

Conclusion

IWG-1 was more suitable than the IWG-2 and AT(N) criteria in detecting AD. IWG-2 criteria was more suitable than AT(N) criteria in detecting preclinical AD.

背景阿尔茨海默病(AD)的诊断标准应具有高度敏感性和特异性。临床医生对包括国际工作组-1(IWG-1)、国际工作组-2(IWG-2)和AT(N)标准在内的不同标准有不同的看法。我们利用阿尔茨海默病神经影像学倡议(ADNI)中 908 名受试者的数据,评估并比较了这些标准在诊断 AD 和临床前 AD 中的表现。此外,我们还选择了622名受试者来评估和比较IWG-2和AT(N)标准在诊断临床前AD中的表现。结果IWG-1、IWG-2和AT(N)标准诊断AD的灵敏度分别为0.850、0.836和0.665。这些标准的特异性分别为 0.788、0.746 和 0.747。IWG-1标准在检测AD方面的尤登指数最高。在诊断临床前AD时,IWG-2和AT(N)标准的灵敏度分别为0.797和0.955。这些标准的特异性分别为 0.922 和 0.720。结论IWG-1比IWG-2和AT(N)更适合检测AD。IWG-2标准比AT(N)标准更适合检测临床前AD。
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引用次数: 0
Association between Cerebrospinal Fluid sTREM2 Levels and Depression: The Alzheimer’s Disease Neuroimaging Initiative Study 脑脊液 sTREM2 水平与抑郁之间的关系:阿尔茨海默病神经影像学倡议研究
IF 6.4 Q1 Medicine Pub Date : 2024-04-02 DOI: 10.14283/jpad.2024.70

Abstract

Objective

Previous studies demonstrated a significant protective effect of elevated cerebrospinal fluid (CSF) sTREM2 levels on brain structure and cognitive decline. Nonetheless, the role of sTREM2 in the depression progression remains unclear. This study aimed to investigate the association between CSF sTREM2 levels and longitudinal trajectories of depression.

Methods

Data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) Study were used. CSF sTREM2 levels and depression were measured using an ELISA-based assay and the Geriatric Depression Scale (GDS-15), respectively. Linear mixed-effect models were employed to assess the relationships between CSF sTREM2 levels and GDS scores.

Results

A total of 1,017 participants were enrolled at baseline, with a mean follow-up time of 4.65 years. Baseline CSF sTREM2 levels were negatively correlated with GDS scores (β=−0.21, P=0.022) after adjustment for age, gender, race/ethnicity, education, APOE ε4 carrier status, TREM2 rare variant carrier status, marital status, smoking, and clinical cognitive status.

Conclusion

Our findings suggested that a higher level of CSF sTREM2 was associated with a lower risk of depression.

摘要 目的 以前的研究表明,脑脊液(CSF)sTREM2 水平升高对大脑结构和认知能力下降有明显的保护作用。然而,sTREM2 在抑郁症进展中的作用仍不清楚。本研究旨在探讨 CSF sTREM2 水平与抑郁症纵向发展轨迹之间的关联。 方法 采用阿尔茨海默病神经影像学倡议(ADNI)研究的数据。CSF sTREM2水平和抑郁程度分别采用酶联免疫吸附测定法和老年抑郁量表(GDS-15)进行测量。采用线性混合效应模型评估 CSF sTREM2 水平与 GDS 评分之间的关系。 结果 共有 1,017 人参与了基线研究,平均随访时间为 4.65 年。在对年龄、性别、种族/民族、教育程度、APOE ε4携带者状态、TREM2罕见变异携带者状态、婚姻状况、吸烟和临床认知状态进行调整后,基线CSF sTREM2水平与GDS评分呈负相关(β=-0.21,P=0.022)。 结论 我们的研究结果表明,CSF sTREM2水平越高,患抑郁症的风险越低。
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引用次数: 0
Interest in and Experience with Genetic Testing for Late-Onset Medical Conditions: Results from the National Poll on Healthy Aging 对晚期病症基因检测的兴趣和经验:全国健康老龄化民意调查结果
IF 6.4 Q1 Medicine Pub Date : 2024-04-02 DOI: 10.14283/jpad.2024.69
S. J. Feldman, D. Blasco, M. Mones, J. Scott Roberts

Background

The increasing availability of genetic testing for late-onset diseases such as Alzheimer’s disease necessitates understanding public perceptions and experiences of such testing among at-risk populations.

Objectives

To assess (a) prior uptake of genetic testing (both in medical and direct-to-consumer settings), (b) future interest in genetic testing for late-onset conditions (e.g., Alzheimer’s disease, Parkinson’s disease), and (c) perceptions of testing pros and cons among middle-to-older aged adults.

Design

Online, cross-sectional survey study.

