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Global Burden of Dementia Death from 1990 to 2019, with Projections to 2050: An Analysis of 2019 Global Burden of Disease Study 1990 年至 2019 年全球痴呆症死亡负担及到 2050 年的预测:2019年全球疾病负担研究分析
IF 6.4 Q2 BUSINESS Pub Date : 2024-05-02 DOI: 10.14283/jpad.2024.21
Z. Li, N. Yang, L. He, J. Wang, Y. Yang, F. Ping, L. Xu, Huabing Zhang, Wei Li, Yuxiu Li

Background

Dementia is a growing global health challenge. Quantifying the current burden and predicting the future increases of dementia-related deaths are necessary to enhance effective policy decisions and health system planning.

Methods

Data on dementia mortality was derived from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 study. The 2020–2050 dementia-related deaths were forecasted using the Bayesian age-period-cohort model.

Results

Globally, the number of dementia-related death increased from 0.56 million in 1990 to 1.62 million in 2019 and were estimated to increase to 4.91 million by the year 2050. Metabolic risk factors would become the most important modifiable risk factors affecting dementia death which account for 28.10% of dementia related death by the year 2050. For different Socio-demographic Index (SDI) regions, the low SDI region would have the highest age-standardized mortality rate (ASMR) (29.16 per 100,000) by 2050. Moreover, the number of dementia-related deaths under the age of 70 years was predicted to reach 0.18 million by 2050.

Conclusions

Dementia related death remains a global health problem, and health policies targeting metabolic risk factors may be an important way to alleviate this problem.

背景痴呆症是一项日益严峻的全球健康挑战。为了加强有效的政策决策和卫生系统规划,有必要量化当前的负担并预测未来痴呆症相关死亡人数的增长。方法痴呆症死亡率数据来自《2019 年全球疾病、伤害和风险因素负担研究》(GBD)。结果在全球范围内,与痴呆症相关的死亡人数从1990年的56万增至2019年的162万,预计到2050年将增至491万。到 2050 年,代谢风险因素将成为影响痴呆症死亡的最重要的可改变风险因素,占痴呆症相关死亡的 28.10%。就不同社会人口指数(SDI)地区而言,到2050年,低社会人口指数地区的年龄标准化死亡率(ASMR)最高(每10万人中29.16人)。此外,预计到 2050 年,70 岁以下与痴呆症相关的死亡人数将达到 18 万人。结论与痴呆症相关的死亡仍然是一个全球性的健康问题,针对代谢风险因素的健康政策可能是缓解这一问题的重要途径。
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引用次数: 0
The Shape Trail Test Is Sensitive in Differentiating Older Adults with Mild Cognitive Impairment: A Culture-neutral Five-minute Test 形状轨迹测试在区分患有轻度认知障碍的老年人方面很敏感:文化中立的五分钟测试
IF 6.4 Q2 BUSINESS Pub Date : 2024-05-02 DOI: 10.14283/jpad.2024.80
Z. Ding, Agnes S. Chan

Introduction

The Shape Trail Test (STT) was developed based upon the Trail Making Test, as a culture-neutral test for measuring processing speed and mental flexibility. This study aims to evaluate the accuracy and validity of this five-minute test for differentiating individuals with normal cognition (NC), subjective memory impairment (SMI), and mild cognitive impairment (MCI).

Method

The study included 210 participants aged 50–80 years, with 70 participants in each group matched for age, education, and gender.

Results

No significant difference in STT measures was found between the NC and SMI groups. In contrast, both the NC and SMI groups exhibited significantly better performance (shorter completion time in STT-A and STT-B and fewer STT-B errors) than the MCI group. No significant group differences were found in STT-A errors. Stepwise regression analysis identified three significant predictors for classifying the MCI group from the NC and/or SMI groups, including the STT-B completion time, the STT-A errors, and the interaction between STT-B completion time and STT-B errors. The composite score of these three predictors demonstrated good discriminatory power for classifying the MCI group from the other groups, with area under the curves (AUCs) of 0.76–0.79 (p < 0.001), sensitivities of 78.6%–80%, and specificities of 60%–61.4%. However, none of the STT measures or their interactions were significant predictors for differentiating the SMI group from the NC group. Besides, the STT measures were significantly correlated with age, education, and executive function measures.

Discussion

The STT could be a culture- and language-free, reliable test for assessing executive function and a sensitive test for predicting MCI.

