首页 > 最新文献

Alzheimer's Research & Therapy最新文献

英文 中文
Different associations between body mass index and Alzheimer's markers depending on metabolic health. 新陈代谢健康状况不同,体重指数与阿尔茨海默氏症标志物之间的关系也不同。
IF 7.9 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-29 DOI: 10.1186/s13195-024-01563-z
Eun Hye Lee, Heejin Yoo, Young Ju Kim, Bo Kyoung Cheon, Seungho Ryu, Yoosoo Chang, Jihwan Yun, Hyemin Jang, Jun Pyo Kim, Hee Jin Kim, Seong-Beom Koh, Jee Hyang Jeong, Duk L Na, Sang Won Seo, Sung Hoon Kang

Background: Increasing evidence supports the association between body mass index (BMI), Alzheimer's disease, and vascular markers. Recently, metabolically unhealthy conditions have been reported to affect the expression of these markers. We aimed to investigate the effects of BMI status on Alzheimer's and vascular markers in relation to metabolic health status.

Methods: We recruited 1,736 Asians without dementia (71.6 ± 8.0 years). Participants were categorized into underweight, normal weight, or obese groups based on their BMI. Each group was further divided into metabolically healthy (MH) and unhealthy (MU) groups based on the International Diabetes Foundation definition of metabolic syndrome. The main outcome was Aβ positivity, defined as a Centiloid value of 20.0 or above and the presence of vascular markers, defined as severe white matter hyperintensities (WMH). Logistic regression analyses were performed for Aβ positivity and severe WMH with BMI status or interaction terms between BMI and metabolic health status as predictors. Mediation analyses were performed with hippocampal volume (HV) and baseline Mini-Mental State Examination (MMSE) scores as the outcomes, and linear mixed models were performed for longitudinal change in MMSE scores.

Results: Being underweight increased the risk of Aβ positivity (odds ratio [OR] = 2.37, 95% confidence interval [CI] 1.13-4.98), whereas obesity decreased Aβ positivity risk (OR = 0.63, 95% CI 0.50-0.80). Especially, obesity decreased the risk of Aβ positivity (OR = 0.38, 95% CI 0.26-0.56) in the MH group, but not in the MU group. Obesity increased the risk of severe WMH (OR = 1.69, 1.16-2.47). Decreased Aβ positivity mediate the relationship between obesity and higher HV and MMSE scores, particularly in the MH group. Obesity demonstrated a slower decline in MMSE (β = 1.423, p = 0.037) compared to being normal weight, especially in the MH group.

Conclusions: Our findings provide new evidence that metabolic health has a significant effect on the relationship between obesity and Alzheimer's markers, which, in turn, lead to better clinical outcomes.

背景:越来越多的证据表明,体重指数(BMI)、阿尔茨海默病和血管标志物之间存在关联。最近有报道称,新陈代谢不健康会影响这些标志物的表达。我们旨在研究 BMI 状态对阿尔茨海默病和血管标记物的影响与代谢健康状况的关系:我们招募了 1736 名无痴呆症的亚洲人(71.6 ± 8.0 岁)。根据体重指数将参与者分为体重不足组、体重正常组和肥胖组。根据国际糖尿病基金会对代谢综合征的定义,每组又分为代谢健康组(MH)和不健康组(MU)。主要结果是 Aβ 阳性(定义为 Centiloid 值达到或超过 20.0)和血管标记物的存在(定义为严重的白质高密度(WMH))。以 BMI 状态或 BMI 与代谢健康状况之间的交互项为预测因素,对 Aβ 阳性和严重 WMH 进行逻辑回归分析。以海马体积(HV)和基线迷你精神状态检查(MMSE)评分为结果进行了中介分析,并对MMSE评分的纵向变化进行了线性混合模型分析:结果:体重不足会增加 Aβ 阳性的风险(几率比 [OR] = 2.37,95% 置信区间 [CI]:1.13-4.98),而肥胖会降低 Aβ 阳性的风险(OR = 0.63,95% 置信区间 [CI]:0.50-0.80)。特别是,肥胖会降低 MH 组 Aβ 阳性的风险(OR = 0.38,95% CI 0.26-0.56),但不会降低 MU 组 Aβ 阳性的风险。肥胖会增加严重 WMH 的风险(OR = 1.69,1.16-2.47)。Aβ 阳性降低是肥胖与较高 HV 和 MMSE 评分之间关系的中介,尤其是在 MH 组。与体重正常者相比,肥胖者的 MMSE 下降较慢(β = 1.423,p = 0.037),尤其是在 MH 组:我们的研究结果提供了新的证据,证明代谢健康对肥胖与阿尔茨海默氏症标志物之间的关系有显著影响,而肥胖反过来又会带来更好的临床结果。
{"title":"Different associations between body mass index and Alzheimer's markers depending on metabolic health.","authors":"Eun Hye Lee, Heejin Yoo, Young Ju Kim, Bo Kyoung Cheon, Seungho Ryu, Yoosoo Chang, Jihwan Yun, Hyemin Jang, Jun Pyo Kim, Hee Jin Kim, Seong-Beom Koh, Jee Hyang Jeong, Duk L Na, Sang Won Seo, Sung Hoon Kang","doi":"10.1186/s13195-024-01563-z","DOIUrl":"10.1186/s13195-024-01563-z","url":null,"abstract":"<p><strong>Background: </strong>Increasing evidence supports the association between body mass index (BMI), Alzheimer's disease, and vascular markers. Recently, metabolically unhealthy conditions have been reported to affect the expression of these markers. We aimed to investigate the effects of BMI status on Alzheimer's and vascular markers in relation to metabolic health status.</p><p><strong>Methods: </strong>We recruited 1,736 Asians without dementia (71.6 ± 8.0 years). Participants were categorized into underweight, normal weight, or obese groups based on their BMI. Each group was further divided into metabolically healthy (MH) and unhealthy (MU) groups based on the International Diabetes Foundation definition of metabolic syndrome. The main outcome was Aβ positivity, defined as a Centiloid value of 20.0 or above and the presence of vascular markers, defined as severe white matter hyperintensities (WMH). Logistic regression analyses were performed for Aβ positivity and severe WMH with BMI status or interaction terms between BMI and metabolic health status as predictors. Mediation analyses were performed with hippocampal volume (HV) and baseline Mini-Mental State Examination (MMSE) scores as the outcomes, and linear mixed models were performed for longitudinal change in MMSE scores.</p><p><strong>Results: </strong>Being underweight increased the risk of Aβ positivity (odds ratio [OR] = 2.37, 95% confidence interval [CI] 1.13-4.98), whereas obesity decreased Aβ positivity risk (OR = 0.63, 95% CI 0.50-0.80). Especially, obesity decreased the risk of Aβ positivity (OR = 0.38, 95% CI 0.26-0.56) in the MH group, but not in the MU group. Obesity increased the risk of severe WMH (OR = 1.69, 1.16-2.47). Decreased Aβ positivity mediate the relationship between obesity and higher HV and MMSE scores, particularly in the MH group. Obesity demonstrated a slower decline in MMSE (β = 1.423, p = 0.037) compared to being normal weight, especially in the MH group.</p><p><strong>Conclusions: </strong>Our findings provide new evidence that metabolic health has a significant effect on the relationship between obesity and Alzheimer's markers, which, in turn, lead to better clinical outcomes.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"16 1","pages":"194"},"PeriodicalIF":7.9,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction: Impact of cumulative exposure to anticholinergic and sedative drugs on cognition in older adults: a memory clinic cohort study. 更正:抗胆碱能药物和镇静药物的累积接触对老年人认知能力的影响:记忆诊所队列研究。
IF 7.9 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-29 DOI: 10.1186/s13195-024-01560-2
Elsa Reallon, Frédéric Gervais, Claire Moutet, Virginie Dauphinot, Pauline Desnavailles, Teddy Novais, Pierre Krolak-Salmon, Antoine Garnier-Crussard, Christelle Mouchoux
{"title":"Correction: Impact of cumulative exposure to anticholinergic and sedative drugs on cognition in older adults: a memory clinic cohort study.","authors":"Elsa Reallon, Frédéric Gervais, Claire Moutet, Virginie Dauphinot, Pauline Desnavailles, Teddy Novais, Pierre Krolak-Salmon, Antoine Garnier-Crussard, Christelle Mouchoux","doi":"10.1186/s13195-024-01560-2","DOIUrl":"10.1186/s13195-024-01560-2","url":null,"abstract":"","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"16 1","pages":"195"},"PeriodicalIF":7.9,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Clinical implications of head trauma in frontotemporal dementia and primary progressive aphasia. 头部创伤对额颞叶痴呆症和原发性进行性失语症的临床影响。
IF 7.9 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-29 DOI: 10.1186/s13195-024-01553-1
Breton M Asken, Jessica M Bove, Russell M Bauer, Jeremy A Tanner, Kaitlin B Casaletto, Adam M Staffaroni, Lawren VandeVrede, Michael L Alosco, Jesse B Mez, Robert A Stern, Bruce L Miller, Lea T Grinberg, Adam L Boxer, Maria Luisa Gorno-Tempini, Howie J Rosen, Gil D Rabinovici, Joel H Kramer