Setting

The National Poll on Healthy Aging at the University of Michigan is a recurring biannual survey of a nationally representative sample of adults aged 50–80. This study reports on a March 2018 fielding of the survey that included a genetic testing module administered to adults aged 50–64.

Participants

Study participants were 991 community-dwelling adults aged 50–64.

Measurements

Survey measures assessed (a) prior use of genetic testing, (b) reasons for engaging in genetic testing, (c) interest in different types of genetic testing, including for Alzheimer’s disease, Parkinson’s disease, and macular degeneration, and (d) perceived benefits, risks, and limitations of testing.

Results

Previous uptake of genetic testing was limited (medical use: 5.1%; direct-to-consumer: 10.8%), with direct-to-consumer test uptake higher among respondents with household incomes of $100,000 or more. Over half of adults endorsed interest in genetic testing for estimation of disease risk (58.9%), ancestry knowledge (58%), and informing medical care (53.8%). Interest in genetic testing for specific late-onset conditions was even higher, including Alzheimer’s disease (70%), Parkinson’s disease (65.3%), and macular degeneration (64.3%). Multivariable logistic regression models showed that older adults more likely to be interested in genetic testing for medical or disease risk purposes were those with higher levels of education (college degree or higher) and who endorsed the benefits of genetic testing, whereas respondents who endorsed testing risks and limitations were less likely to express interest.

Conclusion

While prior use of genetic testing among the middle-to-older age population was low, interest in testing for Alzheimer’s disease and other late-onset conditions was high. This high interest may translate into increased uptake given expanded access to testing and recent treatment advances for Alzheimer’s disease.

背景对阿尔茨海默病等晚发性疾病进行基因检测的机会越来越多,因此有必要了解公众对高危人群进行此类检测的看法和经历。目标评估(a)之前对基因检测的接受情况(包括医疗机构和直接面向消费者的机构),(b)未来对晚发疾病(如阿尔茨海默病、帕金森病)基因检测的兴趣,以及(c)中老年人对检测利弊的看法、设计在线横断面调查研究。背景密歇根大学的全国健康老龄化民意调查是一项针对 50-80 岁成年人的全国代表性抽样调查,每年进行两次。本研究报告了 2018 年 3 月的实地调查情况,其中包括对 50-64 岁成年人进行基因检测的模块.参与者研究参与者为 991 名居住在社区的 50-64 岁成年人。测量方法调查措施评估了(a) 以前使用基因检测的情况,(b) 进行基因检测的原因,(c) 对不同类型基因检测的兴趣,包括对阿尔茨海默病、帕金森病和黄斑变性的兴趣,以及(d) 感知到的检测益处、风险和局限性。结果以前接受基因检测的人数有限(医疗用途:5.1%;直接面向消费者:10.8%),家庭收入在 10 万美元或以上的受访者接受直接面向消费者检测的人数较多。超过半数的成年人表示有兴趣进行基因检测,以估计疾病风险(58.9%)、了解祖先(58%)和为医疗提供信息(53.8%)。对特定晚发疾病进行基因检测的兴趣更高,包括阿尔茨海默病(70%)、帕金森病(65.3%)和黄斑变性(64.3%)。多变量逻辑回归模型显示,教育程度较高(大学或以上学历)且认可基因检测益处的受访者更有可能对出于医疗或疾病风险目的的基因检测感兴趣,而认可检测风险和局限性的受访者则不太可能对基因检测感兴趣。鉴于检测机会的扩大和阿尔茨海默病治疗的最新进展,这种高兴趣可能会转化为更多的接受率。
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引用次数: 0
Visual Event-Related Potentials under External Emotional Stimuli as Early Signs for Mild Cognitive Impairment 外部情绪刺激下的视觉事件相关电位是轻度认知障碍的早期信号
IF 6.4 Q1 Medicine Pub Date : 2024-04-02 DOI: 10.14283/jpad.2024.72

Abstract

Background

Alzheimer’s disease (AD) is a neurodegenerative disorder featured by progressive cognitive decline, which manifests in severe impairment of memory, attention, emotional processing and daily activities, leading to significant disability and social burden. Investigation on Mild Cognitive Impairment (MCI), the prodromal and transitional stage between normal aging and AD, serves as a key in diagnosing and slowing down the progression of AD. Numerous effects have been made up to date, however, the attentional mechanisms under different external emotion stimuli in MCI and AD are still unexplored in deep.

Objective

To further explore the attentional mechanisms under different external emotion stimuli in both MCI and AD patients.

Design/Setting/Participants/Measurements

In 51 healthy volunteers (Controls, 24 males and 27 females), 52 MCI (19 males and 33 females), and 47 AD (15 males and 32 females) patients, we administered the visual oddball event-related potentials (ERPs) under three types of external emotional stimuli: Neutral, Happiness and Sadness, in which the components N1, P2, N2 and P3 as well as the abnormal cortical activations corresponding to the significant ERP differences in the three groups were observed.

