Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring最新文献

筛选
英文 中文
Changes in Alzheimer's disease blood biomarkers in kidney failure before and after kidney transplant. 肾移植前后肾衰竭患者阿尔茨海默病血液生物标志物的变化。
IF 4
Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Pub Date : 2024-07-03 eCollection Date: 2024-07-01 DOI: 10.1002/dad2.12614
Anneka E Blankenship, Lauren Yoksh, Paul J Kueck, Jonathan D Mahnken, Jill K Morris, Aditi Gupta
{"title":"Changes in Alzheimer's disease blood biomarkers in kidney failure before and after kidney transplant.","authors":"Anneka E Blankenship, Lauren Yoksh, Paul J Kueck, Jonathan D Mahnken, Jill K Morris, Aditi Gupta","doi":"10.1002/dad2.12614","DOIUrl":"10.1002/dad2.12614","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease (AD) blood biomarkers show promise for clinical diagnosis but their reliability in chronic kidney disease (CKD) is debated. This study investigates the impact of kidney transplant (KT) on AD biomarkers in CKD.</p><p><strong>Methods: </strong>We assessed AD biomarkers in 46 CKD patients pre-KT, at 12 weeks and 12 months post-KT, with baseline measures from 13 non-CKD controls. Using linear mixed models, we examined associations with participant groups, estimated glomerular filtration rate (eGFR) and cognition.</p><p><strong>Results: </strong>CKD patients showed elevated levels of neurofilament light (117 ± 72 vs. 11 ± 5 pg/mL), phosphorylated tau 181 (75 ± 42 vs. 13 ± 8 pg/mL), glial fibrillary acidic protein (193 ± 127 vs. 94 ± 39 pg/mL), amyloid β 42 (17 ± 5 vs. 5 ± 1 pg/mL), and amyloid β 40 (259 ± 96 vs. 72 ± 17 pg/mL) compared to controls. Post-KT, biomarker levels approached normal with improved eGFR, paralleled by enhanced cognitive function.</p><p><strong>Discussion: </strong>AD blood biomarker elevations in CKD are reversible with improved kidney function through KT.</p><p><strong>Highlights: </strong>AD biomarker levels are extremely high in severe CKD.AD biomarker levels are higher in patients with kidney failure on dialysis when compared to CKD patients not on dialysis.These elevations in AD biomarker levels in kidney failure are reversable and decrease dramatically after kidney transplantation.The change in biomarker levels after transplantation align with changes in kidney function.The change in biomarker levels after transplantation align with changes in cognitive function.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"16 3","pages":"e12614"},"PeriodicalIF":4.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11220407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141535904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Early-phase amyloid PET reproduces metabolic signatures of cognitive decline in Parkinson's disease. 早期淀粉样蛋白 PET 再现了帕金森病认知能力下降的代谢特征。
IF 4
Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Pub Date : 2024-06-22 eCollection Date: 2024-04-01 DOI: 10.1002/dad2.12601
William W T Aye, Megan R Stark, Kyla-Louise Horne, Leslie Livingston, Sophie Grenfell, Daniel J Myall, Toni L Pitcher, Mustafa M Almuqbel, Ross J Keenan, Wassilios G Meissner, John C Dalrymple-Alford, Tim J Anderson, Campbell Le Heron, Tracy R Melzer
{"title":"Early-phase amyloid PET reproduces metabolic signatures of cognitive decline in Parkinson's disease.","authors":"William W T Aye, Megan R Stark, Kyla-Louise Horne, Leslie Livingston, Sophie Grenfell, Daniel J Myall, Toni L Pitcher, Mustafa M Almuqbel, Ross J Keenan, Wassilios G Meissner, John C Dalrymple-Alford, Tim J Anderson, Campbell Le Heron, Tracy R Melzer","doi":"10.1002/dad2.12601","DOIUrl":"10.1002/dad2.12601","url":null,"abstract":"<p><strong>Introduction: </strong>Recent work suggests that amyloid beta (Aβ) positron emission tomography (PET) tracer uptake shortly after injection (\"early phase\") reflects brain metabolism and perfusion. We assessed this modality in a predominantly amyloid-negative neurodegenerative condition, Parkinson's disease (PD), and hypothesized that early-phase <sup>18</sup>F-florbetaben (eFBB) uptake would reproduce characteristic hypometabolism and hypoperfusion patterns associated with cognitive decline in PD.</p><p><strong>Methods: </strong>One hundred fifteen PD patients across the spectrum of cognitive impairment underwent dual-phase Aβ PET, structural and arterial spin labeling (ASL) magnetic resonance imaging (MRI), and neuropsychological assessments. Multiple linear regression models compared eFBB uptake to cognitive performance and ASL MRI perfusion.