Background: Traumatic brain injury (TBI) and repetitive head impacts (RHI) have been linked to increased risk for multiple types of neurodegenerative disease, higher dementia risk, and earlier age of dementia symptom onset, suggesting transdiagnostic implications for later-life brain health. Frontotemporal dementia (FTD) and primary progressive aphasia (PPA) represent a spectrum of clinical phenotypes that are neuropathologically diverse. FTD/PPA diagnoses bring unique challenges due to complex cognitive and behavioral symptoms that disproportionately present as an early-onset dementia (before age 65). We performed a detailed characterization of lifetime head trauma exposure in individuals with FTD and PPA compared to healthy controls to examine frequency of lifetime TBI and RHI and associated clinical implications.

Methods: We studied 132 FTD/PPA (age 68.9 ± 8.1, 65% male) and 132 sex-matched healthy controls (HC; age 73.4 ± 7.6). We compared rates of prior TBI and RHI (contact/collision sports) between FTD/PPA and HC (chi-square, logistic regression, analysis of variance). Within FTD/PPA, we evaluated associations with age of symptom onset (analysis of variance). Within behavioral variant FTD, we evaluated associations with cognitive function and neuropsychiatric symptoms (linear regression controlling for age, sex, and years of education).

Results: Years of participation were greater in FTD/PPA than HC for any contact/collision sport (8.5 ± 6.7yrs vs. 5.3 ± 4.5yrs, p = .008) and for American football (6.2yrs ± 4.3yrs vs. 3.1 ± 2.4yrs; p = .003). Within FTD/PPA, there were dose-dependent associations with earlier age of symptom onset for TBI (0 TBI: 62.1 ± 8.1, 1 TBI: 59.9 ± 6.9, 2 + TBI: 57.3 ± 8.4; p = .03) and years of American football (0yrs: 62.2 ± 8.7, 1-4yrs: 59.7 ± 7.0, 5 + yrs: 55.9 ± 6.3; p = .009). Within bvFTD, those who played American football had worse memory (z-score: -2.4 ± 1.2 vs. -1.4 ± 1.6, p = .02, d = 1.1).

Conclusions: Lifetime head trauma may represent a preventable environmental risk factor for FTD/PPA. Dose-dependent exposure to TBI or RHI influences FTD/PPA symptom onset and memory function in bvFTD. Clinico-pathological studies are needed to better understand the neuropathological correlates linking RHI or TBI to FTD/PPA onset and symptoms.

背景:创伤性脑损伤(TBI)和重复性头部撞击(RHI)与多种类型的神经退行性疾病风险增加、痴呆风险升高和痴呆症状发病年龄提前有关,这表明它们对晚年大脑健康具有跨诊断影响。额颞叶痴呆(FTD)和原发性进行性失语(PPA)代表了神经病理学上多种多样的临床表型。FTD/PPA 的诊断带来了独特的挑战,因为它们具有复杂的认知和行为症状,而且过多地表现为早发性痴呆(65 岁以前)。与健康对照组相比,我们对 FTD 和 PPA 患者终生暴露于头部创伤的情况进行了详细描述,以研究终生 TBI 和 RHI 的频率以及相关的临床影响:我们研究了 132 名 FTD/PPA(年龄为 68.9 ± 8.1,65% 为男性)和 132 名性别匹配的健康对照组(HC;年龄为 73.4 ± 7.6)。我们比较了 FTD/PPA 和 HC 之前的 TBI 和 RHI(接触/碰撞运动)比率(卡方、逻辑回归、方差分析)。在 FTD/PPA 中,我们评估了与症状发作年龄的关系(方差分析)。在行为变异型 FTD 中,我们评估了与认知功能和神经精神症状的关联(线性回归,控制年龄、性别和受教育年限):结果:对于任何接触/碰撞运动(8.5 ± 6.7 年 vs. 5.3 ± 4.5 年,p = .008)和美式足球(6.2 ± 4.3 年 vs. 3.1 ± 2.4 年,p = .003),FTD/PPA 的参与年限均高于 HC。在 FTD/PPA 中,TBI(0 TBI:62.1±8.1,1 TBI:59.9±6.9,2 + TBI:57.3±8.4;p = .03)和美式足球年限(0 年:62.2±8.7,1-4 年:59.7±7.0,5 + 年:55.9±6.3;p = .009)与较早出现症状的年龄存在剂量依赖关系。在bvFTD中,踢美式足球的人记忆力较差(z分数:-2.4 ± 1.2 vs. -1.4 ± 1.6,p = .02,d = 1.1):结论:终生头部创伤可能是导致 FTD/PPA 的一个可预防的环境风险因素。TBI或RHI暴露的剂量依赖性会影响FTD/PPA症状的发作和bvFTD的记忆功能。需要进行临床病理学研究,以更好地了解RHI或创伤性脑损伤与FTD/PPA发病和症状之间的神经病理学相关性。
{"title":"Clinical implications of head trauma in frontotemporal dementia and primary progressive aphasia.","authors":"Breton M Asken, Jessica M Bove, Russell M Bauer, Jeremy A Tanner, Kaitlin B Casaletto, Adam M Staffaroni, Lawren VandeVrede, Michael L Alosco, Jesse B Mez, Robert A Stern, Bruce L Miller, Lea T Grinberg, Adam L Boxer, Maria Luisa Gorno-Tempini, Howie J Rosen, Gil D Rabinovici, Joel H Kramer","doi":"10.1186/s13195-024-01553-1","DOIUrl":"10.1186/s13195-024-01553-1","url":null,"abstract":"<p><strong>Background: </strong>Traumatic brain injury (TBI) and repetitive head impacts (RHI) have been linked to increased risk for multiple types of neurodegenerative disease, higher dementia risk, and earlier age of dementia symptom onset, suggesting transdiagnostic implications for later-life brain health. Frontotemporal dementia (FTD) and primary progressive aphasia (PPA) represent a spectrum of clinical phenotypes that are neuropathologically diverse. FTD/PPA diagnoses bring unique challenges due to complex cognitive and behavioral symptoms that disproportionately present as an early-onset dementia (before age 65). We performed a detailed characterization of lifetime head trauma exposure in individuals with FTD and PPA compared to healthy controls to examine frequency of lifetime TBI and RHI and associated clinical implications.</p><p><strong>Methods: </strong>We studied 132 FTD/PPA (age 68.9 ± 8.1, 65% male) and 132 sex-matched healthy controls (HC; age 73.4 ± 7.6). We compared rates of prior TBI and RHI (contact/collision sports) between FTD/PPA and HC (chi-square, logistic regression, analysis of variance). Within FTD/PPA, we evaluated associations with age of symptom onset (analysis of variance). Within behavioral variant FTD, we evaluated associations with cognitive function and neuropsychiatric symptoms (linear regression controlling for age, sex, and years of education).</p><p><strong>Results: </strong>Years of participation were greater in FTD/PPA than HC for any contact/collision sport (8.5 ± 6.7yrs vs. 5.3 ± 4.5yrs, p = .008) and for American football (6.2yrs ± 4.3yrs vs. 3.1 ± 2.4yrs; p = .003). Within FTD/PPA, there were dose-dependent associations with earlier age of symptom onset for TBI (0 TBI: 62.1 ± 8.1, 1 TBI: 59.9 ± 6.9, 2 + TBI: 57.3 ± 8.4; p = .03) and years of American football (0yrs: 62.2 ± 8.7, 1-4yrs: 59.7 ± 7.0, 5 + yrs: 55.9 ± 6.3; p = .009). Within bvFTD, those who played American football had worse memory (z-score: -2.4 ± 1.2 vs. -1.4 ± 1.6, p = .02, d = 1.1).</p><p><strong>Conclusions: </strong>Lifetime head trauma may represent a preventable environmental risk factor for FTD/PPA. Dose-dependent exposure to TBI or RHI influences FTD/PPA symptom onset and memory function in bvFTD. Clinico-pathological studies are needed to better understand the neuropathological correlates linking RHI or TBI to FTD/PPA onset and symptoms.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"16 1","pages":"193"},"PeriodicalIF":7.9,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Neurodegenerative biomarkers in different chambers of the eye relative to plasma: an agreement validation study. 与血浆相比,眼球不同腔室中的神经退行性病变生物标记物:一项协议验证研究。
IF 7.9 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-26 DOI: 10.1186/s13195-024-01556-y
Konstantina Sampani, Steven Ness, Fatima Tuz-Zahra, Nurgul Aytan, Elizabeth E Spurlock, Sreevardhan Alluri, Xuejing Chen, Nicole H Siegel, Michael L Alosco, Weiming Xia, Yorghos Tripodis, Thor D Stein, Manju L Subramanian