Results

Under all three external emotions, in AD patients, N2 and P3 latencies were significantly prolonged compared to both Controls and MCI. In addition, under Happiness, in MCI, P3 latencies were significantly delayed compared to Controls. Meanwhile, under both Happiness and Sadness, in AD patients, P3 amplitudes were significantly decreased compared to Controls and MCI, respectively. During N2 time window, under Neutral emotion, significant hypoactivation in the right superior temporal gyrus was found in AD patients compared to Controls, and under Happiness, the activation of the right inferior frontal gyrus was significantly attenuated in MCI compared to Controls. Under Sadness, in AD patients, the activation of the right superior frontal gyrus was significantly decreased compared to MCI. During P3 time window, under both Happiness and Sadness, when AD patients compared to MCI, the significantly attenuated activations were located in the right fusiform gyrus and the right middle occipital gyrus, respectively.

Conclusion

Our results demonstrated visual attentional deficits under external emotional stimuli in both MCI and AD patients, highlighting the function of Happiness for early detecting MCI, in which the P3 latency and the hypoactivation of right inferior frontal gyrus during N2 time window can be early signs. The current study sheds further light of attentional mechanisms in MCI and AD patients, and indicates the value of emotional processing in the early detection of cognitive dysfunction.

摘要 背景 阿尔茨海默病(Alzheimer's disease,AD)是一种神经退行性疾病,以进行性认知功能衰退为特征,表现为严重的记忆力、注意力、情绪处理和日常活动障碍,导致严重的残疾和社会负担。轻度认知功能障碍(MCI)是介于正常衰老和老年痴呆症之间的前驱和过渡阶段,对它的研究是诊断和延缓老年痴呆症进展的关键。迄今为止,相关研究已取得了许多成果,但对 MCI 和 AD 在不同外部情绪刺激下的注意机制仍未进行深入探讨。 目的 进一步探讨 MCI 和 AD 患者在不同外部情绪刺激下的注意机制。 设计/设置/参与者/测量 我们对 51 名健康志愿者(对照组,男性 24 人,女性 27 人)、52 名 MCI 患者(男性 19 人,女性 33 人)和 47 名 AD 患者(男性 15 人,女性 32 人)进行了三种外部情绪刺激下的视觉奇异事件相关电位(ERPs)测试:其中,我们观察了 N1、P2、N2 和 P3 成分以及与三组显著 ERP 差异相对应的异常皮层激活。 结果 在所有三种外部情绪下,与对照组和 MCI 相比,AD 患者的 N2 和 P3 潜伏期明显延长。此外,与对照组相比,MCI 患者在 "快乐 "情绪下的 P3 潜伏期明显延迟。同时,与对照组和 MCI 相比,AD 患者在 "快乐 "和 "悲伤 "状态下的 P3 振幅分别明显下降。在N2时间窗中,与对照组相比,在中性情绪下,AD患者右颞上回的激活明显减弱;与对照组相比,在快乐情绪下,MCI患者右额下回的激活明显减弱。在 "悲伤 "状态下,与 MCI 相比,AD 患者右额上回的激活明显减少。在 P3 时间窗中,与 MCI 相比,AD 患者在 "快乐 "和 "悲伤 "时,右侧纺锤回和右侧枕中回的激活明显减弱。 结论 我们的研究结果表明,MCI 和 AD 患者在外部情绪刺激下均存在视觉注意缺陷,突出了幸福感在早期检测 MCI 中的作用,其中 P3 潜伏期和 N2 时间窗期间右额叶下回的低激活可作为早期征兆。本研究进一步揭示了 MCI 和 AD 患者的注意机制,并指出了情绪处理在认知功能障碍早期检测中的价值。
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引用次数: 0
The Effects of Different Exercise Interventions on Patients with Subjective Cognitive Decline: A Systematic Review and Network Meta-Analysis 不同运动干预对主观认知能力下降患者的影响:系统回顾与网络元分析
IF 6.4 Q1 Medicine Pub Date : 2024-03-26 DOI: 10.14283/jpad.2024.65
R. Chen, B. Zhao, J. Huang, M. Zhang, Y. Wang, J. Fu, H. Liang, Hongrui Zhan

Background and Objective

Exercise is a promising non-pharmacological therapy for subjective cognitive decline, but it is unclear which type of exercise is most effective. The objective was to assess the comparative effects and ranks of all exercise-based interventions on cognitive function in patients with subjective cognitive decline (SCD).

Method

In this network meta-analysis, Online databases for Web of Science, PubMed, Embase, Medline, Cochrane Library and PsycINFO were searched from inception to April 30, 2023. The included studies are randomized controlled trials assessing the efficacy of exercise interventions for individuals with SCD. The primary outcome measure is memory, while secondary outcome measures encompass executive function, attention, verbal fluency, and global cognitive function. Represented using Standardized Mean Differences (SMDs) along with their 95% Confidence Intervals (CIs). Bias assessment was conducted in accordance with the ‘Cochrane Risk of Bias Assessment Tool, 2nd Edition’ (RoB 2). Pairwise meta-analysis was carried out using the ‘meta-analysis’ module within STATA 14.0, and network meta-analysis was performed using the ‘mvmeta’ and ‘network’ packages available in STATA 14.0. Registration number CRD42023289687.