</p><p><strong>Results: </strong>Reduced eFBB uptake was associated with cognitive performance in brain regions previously linked to hypometabolism-associated cognitive decline in PD, independent of amyloid status. Furthermore, eFBB uptake correlated with cerebral perfusion across widespread regions.</p><p><strong>Discussion: </strong>EFBB uptake is a potential surrogate measure for cerebral perfusion/metabolism. A dual-phase PET imaging approach may serve as a clinical tool for assessing cognitive impairment.</p><p><strong>Highlights: </strong>Images taken at amyloid beta (Aβ) positron emission tomography tracer injection may reflect brain perfusion and metabolism.Parkinson's disease (PD) is a predominantly amyloid-negative condition.Early-phase florbetaben (eFBB) in PD was associated with cognitive performance.eFBB uptake reflects hypometabolism-related cognitive decline in PD.eFBB correlated with arterial spin labeling magnetic resonance imaging measured cerebral perfusion.eFBB distinguished dementia from normal cognition and mild cognitive impairment.Findings were independent of late-phase Aβ burden.Thus, eFBB may serve as a surrogate measure for brain metabolism/perfusion.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"16 2","pages":"e12601"},"PeriodicalIF":4.0,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
TOMM40 and APOC1 variants differentiate the impacts of the APOE ε4 allele on Alzheimer's disease risk across sexes, ages, and ancestries. TOMM40 和 APOC1 变体可区分 APOE ε4 等位基因对不同性别、年龄和血统的阿尔茨海默病风险的影响。
IF 4
Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Pub Date : 2024-06-22 eCollection Date: 2024-04-01 DOI: 10.1002/dad2.12600
Alexander M Kulminski, Ethan Jain-Washburn, Ian Philipp, Yury Loika, Elena Loiko, Irina Culminskaya
{"title":"<i>TOMM40</i> and <i>APOC1</i> variants differentiate the impacts of the <i>APOE ε</i>4 allele on Alzheimer's disease risk across sexes, ages, and ancestries.","authors":"Alexander M Kulminski, Ethan Jain-Washburn, Ian Philipp, Yury Loika, Elena Loiko, Irina Culminskaya","doi":"10.1002/dad2.12600","DOIUrl":"10.1002/dad2.12600","url":null,"abstract":"<p><strong>Introduction: </strong>The variability in apolipoprotein E (<i>APOE</i>) <i>ε</i>4-attributed susceptibility to Alzheimer's disease (AD) across ancestries, sexes, and ages may stem from the modulating effects of other genetic variants.</p><p><strong>Methods: </strong>We examined associations of compound genotypes (CompGs) comprising the <i>ε</i>4-encoding rs429358, <i>TOMM40</i> rs2075650, and <i>APOC1</i> rs12721046 polymorphisms with AD in White (7181/16,356 AD-affected/unaffected), Hispanic/Latino (2305/2921), and Black American (547/1753) participants across sexes and ages.</p><p><strong>Results: </strong>The absence and presence of the rs2075650 and/or rs12721046 minor alleles in the <i>ε</i>4-bearing CompGs define lower- and higher-AD-risk profiles, respectively, in White participants. They differentially impact AD risks in men and women of different ancestries, exhibiting an increasing, decreasing, flat, and nonlinear-with lower risks at ages younger than 65/70 years and older than 85 years compared to the ages in between-patterns across ages.</p><p><strong>Discussion: </strong>The <i>ε</i>4-bearing CompGs have a potential to differentiate biological mechanisms of sex-, age-, and ancestry-specific AD risks and serve as AD biomarkers.</p><p><strong>Highlights: </strong>Younger White women carrying the lower-risk (LR) CompG are at small risk of AD.Black carriers of the LR CompG are at negligible risk of AD at 85 years and older.The higher-risk (HR) CompGs confer high AD risk in Whites and Blacks at 70 to 85 years.AD risk decreases with age for Hispanic/Lation women carrying the HR CompGs.Hispanic/Lation carriers of the LR CompG but not HR CompGs have higher AD risk than Blacks.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"16 2","pages":"e12600"},"PeriodicalIF":4.0,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Vascular endothelial growth factor is an effective biomarker for vascular dementia, not for Alzheimer's disease: A meta-analysis. 血管内皮生长因子是血管性痴呆症而非阿尔茨海默病的有效生物标志物:荟萃分析
IF 4
Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Pub Date : 2024-06-22 eCollection Date: 2024-04-01 DOI: 10.1002/dad2.12612
Ling-Zhi Xu, Fang-Yu Li, Jin Xu, Bing-Qiu Li, Ying Li, Jian-Ping Jia