导言形状轨迹测验(STT)是在轨迹制作测验的基础上开发出来的,它是一种文化中立的测验,用于测量处理速度和思维灵活性。本研究旨在评估这一五分钟测试在区分认知正常(NC)、主观记忆障碍(SMI)和轻度认知障碍(MCI)个体方面的准确性和有效性。相反,NC 组和 SMI 组的表现(STT-A 和 STT-B 完成时间较短,STT-B 错误较少)明显优于 MCI 组。在 STT-A 错误方面没有发现明显的组间差异。逐步回归分析确定了将 MCI 组与 NC 和/或 SMI 组进行分类的三个重要预测因子,包括 STT-B 完成时间、STT-A 错误以及 STT-B 完成时间与 STT-B 错误之间的交互作用。这三个预测因子的综合得分在将 MCI 组与其他组进行分类方面表现出良好的区分能力,曲线下面积(AUC)为 0.76-0.79(p < 0.001),灵敏度为 78.6%-80%,特异度为 60%-61.4%。然而,STT 测量或其交互作用都不是区分 SMI 组和 NC 组的显著预测指标。讨论 STT是一种不受文化和语言影响的可靠的执行功能测试,也是预测MCI的灵敏测试。
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引用次数: 0
Association between Resting Heart Rate and Machine Learning-Based Brain Age in Middle- and Older-Age 静息心率与基于机器学习的中老年脑年龄之间的关系
IF 6.4 Q2 BUSINESS Pub Date : 2024-04-19 DOI: 10.14283/jpad.2024.76
J. Wang, H. Huang, W. Yang, A. Dove, Xiangyu Ma, Weili Xu

Background

Resting heart rate (RHR), has been related to increased risk of dementia, but the relationship between RHR and brain age is unclear.

Objective

We aimed to investigate the association of RHR with brain age and brain age gap (BAG, the difference between predicted brain age and chronological age) assessed by multimodal Magnetic Resonance Imaging (MRI) in mid- and old-aged adults.

Design

A longitudinal study from the UK Biobank neuroimaging project where participants underwent brain MRI scans 9+ years after baseline.

Setting

A population-based study.

Participants

A total of 33,381 individuals (mean age 54.74 ± 7.49 years; 53.44% female).

Measurements

Baseline RHR was assessed by blood pressure monitor and categorized as <60, 60–69 (reference), 70–79, or ≥80 beats per minute (bpm). Brain age was predicted using LASSO through 1,079 phenotypes in six MRI modalities (including T1-weighted MRI, T2-FLAIR, T2*, diffusion-MRI, task fMRI, and resting-state fMRI). Data were analyzed using linear regression models.

Results

As a continuous variable, higher RHR was associated with older brain age (β for per 1-SD increase: 0.331, 95% [95% confidence interval, CI]: 0.265, 0.398) and larger BAG (β: 0.263, 95% CI: 0.202, 0.324). As a categorical variable, RHR 70–79 bpm and RHR ≥80 bpm were associated with older brain age (β [95% CI]: 0.361 [0.196, 0.526] / 0.737 [0.517, 0.957]) and larger BAG (0.256 [0.105, 0.407] / 0.638 [0.436, 0.839]), but RHR< 60 bpm with younger brain age (−0.324 [−0.500, −0.147]) and smaller BAG (−0.230 [−0.392, −0.067]), compared to the reference group. These associations between elevated RHR and brain age were similar in both middle-aged (<60) and older (≥60) adults, whereas the association of RHR< 60 bpm with younger brain age and larger BAG was only significant among middle-aged adults. In stratification analysis, the association between RHR ≥80 bpm and older brain age was present in people with and without CVDs, while the relation of RHR 70–79 bpm to brain age present only in people with CVD.

Conclusion

Higher RHR (>80 bpm) is associated with older brain age, even among middle-aged adults, but RHR< 60 bpm is associated with younger brain age. Greater RHR could be an indicator for accelerated brain aging.