Result

This study included a total of 11 randomized controlled trials, encompassing 1,166 patients. Mind-body exercise was found to be efficacious in enhancing or sustaining memory (SMD: 0.58, 95%CI: 0.06 ∼ 1.10) and executive function (SMD: 0.41, 95%CI: 0.09 ∼ 0.73) in individuals with subjective cognitive decline. Furthermore, mind-body exercise exhibited the highest probability of being the most effective measures for improving or preventing the decline in memory (surface under cumulative ranking curve (SUCRA) value: 90.4) and executive function (SUCRA value: 91.8). The second-ranked moderate-intensity aerobic exercise has also shown a positive effect on the improvement of executive function in patients with subjective cognitive decline (SMD: 0.23, 95%CI: 0.03 ∼ 0.43, SUCRA value: 68.2). However, we did not observe a significant effectiveness of exercise interventions on verbal fluency, attention, and overall cognitive function in subjective cognitive decline.

Conclusion

Mind-body exercise may potentially be the optimal strategies for enhancing memory and executive function in individuals with subjective cognitive decline. Additionally, moderate-intensity aerobic exercise has shown a modest positive effect on executive function in subjective cognitive decline. When resources permit, practical application of these findings may be considered. Nevertheless, further support for the conclusions of this study is warranted through larger sample sizes and well-designed multicenter trials.

背景和目的运动是治疗主观认知功能下降的一种很有前景的非药物疗法,但目前还不清楚哪种运动最有效。方法在这项网络荟萃分析中,检索了从开始到 2023 年 4 月 30 日的 Web of Science、PubMed、Embase、Medline、Cochrane Library 和 PsycINFO 等在线数据库。纳入的研究都是评估运动干预对 SCD 患者疗效的随机对照试验。主要结果指标是记忆力,次要结果指标包括执行功能、注意力、语言流畅性和整体认知功能。使用标准化平均差 (SMD) 及其 95% 置信区间 (CI) 表示。偏倚评估根据 "科克伦偏倚风险评估工具第二版"(RoB 2)进行。配对荟萃分析使用 STATA 14.0 中的 "荟萃分析 "模块进行,网络荟萃分析使用 STATA 14.0 中的 "mvmeta "和 "网络 "软件包进行。注册编号:CRD42023289687.结果本研究共纳入11项随机对照试验,涉及1166名患者。研究发现,心身锻炼能有效增强或维持主观认知能力下降患者的记忆力(SMD:0.58,95%CI:0.06 ∼ 1.10)和执行功能(SMD:0.41,95%CI:0.09 ∼ 0.73)。此外,心身锻炼最有可能成为改善或预防记忆力(累积排名曲线下表面值:90.4)和执行功能(累积排名曲线下表面值:91.8)下降的最有效措施。排名第二的中等强度有氧运动对改善主观认知能力下降患者的执行功能也有积极作用(SMD:0.23,95%CI:0.03 ∼ 0.43,SUCRA 值:68.2)。结论心身锻炼可能是增强主观认知功能下降患者记忆力和执行功能的最佳策略。此外,中等强度的有氧运动对主观认知能力下降患者的执行功能也有一定的积极作用。在资源允许的情况下,可以考虑实际应用这些研究结果。不过,还需要通过更大的样本量和精心设计的多中心试验来进一步支持本研究的结论。
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引用次数: 0
Alzheimer’s Disease Prediction Using Fly-Optimized Densely Connected Convolution Neural Networks Based on MRI Images 利用基于核磁共振成像图像的蝇优化密集连接卷积神经网络预测阿尔茨海默病
IF 6.4 Q1 Medicine Pub Date : 2024-03-26 DOI: 10.14283/jpad.2024.66

Abstract

Alzheimer’s is a degenerative brain cell disease that affects around 5.8 million people globally. The progressive neurodegenerative disease known as Alzheimer’s Disease (AD), affects the frontal cortex, the part of the brain in charge of memory, language, and cognition. As a result, researchers are utilizing a variety of machine-learning techniques to create an automated method for AD detection. The massive data collected during ROI and biomarker identification takes longer to handle using current methods. This study uses metaheuristic-tuned deep learning to detect the AD-affected region. The research utilizes advanced deep learning and image processing techniques to enhance early and accurate diagnosis of Alzheimer’s disease, potentially enhancing patient outcomes and prompt therapy. The capacity of deep neural networks to extract complex patterns from magnetic resonance imaging (MRI) scans makes them indispensable in the diagnosis of AD since they allow the detection of minor aberrations and complex alterations in brain structure and composition. An adaptive histogram approach processes the collected photographs, and a weighted median filter is used in place of the noisy pixels. The next step is to identify the issue region using a deep convolution network-based clustering segmentation process. A correlated information theory approach is used to extract various textural and statistical features from the separated regions. Lastly, the selected features are probed by the fly-optimized densely linked convolution neural networks. The method surpasses state-of-the-art techniques in sensitivity (15.52%), specificity (15.62%), accuracy (9.01%), error rate (11.29%), and F-measure (10.52%) for recognizing AD-impacted regions in MRI scans using the Kaggle dataset.

