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1.
Dallas P. Veitch Michael W. Weiner Paul S. Aisen Laurel A. Beckett Nigel J. Cairns Robert C. Green Danielle Harvey Clifford R. Jack William Jagust John C. Morris Ronald C. Petersen Andrew J. Saykin Leslie M. Shaw Arthur W. Toga John Q. Trojanowski 《Alzheimer's & dementia》2019,15(1):106-152
Introduction
The overall goal of the Alzheimer's Disease Neuroimaging Initiative (ADNI) is to validate biomarkers for Alzheimer's disease (AD) clinical trials. ADNI is a multisite, longitudinal, observational study that has collected many biomarkers since 2004. Recent publications highlight the multifactorial nature of late-onset AD. We discuss selected topics that provide insights into AD progression and outline how this knowledge may improve clinical trials.Methods
We used standard methods to identify nearly 600 publications using ADNI data from 2016 and 2017 (listed in Supplementary Material and searchable at http://adni.loni.usc.edu/news-publications/publications/).Results
(1) Data-driven AD progression models supported multifactorial interactions rather than a linear cascade of events. (2) β-Amyloid (Aβ) deposition occurred concurrently with functional connectivity changes within the default mode network in preclinical subjects and was followed by specific and progressive disconnection of functional and anatomical networks. (3) Changes in functional connectivity, volumetric measures, regional hypometabolism, and cognition were detectable at subthreshold levels of Aβ deposition. 4. Tau positron emission tomography imaging studies detailed a specific temporal and spatial pattern of tau pathology dependent on prior Aβ deposition, and related to subsequent cognitive decline. 5. Clustering studies using a wide range of modalities consistently identified a “typical AD” subgroup and a second subgroup characterized by executive impairment and widespread cortical atrophy in preclinical and prodromal subjects. 6. Vascular pathology burden may act through both Aβ dependent and independent mechanisms to exacerbate AD progression. 7. The APOE ε4 allele interacted with cerebrovascular disease to impede Aβ clearance mechanisms. 8. Genetic approaches identified novel genetic risk factors involving a wide range of processes, and demonstrated shared genetic risk for AD and vascular disorders, as well as the temporal and regional pathological associations of established AD risk alleles. 9. Knowledge of early pathological changes guided the development of novel prognostic biomarkers for preclinical subjects. 10. Placebo populations of randomized controlled clinical trials had highly variable trajectories of cognitive change, underscoring the importance of subject selection and monitoring. 11. Selection criteria based on Aβ positivity, hippocampal volume, baseline cognitive/functional measures, and APOE ε4 status in combination with improved cognitive outcome measures were projected to decrease clinical trial duration and cost. 12. Multiple concurrent therapies targeting vascular health and other AD pathology in addition to Aβ may be more effective than single therapies.Discussion
ADNI publications from 2016 and 2017 supported the idea of AD as a multifactorial disease and provided insights into the complexities of AD disease progression. These findings guided the development of novel biomarkers and suggested that subject selection on the basis of multiple factors may lower AD clinical trial costs and duration. The use of multiple concurrent therapies in these trials may prove more effective in reversing AD disease progression. 相似文献2.