背景巢式心率(RHR)与痴呆症风险的增加有关,但 RHR 与脑年龄之间的关系尚不清楚。目的我们旨在调查 RHR 与中老年人的脑年龄以及通过多模态磁共振成像(MRI)评估的脑年龄差距(BAG,预测脑年龄与实际年龄之间的差异)之间的关系。设计英国生物库神经影像学项目的一项纵向研究,参与者在基线后 9 年以上接受脑部核磁共振成像扫描。通过六种核磁共振成像模式(包括 T1 加权核磁共振成像、T2-FLAIR、T2*、弥散核磁共振成像、任务核磁共振成像和静息状态核磁共振成像)中的 1079 种表型,使用 LASSO 预测大脑年龄。结果 作为一个连续变量,较高的 RHR 与较老的脑年龄相关(每增加 1-SD β:0.331,95% [95%置信区间,CI]:0.265,0.398)和更大的 BAG(β:0.263,95% 置信区间:0.202,0.324)。作为一个分类变量,RHR 70-79 bpm 和 RHR≥80 bpm 与脑年龄较大(β [95% CI]: 0.361 [0.196, 0.526] / 0.737 [0.517, 0.957])和 BAG 较大(0.256 [0.105, 0.407]/0.638[0.436,0.839]),但与参照组相比,RHR< 60 bpm 与较年轻的脑年龄(-0.324 [-0.500,-0.147])和较小的 BAG(-0.230 [-0.392,-0.067])有关。在中年(60 岁)和老年(≥60 岁)成人中,RHR 升高与脑年龄之间的关系相似,而 RHR< 60 bpm 与脑年龄较小和 BAG 较大之间的关系仅在中年成人中显著。在分层分析中,RHR≥80 bpm 与年龄较大的脑年龄之间的关系在患有和未患有心血管疾病的人群中均存在,而 RHR 70-79 bpm 与脑年龄之间的关系仅在患有心血管疾病的人群中存在。更高的 RHR 可能是大脑加速衰老的指标。
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引用次数: 0
Periodontal Disease and Alzheimer’s: Insights from a Systematic Literature Network Analysis 牙周病与阿尔茨海默氏症:系统文献网络分析的启示
IF 6.4 Q2 BUSINESS Pub Date : 2024-04-19 DOI: 10.14283/jpad.2024.79
Alice Villar, S. Paladini, J. Cossatis

Evidence This study investigated the relationship between periodontal disease (PD) and Alzheimer’s Disease (AD) through a Systematic Literature Network Analysis (SLNA), combining bibliometric analysis with a Systematic Literature Review (SLR). Analyzing 328 documents from 2000 to 2023, we utilized the Bibliometrix R-package for multiple bibliometric analysis. The SLR primarily centered on the 47 most globally cited papers, highlighting influential research. Our study reveals a positive correlation between Periodontal Disease (PD) and Alzheimer’s Disease (AD), grounded in both biological plausibility and a comprehensive review of the literature, yet the exact causal relationship remains a subject of ongoing scientific investigation. We conducted a detailed analysis of the two main pathways by which PD could contribute to brain inflammation: (a) the Inflammatory Cascade, and (b) Microbial Involvement. The results of our SLNA emphasize the importance of oral health in reducing Alzheimer’s risk, suggesting that managing periodontal health could be an integral part of Alzheimer’s prevention and treatment strategies. The insights from this SLNA pave the way for future research and clinical practices, underscoring the necessity of interdisciplinary methods in both the investigation and treatment of neurodegenerative diseases like Alzheimer’s. Furthermore, our study presents a prospective research roadmap to support ongoing advancement in this field.

证据 本研究通过系统文献网络分析(SLNA),结合文献计量分析和系统文献综述(SLR),研究了牙周病(PD)和阿尔茨海默病(AD)之间的关系。我们分析了 2000 年至 2023 年的 328 篇文献,利用 Bibliometrix R 软件包进行了多重文献计量分析。系统文献综述主要以全球引用率最高的 47 篇论文为中心,突出了有影响力的研究。我们的研究揭示了牙周病(PD)和阿尔茨海默病(AD)之间的正相关性,这种正相关性建立在生物学合理性和文献综述的基础上,但两者之间的确切因果关系仍是科学界正在研究的课题。我们详细分析了牙周病可能导致脑部炎症的两个主要途径:(a) 炎症级联和 (b) 微生物参与。我们的 SLNA 结果强调了口腔健康对降低阿尔茨海默氏症风险的重要性,表明牙周健康管理可以成为阿尔茨海默氏症预防和治疗策略不可或缺的一部分。这项 SLNA 的见解为未来的研究和临床实践铺平了道路,强调了在调查和治疗阿尔茨海默氏症等神经退行性疾病时采用跨学科方法的必要性。此外,我们的研究还提出了一个前瞻性的研究路线图,以支持该领域的不断进步。
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引用次数: 0
Predicting Brain Amyloid Status Using the National Institute of Health Toolbox (NIHTB) for Assessment of Neurological and Behavioral Function 利用美国国家卫生研究院用于评估神经和行为功能的工具箱(NIHTB)预测脑淀粉样蛋白状态
IF 6.4 Q2 BUSINESS Pub Date : 2024-04-17 DOI: 10.14283/jpad.2024.77
Y. Cheng, E. Ho, S. Weintraub, D. Rentz, R. Gershon, Sudeshna Das, Hiroko H. Dodge

Background

Amyloid-beta (Aβ) plaque is a neuropathological hallmark of Alzheimer’s disease (AD). As anti-amyloid monoclonal antibodies enter the market, predicting brain amyloid status is critical to determine treatment eligibility.

Objective

To predict brain amyloid status utilizing machine learning approaches in the Advancing Reliable Measurement in Alzheimer’s Disease and Cognitive Aging (ARMADA) study.