摘要 阿尔茨海默氏症是一种脑细胞退化性疾病,全球约有 580 万人患有此病。被称为阿尔茨海默病(AD)的渐进性神经退行性疾病会影响大脑额叶皮层,而额叶皮层是大脑中负责记忆、语言和认知的部分。因此,研究人员正在利用各种机器学习技术来创建一种自动检测阿尔茨海默病的方法。在 ROI 和生物标记物识别过程中收集的海量数据需要更长的时间才能用现有方法处理。本研究利用元启发式调整的深度学习来检测注意力缺失症的影响区域。该研究利用先进的深度学习和图像处理技术来提高阿尔茨海默病的早期准确诊断率,从而改善患者的预后并及时进行治疗。深度神经网络能够从磁共振成像(MRI)扫描中提取复杂的模式,这使它们成为诊断阿尔茨海默病不可或缺的工具,因为它们能够检测大脑结构和组成中的微小畸变和复杂变化。自适应直方图方法处理收集到的照片,并使用加权中值滤波器代替噪声像素。下一步是使用基于深度卷积网络的聚类分割过程来识别问题区域。使用相关信息理论方法从分离的区域中提取各种纹理和统计特征。最后,选定的特征将通过密集链接的卷积神经网络进行探测。在使用 Kaggle 数据集识别磁共振成像扫描中的注意力缺失症影响区域时,该方法在灵敏度(15.52%)、特异性(15.62%)、准确性(9.01%)、错误率(11.29%)和 F 测量(10.52%)方面均超越了最先进的技术。
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引用次数: 0
China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI) to Prevent Cognitive Decline: Study Design and Progress 中国预防认知功能减退多领域干预行动(CHINA-IN-MUDI):研究设计与进展
IF 6.4 Q1 Medicine Pub Date : 2024-03-26 DOI: 10.14283/jpad.2024.63

Abstract

Background

Alzheimer’s disease (AD), the most common type of irreversible dementia, is predicted to affect 152 million people by 2050. Evidence from large-scale preventive randomized controlled trials (RCTs) on modifiable risk variables in Europe has shown that multi-domain lifestyle treatments for older persons at high risk of dementia may be practical and effective. Given the substantial differences between the Chinese and European populations in terms of demographics and living conditions, direct adoption of the European program in China remains unfeasible. Although a RCT has been conducted in China previously, its participants were mainly from rural areas in northern China and, thus, are not representative of the entire nation.There is an urgent need to establish cohorts that represent different economic, cultural, and geographical situations in order to explore implementation strategies and evaluate the effects of early multi-domain interventions more comprehensively and accurately.

Medtods

We developed an integrated intervention procedure implemented in urban neighborhood settings, namely China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI). CHINA-IN-MUDI is a 2-year multicenter open-label cluster-randomised controlled trial centered around a Chinese-style multi-domain intervention to prevent cognitive decline. Participants aged 60–80 years were recruited from a nationally representative study, i.e. China Healthy Aging and Dementia Study cohort. An external harmonization process was carried out to preserve the original FINGER design. Subsequently, we standardized a series of Chinese-style intervention programs to align with cultural and socioeconomic status. Additionally, we expanded the secondary outcome list to include genomic and proteomic analyses. To enhance adherence and facilitate implementation, we leveraged an e-health application.

Results

Screening commenced in July 2022. Currently, 1,965 participants have been randomized into lifestyle intervention (n = 772) and control groups (n = 1,193). Both the intervention and control groups exhibited similar baseline characteristics. Several lifestyle and vascular risk factors were present, indicating a potential window of opportunity for intervention. The intervention will be completed by 2025.

Conclusions

This project will contribute to the evaluation of the effectiveness and safety of intervention strategies in controlling AD risk and reducing clinical events, providing a basis for public health decision-making in China.