Background: Protein biomarkers have been broadly investigated in cerebrospinal fluid and blood for the detection of neurodegenerative diseases, yet a clinically useful diagnostic test to detect early, pre-symptomatic Alzheimer's disease (AD) remains elusive. We conducted this study to quantify Aβ40, Aβ42, total Tau (t-Tau), hyperphosphorylated Tau (ptau181), glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) in eye fluids relative to blood.

Methods: In this cross-sectional study we collected vitreous humor, aqueous humor, tear fluid and plasma in patients undergoing surgery for eye disease. All six biomarkers were quantitatively measured by digital immunoassay. Spearman and Bland-Altman correlation analyses were performed to assess the agreement of levels between ocular fluids and plasma.

Results: Seventy-nine adults underwent pars-plana vitrectomy in at least one eye. Of the 79, there were 77 vitreous, 67 blood, 56 tear fluid, and 51 aqueous samples. All six biomarkers were quantified in each bio-sample, except GFAP and NfL in tear fluid due to low sample volume. All six biomarkers were elevated in vitreous humor compared to plasma samples. T-Tau, ptau181, GFAP and NfL were higher in aqueous than in plasma, and t-Tau and ptau181 concentrations were higher in tear fluid than in plasma. Significant correlations were found between Aβ40 in plasma and tears (r = 0.5; p = 0.019), t-Tau in plasma and vitreous (r = 0.4; p = 0.004), NfL in plasma and vitreous (r = 0.3; p = 0.006) and plasma and aqueous (r = 0.5; p = 0.004). No significant associations were found for Aβ42, ptau181 and GFAP among ocular fluids relative to plasma. Bland-Altman analysis showed aqueous humor had the closest agreement to plasma across all biomarkers. Biomarker levels in ocular fluids revealed statistically significant associations between vitreous and aqueous for t-Tau (r = 0.5; p = 0.001), GFAP (r = 0.6; p < 0.001) and NfL (r = 0.7; p < 0.001).

Conclusion: AD biomarkers are detectable in greater quantities in eye fluids than in plasma and show correlations with levels in plasma. Future studies are needed to assess the utility of ocular fluid biomarkers as diagnostic and prognostic markers for AD, especially in those at risk with eye disease.

背景:人们已经对脑脊液和血液中的蛋白质生物标志物进行了广泛研究,以检测神经退行性疾病,但检测早期、症状前阿尔茨海默病(AD)的临床有用诊断测试仍未出现。我们进行了这项研究,对眼液中的 Aβ40、Aβ42、总 Tau(t-Tau)、高磷酸化 Tau(ptau181)、神经纤维酸性蛋白(GFAP)和神经丝轻链(NfL)进行量化:在这项横断面研究中,我们收集了眼疾手术患者的玻璃体、房水、泪液和血浆。所有六种生物标志物均采用数字免疫测定法进行定量测定。通过斯皮尔曼和布兰德-阿尔特曼相关分析来评估眼液和血浆之间的水平一致性:79名成人至少有一只眼睛接受了眼旁玻璃体切除术。在这 79 例样本中,有 77 例玻璃体样本、67 例血液样本、56 例泪液样本和 51 例水样本。除了泪液样本中的 GFAP 和 NfL 因样本量较少而无法定量外,其他六个生物标记物均在每个生物样本中进行了定量。与血浆样本相比,玻璃体样本中的六种生物标记物均有所升高。水样中T-Tau、ptau181、GFAP和NfL的浓度高于血浆,泪液中t-Tau和ptau181的浓度高于血浆。血浆和泪液中的 Aβ40(r = 0.5;p = 0.019)、血浆和玻璃体中的 t-Tau(r = 0.4;p = 0.004)、血浆和玻璃体中的 NfL(r = 0.3;p = 0.006)以及血浆和水液(r = 0.5;p = 0.004)之间存在显著相关性。与血浆相比,眼液中的 Aβ42、ptau181 和 GFAP 没有发现明显的关联。Bland-Altman分析显示,在所有生物标记物中,眼液与血浆的一致性最接近。眼液中的生物标记物水平显示,玻璃体和水液中的t-Tau(r = 0.5; p = 0.001)、GFAP(r = 0.6; p 结论:玻璃体和水液中的生物标记物水平与血浆中的t-Tau(r = 0.5; p = 0.001)和GFAP(r = 0.6; p = 0.001)有统计学意义:眼液中AD生物标志物的检测量高于血浆,并与血浆中的水平存在相关性。今后还需要进行研究,以评估眼液生物标志物作为 AD 诊断和预后标志物的效用,尤其是对眼疾高危人群的效用。
{"title":"Neurodegenerative biomarkers in different chambers of the eye relative to plasma: an agreement validation study.","authors":"Konstantina Sampani, Steven Ness, Fatima Tuz-Zahra, Nurgul Aytan, Elizabeth E Spurlock, Sreevardhan Alluri, Xuejing Chen, Nicole H Siegel, Michael L Alosco, Weiming Xia, Yorghos Tripodis, Thor D Stein, Manju L Subramanian","doi":"10.1186/s13195-024-01556-y","DOIUrl":"10.1186/s13195-024-01556-y","url":null,"abstract":"<p><strong>Background: </strong>Protein biomarkers have been broadly investigated in cerebrospinal fluid and blood for the detection of neurodegenerative diseases, yet a clinically useful diagnostic test to detect early, pre-symptomatic Alzheimer's disease (AD) remains elusive. We conducted this study to quantify Aβ40, Aβ42, total Tau (t-Tau), hyperphosphorylated Tau (ptau181), glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) in eye fluids relative to blood.</p><p><strong>Methods: </strong>In this cross-sectional study we collected vitreous humor, aqueous humor, tear fluid and plasma in patients undergoing surgery for eye disease. All six biomarkers were quantitatively measured by digital immunoassay. Spearman and Bland-Altman correlation analyses were performed to assess the agreement of levels between ocular fluids and plasma.</p><p><strong>Results: </strong>Seventy-nine adults underwent pars-plana vitrectomy in at least one eye. Of the 79, there were 77 vitreous, 67 blood, 56 tear fluid, and 51 aqueous samples. All six biomarkers were quantified in each bio-sample, except GFAP and NfL in tear fluid due to low sample volume. All six biomarkers were elevated in vitreous humor compared to plasma samples. T-Tau, ptau181, GFAP and NfL were higher in aqueous than in plasma, and t-Tau and ptau181 concentrations were higher in tear fluid than in plasma. Significant correlations were found between Aβ40 in plasma and tears (r = 0.5; p = 0.019), t-Tau in plasma and vitreous (r = 0.4; p = 0.004), NfL in plasma and vitreous (r = 0.3; p = 0.006) and plasma and aqueous (r = 0.5; p = 0.004). No significant associations were found for Aβ42, ptau181 and GFAP among ocular fluids relative to plasma. Bland-Altman analysis showed aqueous humor had the closest agreement to plasma across all biomarkers. Biomarker levels in ocular fluids revealed statistically significant associations between vitreous and aqueous for t-Tau (r = 0.5; p = 0.001), GFAP (r = 0.6; p < 0.001) and NfL (r = 0.7; p < 0.001).</p><p><strong>Conclusion: </strong>AD biomarkers are detectable in greater quantities in eye fluids than in plasma and show correlations with levels in plasma. Future studies are needed to assess the utility of ocular fluid biomarkers as diagnostic and prognostic markers for AD, especially in those at risk with eye disease.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"16 1","pages":"192"},"PeriodicalIF":7.9,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Association between glycemic status and all-cause mortality among individuals with dementia: a nationwide cohort study. 痴呆症患者的血糖状况与全因死亡率之间的关系:一项全国性队列研究。
IF 7.9 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-22 DOI: 10.1186/s13195-024-01557-x
Youn Huh, Kye-Yeung Park, Kyungdo Han, Jin-Hyung Jung, Yoon Jeong Cho, Hye Soon Park, Ga Eun Nam, Soo Lim

Background: To examine the association between glycemic status and all-cause mortality risk among individuals with dementia.