{"title":"Vascular endothelial growth factor is an effective biomarker for vascular dementia, not for Alzheimer's disease: A meta-analysis.","authors":"Ling-Zhi Xu, Fang-Yu Li, Jin Xu, Bing-Qiu Li, Ying Li, Jian-Ping Jia","doi":"10.1002/dad2.12612","DOIUrl":"10.1002/dad2.12612","url":null,"abstract":"<p><strong>Introduction: </strong>Vascular pathology is known to contribute to dementia and vascular endothelial growth factor (VEGF) is a well-established biomarker associated with vascular alterations. Nonetheless, research findings on VEGF in Alzheimer's disease (AD) and vascular dementia (VaD) are inconsistent across various studies.</p><p><strong>Methods: </strong>We conducted a meta-analysis to elucidate relationships between VEGF and AD/VaD.</p><p><strong>Results: </strong>Twenty-four studies were included. Pooled data showed that both blood and cerebrospinal fluid (CSF) VEGF levels were higher in VaD patients, whereas no significant difference was found between AD patients and healthy controls. However, the correlation between blood VEGF and AD was found among studies with AD pathology verification. And blood VEGF levels were higher in AD patients than controls in \"age difference < 5 years\" subgroup and CSF samples for European cohorts.</p><p><strong>Discussion: </strong>This study highlights that VEGF is more effective for the diagnosis of VaD and vascular factors are also an important contributor in AD.</p><p><strong>Highlights: </strong>Vascular endothelial growth factor (VEGF) levels were higher in the vascular dementia group, but not in the overall Alzheimer's disease (AD) group.Correlation between VEGF and AD was found among studies with clear AD pathological verification.Elevated VEGF in the cerebrospinal fluid might be a diagnostic marker for AD in European populations.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"16 2","pages":"e12612"},"PeriodicalIF":4.0,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Relationship between alcohol consumption and dementia with Mendelian randomization approaches among older adults in the United States. 用孟德尔随机方法研究美国老年人饮酒与痴呆症之间的关系。
IF 4
Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Pub Date : 2024-06-20 eCollection Date: 2024-04-01 DOI: 10.1002/dad2.12598
Kyle A Campbell, Mingzhou Fu, Elizabeth MacDonald, Matthew Zawistowski, Kelly M Bakulski, Erin B Ware
{"title":"Relationship between alcohol consumption and dementia with Mendelian randomization approaches among older adults in the United States.","authors":"Kyle A Campbell, Mingzhou Fu, Elizabeth MacDonald, Matthew Zawistowski, Kelly M Bakulski, Erin B Ware","doi":"10.1002/dad2.12598","DOIUrl":"10.1002/dad2.12598","url":null,"abstract":"<p><strong>Introduction: </strong>In observational studies, the association between alcohol consumption and dementia is mixed.</p><p><strong>Methods: </strong>We performed two-sample Mendelian randomization (MR) using summary statistics from genome-wide association studies of weekly alcohol consumption and late-onset Alzheimer's disease and one-sample MR in the Health and Retirement Study (HRS), wave 2012. Inverse variance weighted two-stage regression provided odds ratios of association between alcohol exposure and dementia or cognitively impaired, non-dementia relative to cognitively normal.</p><p><strong>Results: </strong>Alcohol consumption was not associated with late-onset Alzheimer's disease using two-sample MR (odds ratio [OR] = 1.15, 95% confidence interval [CI]: [0.78, 1.72]). In HRS, doubling weekly alcohol consumption was not associated with dementia (African ancestries, <i>n</i> = 1,322, OR = 1.00, 95% CI [0.45, 2.25]; European ancestries, <i>n</i> = 7,160, OR = 1.37, 95% CI [0.53, 3.51]) or cognitively impaired, non-dementia (African ancestries, <i>n</i> = 1,322, OR = 1.17, 95% CI [0.69, 1.98]; European ancestries, <i>n</i> = 7,160, OR = 0.75, 95% CI [0.47, 1.22]).</p><p><strong>Discussion: </strong>Alcohol consumption was not associated with cognitively impaired, non-dementia or dementia status.</p><p><strong>Highlights: </strong>Cross-sectionally in a large, diverse sample, alcohol appears protective for dementia.We apply two- and one-sample Mendelian randomization to test inferred causality.Mendelian randomization approaches show no association with alcohol and dementia.We conclude that alcohol consumption should not be considered protective.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"16 2","pages":"e12598"},"PeriodicalIF":4.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11187745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141433351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Perceptions of cognitive decline among American Indian and Alaska Native elders. 美国印第安人和阿拉斯加原住民老年人对认知能力下降的看法。