摘要 背景 阿尔茨海默病(AD)是最常见的一种不可逆转的痴呆症,预计到 2050 年将影响 1.52 亿人。欧洲针对可改变风险变量的大规模预防性随机对照试验(RCT)的证据表明,针对痴呆症高风险老年人的多领域生活方式治疗可能是切实有效的。鉴于中国与欧洲在人口结构和生活条件方面的巨大差异,在中国直接采用欧洲的方案仍不可行。目前迫切需要建立代表不同经济、文化和地理状况的队列,以便更全面、更准确地探讨早期多领域干预的实施策略和效果评估。 我们开发了一种在城市社区环境中实施的综合干预程序,即中国多领域干预行动(CHINA-IN-MUDI)。CHINA-IN-MUDI是一项为期2年的多中心开放标签群组随机对照试验,以中国式多领域干预为中心,旨在预防认知功能衰退。参与者年龄在 60-80 岁之间,来自一项具有全国代表性的研究,即中国健康老龄化与痴呆症研究队列。在保留 FINGER 原始设计的基础上,我们进行了外部协调。随后,我们根据文化和社会经济状况对一系列中国式干预方案进行了标准化。此外,我们还扩展了次要结果列表,纳入了基因组和蛋白质组分析。为了提高依从性并促进实施,我们利用了电子健康应用程序。 结果 筛选于 2022 年 7 月开始。目前,1965 名参与者被随机分为生活方式干预组(772 人)和对照组(1193 人)。干预组和对照组的基线特征相似。存在一些生活方式和血管风险因素,这表明存在潜在的干预机会。干预将于 2025 年完成。 结论 该项目将有助于评估干预策略在控制AD风险和减少临床事件方面的有效性和安全性,为中国的公共卫生决策提供依据。
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引用次数: 0
The Multi-domain Lifestyle Intervention for Cognitive Impairment in Community-Dwelling Older Adults in Hangzhou (The Heritage Study): Study Design and Protocol 杭州市社区老年人认知障碍的多领域生活方式干预(遗产研究):研究设计与方案
IF 6.4 Q1 Medicine Pub Date : 2024-03-19 DOI: 10.14283/jpad.2024.59
Xin Xu, T. Pang, Y. Zhou, H. Zhang, A. Ma, C. Yuan, H. Chen, X. Wen, Q. Yang, X. Xu

Background

The globe has been working to promote a multi-domain lifestyle intervention for dementia prevention in older adults, referring to the Worldwide-FINGERS (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability) initiative. In China, the multi-domain lifestyle intervention has been implemented in rural communities (MIND-China), yet the adaptability of such intervention based on the urban communities in China has not been verified.

Objective

To examine the effectiveness and feasibility of the multi-domain lifestyle intervention on dementia prevention in at-risk community-dwelling older adults in China.

Design, Setting, Participants

The multi-domain lifestyle intervention study is a community-based 2-year cluster randomized controlled trial (RCT). A total of 1200 participants aged 60–80 years old will be recruited from twelve communities in Hangzhou, Zhejiang. Inclusion criteria were the Montreal Cognitive Assessment 5 minutes protocol (5 min MoCA) score of 6–9 or the Ascertain Dementia 8 (AD 8) score of ≥2, and having modifiable lifestyle factors.

Intervention, Measurements, Results

Participating communities will be randomized into either the structured multi-domain intervention (SMI) arm or the self-guided intervention (SGI, general health education) arm. The SMI consists of cognitive training, physical exercise, and nutritional and dietary instruction for the first 12 months; and vascular risks monitoring and control for 24 months. The primary outcome is the global cognitive performance, measured by the comprehensive Neuropsychological Test Battery (NTB). The secondary outcomes include domain-specific cognitive performances, physical function, mental health, physiological and biochemical indices, adherence to healthy lifestyles, and neuroimaging metrics. The feasibility of intervention will be evaluated around the five dimensions of the RE-AIM framework and in conjunction with quantitative data, operational data and results of focus group discussions.

Conclusions

Following the Worldwide-FINGERS, this cluster RCT will verify the adaptability of the multi-domain lifestyle intervention in the urban community settings in China. This study will add evidence for global dementia prevention and management among older adults.

背景全球一直致力于推广多领域的生活方式干预,以预防老年人痴呆症的发生,并参考了 "芬兰预防认知障碍和残疾的老年干预研究"(Worldwide-FINGERS)项目。目的探讨多领域生活方式干预对中国高危社区老年人痴呆预防的有效性和可行性。设计、地点、参与者多领域生活方式干预研究是一项为期两年的社区分组随机对照试验(RCT)。研究将从浙江省杭州市的 12 个社区招募 1200 名 60-80 岁的参与者。纳入标准为蒙特利尔认知评估5分钟方案(5 min MoCA)评分6-9分或老年痴呆8分(AD 8)评分≥2分,且具有可改变的生活方式因素。干预、测量、结果参与社区将被随机分为结构化多领域干预(SMI)组或自我指导干预(SGI,普通健康教育)组。SMI 包括前 12 个月的认知训练、体育锻炼以及营养和饮食指导;24 个月的血管风险监测和控制。主要结果是全面认知能力,由综合神经心理测试电池(NTB)测量。次要结果包括特定领域的认知表现、身体功能、心理健康、生理和生化指标、健康生活方式的坚持情况以及神经影像学指标。干预的可行性将围绕 RE-AIM 框架的五个维度,结合定量数据、操作数据和焦点小组讨论结果进行评估。这项研究将为全球老年人痴呆症的预防和管理提供更多证据。
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引用次数: 0
At-home Administration of Gantenerumab by Care Partners to People with Early Alzheimer’s Disease: Feasibility, Safety and Pharmacodynamic Impact 由护理伙伴在家中为早期阿尔茨海默病患者注射甘特纳单抗:可行性、安全性和药效学影响
IF 6.4 Q1 Medicine Pub Date : 2024-03-19 DOI: 10.14283/jpad.2024.60
Frank G. Boess, M. A. Scelsi, T. Grimmer, R. J. Perry, M. Tonietto, G. Klein, C. Hofmann, M. Salami, J. Wojtowicz, C. J. Lansdall, C. Lane, G. A. Kerchner, J. Smith, R. S. Doody

