Journal of Alzheimer's disease : JAD最新文献

{"title":"A Stacking Framework for Multi-Classification of Alzheimer's Disease Using Neuroimaging and Clinical Features.","authors":"Durong Chen, Fuliang Yi, Yao Qin, Jiajia Zhang, Xiaoyan Ge, Hongjuan Han, Jing Cui, Wenlin Bai, Yan Wu, Hongmei Yu","doi":"10.3233/jad-215654","DOIUrl":"https://doi.org/10.3233/jad-215654","url":null,"abstract":"BACKGROUND\u0000Alzheimer's disease (AD) is a severe health problem. Challenges still remain in early diagnosis.\u0000\u0000\u0000OBJECTIVE\u0000The objective of this study was to build a Stacking framework for multi-classification of AD by a combination of neuroimaging and clinical features to improve the performance.\u0000\u0000\u0000METHODS\u0000The data we used were from the Alzheimer's Disease Neuroimaging Initiative database with a total of 493 subjects, including 125 normal control (NC), 121 early mild cognitive impairment, 109 late mild cognitive impairment (LMCI), and 138 AD. We selected structural magnetic resonance imaging (sMRI) features by voting strategy. The imaging features, demographic information, Mini-Mental State Examination, and Alzheimer's Disease Assessment Scale-Cognitive Subscale were combined together as classification features. We proposed a two-layer Stacking ensemble framework to classify four types of people. The first layer represented support vector machine, random forests, adaptive boosting, and gradient boosting decision tree; the second layer was a logistic regression classifier. Additionally, we analyzed performance of only sMRI feature and combined features and compared the proposed model with four base classifiers.\u0000\u0000\u0000RESULTS\u0000The Stacking model combined with sMRI and non-imaging features outshined four base classifiers with an average accuracy of 86.96% . Compared with using sMRI data alone, sMRI combined with non-imaging features significantly improved diagnostic accuracy, especially in NC versus LMCI and LMCI versus AD by 14.08% .\u0000\u0000\u0000CONCLUSION\u0000The Stacking framework we used can improve performance in diagnosis of AD using combined features.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129254131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood Phosphorylated Tau 181 as a Biomarker for Amyloid Burden on Brain PET in Cognitively Healthy Adults.","authors":"Emer R. McGrath, A. Beiser, A. O’Donnell, Qiong Yang, Saptaparni Ghosh, M. Gonzales, J. Himali, C. Satizabal, Keith A. Johnson, R. Tracy, S. Seshadri","doi":"10.3233/jad-215639","DOIUrl":"https://doi.org/10.3233/jad-215639","url":null,"abstract":"BACKGROUND\u0000Plasma phosphorylated-tau181 (p-tau181) is a promising biomarker for Alzheimer's disease (AD) and may offer utility for predicting preclinical disease.\u0000\u0000\u0000OBJECTIVE\u0000To evaluate the prospective association between plasma p-tau181 and amyloid-β (Aβ) and tau-PET deposition in cognitively unimpaired individuals.\u0000\u0000\u0000METHODS\u0000Plasma p-tau181 levels were measured at baseline in 52 [48% women, mean 64.4 (SD 5.5) years] cognitively unimpaired Framingham Offspring cohort participants using samples stored between 2011-2014 who subsequently underwent 11C-Pittsburgh Compound-B (PiB)-PET and/or 18F-Flortaucipir (FTP)-PET scans (n = 18 with tau-PET) a mean of 6.8 (SD 0.6) years later. Our primary outcomes included Aβ-precuneus, Aβ-FLR (frontal, lateral, and retrosplenial cortices) and tau-global composite region PET deposition. Secondary outcomes included individual regional Aβ and tau PET-deposition. P-tau181 was compared with plasma neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP) in predicting PET outcomes.\u0000\u0000\u0000RESULTS\u0000P-tau181 was associated with increased Aβ deposition in the FLR (β±SE, 1.25±0.30, p < 0.0001), precuneus (1.35±0.29, p < 0.001), and other cortical regions. Plasma NFL (1.30±0.49, p = 0.01) and GFAP (1.46±0.39, p < 0.001) were also associated with FLR Aβ deposition. In models including all three biomarkers adjusted for age, sex, APOE E4 allele, AD polygenic risk score and cortical atrophy score, p-tau181 (0.93±0.31, p < 0.01, R2 = 0.18) and GFAP (0.93±0.41, p = 0.03, R2 = 0.11), but not NFL (0.25±0.51, p = 0.62, R2 = 0.01), were associated with FLR-Aβ deposition. Plasma p-tau181 was not associated with tau-PET burden.\u0000\u0000\u0000CONCLUSION\u0000In cognitively unimpaired adults, elevated plasma p-tau181 is associated with future increased Aβ deposition across multiple brain regions. Our results highlight the potential utility of p-tau181 as a blood-biomarker to screen for brain-amyloid deposition in cognitively healthy individuals in a community-setting.