Michael W. Weiner Dallas P. Veitch Paul S. Aisen Laurel A. Beckett Nigel J. Cairns Robert C. Green Danielle Harvey Clifford R. Jack William Jagust John C. Morris Ronald C. Petersen Andrew J. Saykin Leslie M. Shaw Arthur W. Toga John Q. Trojanowski 《Alzheimer's & dementia》2017,13(4):e1-e85
Introduction
The Alzheimer's Disease Neuroimaging Initiative (ADNI) has continued development and standardization of methodologies for biomarkers and has provided an increased depth and breadth of data available to qualified researchers. This review summarizes the over 400 publications using ADNI data during 2014 and 2015.Methods
We used standard searches to find publications using ADNI data.Results
(1) Structural and functional changes, including subtle changes to hippocampal shape and texture, atrophy in areas outside of hippocampus, and disruption to functional networks, are detectable in presymptomatic subjects before hippocampal atrophy; (2) In subjects with abnormal β-amyloid deposition (Aβ+), biomarkers become abnormal in the order predicted by the amyloid cascade hypothesis; (3) Cognitive decline is more closely linked to tau than Aβ deposition; (4) Cerebrovascular risk factors may interact with Aβ to increase white-matter (WM) abnormalities which may accelerate Alzheimer's disease (AD) progression in conjunction with tau abnormalities; (5) Different patterns of atrophy are associated with impairment of memory and executive function and may underlie psychiatric symptoms; (6) Structural, functional, and metabolic network connectivities are disrupted as AD progresses. Models of prion-like spreading of Aβ pathology along WM tracts predict known patterns of cortical Aβ deposition and declines in glucose metabolism; (7) New AD risk and protective gene loci have been identified using biologically informed approaches; (8) Cognitively normal and mild cognitive impairment (MCI) subjects are heterogeneous and include groups typified not only by “classic” AD pathology but also by normal biomarkers, accelerated decline, and suspected non-Alzheimer's pathology; (9) Selection of subjects at risk of imminent decline on the basis of one or more pathologies improves the power of clinical trials; (10) Sensitivity of cognitive outcome measures to early changes in cognition has been improved and surrogate outcome measures using longitudinal structural magnetic resonance imaging may further reduce clinical trial cost and duration; (11) Advances in machine learning techniques such as neural networks have improved diagnostic and prognostic accuracy especially in challenges involving MCI subjects; and (12) Network connectivity measures and genetic variants show promise in multimodal classification and some classifiers using single modalities are rivaling multimodal classifiers.Discussion
Taken together, these studies fundamentally deepen our understanding of AD progression and its underlying genetic basis, which in turn informs and improves clinical trial design. 相似文献3.
Kelsey R. Thomas Joel S. Eppig Alexandra J. Weigand Emily C. Edmonds Christina G. Wong Amy J. Jak Lisa Delano-Wood Douglas R. Galasko David P. Salmon Steven D. Edland Mark W. Bondi 《Alzheimer's & dementia》2019,15(4):561-569
Introduction
We examined reasons for low mild cognitive impairment (MCI)-to-cognitively normal (CN) reversion rates in the Alzheimer's Disease Neuroimaging Initiative (ADNI).Methods
CN and MCI participants were identified as remaining stable, progressing, or reverting at 1-year of follow-up (Year 1). Application of ADNI's MCI criteria at Year 1 in addition to Alzheimer's disease biomarkers by group were examined.Results
The MCI-to-CN reversion rate was 3.0%. When specific components were examined, 22.5% of stable MCI participants had normal memory performance at Year 1 and their Alzheimer's disease biomarkers were consistent with the stable CN group. At Year 1, when all MCI criteria were not met, the more subjective Clinical Dementia Rating rather than objective memory measure appeared to drive continuation of the MCI diagnosis.Discussion
Results demonstrate an artificially low 1-year MCI-to-CN reversion rate in ADNI-diagnosed participants. If the Logical Memory cutoffs had been consistently applied, the reversion rate would have been at least 21.8%. 相似文献4.
Michael W. Weiner Dallas P. Veitch Paul S. Aisen Laurel A. Beckett Nigel J. Cairns Robert C. Green Danielle Harvey Clifford R. Jack William Jagust John C. Morris Ronald C. Petersen Jennifer Salazar Andrew J. Saykin Leslie M. Shaw Arthur W. Toga John Q. Trojanowski 《Alzheimer's & dementia》2017,13(5):561-571
Introduction
The overall goal of the Alzheimer's Disease Neuroimaging Initiative (ADNI) is to validate biomarkers for Alzheimer's disease (AD) clinical trials. ADNI-3, which began on August 1, 2016, is a 5-year renewal of the current ADNI-2 study.Methods
ADNI-3 will follow current and additional subjects with normal cognition, mild cognitive impairment, and AD using innovative technologies such as tau imaging, magnetic resonance imaging sequences for connectivity analyses, and a highly automated immunoassay platform and mass spectroscopy approach for cerebrospinal fluid biomarker analysis. A Systems Biology/pathway approach will be used to identify genetic factors for subject selection/enrichment. Amyloid positron emission tomography scanning will be standardized using the Centiloid method. The Brain Health Registry will help recruit subjects and monitor subject cognition.Results
Multimodal analyses will provide insight into AD pathophysiology and disease progression.Discussion
ADNI-3 will aim to inform AD treatment trials and facilitate development of AD disease-modifying treatments. 相似文献5.