IF 5.3
Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Pub Date : 2024-06-17 eCollection Date: 2024-04-01 DOI: 10.1002/dad2.12611
Cole Allick
{"title":"Perceptions of cognitive decline among American Indian and Alaska Native elders.","authors":"Cole Allick","doi":"10.1002/dad2.12611","DOIUrl":"10.1002/dad2.12611","url":null,"abstract":"<p><strong>Introduction: </strong>American Indian and Alaska Native elders aged ≥ 65 years are experiencing increased life expectancy. Elders are critical to intergenerational knowledge, yet limited data exist on the health challenges faced by this group.</p><p><strong>Methods: </strong>This study engaged individuals attending the National Indian Council on Aging 2021 Annual Meeting in Reno, Nevada. A 19-question survey, designed to examine perceptions about cognitive decline and to identify comfort with potential risk and protective factors, was disseminated to 50 participants.</p><p><strong>Results: </strong>Participants indicated that they are concerned about cognitive decline, are willing to plan for their future care and cognitive testing, and articulated a desire for Tribally led long-term support services.</p><p><strong>Discussion: </strong>This study found similar results to studies on White individuals, which include a lack of knowledge, stigma around the aging process, and gaps in services available. More work is necessary to address the gap in literature and policy.</p><p><strong>Highlights: </strong>American Indian and Alaska Natives (AI/ANs) are underrepresented in literature on Alzheimer's disease and related dementia (ADRD).AI/ANs believe that they will experience cognitive decline as they age.AI/ANs indicate a willingness to plan for future care and participate in future research on ADRD.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"16 2","pages":"e12611"},"PeriodicalIF":5.3,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11180990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A machine learning approach for potential Super-Agers identification using neuronal functional connectivity networks. 利用神经元功能连接网络识别潜在超级黑客的机器学习方法。
IF 4
Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Pub Date : 2024-06-10 eCollection Date: 2024-04-01 DOI: 10.1002/dad2.12595
Mohammad Fili, Parvin Mohammadiarvejeh, Brandon S Klinedinst, Qian Wang, Shannin Moody, Neil Barnett, Amy Pollpeter, Brittany Larsen, Tianqi Li, Sara A Willette, Jonathan P Mochel, Karin Allenspach, Guiping Hu, Auriel A Willette
{"title":"A machine learning approach for potential Super-Agers identification using neuronal functional connectivity networks.","authors":"Mohammad Fili, Parvin Mohammadiarvejeh, Brandon S Klinedinst, Qian Wang, Shannin Moody, Neil Barnett, Amy Pollpeter, Brittany Larsen, Tianqi Li, Sara A Willette, Jonathan P Mochel, Karin Allenspach, Guiping Hu, Auriel A Willette","doi":"10.1002/dad2.12595","DOIUrl":"10.1002/dad2.12595","url":null,"abstract":"<p><strong>Introduction: </strong>Aging is often associated with cognitive decline. Understanding neural factors that distinguish adults in midlife with superior cognitive abilities (Positive-Agers) may offer insight into how the aging brain achieves resilience. The goals of this study are to (1) introduce an optimal labeling mechanism to distinguish between Positive-Agers and Cognitive Decliners, and (2) identify Positive-Agers using neuronal functional connectivity networks data and demographics.</p><p><strong>Methods: </strong>In this study, principal component analysis initially created latent cognitive trajectories groups. A hybrid algorithm of machine learning and optimization was then designed to predict latent groups using neuronal functional connectivity networks derived from resting state functional magnetic resonance imaging. Specifically, the Optimal Labeling with Bayesian Optimization (OLBO) algorithm used an unsupervised approach, iterating a logistic regression function with Bayesian posterior updating. This study encompassed 6369 adults from the UK Biobank cohort.</p><p><strong>Results: </strong>OLBO outperformed baseline models, achieving an area under the curve of 88% when distinguishing between Positive-Agers and cognitive decliners.