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"115 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131738546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mild Traumatic Brain Injuries and Future Risk of Developing Alzheimer's Disease: Systematic Review and Meta-Analysis.","authors":"A. Graham, G. Livingston, Lucy R Purnell, J. Huntley","doi":"10.3233/jad-220069","DOIUrl":"https://doi.org/10.3233/jad-220069","url":null,"abstract":"BACKGROUND\u0000Traumatic brain injury (TBI) increases the risk of future dementia and Alzheimer's disease (AD). However, it is unclear whether this is true for mild TBI (mTBI).\u0000\u0000\u0000OBJECTIVE\u0000To explore the association between mTBI and subsequent risk of developing AD.\u0000\u0000\u0000METHOD\u0000We systematically searched four electronic databases from January 1954 to April 2020. We included studies reporting primary data and where mTBI preceded AD by≥5 years. We meta-analyzed included studies for both high quality studies and studies with a follow up of > 10 years.\u0000\u0000\u0000RESULT\u0000We included 5 of the 10,435 results found. Meta-analysis found a history of mTBI increased risk of AD (pooled relative risk = 1.18, 95% CI 1.11-1.25, N = 3,149,740). The sensitivity analysis including only studies in which mTBI preceded AD by > 10 years, excluded two very large studies and resulted in wider confidence intervals (RR = 2.02, 95% CI 0.66-6.21, N = 2307).\u0000\u0000\u0000CONCLUSION\u0000There is an increased risk of AD following mTBI. Our findings of increased risk even with mTBI means it cannot be assumed that mild head injuries from sports are harmless. The sensitivity analysis suggests that we cannot exclude reverse causation, and longer follow up times are needed. Implementation of policy to reduce mTBIs, including in children and sportsmen, are urgently needed. Further research is needed on the effect of frequency and age at injury of mTBIs.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"34 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130666283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer History Is Associated with Slower Speed of Cognitive Decline in Patients with Amnestic Cognitive Impairment.","authors":"Rolando I Castillo-Passi, Rodrigo C. Vergara, N. Rogers, D. Ponce, Magdalena Bennett, M. Behrens","doi":"10.3233/jad-215660","DOIUrl":"https://doi.org/10.3233/jad-215660","url":null,"abstract":"BACKGROUND\u0000Several epidemiological studies report a negative association between Cancer and Alzheimer's disease (AD).\u0000\u0000\u0000OBJECTIVE\u0000To characterize the trajectories of memory loss in individuals with early amnestic cognitive impairment with and without history of previous cancer.\u0000\u0000\u0000METHODS\u0000Cognitive deterioration was assessed using the Montreal Cognitive Assessment (MoCA) or MoCA-Memory Index Score (MoCA-MIS) biannually in subjects with early amnestic cognitive impairment followed-up retrospectively from 2007 to 2021. History of Cancer was obtained from clinical records. Simple linear regressions of MoCA-MIS scores were calculated for each subject and analyzed with K-means cluster analysis to identify subgroups with different cognitive decline trajectories. χ 2 and t tests were used for descriptive categorical and continuous variables and mixed multiple linear regressions to determine cognitive decline covariates.\u0000\u0000\u0000RESULTS\u0000Analysis of the trajectory of cognitive decline in 141 subjects with early amnestic cognitive impairment identified two subgroups: Fast (n = 60) and Slow (n = 81) progressors. At baseline Fast progressors had better MoCA-MIS (p <  0.001) and functionality (CDR p = 0.02, AD8 p = 0.05), took less anti-dementia medications (p = 0.005), and had higher depression rates (p = 0.02). Interestingly, Fast progressors slowed their speed of memory decline (from 1.6 to 1.1 MoCA-MIS points/year) and global cognitive decline (from 2.0 to 1.4 total MoCA points/year) when Cancer history was present.\u0000\u0000\u0000CONCLUSION\u0000Two trajectories of amnestic cognitive decline were identified, possibly derived from different neurophysiopathologies or clinical stages. This study suggests that a history of previous Cancer slows down amnestic cognitive decline, specifically in a subgroup of subjects with depression at baseline and accelerated deterioration at follow-up.