Clifford R. Jack Heather J. Wiste Stephen D. Weigand Terry M. Therneau Val J. Lowe David S. Knopman Jeffrey L. Gunter Matthew L. Senjem David T. Jones Kejal Kantarci Mary M. Machulda Michelle M. Mielke Rosebud O. Roberts Prashanthi Vemuri Denise A. Reyes Ronald C. Petersen 《Alzheimer's & dementia》2017,13(3):205-216
Introduction
Our goal was to develop cut points for amyloid positron emission tomography (PET), tau PET, flouro-deoxyglucose (FDG) PET, and MRI cortical thickness.Methods
We examined five methods for determining cut points.Results
The reliable worsening method produced a cut point only for amyloid PET. The specificity, sensitivity, and accuracy of cognitively impaired versus young clinically normal (CN) methods labeled the most people abnormal and all gave similar cut points for tau PET, FDG PET, and cortical thickness. Cut points defined using the accuracy of cognitively impaired versus age-matched CN method labeled fewer people abnormal.Discussion
In the future, we will use a single cut point for amyloid PET (standardized uptake value ratio, 1.42; centiloid, 19) based on the reliable worsening cut point method. We will base lenient cut points for tau PET, FDG PET, and cortical thickness on the accuracy of cognitively impaired versus young CN method and base conservative cut points on the accuracy of cognitively impaired versus age-matched CN method. 相似文献6.
Clifford R. Jack David A. Bennett Kaj Blennow Maria C. Carrillo Billy Dunn Samantha Budd Haeberlein David M. Holtzman William Jagust Frank Jessen Jason Karlawish Enchi Liu Jose Luis Molinuevo Thomas Montine Creighton Phelps Katherine P. Rankin Christopher C. Rowe Philip Scheltens Eric Siemers Nina Silverberg 《Alzheimer's & dementia》2018,14(4):535-562
In 2011, the National Institute on Aging and Alzheimer's Association created separate diagnostic recommendations for the preclinical, mild cognitive impairment, and dementia stages of Alzheimer's disease. Scientific progress in the interim led to an initiative by the National Institute on Aging and Alzheimer's Association to update and unify the 2011 guidelines. This unifying update is labeled a “research framework” because its intended use is for observational and interventional research, not routine clinical care. In the National Institute on Aging and Alzheimer's Association Research Framework, Alzheimer's disease (AD) is defined by its underlying pathologic processes that can be documented by postmortem examination or in vivo by biomarkers. The diagnosis is not based on the clinical consequences of the disease (i.e., symptoms/signs) in this research framework, which shifts the definition of AD in living people from a syndromal to a biological construct. The research framework focuses on the diagnosis of AD with biomarkers in living persons. Biomarkers are grouped into those of β amyloid deposition, pathologic tau, and neurodegeneration [AT(N)]. This ATN classification system groups different biomarkers (imaging and biofluids) by the pathologic process each measures. The AT(N) system is flexible in that new biomarkers can be added to the three existing AT(N) groups, and new biomarker groups beyond AT(N) can be added when they become available. We focus on AD as a continuum, and cognitive staging may be accomplished using continuous measures. However, we also outline two different categorical cognitive schemes for staging the severity of cognitive impairment: a scheme using three traditional syndromal categories and a six-stage numeric scheme. It is important to stress that this framework seeks to create a common language with which investigators can generate and test hypotheses about the interactions among different pathologic processes (denoted by biomarkers) and cognitive symptoms. We appreciate the concern that this biomarker-based research framework has the potential to be misused. Therefore, we emphasize, first, it is premature and inappropriate to use this research framework in general medical practice. Second, this research framework should not be used to restrict alternative approaches to hypothesis testing that do not use biomarkers. There will be situations where biomarkers are not available or requiring them would be counterproductive to the specific research goals (discussed in more detail later in the document). Thus, biomarker-based research should not be considered a template for all research into age-related cognitive impairment and dementia; rather, it should be applied when it is fit for the purpose of the specific research goals of a study. Importantly, this framework should be examined in diverse populations. Although it is possible that β-amyloid plaques and neurofibrillary tau deposits are not causal in AD pathogenesis, it is these abnormal protein deposits that define AD as a unique neurodegenerative disease among different disorders that can lead to dementia. We envision that defining AD as a biological construct will enable a more accurate characterization and understanding of the sequence of events that lead to cognitive impairment that is associated with AD, as well as the multifactorial etiology of dementia. This approach also will enable a more precise approach to interventional trials where specific pathways can be targeted in the disease process and in the appropriate people. 相似文献
7.