Design

ARMADA is a multisite study that implemented the National Institute of Health Toolbox for Assessment of Neurological and Behavioral Function (NIHTB) in older adults with different cognitive ability levels (normal, mild cognitive impairment, early-stage dementia of the AD type).

Setting

Participants across various sites were involved in the ARMADA study for validating the NIHTB.

Participants

199 ARMADA participants had either PET or CSF information (mean age 76.3 ± 7.7, 51.3% women, 42.3% some or complete college education, 50.3% graduate education, 88.9% White, 33.2% with positive AD biomarkers).

Measurements

We used cognition, emotion, motor, sensation scores from NIHTB, and demographics to predict amyloid status measured by PET or CSF. We applied LASSO and random forest models and used the area under the receiver operating curve (AUROC) to evaluate the ability to identify amyloid positivity.

Results

The random forest model reached AUROC of 0.74 with higher specificity than sensitivity (AUROC 95% CI:0.73 -0.76, Sensitivity 0.50, Specificity 0.88) on the held-out test set; higher than the LASSO model (0.68 (95% CI:0.68 – 0.69)). The 10 features with the highest importance from the random forest model are: picture sequence memory, cognition total composite, cognition fluid composite, list sorting working memory, words-in-noise test (hearing), pattern comparison processing speed, odor identification, 2-minutes-walk endurance, 4-meter walk gait speed, and picture vocabulary. Overall, our model revealed the validity of measurements in cognition, motor, and sensation domains, in associating with AD biomarkers.

Conclusion

Our results support the utilization of the NIH toolbox as an efficient and standardizable AD biomarker measurement that is better at identifying amyloid negative (i.e., high specificity) than positive cases (i.e., low sensitivity).

背景淀粉样蛋白-β(Aβ)斑块是阿尔茨海默病(AD)的神经病理学标志。随着抗淀粉样蛋白单克隆抗体进入市场,预测脑淀粉样蛋白状态对于确定治疗资格至关重要。目的在阿尔茨海默病和认知老化的可靠测量研究(ARMADA)中利用机器学习方法预测脑淀粉样蛋白状态。设计ARMADA是一项多站点研究,在不同认知能力水平(正常、轻度认知障碍、AD型早期痴呆)的老年人中实施美国国立卫生研究院神经和行为功能评估工具箱(NIHTB)。参与者199名ARMADA参与者拥有PET或CSF信息(平均年龄76.3 ± 7.7岁,51.3%为女性,42.3%受过一些或完整的大学教育,50.3%受过研究生教育,88.9%为白人,33.2%具有阳性AD生物标记物)。测量我们使用NIHTB的认知、情绪、运动、感觉评分和人口统计学来预测PET或CSF测量的淀粉样蛋白状态。结果随机森林模型的AUROC为0.74,特异性高于敏感性(AUROC 95% CI:0.73 -0.76,敏感性0.50,特异性0.88);高于LASSO模型(0.68 (95% CI:0.68-0.69))。随机森林模型中重要性最高的 10 个特征是:图片序列记忆、认知总综合、认知流体综合、列表排序工作记忆、噪声词测试(听力)、模式比较处理速度、气味识别、2 分钟步行耐力、4 米步行步态速度和图片词汇量。总之,我们的模型揭示了认知、运动和感觉领域的测量结果在与注意力缺失症生物标志物相关联方面的有效性。结论我们的研究结果支持将美国国立卫生研究院工具箱作为一种高效、可标准化的注意力缺失症生物标志物测量方法来使用,它在识别淀粉样蛋白阴性病例(即特异性高)方面优于阳性病例(即灵敏度低)。
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引用次数: 0
Disease-Modifying Antirheumatic Drugs and Dementia Prevention: A Systematic Review of Observational Evidence in Rheumatoid Arthritis 改变病情的抗风湿药物与痴呆症的预防:类风湿关节炎观察证据的系统回顾
IF 6.4 Q2 BUSINESS Pub Date : 2024-04-15 DOI: 10.14283/jpad.2024.78
C.-Y. Wu, L. Y. Xiong, Y. Y. Wong, S. Noor, G. Bradley-Ridout, Walter Swardfager

Background

Many observational studies have examined the association of disease-modifying antirheumatic drugs (DMARDs) with dementia risk, but the evidence has been mixed, possibly due to methodological reasons. This systematic review (PROSPERO: CRD42023432122) aims to assess existing observational evidence and to suggest if repurposing DMARDs for dementia prevention merits further investigation.

Methods

Four electronic databases up to October 26, 2023, were searched. Cohort or case-control studies that examined dementia risk associated with DMARDs in people with rheumatoid arthritis were included. Risk of bias was evaluated using the Cochrane Collaboration’s Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) criteria. Findings were summarized by individual drug classes and by risk of bias.