Background

Monoclonal antibodies that target amyloid-beta and remove amyloid plaques can slow cognitive and functional decline in early Alzheimer’s disease. Gantenerumab is a subcutaneously administered fully-human anti-amyloid-beta monoclonal antibody with highest affinity for aggregated amyloid-beta. Since the phase 3 GRADUATE trials did not meet the primary endpoint (change from baseline to Week 116 in Clinical Dementia Rating scale–Sum of Boxes), development of gantenerumab in sporadic Alzheimer’s disease was stopped and all ongoing trials were terminated early due to sponsor decision. Subcutaneous administration at the clinic or at home by care partner would be an important option for other therapies in this class in order to increase flexibility and reduce overall burden. The insights obtained from the experience with gantenerumab home administration by care partner in the phase 2 GRADUATION trial will serve to guide the ongoing efforts with other anti-amyloid-beta antibodies.

Objectives

To evaluate the pharmacodynamic effects on brain amyloid load of once weekly subcutaneous administration of gantenerumab and the safety and feasibility of home administration by care partners.

Design

Phase 2, open-label, single arm study.

Setting

Multicenter trial conducted in 33 sites in 8 countries from November 2020 to March 2023.

Participants

Participants aged 50 to 90 with early symptomatic Alzheimer’s disease (mild cognitive impairment/ mild dementia due to Alzheimer’s disease), and evidence of amyloid positron emission tomography positivity.

Intervention

Participants could receive up to 255 mg gantenerumab once-weekly, administered subcutaneously at site or at home by healthcare professionals or non-healthcare-professional care partners.

Measurements

The primary endpoint was the change from baseline to Week 52 and to Week 104 in brain amyloid load as measured by PET centiloid levels. The secondary endpoints were responses to the home administration questionnaire, plasma concentrations and safety.

Results

The overall number of participants enrolled was 192, with a mean (standard deviation) amyloid PET load at baseline of 101.80 (29.80) centiloids. At the time of early study termination by sponsor, 149 participants had valid Week 52 amyloid PET data (primary endpoint), and 12 participants had an early termination PET within the pre-defined time range of Week 104. The mean change in amyloid PET from baseline to Week 52 and Week 104 was −26.19 centiloids (range: −75.6–15.8; n=149) and −35.48 centiloids (range: −63.2–−7.0; n=12), respectively. Responses to the home administration questionn