Methods: We enrolled 146,832 individuals aged 40 and older with dementia as identified through the Korean National Health Insurance Service health screening test between 2008 and 2016. Mortality status was evaluated at the end of 2019. Participants were classified into normoglycemia, prediabetes, or diabetes mellitus (DM) categories. The duration of diabetes was noted in those with DM. This study focused on the association between glycemic status and all-cause mortality.

Results: The cohort, which was predominantly elderly (average age 75.1 years; 35.5% male), had a 35.2% mortality rate over an average 3.7-year follow-up. DM was linked with increased all-cause mortality risk (hazard ratio [HR] 1.34; 95% confidence interval [CI]: 1.32-1.37) compared to non-DM counterparts. The highest mortality risk was observed in long-term DM patients (≥ 5 years) (HR 1.43; 95% CI: 1.40-1.47), followed by newly diagnosed DM (HR 1.35; 95% CI: 1.30-1.40), shorter-term DM (< 5 years) (HR 1.17; 95% CI: 1.13-1.21), and prediabetes (HR 1.03; 95% CI: 1.01-1.05). These patterns persisted across Alzheimer's disease and vascular dementia, with more pronounced effects observed in younger patients.

Conclusions: Glucose dysregulation in dementia significantly increased mortality risk, particularly in newly diagnosed or long-standing DM. These findings suggest the potential benefits of maintaining normal glycemic levels in improving the survival of patients with dementia.

背景:研究老年痴呆症患者的血糖状况与全因死亡风险之间的关系:研究痴呆症患者的血糖状况与全因死亡风险之间的关系:方法:我们在 2008 年至 2016 年间招募了 146,832 名 40 岁及以上的痴呆症患者,这些患者是通过韩国国民健康保险服务健康筛查测试确定的。在 2019 年底对死亡率状况进行了评估。参与者被分为正常血糖、糖尿病前期或糖尿病(DM)类别。糖尿病患者的糖尿病持续时间也被记录在案。这项研究的重点是血糖状况与全因死亡率之间的关系:研究对象主要为老年人(平均年龄 75.1 岁;35.5% 为男性),在平均 3.7 年的随访中,死亡率为 35.2%。与非糖尿病患者相比,糖尿病增加了全因死亡风险(危险比 [HR] 1.34;95% 置信区间 [CI]:1.32-1.37)。长期糖尿病患者(≥ 5 年)的死亡风险最高(HR 1.43;95% 置信区间:1.40-1.47),其次是新诊断的糖尿病患者(HR 1.35;95% 置信区间:1.30-1.40)、短期糖尿病患者(结论:新诊断的糖尿病患者死亡风险最高,其次是短期糖尿病患者):痴呆症患者的血糖失调会显著增加死亡风险,尤其是新诊断的或病程较长的糖尿病患者。这些研究结果表明,维持正常的血糖水平对提高痴呆症患者的生存率具有潜在的益处。
{"title":"Association between glycemic status and all-cause mortality among individuals with dementia: a nationwide cohort study.","authors":"Youn Huh, Kye-Yeung Park, Kyungdo Han, Jin-Hyung Jung, Yoon Jeong Cho, Hye Soon Park, Ga Eun Nam, Soo Lim","doi":"10.1186/s13195-024-01557-x","DOIUrl":"10.1186/s13195-024-01557-x","url":null,"abstract":"<p><strong>Background: </strong>To examine the association between glycemic status and all-cause mortality risk among individuals with dementia.</p><p><strong>Methods: </strong>We enrolled 146,832 individuals aged 40 and older with dementia as identified through the Korean National Health Insurance Service health screening test between 2008 and 2016. Mortality status was evaluated at the end of 2019. Participants were classified into normoglycemia, prediabetes, or diabetes mellitus (DM) categories. The duration of diabetes was noted in those with DM. This study focused on the association between glycemic status and all-cause mortality.</p><p><strong>Results: </strong>The cohort, which was predominantly elderly (average age 75.1 years; 35.5% male), had a 35.2% mortality rate over an average 3.7-year follow-up. DM was linked with increased all-cause mortality risk (hazard ratio [HR] 1.34; 95% confidence interval [CI]: 1.32-1.37) compared to non-DM counterparts. The highest mortality risk was observed in long-term DM patients (≥ 5 years) (HR 1.43; 95% CI: 1.40-1.47), followed by newly diagnosed DM (HR 1.35; 95% CI: 1.30-1.40), shorter-term DM (< 5 years) (HR 1.17; 95% CI: 1.13-1.21), and prediabetes (HR 1.03; 95% CI: 1.01-1.05). These patterns persisted across Alzheimer's disease and vascular dementia, with more pronounced effects observed in younger patients.</p><p><strong>Conclusions: </strong>Glucose dysregulation in dementia significantly increased mortality risk, particularly in newly diagnosed or long-standing DM. These findings suggest the potential benefits of maintaining normal glycemic levels in improving the survival of patients with dementia.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"16 1","pages":"191"},"PeriodicalIF":7.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Rationale and design of the BeyeOMARKER study: prospective evaluation of blood- and eye-based biomarkers for early detection of Alzheimer's disease pathology in the eye clinic. BeyeOMARKER 研究的原理和设计:前瞻性评估眼科诊所早期检测阿尔茨海默病病理变化的血液和眼部生物标记物。
IF 7.9 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-21 DOI: 10.1186/s13195-024-01545-1
Ilse Bader, Colin Groot, H Stevie Tan, Jean-Marie A Milongo, Jurre den Haan, Inge M W Verberk, Keir Yong, Julie Orellina, Shannon Campbell, David Wilson, Argonde C van Harten, Pauline H B Kok, Wiesje M van der Flier, Yolande A L Pijnenburg, Frederik Barkhof, Elsmarieke van de Giessen, Charlotte E Teunissen, Femke H Bouwman, Rik Ossenkoppele

Background: Alzheimer's disease (AD) is a common, complex and multifactorial disease that may require screening across multiple routes of referral to enable early detection and subsequent future implementation of tailored interventions. Blood- and eye-based biomarkers show promise as low-cost, scalable and patient-friendly tools for early AD detection given their ability to provide information on AD pathophysiological changes and manifestations in the retina, respectively. Eye clinics provide an intriguing real-world proof-of-concept setting to evaluate the performance of these potential AD screening tools given the intricate connections between the eye and brain, presumed enrichment for AD pathology in the aging population with eye disorders, and the potential for an accelerated diagnostic pathway for under-recognized patient groups.

Methods: The BeyeOMARKER study is a prospective, observational, longitudinal cohort study aiming to include individuals visiting an eye-clinic. Inclusion criteria entail being ≥ 50 years old and having no prior dementia diagnosis. Excluded eye-conditions include traumatic insults, superficial inflammation, and conditions in surrounding structures of the eye that are not engaged in vision. The BeyeOMARKER cohort (n = 700) will undergo blood collection to assess plasma p-tau217 levels and a brief cognitive screening at the eye clinic. All participants will subsequently be invited for annual longitudinal follow-up including remotely administered cognitive screening and questionnaires. The BeyeOMARKER + cohort (n = 150), consisting of 100 plasma p-tau217 positive participants and 50 matched negative controls selected from the BeyeOMARKER cohort, will additionally undergo Aβ-PET and tau-PET, MRI, retinal imaging including hyperspectral imaging (primary), widefield imaging, optical coherence tomography (OCT) and OCT-Angiography (secondary), and cognitive and cortical vision assessments.

Results: We aim to implement the current protocol between April 2024 until March 2027. Primary outcomes include the performance of plasma p-tau217 and hyperspectral retinal imaging to detect AD pathology (using Aβ- and tau-PET visual read as reference standard) and to detect cognitive decline. Initial follow-up is ~ 2 years but may be extended with additional funding.

Conclusions: We envision that the BeyeOMARKER study will demonstrate the feasibility of early AD detection based on blood- and eye-based biomarkers in alternative screening settings, and will improve our understanding of the eye-brain connection.