Results

Of 12,180 unique records, 14 studies (4 case-control studies, 10 cohort studies) were included. According to the ROBINS-I criteria, there were 2 studies with low risk of bias, 1 study with moderate risk, and 11 studies with serious or critical risk. Among studies with low risk of bias, one study suggested that hydroxychloroquine versus methotrexate was associated with lower incident dementia, and the other study showed no associations of tumor necrosis factor (TNF) inhibitors, tocilizumab, and tofacitinib, compared to abatacept, with incident dementia.

Conclusion

Studies that adequately addressed important biases were limited. Studies with low risk of bias did not support repurposing TNF inhibitors, tocilizumab, abatacept or tofacitinib for dementia prevention, but hydroxychloroquine may be a potential candidate. Further studies that carefully mitigate important sources of biases are warranted, and long-term evidence will be preferred.

背景许多观察性研究探讨了改变病情抗风湿药(DMARDs)与痴呆风险之间的关系,但可能由于方法学方面的原因,相关证据参差不齐。本系统综述(PROSPERO:CRD42023432122)旨在评估现有的观察性证据,并提出是否值得进一步研究将 DMARDs 用于痴呆症预防。方法检索了截至 2023 年 10 月 26 日的四个电子数据库,纳入了对类风湿关节炎患者使用 DMARDs 相关痴呆症风险进行研究的队列研究或病例对照研究。采用 Cochrane 协作组织的非随机干预研究偏倚风险(ROBINS-I)标准对偏倚风险进行了评估。结果 在 12180 条记录中,共纳入了 14 项研究(4 项病例对照研究和 10 项队列研究)。根据 ROBINS-I 标准,2 项研究存在低偏倚风险,1 项研究存在中度偏倚风险,11 项研究存在严重或临界偏倚风险。在偏倚风险较低的研究中,一项研究表明羟氯喹与甲氨蝶呤相比与较低的痴呆发病率有关,另一项研究表明肿瘤坏死因子(TNF)抑制剂、托西珠单抗和托法替尼与阿帕他赛相比与痴呆发病率无关。偏倚风险较低的研究不支持将TNF抑制剂、托西珠单抗、阿帕赛普或托法替尼重新用于痴呆症的预防,但羟氯喹可能是一个潜在的候选药物。有必要开展进一步的研究,仔细减少重要的偏倚来源,并优先考虑长期证据。
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引用次数: 0
Effectiveness of Resistance Exercise on Cognitive Function in Animal Models of Alzheimer Disease: A Systematic Review and Meta-Analysis 阻力运动对阿尔茨海默病动物模型认知功能的影响:系统回顾与元分析
IF 6.4 Q2 BUSINESS Pub Date : 2024-04-10 DOI: 10.14283/jpad.2024.75
F. O. de Andrade Santos, A. A. Passos, Ricardo Mario Arida, L. Teixeira-Machado

Aim

Alzheimer’s disease (AD) is among common cause of dementia. Complementary therapies, such as resistance exercise (RE), have been proposed as an alternative for the treatment of AD. We performed a systematic review and meta-analysis to investigate the effects of RE on the cognitive function of AD animal models and their physiological mechanisms.

Methods

This review was submitted to PROSPERO (CRD42019131266) and was done according to PRISMA checklist. Four databases were used in the search: MEDLINE/PUBMED, SCOPUS, Web of Science and Google Scholar. We used SYRCLE and CAMAREDES to assess the risk of bias and methodological quality. We calculated the standardized mean difference using 95% confidence intervals and considered the random effects model and p < 0.05 to determine significance.

Key Findings

A total of 1,807 studies were founded, and after the selection process, only 11 studies were included in this review and 8 studies were included for meta-analysis. Four studies applied RE before AD induction, 7 studies applied RE after AD induction or in the AD condition. All studies included 550 adult and older animals weighing 25–280g. Our analysis revealed that RE had a positive effect on memory in AD animal models but did not show a significant impact on anxiety.

Conclusion

RE performed four or six weeks, more than three days a week, had a significant protective effect on memory. The included studies had a high risk of bias and moderate methodological quality. Therefore, RE can be a potential strategy for preventing cognitive decline in animal models.