</p><p><strong>Discussion: </strong>OLBO may be a novel algorithm that distinguishes cognitive trajectories with a high degree of accuracy in cognitively unimpaired adults.</p><p><strong>Highlights: </strong>Design an algorithm to distinguish between a Positive-Ager and a Cognitive-Decliner.Introduce a mathematical definition for cognitive classes based on cognitive tests.Accurate Positive-Ager identification using rsfMRI and demographic data (AUC = 0.88).Posterior default mode network has the highest impact on Positive-Aging odds ratio.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"16 2","pages":"e12595"},"PeriodicalIF":4.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11163506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141302064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Detecting time-varying genetic effects in Alzheimer's disease using a longitudinal genome-wide association studies model. 利用纵向全基因组关联研究模型检测阿尔茨海默病的时变遗传效应。
IF 4
Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Pub Date : 2024-06-07 eCollection Date: 2024-04-01 DOI: 10.1002/dad2.12597
Xiaowei Zhuang, Gang Xu, Amei Amei, Dietmar Cordes, Zuoheng Wang, Edwin C Oh
{"title":"Detecting time-varying genetic effects in Alzheimer's disease using a longitudinal genome-wide association studies model.","authors":"Xiaowei Zhuang, Gang Xu, Amei Amei, Dietmar Cordes, Zuoheng Wang, Edwin C Oh","doi":"10.1002/dad2.12597","DOIUrl":"10.1002/dad2.12597","url":null,"abstract":"<p><strong>Introduction: </strong>The development and progression of Alzheimer's disease (AD) is a complex process, during which genetic influences on phenotypes may also change. Incorporating longitudinal phenotypes in genome-wide association studies (GWAS) could unmask these genetic loci.</p><p><strong>Methods: </strong>We conducted a longitudinal GWAS using a varying coefficient test to identify age-dependent single nucleotide polymorphisms (SNPs) in AD. Data from 1877 Alzheimer's Neuroimaging Data Initiative participants, including impairment status and amyloid positron emission tomography (PET) scan standardized uptake value ratio (SUVR) scores, were analyzed using a retrospective varying coefficient mixed model association test (RVMMAT).</p><p><strong>Results: </strong>RVMMAT identified 244 SNPs with significant time-varying effects on AD impairment status, with 12 SNPs on chromosome 19 validated using National Alzheimer's Coordinating Center data. Age-stratified analyses showed these SNPs' effects peaked between 70 and 80 years. Additionally, 73 SNPs were linked to longitudinal amyloid accumulation changes. Pathway analyses implicated immune and neuroinflammation-related disruptions.</p><p><strong>Discussion: </strong>Our findings demonstrate that longitudinal GWAS models can uncover time-varying genetic signals in AD.</p><p><strong>Highlights: </strong>Identify time-varying genetic effects using a longitudinal GWAS model in AD.Illustrate age-dependent genetic effects on both diagnoses and amyloid accumulation.Replicate time-varying effect of APOE in a second dataset.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"16 2","pages":"e12597"},"PeriodicalIF":4.0,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11157162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141297284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cerebrospinal fluid soluble insulin receptor levels in Alzheimer's disease. 阿尔茨海默病的脑脊液可溶性胰岛素受体水平。
IF 5.3
Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Pub Date : 2024-05-25 eCollection Date: 2024-04-01 DOI: 10.1002/dad2.12603
Peter Thomas, Manon Leclerc, Kira Evitts, Caitlin Brown, Wyatt Miller, Angela J Hanson, William A Banks, Laura Gibbons, Kimiko Domoto-Reilly, Suman Jayadev, Ge Li, Elaine Peskind, Jessica E Young, Frederic Calon, Elizabeth M Rhea
{"title":"Cerebrospinal fluid soluble insulin receptor levels in Alzheimer's disease.","authors":"Peter Thomas, Manon Leclerc, Kira Evitts, Caitlin Brown, Wyatt Miller, Angela J Hanson, William A Banks, Laura Gibbons, Kimiko Domoto-Reilly, Suman Jayadev, Ge Li, Elaine Peskind, Jessica E Young, Frederic Calon, Elizabeth M Rhea","doi":"10.1002/dad2.12603","DOIUrl":"10.1002/dad2.12603","url":null,"abstract":"<p><strong>Introduction: </strong>Brain insulin resistance and deficiency is a consistent feature of Alzheimer's disease (AD). Insulin resistance can be mediated by the surface expression of the insulin receptor (IR). Cleavage of the IR generates the soluble IR (sIR).