Trial registration: The BeyeOMARKER study (Eudamed CIV ID: CIV-NL-23-09-044086; registration date: 19th of March 2024) is approved by the ethical review board of the Amsterdam UMC.

背景:阿尔茨海默病(AD)是一种常见、复杂和多因素的疾病,可能需要通过多种转诊途径进行筛查,以便及早发现并在未来实施有针对性的干预措施。血液和眼部生物标志物分别能提供有关注意力缺失症病理生理变化和视网膜表现的信息,因此有望成为低成本、可扩展且方便患者的注意力缺失症早期检测工具。眼科诊所为评估这些潜在的注意力缺失症筛查工具的性能提供了一个令人感兴趣的真实世界概念验证环境,因为眼睛和大脑之间存在着错综复杂的联系,患有眼部疾病的老龄人口中可能富含注意力缺失症病理,而且有可能为认识不足的患者群体提供加速诊断途径:BeyeOMARKER研究是一项前瞻性、观察性、纵向队列研究,旨在纳入到眼科门诊就诊的患者。纳入标准为年龄≥ 50 岁且之前未确诊过痴呆症。排除的眼部疾病包括外伤性损伤、表皮炎症以及眼睛周围结构中与视觉无关的疾病。BeyeOMARKER 队列(n = 700)将在眼科诊所进行采血,以评估血浆 p-tau217 水平和简短的认知筛查。随后将邀请所有参与者进行年度纵向随访,包括远程认知筛查和问卷调查。BeyeOMARKER + 队列(n = 150)由 100 名血浆 p-tau217 阳性参与者和 50 名从 BeyeOMARKER 队列中选出的匹配阴性对照组成,他们还将接受 Aβ-PET 和 tau-PET、核磁共振成像、视网膜成像(包括高光谱成像(主要)、宽视场成像、光学相干断层扫描(OCT)和 OCT-血管成像(次要)))以及认知和皮层视力评估:我们的目标是在 2024 年 4 月至 2027 年 3 月期间实施目前的方案。主要结果包括血浆p-tau217和高光谱视网膜成像检测AD病理的性能(以Aβ和tau-PET视觉读数为参考标准)以及检测认知功能下降的性能。最初的随访期约为 2 年,但如果获得额外资助,随访期可能会延长:我们预计,BeyeOMARKER 研究将证明在其他筛查环境中基于血液和眼部生物标志物进行早期注意力缺失症检测的可行性,并将提高我们对眼脑联系的认识:BeyeOMARKER研究(Eudamed CIV ID:CIV-NL-23-09-044086;注册日期:2024年3月19日)已获得阿姆斯特丹UMC伦理审查委员会的批准。
{"title":"Rationale and design of the BeyeOMARKER study: prospective evaluation of blood- and eye-based biomarkers for early detection of Alzheimer's disease pathology in the eye clinic.","authors":"Ilse Bader, Colin Groot, H Stevie Tan, Jean-Marie A Milongo, Jurre den Haan, Inge M W Verberk, Keir Yong, Julie Orellina, Shannon Campbell, David Wilson, Argonde C van Harten, Pauline H B Kok, Wiesje M van der Flier, Yolande A L Pijnenburg, Frederik Barkhof, Elsmarieke van de Giessen, Charlotte E Teunissen, Femke H Bouwman, Rik Ossenkoppele","doi":"10.1186/s13195-024-01545-1","DOIUrl":"10.1186/s13195-024-01545-1","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a common, complex and multifactorial disease that may require screening across multiple routes of referral to enable early detection and subsequent future implementation of tailored interventions. Blood- and eye-based biomarkers show promise as low-cost, scalable and patient-friendly tools for early AD detection given their ability to provide information on AD pathophysiological changes and manifestations in the retina, respectively. Eye clinics provide an intriguing real-world proof-of-concept setting to evaluate the performance of these potential AD screening tools given the intricate connections between the eye and brain, presumed enrichment for AD pathology in the aging population with eye disorders, and the potential for an accelerated diagnostic pathway for under-recognized patient groups.</p><p><strong>Methods: </strong>The BeyeOMARKER study is a prospective, observational, longitudinal cohort study aiming to include individuals visiting an eye-clinic. Inclusion criteria entail being ≥ 50 years old and having no prior dementia diagnosis. Excluded eye-conditions include traumatic insults, superficial inflammation, and conditions in surrounding structures of the eye that are not engaged in vision. The BeyeOMARKER cohort (n = 700) will undergo blood collection to assess plasma p-tau217 levels and a brief cognitive screening at the eye clinic. All participants will subsequently be invited for annual longitudinal follow-up including remotely administered cognitive screening and questionnaires. The BeyeOMARKER + cohort (n = 150), consisting of 100 plasma p-tau217 positive participants and 50 matched negative controls selected from the BeyeOMARKER cohort, will additionally undergo Aβ-PET and tau-PET, MRI, retinal imaging including hyperspectral imaging (primary), widefield imaging, optical coherence tomography (OCT) and OCT-Angiography (secondary), and cognitive and cortical vision assessments.</p><p><strong>Results: </strong>We aim to implement the current protocol between April 2024 until March 2027. Primary outcomes include the performance of plasma p-tau217 and hyperspectral retinal imaging to detect AD pathology (using Aβ- and tau-PET visual read as reference standard) and to detect cognitive decline. Initial follow-up is ~ 2 years but may be extended with additional funding.</p><p><strong>Conclusions: </strong>We envision that the BeyeOMARKER study will demonstrate the feasibility of early AD detection based on blood- and eye-based biomarkers in alternative screening settings, and will improve our understanding of the eye-brain connection.</p><p><strong>Trial registration: </strong>The BeyeOMARKER study (Eudamed CIV ID: CIV-NL-23-09-044086; registration date: 19th of March 2024) is approved by the ethical review board of the Amsterdam UMC.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"16 1","pages":"190"},"PeriodicalIF":7.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cancer research provides a model for advancing clinical trials in dementia in the era of disease-modifying Alzheimer's-type dementia therapies. 在改变阿尔茨海默氏症类型的痴呆症疗法时代,癌症研究为推进痴呆症临床试验提供了一种模式。
IF 7.9 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-21 DOI: 10.1186/s13195-024-01532-6
Gregory A Jicha, Thomas C Tucker, Susanne M Arnold, Peter T Nelson

Dementia and cancer are multifactorial, widely-feared, age-associated clinical syndromes that are increasing in prevalence. There have been major breakthroughs in clinical cancer research leading to some effective treatments, whereas the field of dementia has achieved comparatively limited success in clinical research. The lessons of cancer research may help those in the dementia research field in confronting some of the dilemmas faced when the clinical care regimen is not entirely safe or efficacious. Cancer clinical trials have assumed that untreated individuals with cancer are at high risk for morbidity and mortality after primary diagnoses. Thus, patients deserve a choice of clinical interventions, either standard of care or experimental, even if the benefits are not certain and the therapy's side effects are potentially severe. The prognosis for many individuals at risk for dementia carries a correspondingly high level of risk for both mortality and severe morbidity, particularly if one focuses on "health-span" rather than lifespan. Caregivers and patients can be strongly impacted by dementia and the many troubling associated symptoms that often go well beyond amnesia. Polls, surveys, and a literature on "dementia worry" strongly underscore that the public fears dementia. While there are institutional and industry hurdles that complicate enrollment in randomized trials, the gravity of the future morbidity and mortality inherent in a dementia diagnosis may require reconsideration of the current protective stance that limits the freedom of at-risk individuals (either symptomatic or asymptomatic) to participate and potentially benefit from ongoing clinical research. There is also evidence from both cancer and dementia research that individuals enrolled in the placebo arms of clinical trials have unexpectedly good outcomes, indicating that participation in clinical trial can have medical benefits to enrollees. To highlight aspects of cancer clinical research that may inform present and future dementia clinical research, this review highlights three main themes: the risk of side effects should be weighed against the often dire consequences of non-treatment; the desirability of long-term incremental (rather than "magic bullet") clinical advances; and, the eventual importance of combination therapies, reflecting that the dementia clinical syndrome has many underlying biological pathways.