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127960656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Saliva is a Good Candidate to be the New Gold-Standard Sample for Neurodegenerative Diseases.","authors":"G. Orive, F. Lopera, E. Carro","doi":"10.3233/jad-220144","DOIUrl":"https://doi.org/10.3233/jad-220144","url":null,"abstract":"Gorka Orivea,b,c,∗, Francisco Loperad and Eva Carroe,f,∗ aLaboratory of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), Vitoria, Spain bBioaraba, NanoBioCel Research Group, Vitoria-Gasteiz, Spain cNetworking Center for Biomedical Research in Bioengineering Biomaterials and Nanomedicine (CIBER-BBN) Barcelona, Spain dGrupo de Neurociencias, Universidad de Antioquia. Medellı́n, Colombia eNeurobiology of Alzheimer’s Disease Unit, Chronic Disease Programme, Instituto de Salud Carlos III, Madrid, Spain f Network Centre for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Spain","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"47 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123611291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Making the Case for the Accelerated Withdrawal of Aducanumab.","authors":"P. Whitehouse, Vikas Saini","doi":"10.3233/jad-220264","DOIUrl":"https://doi.org/10.3233/jad-220264","url":null,"abstract":"U.S. Food and Drug Administration-s (FDA) approval of aducanumab (Aduhelm® in the US) as a treatment for mild cognitive impairment of the Alzheimer type and Alzheimer-s disease has raised such major concerns about efficacy, safety, FDA processes, and regulatory capture that Biogen-s license to market this biologic should be immediately withdrawn. Aducanumab has not demonstrated benefit to patients, failed to meet regulatory guidelines, and is likely to cause both individual and societal harm.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"15 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127973102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alzheimer's Disease Mortality as a Function of Urbanization Level: 1999-2019.","authors":"Sarah Cato, S. Ramer, I. Hajjar, A. Kulshreshtha","doi":"10.3233/jad-215586","DOIUrl":"https://doi.org/10.3233/jad-215586","url":null,"abstract":"This study investigated Alzheimer's disease (AD) mortality trends by urbanization level and geographical location in the U.S. The CDC's WONDER database was used to investigate AD mortality from 1999-2019 stratified by urbanization level, census division, race, and sex. Data showed that while AD mortality increased across the U.S., rural areas, particularly in the South, had higher mortality compared to urban counterparts. AD mortality was higher among the female and White population. Data suggested that the urban-rural discrepancy is widening over time. Identifying health disparities underlying the urban-rural discrepancy in AD mortality is critical for allocating social and public health resources.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"27 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114792440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Boston Process Approach and Digital Neuropsychological Assessment: Past Research and Future Directions.","authors":"D. Libon, R. Swenson, M. Lamar, C. Price, Ganesh Baliga, Á. Pascual-Leone, R. Au, Stephanie Cosentino, S. Andersen","doi":"10.3233/jad-220096","DOIUrl":"https://doi.org/10.3233/jad-220096","url":null,"abstract":"Neuropsychological assessment using the Boston Process Approach (BPA) suggests that an analysis of the strategy or the process by which tasks and neuropsychological tests are completed, and the errors made during test completion convey much information regarding underlying brain and cognition and are as important as overall summary scores. Research over the last several decades employing an analysis of process and errors has been able to dissociate between dementia patients diagnosed with Alzheimer's disease, vascular dementia associated with MRI-determined white matter alterations, and Parkinson's disease; and between mild cognitive impairment subtypes. Nonetheless, BPA methods can be labor intensive to deploy. However, the recent availability of digital platforms for neuropsychological test administration and scoring now enables reliable, rapid, and objective data collection. Further, digital technology can quantify highly nuanced data previously unobtainable to define neurocognitive constructs with high accuracy. In this paper, a brief review of the BPA is provided. Studies that demonstrate how digital technology translates BPA into specific neurocognitive constructs using the Clock Drawing Test, Backward Digit Span Test, and a Digital Pointing Span Test are described. Implications for using data driven artificial intelligence-supported analytic approaches enabling the creation of more sensitive and specific detection/diagnostic algorithms for putative neurodegenerative illness are also discussed.