目的阿尔茨海默病(AD)是导致痴呆症的常见原因之一。阻力运动(RE)等辅助疗法被认为是治疗老年痴呆症的替代疗法。我们进行了一项系统综述和荟萃分析,以研究 RE 对 AD 动物模型认知功能的影响及其生理机制。检索使用了四个数据库:MEDLINE/PUBMED、SCOPUS、Web of Science 和 Google Scholar。我们使用 SYRCLE 和 CAMAREDES 评估偏倚风险和方法学质量。我们使用 95% 的置信区间计算了标准化平均差,并考虑了随机效应模型和 p < 0.05 来确定显著性。4项研究在诱导AD之前应用RE,7项研究在诱导AD之后或在AD状态下应用RE。所有研究都纳入了 550 只体重为 25-280 克的成年和老年动物。我们的分析表明,RE 对注意力缺失症动物模型的记忆力有积极影响,但对焦虑没有显著影响。纳入的研究偏倚风险较高,方法质量中等。因此,RE 可以作为预防动物模型认知能力下降的一种潜在策略。
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引用次数: 0
The Insulin Sensitizer KBP-336 Prevents Diabetes-Induced Cognitive decline in ZDF Rats 胰岛素增敏剂 KBP-336 可预防糖尿病诱导的 ZDF 大鼠认知能力下降
IF 6.4 Q2 BUSINESS Pub Date : 2024-04-10 DOI: 10.14283/jpad.2024.74
Anna Thorsø Larsen, K. E. Mohamed, E. A. Petersen, M. A. Karsdal, K. Henriksen

Background and Objectives

Diabetes and especially insulin resistance are associated with an increased risk of developing cognitive dysfunction, making anti-diabetic drugs an interesting therapeutic option for the treatment of neurodegenerative disorders. Dual amylin and calcitonin receptor agonists (DACRAs) elicit beneficial effects on glycemic control and insulin sensitivity. However, whether DACRAs affect cognition is unknown.

Design and Intervention

Zucker Diabetic Fatty rats were treated with either the DACRA KBP-336 (4.5 nmol/kg Q3D), the amylin analog AM1213 (25 nmol/kg QD), or vehicle for 18 weeks. Further, the efficacy of a late KBP-336 intervention was evaluated by including a group starting treatment on day 30. Glucose control and tolerance were evaluated throughout the study and spatial learning and memory were evaluated by Morris Water Maze after 17 weeks of treatment.

Results

When evaluating spatial learning, rats receiving KBP-336 throughout the study performed significantly better than AM1213, vehicle, and late intervention KBP-336. Both KBP-336 and AM1213 treatments improved spatial memory compared to the vehicle. The overall performance in the cognitive tests was reflected in the treatment efficacy on glycemic control, where KBP-336 was superior to AM1213.

Conclusion

In summary, the DACRA KBP-336 ameliorates diabetes-induced spatial learning and memory impairment in diabetic rats. Further, KBP-336 improves long-term glycemic control superior to the amylin analog AM1213. Taken together, KBP-336 is, due to its anti-diabetic and insulin-sensitizing properties, a promising candidate for the treatment of cognitive impairments.

背景和目的糖尿病尤其是胰岛素抵抗与认知功能障碍的发病风险增加有关,因此抗糖尿病药物成为治疗神经退行性疾病的一种有趣的治疗选择。双淀粉样蛋白和降钙素受体激动剂(DACRAs)可对血糖控制和胰岛素敏感性产生有益影响。设计与干预用 DACRA KBP-336(4.5 nmol/kg Q3D)、淀粉样蛋白类似物 AM1213(25 nmol/kg QD)或药物治疗扎克糖尿病肥胖大鼠 18 周。此外,还评估了 KBP-336 后期干预的疗效,其中包括从第 30 天开始治疗的一组。结果在评估空间学习能力时,在整个研究期间接受 KBP-336 治疗的大鼠的表现明显优于 AM1213、药物和后期干预的 KBP-336。与车辆相比,KBP-336 和 AM1213 治疗都能改善空间记忆。结论综上所述,DACRA KBP-336 可改善糖尿病诱导的糖尿病大鼠空间学习和记忆损伤。此外,KBP-336 改善长期血糖控制的效果优于淀粉样蛋白类似物 AM1213。综上所述,KBP-336 因其抗糖尿病和胰岛素增敏特性,有望成为治疗认知障碍的候选药物。
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引用次数: 0
Optimising Alzheimer’s Disease Diagnosis and Treatment: Assessing Cost-Utility of Integrating Blood Biomarkers in Clinical Practice for Disease-Modifying Treatment 优化阿尔茨海默病诊断和治疗:评估在临床实践中整合血液生物标记物进行疾病调整治疗的成本效益
IF 6.4 Q2 BUSINESS Pub Date : 2024-04-10 DOI: 10.14283/jpad.2024.67
Sandar Aye, R. Handels, B. Winblad, L. Jönsson

Background

Recent developments in blood biomarkers (BBM) have shown promising results in diagnosing amyloid pathology in Alzheimer’s Disease (AD). However, information on how these BBMs can best be used in clinical settings to optimise clinical decision-making and long-term health outcomes for individuals with AD is still lacking.