痴呆症和癌症都是多因素、广受关注、与年龄相关的临床综合征,而且发病率越来越高。癌症的临床研究已经取得了重大突破,并产生了一些有效的治疗方法,而痴呆症领域的临床研究成果却相对有限。癌症研究的经验教训可能有助于痴呆症研究领域的人员应对临床治疗方案不完全安全或有效时所面临的一些困境。癌症临床试验假定,未经治疗的癌症患者在初诊后发病和死亡的风险很高。因此,即使疗效不确定,治疗的副作用可能很严重,患者也应该选择标准治疗或试验性临床干预措施。许多有痴呆风险的人的预后都具有相应的高死亡率和严重发病率风险,特别是如果我们关注的是 "健康寿命 "而不是寿命的话。痴呆症和许多令人不安的相关症状会对照顾者和患者造成严重影响,而这些症状往往远不止失忆这么简单。民调、调查和有关 "痴呆症担忧 "的文献都强烈强调了公众对痴呆症的恐惧。虽然机构和行业方面的障碍会使随机试验的入组复杂化,但痴呆症诊断所固有的未来发病率和死亡率的严重性可能需要重新考虑当前的保护立场,这种立场限制了高危人群(无论是有症状还是无症状)参与正在进行的临床研究并从中获益的自由。癌症和痴呆症研究中也有证据表明,参加临床试验安慰剂组的患者会获得意想不到的良好结果,这表明参加临床试验会给参加者带来医疗益处。为了突出癌症临床研究中可以为现在和未来的痴呆症临床研究提供借鉴的方面,本综述强调了三大主题:应权衡副作用的风险和不治疗的可怕后果;长期渐进(而非 "灵丹妙药")临床进展的可取性;以及综合疗法的最终重要性,这反映出痴呆症临床综合征有许多潜在的生物学途径。
{"title":"Cancer research provides a model for advancing clinical trials in dementia in the era of disease-modifying Alzheimer's-type dementia therapies.","authors":"Gregory A Jicha, Thomas C Tucker, Susanne M Arnold, Peter T Nelson","doi":"10.1186/s13195-024-01532-6","DOIUrl":"10.1186/s13195-024-01532-6","url":null,"abstract":"<p><p>Dementia and cancer are multifactorial, widely-feared, age-associated clinical syndromes that are increasing in prevalence. There have been major breakthroughs in clinical cancer research leading to some effective treatments, whereas the field of dementia has achieved comparatively limited success in clinical research. The lessons of cancer research may help those in the dementia research field in confronting some of the dilemmas faced when the clinical care regimen is not entirely safe or efficacious. Cancer clinical trials have assumed that untreated individuals with cancer are at high risk for morbidity and mortality after primary diagnoses. Thus, patients deserve a choice of clinical interventions, either standard of care or experimental, even if the benefits are not certain and the therapy's side effects are potentially severe. The prognosis for many individuals at risk for dementia carries a correspondingly high level of risk for both mortality and severe morbidity, particularly if one focuses on \"health-span\" rather than lifespan. Caregivers and patients can be strongly impacted by dementia and the many troubling associated symptoms that often go well beyond amnesia. Polls, surveys, and a literature on \"dementia worry\" strongly underscore that the public fears dementia. While there are institutional and industry hurdles that complicate enrollment in randomized trials, the gravity of the future morbidity and mortality inherent in a dementia diagnosis may require reconsideration of the current protective stance that limits the freedom of at-risk individuals (either symptomatic or asymptomatic) to participate and potentially benefit from ongoing clinical research. There is also evidence from both cancer and dementia research that individuals enrolled in the placebo arms of clinical trials have unexpectedly good outcomes, indicating that participation in clinical trial can have medical benefits to enrollees. To highlight aspects of cancer clinical research that may inform present and future dementia clinical research, this review highlights three main themes: the risk of side effects should be weighed against the often dire consequences of non-treatment; the desirability of long-term incremental (rather than \"magic bullet\") clinical advances; and, the eventual importance of combination therapies, reflecting that the dementia clinical syndrome has many underlying biological pathways.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"16 1","pages":"184"},"PeriodicalIF":7.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11337902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Association of outer retinal and choroidal alterations with neuroimaging and clinical features in posterior cortical atrophy. 后皮质萎缩患者的视网膜外层和脉络膜改变与神经影像学和临床特征的关联。
IF 7.9 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-19 DOI: 10.1186/s13195-024-01551-3
Yuzhu Gao, Ruihan Wang, Kefan Mou, Yifan Zhang, Hanyue Xu, Yilin Liu, Feng Yang, Yunxia Gao, Xiaoyue Wang, Li Bao, Jie Zhang, Qin Chen, Hongbo Yin, Ming Zhang

Background: Posterior cortical atrophy (PCA) is a rare condition characterized by early-onset and progressive visual impairment. Individuals with PCA have relatively early-onset and progressive dementia, posing certain needs for early detection. Hence, this study aimed to investigate the association of alterations in outer retinal and choroidal structure and microvasculature with PCA neuroimaging and clinical features and the possible effects of apolipoprotein E(APOE) ε4 allele on outer retinal and choroidal alterations in participants with PCA, to detect potential ocular biomarkers for PCA screening.

Methods: This cross-sectional study included PCA and age- and sex-matched healthy control participants from June 2022 to December 2023. All participants with PCA completed a comprehensive neurological evaluation. All participants were recorded baseline information and underwent an ophthalmic evaluation. Quantitative analyses were performed using swept-source optical coherence tomography (SS-OCT) and angiography (SS-OCTA). Adaptive optics scanning laser ophthalmoscopy (AO-SLO) was performed in some patients. In participants with PCA, the influence of APOE ε4 on outer retinal and choroidal alterations and the correlation of outer retinal and choroidal alterations with PCA neuroimaging and clinical features in participants with PCA were investigated.

Results: A total of 28 participants (53 eyes) with PCA and 56 healthy control participants (112 eyes) were included in the current study. Compared with healthy control participants, participants with PCA had significantly reduced outer retinal thickness (ORT) (p < 0.001), choriocapillaris vessel density (VD) (p = 0.007), choroidal vascular index (CVI) (p = 0.005) and choroidal vascular volume (CVV) (p = 0.003). In participants with PCA, APOE ε4 carriers showed thinner ORT (p = 0.009), and increased choriocapillaris VD (p = 0.004) and CVI (p = 0.004). The PCA neuroimaging features were positively associated with the ORT, CVI and CVV. Furthermore, differential correlations were observed of PCA clinical features with the CRT, CVV and CVI.

Conclusions: Our findings highlighted the association of outer retinal and choroidal alterations with PCA neuroimaging and clinical features in participants with PCA. Noninvasive SS-OCT and SS-OCTA can provide potential biomarkers for the diagnosis and management of PCA, improving awareness of PCA syndrome among ophthalmologists, neurologists, and primary care providers.