</p><p><strong>Methods: </strong>We measured the levels of sIR present in cerebrospinal fluid (CSF) from individuals along the AD diagnostic spectrum from two cohorts: Seattle (<i>n</i> = 58) and the Consortium for the Early Identification of Alzheimer's Disease-Quebec (CIMA-Q; <i>n</i> = 61). We further investigated the brain cellular contribution for sIR using human cell lines.</p><p><strong>Results: </strong>CSF sIR levels were not statistically different in AD. CSF sIR and amyloid beta (Aβ)42 and Aβ40 levels significantly correlated as well as CSF sIR and cognition in the CIMA-Q cohort. Human neurons expressing the amyloid precursor protein \"Swedish\" mutation generated significantly greater sIR and human astrocytes were also able to release sIR in response to both an inflammatory and insulin stimulus.</p><p><strong>Discussion: </strong>These data support further investigation into the generation and role of sIR in AD.</p><p><strong>Highlights: </strong>Cerebrospinal fluid (CSF) soluble insulin receptor (sIR) levels positively correlate with amyloid beta (Aβ)42 and Aβ40.CSF sIR levels negatively correlate with cognitive performance (Montreal Cognitive Assessment score).CSF sIR levels in humans remain similar across Alzheimer's disease diagnostic groups.Neurons derived from humans with the \"Swedish\" mutation in which Aβ42 is increased generate increased levels of sIR.Human astrocytes can also produce sIR and generation is stimulated by tumor necrosis factor α and insulin.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"16 2","pages":"e12603"},"PeriodicalIF":5.3,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11127683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prediction of dementia risk from multimodal repeated measures: The added value of brain MRI biomarkers. 通过多模态重复测量预测痴呆症风险:脑磁共振成像生物标志物的附加价值
IF 5.3
Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Pub Date : 2024-05-25 eCollection Date: 2024-04-01 DOI: 10.1002/dad2.12578
Ariane Bercu, Carole Dufouil, Stéphanie Debette, Marc Joliot, Ami Tsuchida, Catherine Helmer, Anthony Devaux, Vincent Bouteloup, Cécile Proust-Lima, Hélène Jacqmin-Gadda
{"title":"Prediction of dementia risk from multimodal repeated measures: The added value of brain MRI biomarkers.","authors":"Ariane Bercu, Carole Dufouil, Stéphanie Debette, Marc Joliot, Ami Tsuchida, Catherine Helmer, Anthony Devaux, Vincent Bouteloup, Cécile Proust-Lima, Hélène Jacqmin-Gadda","doi":"10.1002/dad2.12578","DOIUrl":"10.1002/dad2.12578","url":null,"abstract":"<p><strong>Abstract: </strong>The utility of brain magnetic resonance imaging (MRI) for predicting dementia is debated. We evaluated the added value of repeated brain MRI, including atrophy and cerebral small vessel disease markers, for dementia prediction. We conducted a landmark competing risk analysis in 1716 participants of the French population-based Three-City Study to predict the 5-year risk of dementia using repeated measures of 41 predictors till year 4 of follow-up. Brain MRI markers improved significantly the individual prediction of dementia after accounting for demographics, health measures, and repeated measures of cognition and functional dependency (area under the ROC curve [95% CI] improved from 0.80 [0.79 to 0.82] to 0.83 [0.81 to 0.84]). Nonetheless, accounting for the change over time through repeated MRIs had little impact on predictive abilities. These results highlight the importance of multimodal analysis to evaluate the added predictive abilities of repeated brain MRI for dementia and offer new insights into the predictive performances of various MRI markers.</p><p><strong>Highlights: </strong>We evaluated whether repeated brain volumes and cSVD markers improve dementia prediction.The 5-year prediction of dementia is slightly improved when considering brain MRI markers.Measures of hippocampus volume are the main MRI predictors of dementia.Adjusted on cognition, repeated MRI has poor added value over single MRI for dementia prediction.We utilized a longitudinal analysis that considers error-and-missing-prone predictors, and competing death.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"16 2","pages":"e12578"},"PeriodicalIF":5.3,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11127684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
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
确定
请完成安全验证×
相关产品
×
本文献相关产品
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信