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"13 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126680559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Apolipoprotein E ɛ4 and Risk Factors on Domains of Cognition in Mild Cognitive Impairment and Dementia.","authors":"Seung-Hyup Han, Dong-hee Noh, Eun-Ju Jo, K. Kam","doi":"10.3233/jad-215075","DOIUrl":"https://doi.org/10.3233/jad-215075","url":null,"abstract":"BACKGROUND\u0000The apolipoprotein E (APOE) gene is the most potent genetic risk factor for dementia. However, there are few studies on how the APOE gene affects cognitive domain functions.\u0000\u0000\u0000OBJECTIVE\u0000This study aimed to investigate the effects of risk factors for dementia on cognitive function in patients with mild cognitive impairment and Alzheimer's disease (AD).\u0000\u0000\u0000METHODS\u0000This study included subjects whose Clinical Dementia Rating scores ranged from 0.5 to 2 and who were older than 65 years. Risk factors for dementia included the APOE ɛ4 allele, age, education period, employment period, body mass index, and exercise. APOE genotyping was performed by polymerase chain reaction, and other factors were identified using medical charts or structured checklists. Cognitive function was measured using the Seoul Neuropsychological Screening Battery II.\u0000\u0000\u0000RESULTS\u0000General cognitive function did not show a significant difference according to APOE ɛ4 status. However, the score for delayed verbal memory was lower in the APOE ɛ4-carrier group than in the non-carrier group (p <  0.05). In addition, age, education period, employment period, and exercise were correlated with different cognitive function domains in the non-carrier group (p <  0.05); however, the carrier group was showed a significant correlation between age, body mass index, and cognitive domains.\u0000\u0000\u0000CONCLUSION\u0000Our findings suggest that APOE ɛ4 significantly decreases verbal memory in patients with AD. Moreover, the effects of risk factors on cognitive function were significantly different according to the APOE ɛ4 status.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"69 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129980080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid Peroxidation Induced ApoE Receptor-Ligand Disruption as a Unifying Hypothesis Underlying Sporadic Alzheimer's Disease in Humans.","authors":"C. Ramsden, G. Keyes, E. Calzada, M. Horowitz, Daisy Zamora, J. Jahanipour, A. Sedlock, F. Indig, R. Moaddel, D. Kapogiannis, D. Maric","doi":"10.3233/jad-220071","DOIUrl":"https://doi.org/10.3233/jad-220071","url":null,"abstract":"BACKGROUND\u0000Sporadic Alzheimer's disease (sAD) lacks a unifying hypothesis that can account for the lipid peroxidation observed early in the disease, enrichment of ApoE in the core of neuritic plaques, hallmark plaques and tangles, and selective vulnerability of entorhinal-hippocampal structures.\u0000\u0000\u0000OBJECTIVE\u0000We hypothesized that 1) high expression of ApoER2 (receptor for ApoE and Reelin) helps explain this anatomical vulnerability; 2) lipid peroxidation of ApoE and ApoER2 contributes to sAD pathogenesis, by disrupting neuronal ApoE delivery and Reelin-ApoER2-Dab1 signaling cascades.\u0000\u0000\u0000METHODS\u0000In vitro biochemical experiments; Single-marker and multiplex fluorescence-immunohistochemistry (IHC) in postmortem specimens from 26 individuals who died cognitively normal, with mild cognitive impairment or with sAD.\u0000\u0000\u0000RESULTS\u0000ApoE and ApoER2 peptides and proteins were susceptible to attack by reactive lipid aldehydes, generating lipid-protein adducts and crosslinked ApoE-ApoER2 complexes. Using in situ hybridization alongside IHC, we observed that: 1) ApoER2 is strongly expressed in terminal zones of the entorhinal-hippocampal 'perforant path' projections that underlie memory; 2) ApoE, lipid aldehyde-modified ApoE, Reelin, ApoER2, and the downstream Reelin-ApoER2 cascade components Dab1 and Thr19-phosphorylated PSD95 accumulated in the vicinity of neuritic plaques in perforant path terminal zones in sAD cases; 3) several ApoE/Reelin-ApoER2-Dab1 pathway markers were higher in sAD cases and positively correlated with histological progression and cognitive deficits.\u0000\u0000\u0000CONCLUSION\u0000Results demonstrate derangements in multiple ApoE/Reelin-ApoER2-Dab1 axis components in perforant path terminal zones in sAD and provide proof-of-concept that ApoE and ApoER2 are vulnerable to aldehyde-induced adduction and crosslinking. Findings provide the foundation for a unifying hypothesis implicating lipid peroxidation of ApoE and ApoE receptors in sAD.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"15 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114148638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}