背景:后皮质萎缩(PCA)是一种罕见的疾病,其特征是早发性和进行性视力损伤。PCA 患者的痴呆症发病相对较早且呈进行性发展,因此需要及早发现。因此,本研究旨在探讨PCA患者视网膜外层和脉络膜结构及微血管的改变与PCA神经影像学和临床特征的相关性,以及载脂蛋白E(APOE)ε4等位基因对视网膜外层和脉络膜改变的可能影响,从而为PCA筛查检测潜在的眼部生物标志物:这项横断面研究纳入了2022年6月至2023年12月期间的PCA患者以及年龄和性别匹配的健康对照者。所有患有 PCA 的参与者都完成了全面的神经学评估。所有参与者都记录了基线信息并接受了眼科评估。采用扫源光学相干断层扫描(SS-OCT)和血管造影术(SS-OCTA)进行定量分析。部分患者还进行了自适应光学扫描激光眼底镜检查(AO-SLO)。在 PCA 患者中,研究了 APOE ε4 对视网膜外层和脉络膜改变的影响,以及视网膜外层和脉络膜改变与 PCA 神经影像学和临床特征的相关性:本研究共纳入 28 名 PCA 患者(53 只眼)和 56 名健康对照组患者(112 只眼)。与健康对照组相比,PCA 患者的视网膜外层厚度(ORT)明显降低(p 结论:我们的研究结果表明,PCA 与视网膜外层厚度有关:我们的研究结果表明,外层视网膜和脉络膜的改变与 PCA 患者的神经影像学和临床特征有关。无创 SS-OCT 和 SS-OCTA 可为 PCA 的诊断和管理提供潜在的生物标志物,提高眼科医生、神经科医生和初级保健提供者对 PCA 综合征的认识。
{"title":"Association of outer retinal and choroidal alterations with neuroimaging and clinical features in posterior cortical atrophy.","authors":"Yuzhu Gao, Ruihan Wang, Kefan Mou, Yifan Zhang, Hanyue Xu, Yilin Liu, Feng Yang, Yunxia Gao, Xiaoyue Wang, Li Bao, Jie Zhang, Qin Chen, Hongbo Yin, Ming Zhang","doi":"10.1186/s13195-024-01551-3","DOIUrl":"10.1186/s13195-024-01551-3","url":null,"abstract":"<p><strong>Background: </strong>Posterior cortical atrophy (PCA) is a rare condition characterized by early-onset and progressive visual impairment. Individuals with PCA have relatively early-onset and progressive dementia, posing certain needs for early detection. Hence, this study aimed to investigate the association of alterations in outer retinal and choroidal structure and microvasculature with PCA neuroimaging and clinical features and the possible effects of apolipoprotein E(APOE) ε4 allele on outer retinal and choroidal alterations in participants with PCA, to detect potential ocular biomarkers for PCA screening.</p><p><strong>Methods: </strong>This cross-sectional study included PCA and age- and sex-matched healthy control participants from June 2022 to December 2023. All participants with PCA completed a comprehensive neurological evaluation. All participants were recorded baseline information and underwent an ophthalmic evaluation. Quantitative analyses were performed using swept-source optical coherence tomography (SS-OCT) and angiography (SS-OCTA). Adaptive optics scanning laser ophthalmoscopy (AO-SLO) was performed in some patients. In participants with PCA, the influence of APOE ε4 on outer retinal and choroidal alterations and the correlation of outer retinal and choroidal alterations with PCA neuroimaging and clinical features in participants with PCA were investigated.</p><p><strong>Results: </strong>A total of 28 participants (53 eyes) with PCA and 56 healthy control participants (112 eyes) were included in the current study. Compared with healthy control participants, participants with PCA had significantly reduced outer retinal thickness (ORT) (p < 0.001), choriocapillaris vessel density (VD) (p = 0.007), choroidal vascular index (CVI) (p = 0.005) and choroidal vascular volume (CVV) (p = 0.003). In participants with PCA, APOE ε4 carriers showed thinner ORT (p = 0.009), and increased choriocapillaris VD (p = 0.004) and CVI (p = 0.004). The PCA neuroimaging features were positively associated with the ORT, CVI and CVV. Furthermore, differential correlations were observed of PCA clinical features with the CRT, CVV and CVI.</p><p><strong>Conclusions: </strong>Our findings highlighted the association of outer retinal and choroidal alterations with PCA neuroimaging and clinical features in participants with PCA. Noninvasive SS-OCT and SS-OCTA can provide potential biomarkers for the diagnosis and management of PCA, improving awareness of PCA syndrome among ophthalmologists, neurologists, and primary care providers.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"16 1","pages":"187"},"PeriodicalIF":7.9,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11331764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Performance of plasma p-tau217 for the detection of amyloid-β positivity in a memory clinic cohort using an electrochemiluminescence immunoassay. 用电化学发光免疫测定法检测记忆门诊队列中血浆 p-tau217 的淀粉样蛋白-β阳性率。
IF 7.9 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-19 DOI: 10.1186/s13195-024-01555-z
Adam H Dyer, Helena Dolphin, Antoinette O'Connor, Laura Morrison, Gavin Sedgwick, Conor Young, Emily Killeen, Conal Gallagher, Aoife McFeely, Eimear Connolly, Naomi Davey, Paul Claffey, Paddy Doyle, Shane Lyons, Christine Gaffney, Ruth Ennis, Cathy McHale, Jasmine Joseph, Graham Knight, Emmet Kelly, Cliona O'Farrelly, Aoife Fallon, Sean O'Dowd, Nollaig M Bourke, Sean P Kennelly

Background: Plasma p-tau217 has emerged as the most promising blood-based marker (BBM) for the detection of Alzheimer Disease (AD) pathology, yet few studies have evaluated plasma p-tau217 performance in memory clinic settings. We examined the performance of plasma p-tau217 for the detection of AD using a high-sensitivity immunoassay in individuals undergoing diagnostic lumbar puncture (LP).

Methods: Paired plasma and cerebrospinal fluid (CSF) samples were analysed from the TIMC-BRAiN cohort. Amyloid (Aβ) and Tau (T) pathology were classified based on established cut-offs for CSF Aβ42 and CSF p-tau181 respectively. High-sensitivity electrochemiluminescence (ECL) immunoassays were performed on paired plasma/CSF samples for p-tau217, p-tau181, Glial Fibrillary Acidic Protein (GFAP), Neurofilament Light (NfL) and total tau (t-tau). Biomarker performance was evaluated using Receiver-Operating Curve (ROC) and Area-Under-the-Curve (AUC) analysis.

Results: Of 108 participants (age: 69 ± 6.5 years; 54.6% female) with paired samples obtained at time of LP, 64.8% (n = 70/108) had Aβ pathology detected (35 with Mild Cognitive Impairment and 35 with mild dementia). Plasma p-tau217 was over three-fold higher in Aβ + (12.4 pg/mL; 7.3-19.2 pg/mL) vs. Aβ- participants (3.7 pg/mL; 2.8-4.1 pg/mL; Mann-Whitney U = 230, p < 0.001). Plasma p-tau217 exhibited excellent performance for the detection of Aβ pathology (AUC: 0.91; 95% Confidence Interval [95% CI]: 0.86-0.97)-greater than for T pathology (AUC: 0.83; 95% CI: 0.75-0.90; z = 1.75, p = 0.04). Plasma p-tau217 outperformed plasma p-tau181 for the detection of Aβ pathology (z = 3.24, p < 0.001). Of the other BBMs, only plasma GFAP significantly differed by Aβ status which significantly correlated with plasma p-tau217 in Aβ + (but not in Aβ-) individuals. Application of a two-point threshold at 95% and 97.5% sensitivities & specificities may have enabled avoidance of LP in 58-68% of cases.

Conclusions: Plasma p-tau217 measured using a high-sensitivity ECL immunoassay demonstrated excellent performance for detection of Aβ pathology in a real-world memory clinic cohort. Moving forward, clinical use of plasma p-tau217 to detect AD pathology may substantially reduce need for confirmatory diagnostic testing for AD pathology with diagnostic LP in specialist memory services.