Objectives

We aim to assess the potential value of BBM in AD diagnosis within the context of disease-modifying treatment (DMT).

Design

We developed a decision analytic model to evaluate the long-term health outcomes using BBM in AD diagnosis. We compared standard of care (SOC) diagnosis workflow to the integration of BBM as a (1) referral decision tool in primary health center (PHC) and (2) triaging tool for invasive CSF examination in specialist memory clinic (MC). We combined a decision tree and a Markov model to simulate the patient’s diagnostic journey, treatment decisions following diagnosis and long-term health outcomes. Input parameters for the model were identified from published literature and registry data analysis. We conducted a cost-utility analysis from the societal perspective using a one-year cycle length and a 30-year (lifetime) horizon.

Measurements

We reported the simulated outcomes in the percentage of correct diagnosis, costs (in 2022 Euros), quality-adjusted life year (QALY), and incremental cost-effectiveness ratios (ICER) associated with each diagnosis strategy.

Results

Compared to SOC, integrating BBM in PHC increased patient referrals by 8% and true positive AD diagnoses by 10.4%. The lifetime costs for individuals diagnosed with AD were € 249,685 and €250,287, and QALYs were 9.5 and 9.52 in SOC and PHC pathways, respectively. The cost increments were €603, and QALYs gained were 0.01, resulting in an ICER of €48,296. Using BBM in MC reduced the exposure to invasive CSF procedures and costs but also reduced true positive AD diagnoses and QALYs.

Conclusions

Using BBM at PHC to make referral decisions might increase initial diagnostic costs but can prevent high costs associated with disease progression, providing a cost-effective DMT is available, whereas using BBM in MC could reduce the initial evaluation cost but incur high costs associated with disease progression.

背景近期血液生物标记物(BBM)的发展在诊断阿尔茨海默病(AD)的淀粉样病理方面取得了令人鼓舞的成果。目标我们旨在评估在疾病调整治疗(DMT)背景下血液生物标志物在阿尔茨海默病诊断中的潜在价值。设计我们开发了一个决策分析模型,以评估在阿尔茨海默病诊断中使用血液生物标志物的长期健康结果。我们比较了标准护理(SOC)诊断工作流程与 BBM 作为(1)初级保健中心(PHC)转诊决策工具和(2)专科记忆诊所(MC)侵入性 CSF 检查分流工具的整合情况。我们将决策树和马尔可夫模型相结合,模拟患者的诊断过程、诊断后的治疗决策和长期健康结果。模型的输入参数来自已发表的文献和登记数据分析。我们从社会角度进行了成本效用分析,周期为一年,期限为 30 年(终生)。我们报告了与每种诊断策略相关的正确诊断百分比、成本(2022 欧元)、质量调整生命年 (QALY) 和增量成本效益比 (ICER) 等模拟结果。在 SOC 和 PHC 路径中,被诊断为 AD 患者的终生成本分别为 249,685 欧元和 250,287 欧元,QALY 分别为 9.5 和 9.52。成本增量为 603 欧元,QALYs 收益为 0.01,ICER 为 48,296 欧元。结论在PHC使用BBM做出转诊决定可能会增加初始诊断成本,但可以避免与疾病进展相关的高成本,前提是可以获得具有成本效益的DMT,而在MC使用BBM可以降低初始评估成本,但会产生与疾病进展相关的高成本。
{"title":"Optimising Alzheimer’s Disease Diagnosis and Treatment: Assessing Cost-Utility of Integrating Blood Biomarkers in Clinical Practice for Disease-Modifying Treatment","authors":"Sandar Aye, R. Handels, B. Winblad, L. Jönsson","doi":"10.14283/jpad.2024.67","DOIUrl":"https://doi.org/10.14283/jpad.2024.67","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Recent developments in blood biomarkers (BBM) have shown promising results in diagnosing amyloid pathology in Alzheimer’s Disease (AD). However, information on how these BBMs can best be used in clinical settings to optimise clinical decision-making and long-term health outcomes for individuals with AD is still lacking.</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>We aim to assess the potential value of BBM in AD diagnosis within the context of disease-modifying treatment (DMT).</p><h3 data-test=\"abstract-sub-heading\">Design</h3><p>We developed a decision analytic model to evaluate the long-term health outcomes using BBM in AD diagnosis. We compared standard of care (SOC) diagnosis workflow to the integration of BBM as a (1) referral decision tool in primary health center (PHC) and (2) triaging tool for invasive CSF examination in specialist memory clinic (MC). We combined a decision tree and a Markov model to simulate the patient’s diagnostic journey, treatment decisions following diagnosis and long-term health outcomes. Input parameters for the model were identified from published literature and registry data analysis. We conducted a cost-utility analysis from the societal perspective using a one-year cycle length and a 30-year (lifetime) horizon.</p><h3 data-test=\"abstract-sub-heading\">Measurements</h3><p>We reported the simulated outcomes in the percentage of correct diagnosis, costs (in 2022 Euros), quality-adjusted life year (QALY), and incremental cost-effectiveness ratios (ICER) associated with each diagnosis strategy.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Compared to SOC, integrating BBM in PHC increased patient referrals by 8% and true positive AD diagnoses by 10.4%. The lifetime costs for individuals diagnosed with AD were € 249,685 and €250,287, and QALYs were 9.5 and 9.52 in SOC and PHC pathways, respectively. The cost increments were €603, and QALYs gained were 0.01, resulting in an ICER of €48,296. Using BBM in MC reduced the exposure to invasive CSF procedures and costs but also reduced true positive AD diagnoses and QALYs.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>Using BBM at PHC to make referral decisions might increase initial diagnostic costs but can prevent high costs associated with disease progression, providing a cost-effective DMT is available, whereas using BBM in MC could reduce the initial evaluation cost but incur high costs associated with disease progression.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"35 1","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140562892","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
“Time Saved” Calculations to Improve Decision-Making in Progressive Disease Studies "节省时间 "计算改善进展性疾病研究中的决策制定
IF 6.4 Q2 BUSINESS Pub Date : 2024-04-02 DOI: 10.14283/jpad.2024.64
S. P. Dickson, B. Haaland, C. H. Mallinckrodt, B. Dubois, P. O’Keefe, M. Morgan, O. Peters, A. Fernández Santana, J. Harrison, Achim Schneeberger, S. Hendrix