背景以淀粉样蛋白-β为靶点并清除淀粉样蛋白斑块的单克隆抗体可减缓早期阿尔茨海默氏症患者的认知和功能衰退。Gantenerumab是一种皮下注射的全人源抗淀粉样蛋白-β单克隆抗体,对聚集的淀粉样蛋白-β具有最高的亲和力。由于 3 期 GRADUATE 试验未达到主要终点(临床痴呆评分量表-方框总和从基线到第 116 周的变化),Gantenerumab 在散发性阿尔茨海默病领域的开发已停止,所有正在进行的试验也因赞助商的决定而提前终止。为了提高灵活性并减轻总体负担,在诊所或由护理伙伴在家进行皮下注射将成为该类其他疗法的重要选择。目标评估每周一次皮下注射甘特奈鲁单抗对脑淀粉样蛋白负荷的药效学影响,以及由护理伙伴在家给药的安全性和可行性。设计2期、开放标签、单臂研究。参与者年龄在50至90岁之间,患有早期症状性阿尔茨海默病(轻度认知障碍/阿尔茨海默病导致的轻度痴呆),且有证据表明淀粉样蛋白正电子发射断层扫描呈阳性。干预措施参与者可接受最多255毫克的甘特瑞单抗,每周一次,由医疗保健专业人员或非医疗保健专业护理伙伴在现场或家中皮下注射。次要终点是对家庭管理问卷的答复、血浆浓度和安全性。结果参加研究的总人数为 192 人,基线时淀粉样蛋白 PET 负荷的平均值(标准差)为 101.80 (29.80) centiloids。在申办者提前终止研究时,149名参与者拥有第52周有效的淀粉样蛋白PET数据(主要终点),12名参与者的提前终止PET在第104周的预定时间范围内。从基线到第52周和第104周,淀粉样蛋白PET的平均变化分别为-26.19厘立德(范围:-75.6-15.8;n=149)和-35.48厘立德(范围:-63.2--7.0;n=12)。第 52 周的居家用药问卷调查(样本数=148)显示,大多数护理伙伴(88%-97%)认为居家用药容易(30.4%)或非常容易(57.4%),方便(25.7%)或非常方便(70.9%)。护理伙伴对在家注射有信心(31.1%)或非常有信心(62.2%),满意(29.7%)或非常满意(64.9%)。护理伙伴在第 36 周(72 人)、第 76 周(126 人)和第 104 周(29 人)的反应以及参与者(患者)在这些时间点对方便性和满意度的评价相似。结论由非医疗保健专业护理伙伴为早期阿尔茨海默病参与者每周一次皮下注射抗淀粉样蛋白-β抗体甘特纳鲁单抗是可行的、安全的、耐受性良好的,护理伙伴和阿尔茨海默病参与者都认为这是一种方便的选择。虽然 gantenerumab 的开发因缺乏疗效而停止,但这种方法有可能减少其他抗淀粉样蛋白-β 抗体治疗所需的医院/门诊就诊次数,并能提高阿尔茨海默病患者及其家人用药的灵活性。
{"title":"At-home Administration of Gantenerumab by Care Partners to People with Early Alzheimer’s Disease: Feasibility, Safety and Pharmacodynamic Impact","authors":"Frank G. Boess, M. A. Scelsi, T. Grimmer, R. J. Perry, M. Tonietto, G. Klein, C. Hofmann, M. Salami, J. Wojtowicz, C. J. Lansdall, C. Lane, G. A. Kerchner, J. Smith, R. S. Doody","doi":"10.14283/jpad.2024.60","DOIUrl":"https://doi.org/10.14283/jpad.2024.60","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Monoclonal antibodies that target amyloid-beta and remove amyloid plaques can slow cognitive and functional decline in early Alzheimer’s disease. Gantenerumab is a subcutaneously administered fully-human anti-amyloid-beta monoclonal antibody with highest affinity for aggregated amyloid-beta. Since the phase 3 GRADUATE trials did not meet the primary endpoint (change from baseline to Week 116 in Clinical Dementia Rating scale–Sum of Boxes), development of gantenerumab in sporadic Alzheimer’s disease was stopped and all ongoing trials were terminated early due to sponsor decision. Subcutaneous administration at the clinic or at home by care partner would be an important option for other therapies in this class in order to increase flexibility and reduce overall burden. The insights obtained from the experience with gantenerumab home administration by care partner in the phase 2 GRADUATION trial will serve to guide the ongoing efforts with other anti-amyloid-beta antibodies.</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>To evaluate the pharmacodynamic effects on brain amyloid load of once weekly subcutaneous administration of gantenerumab and the safety and feasibility of home administration by care partners.</p><h3 data-test=\"abstract-sub-heading\">Design</h3><p>Phase 2, open-label, single arm study.</p><h3 data-test=\"abstract-sub-heading\">Setting</h3><p>Multicenter trial conducted in 33 sites in 8 countries from November 2020 to March 2023.</p><h3 data-test=\"abstract-sub-heading\">Participants</h3><p>Participants aged 50 to 90 with early symptomatic Alzheimer’s disease (mild cognitive impairment/ mild dementia due to Alzheimer’s disease), and evidence of amyloid positron emission tomography positivity.</p><h3 data-test=\"abstract-sub-heading\">Intervention</h3><p>Participants could receive up to 255 mg gantenerumab once-weekly, administered subcutaneously at site or at home by healthcare professionals or non-healthcare-professional care partners.</p><h3 data-test=\"abstract-sub-heading\">Measurements</h3><p>The primary endpoint was the change from baseline to Week 52 and to Week 104 in brain amyloid load as measured by PET centiloid levels. The secondary endpoints were responses to the home administration questionnaire, plasma concentrations and safety.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The overall number of participants enrolled was 192, with a mean (standard deviation) amyloid PET load at baseline of 101.80 (29.80) centiloids. At the time of early study termination by sponsor, 149 participants had valid Week 52 amyloid PET data (primary endpoint), and 12 participants had an early termination PET within the pre-defined time range of Week 104. The mean change in amyloid PET from baseline to Week 52 and Week 104 was −26.19 centiloids (range: −75.6–15.8; n=149) and −35.48 centiloids (range: −63.2–−7.0; n=12), respectively. Responses to the home administration questionn","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":"140147153","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}
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The Journal of Prevention of Alzheimer's Disease
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