背景:血浆p-tau217已成为检测阿尔茨海默病(AD)病理的最有前途的血液标记物(BBM),但很少有研究评估血浆p-tau217在记忆门诊中的表现。我们使用一种高灵敏度免疫测定方法检测了接受诊断性腰椎穿刺(LP)者血浆 p-tau217 在检测 AD 方面的性能:方法:对TIMC-BRAiN队列中的配对血浆和脑脊液(CSF)样本进行分析。淀粉样蛋白(Aβ)和Tau(T)病理学分别根据CSF Aβ42和CSF p-tau181的既定临界值进行分类。对配对血浆/脑脊液样本进行高灵敏度电化学发光(ECL)免疫测定,检测p-tau217、p-tau181、胶质纤维酸性蛋白(GFAP)、神经丝光(NfL)和总tau(t-tau)。生物标记物的性能采用接收者操作曲线(ROC)和曲线下面积(AUC)分析法进行评估:108名参与者(年龄:69 ± 6.5岁;54.6%为女性)在LP时获得了配对样本,其中64.8%(n = 70/108)的参与者检测到了Aβ病变(35人患有轻度认知障碍,35人患有轻度痴呆)。Aβ +参与者(12.4 pg/mL;7.3-19.2 pg/mL)与Aβ-参与者(3.7 pg/mL;2.8-4.1 pg/mL;Mann-Whitney U = 230,p 结论)相比,血浆p-tau217高出三倍多:使用高灵敏度 ECL 免疫测定法测量的血浆 p-tau217 在检测真实世界记忆诊所队列中的 Aβ 病理学方面表现出色。展望未来,临床使用血浆p-tau217检测AD病理变化可能会大大减少专科记忆服务机构对诊断LP的AD病理变化确诊测试的需求。
{"title":"Performance of plasma p-tau217 for the detection of amyloid-β positivity in a memory clinic cohort using an electrochemiluminescence immunoassay.","authors":"Adam H Dyer, Helena Dolphin, Antoinette O'Connor, Laura Morrison, Gavin Sedgwick, Conor Young, Emily Killeen, Conal Gallagher, Aoife McFeely, Eimear Connolly, Naomi Davey, Paul Claffey, Paddy Doyle, Shane Lyons, Christine Gaffney, Ruth Ennis, Cathy McHale, Jasmine Joseph, Graham Knight, Emmet Kelly, Cliona O'Farrelly, Aoife Fallon, Sean O'Dowd, Nollaig M Bourke, Sean P Kennelly","doi":"10.1186/s13195-024-01555-z","DOIUrl":"10.1186/s13195-024-01555-z","url":null,"abstract":"<p><strong>Background: </strong>Plasma p-tau217 has emerged as the most promising blood-based marker (BBM) for the detection of Alzheimer Disease (AD) pathology, yet few studies have evaluated plasma p-tau217 performance in memory clinic settings. We examined the performance of plasma p-tau217 for the detection of AD using a high-sensitivity immunoassay in individuals undergoing diagnostic lumbar puncture (LP).</p><p><strong>Methods: </strong>Paired plasma and cerebrospinal fluid (CSF) samples were analysed from the TIMC-BRAiN cohort. Amyloid (Aβ) and Tau (T) pathology were classified based on established cut-offs for CSF Aβ<sub>42</sub> and CSF p-tau181 respectively. High-sensitivity electrochemiluminescence (ECL) immunoassays were performed on paired plasma/CSF samples for p-tau217, p-tau181, Glial Fibrillary Acidic Protein (GFAP), Neurofilament Light (NfL) and total tau (t-tau). Biomarker performance was evaluated using Receiver-Operating Curve (ROC) and Area-Under-the-Curve (AUC) analysis.</p><p><strong>Results: </strong>Of 108 participants (age: 69 ± 6.5 years; 54.6% female) with paired samples obtained at time of LP, 64.8% (n = 70/108) had Aβ pathology detected (35 with Mild Cognitive Impairment and 35 with mild dementia). Plasma p-tau217 was over three-fold higher in Aβ + (12.4 pg/mL; 7.3-19.2 pg/mL) vs. Aβ- participants (3.7 pg/mL; 2.8-4.1 pg/mL; Mann-Whitney U = 230, p < 0.001). Plasma p-tau217 exhibited excellent performance for the detection of Aβ pathology (AUC: 0.91; 95% Confidence Interval [95% CI]: 0.86-0.97)-greater than for T pathology (AUC: 0.83; 95% CI: 0.75-0.90; z = 1.75, p = 0.04). Plasma p-tau217 outperformed plasma p-tau181 for the detection of Aβ pathology (z = 3.24, p < 0.001). Of the other BBMs, only plasma GFAP significantly differed by Aβ status which significantly correlated with plasma p-tau217 in Aβ + (but not in Aβ-) individuals. Application of a two-point threshold at 95% and 97.5% sensitivities & specificities may have enabled avoidance of LP in 58-68% of cases.</p><p><strong>Conclusions: </strong>Plasma p-tau217 measured using a high-sensitivity ECL immunoassay demonstrated excellent performance for detection of Aβ pathology in a real-world memory clinic cohort. Moving forward, clinical use of plasma p-tau217 to detect AD pathology may substantially reduce need for confirmatory diagnostic testing for AD pathology with diagnostic LP in specialist memory services.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"16 1","pages":"186"},"PeriodicalIF":7.9,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11331802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Risk factors for cognitive decline in non-demented elders with amyloid-beta positivity. 淀粉样蛋白-β阳性非痴呆老人认知能力下降的风险因素。
IF 7.9 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-19 DOI: 10.1186/s13195-024-01554-0
An-Yi Wang, He-Ying Hu, Liang-Yu Huang, Chu-Yun Xiao, Qiong-Yao Li, Lan Tan, Hao Hu

Background: As a currently incurable but preventable disease, the prevention and early diagnosis of Alzheimer's disease (AD) has long been a research hotspot. Amyloid deposition has been shown to be a major pathological feature of AD. Notably, not all the people with amyloid-beta (Aβ) pathology will have significant cognitive declines and eventually develop AD. Therefore, the aim of this study was to explore the risk factors for cognitive decline in Aβ-positive participants.

Methods: We included 650 non-demented participants who were Aβ-positive at baseline from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Mixed effects and COX regression models were applied to assess 37 potential risk factors. Mixed effects models were employed to assess the temporal associations between potential risk factors and four cognitive assessment scales. COX regression models were used to assess the impact of potential risk factors on cognitive diagnosis conversion. Univariate and multivariate analyses were applied to the above models. Additionally, we used the Cochran-Armitage trend test to examine whether the incidence of cognitive decline increased with the number concurrent of risk factors.

Results: Six factors (low diastolic pressure, low body mass index, retired status, a history of drug abuse, Parkinsonism, and depression) were the identified risk factors and four factors (a history of urinary disease, musculoskeletal diseases, no major surgical history, and no prior dermatologic-connective tissue diseases) were found to be suggestive risk factors. The incidence of cognitive decline in the Aβ-positive participants gradually increased as the number of concurrent risk factors increased (p for trend = 0.0005).

Conclusions: Our study may facilitate the understanding of the potential pathological processes in AD and provide novel targets for the prevention of cognitive decline among participants with Aβ positivity.

背景:阿尔茨海默病(AD)是一种目前无法治愈但可以预防的疾病,其预防和早期诊断一直是研究热点。淀粉样蛋白沉积已被证明是阿尔茨海默病的主要病理特征。值得注意的是,并非所有出现淀粉样蛋白-β(Aβ)病理变化的人都会出现明显的认知能力下降,并最终发展为阿兹海默症。因此,本研究旨在探讨Aβ阳性参与者认知能力下降的风险因素:我们从阿尔茨海默病神经影像学倡议(ADNI)数据库中纳入了 650 名基线时 Aβ 阳性的非痴呆参与者。采用混合效应和 COX 回归模型评估了 37 个潜在风险因素。混合效应模型用于评估潜在风险因素与四个认知评估量表之间的时间关联。COX 回归模型用于评估潜在风险因素对认知诊断转换的影响。对上述模型进行了单变量和多变量分析。此外,我们还使用 Cochran-Armitage 趋势检验法来检测认知能力下降的发生率是否会随着风险因素并发数量的增加而增加:结果:六个因素(低舒张压、低体重指数、退休状态、药物滥用史、帕金森病和抑郁症)是已确定的危险因素,四个因素(泌尿系统疾病史、肌肉骨骼疾病史、无重大手术史和无皮肤-结缔组织疾病史)是提示性危险因素。随着并发风险因素数量的增加,Aβ阳性参与者认知能力下降的发生率逐渐增加(趋势 p = 0.0005):我们的研究可能有助于了解注意力缺失症的潜在病理过程,并为预防Aβ阳性参与者的认知能力下降提供新的靶点。
{"title":"Risk factors for cognitive decline in non-demented elders with amyloid-beta positivity.","authors":"An-Yi Wang, He-Ying Hu, Liang-Yu Huang, Chu-Yun Xiao, Qiong-Yao Li, Lan Tan, Hao Hu","doi":"10.1186/s13195-024-01554-0","DOIUrl":"10.1186/s13195-024-01554-0","url":null,"abstract":"<p><strong>Background: </strong>As a currently incurable but preventable disease, the prevention and early diagnosis of Alzheimer's disease (AD) has long been a research hotspot. Amyloid deposition has been shown to be a major pathological feature of AD. Notably, not all the people with amyloid-beta (Aβ) pathology will have significant cognitive declines and eventually develop AD. Therefore, the aim of this study was to explore the risk factors for cognitive decline in Aβ-positive participants.</p><p><strong>Methods: </strong>We included 650 non-demented participants who were Aβ-positive at baseline from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Mixed effects and COX regression models were applied to assess 37 potential risk factors. Mixed effects models were employed to assess the temporal associations between potential risk factors and four cognitive assessment scales. COX regression models were used to assess the impact of potential risk factors on cognitive diagnosis conversion. Univariate and multivariate analyses were applied to the above models. Additionally, we used the Cochran-Armitage trend test to examine whether the incidence of cognitive decline increased with the number concurrent of risk factors.</p><p><strong>Results: </strong>Six factors (low diastolic pressure, low body mass index, retired status, a history of drug abuse, Parkinsonism, and depression) were the identified risk factors and four factors (a history of urinary disease, musculoskeletal diseases, no major surgical history, and no prior dermatologic-connective tissue diseases) were found to be suggestive risk factors. The incidence of cognitive decline in the Aβ-positive participants gradually increased as the number of concurrent risk factors increased (p for trend = 0.0005).</p><p><strong>Conclusions: </strong>Our study may facilitate the understanding of the potential pathological processes in AD and provide novel targets for the prevention of cognitive decline among participants with Aβ positivity.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"16 1","pages":"189"},"PeriodicalIF":7.9,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11331665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Alzheimer's Research & Therapy
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1