Background

Disease modifying therapies (DMTs) may be most beneficial in early disease, when progression is slow and changes small, with clinical relevance difficult to interpret.

Objectives

Time component tests (TCTs) translate differences between treatments from mean change, vertical distance between longitudinal trajectories, into intuitively understood time saved, horizontal distance between trajectories, which can be readily combined across endpoints in a global TCT (gTCT).

Design

The value of composites, time savings estimates, and combination scores to optimize measurement and interpretation of DMTs are demonstrated, along with construction details and simulation studies.

Setting

TCT methods were applied to a randomized phase II clinical trial.

Participants

Patients with early Alzheimer’s disease (N=332).

Intervention

Three treatment groups with AFFITOPE® AD02 and two control groups with aluminum oxyhydroxide, AD04.

Measurements

The co-primary efficacy outcomes were an adapted ADAS-Cog (aADAS) and adapted ADCS-ADL (aADL), which were optimized composite scales specific to cognitive and functional domains. A composite based on these two scores was the study’s prespecified primary outcome. The CDR-sb and standard non-adapted ADCS-ADL and ADAS-Cog scales were prespecified secondary outcomes.

Results

The AD04 2 mg group showed some statistically significant effects compared with other study arms. It is unclear whether the observed 3.8-point difference on the composite is clinically meaningful. TCT results show a time savings of 11 months in an 18-month study with AD04 2 mg.

Conclusion

The relevance of 11 months saved is more universally understood than a mean difference of 3.8 points in the composite outcome. These results suggest that a combination of a composite approach and a time savings interpretation offers a powerful approach for detecting and interpreting disease modifying effects.

背景改变病情疗法(DMT)在疾病早期可能最有益,因为此时病情进展缓慢,变化较小,临床相关性难以解释。目标时间成分测试(TCT)将平均变化(纵向轨迹之间的垂直距离)中不同治疗方法之间的差异转化为直观理解的节省时间(轨迹之间的水平距离),这些时间可以很容易地在全局TCT(gTCT)中结合不同的终点。设计展示了综合评分、节省时间估算和组合评分在优化 DMT 测量和解释方面的价值,以及构建细节和模拟研究。干预三组使用 AFFITOPE® AD02 的治疗组和两组使用氢氧化铝 AD04 的对照组。测量共同主要疗效结果为改编的 ADAS-Cog (aADAS) 和改编的 ADCS-ADL (aADL),它们是针对认知和功能领域的优化复合量表。基于这两项评分的综合评分是该研究预设的主要结果。CDR-sb 和标准非适应性 ADCS-ADL 和 ADAS-Cog 量表是预设的次要结果。结果与其他研究臂相比,AD04 2 毫克组显示出一些具有统计学意义的效果。目前还不清楚所观察到的 3.8 分的综合差异是否具有临床意义。TCT 结果显示,在一项为期 18 个月的研究中,AD04 2 毫克组节省了 11 个月的时间。这些结果表明,综合方法和节省时间解释相结合,为检测和解释疾病改变效应提供了一种强有力的方法。
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引用次数: 0
期刊
The Journal of Prevention of Alzheimer's Disease
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