《Alzheimer's & dementia》2014,10(4):421-429.e3
BackgroundRegulatory qualification of a biomarker for a defined context of use provides scientifically robust assurances to sponsors and regulators that accelerate appropriate adoption of biomarkers into drug development.MethodsThe Coalition Against Major Diseases submitted a dossier to the Scientific Advice Working Party of the European Medicines Agency requesting a qualification opinion on the use of hippocampal volume as a biomarker for enriching clinical trials in subjects with mild cognitive impairment, incorporating a scientific rationale, a literature review and a de novo analysis of Alzheimer's Disease Neuroimaging Initiative data.ResultsThe literature review and de novo analysis were consistent with the proposed context of use, and the Committee for Medicinal Products for Human Use released an opinion in November 2011.ConclusionsWe summarize the scientific rationale and the data that supported the first qualification of an imaging biomarker by the European Medicines Agency. 相似文献
8.
Jeffrey Cummings 《Alzheimer's & dementia》2019,15(1):172-178
Introduction
The National Institute on Aging—Alzheimer's Association Research Framework on Alzheimer's disease (AD) represents an important advance in the biological characterization of the AD spectrum.Methods
The National Institute on Aging—Alzheimer's Association Framework is considered as it applies to clinical trials.Results
Using the combination of amyloid (A), tau (T), and neurodegeneration (N) biomarkers, the Framework provides a means of defining the state of patients with regard to Alzheimer pathologic change. The Framework is relevant to clinical trials of disease-modifying agents, allowing participants to be characterized biologically at baseline. The ATN Framework can also inform trial outcomes. The preclinical phase of the disease after amyloid deposition is defined by A+T?N?, and the transition to prodromal disease and dementia is characterized by the addition of T and N. Most symptomatic patients in clinical trials are in the class of A+T+N? and A+T+N+.Discussion
The National Institute on Aging—Alzheimer's Association Framework on AD represents progress in providing biomarker profiles of participants in the AD spectrum that can be used to help design clinical trials. 相似文献9.
Olivier Hanon Jean-Sébastien Vidal Sylvain Lehmann Stéphanie Bombois Bernadette Allinquant Jean-Marc Tréluyer Patrick Gelé Christine Delmaire Fredéric Blanc Jean-François Mangin Luc Buée Jacques Touchon Jacques Hugon Bruno Vellas Evelyne Galbrun Athanase Benetos Gilles Berrut Elèna Paillaud Suzanna Schraen-Maschke 《Alzheimer's & dementia》2018,14(7):858-868
Introduction
Diagnostic relevance of plasma amyloid β (Aβ) for Alzheimer's disease (AD) process yields conflicting results. The objective of the study was to assess plasma levels of Aβ42 and Aβ40 in amnestic mild cognitive impairment (MCI), nonamnestic MCI, and AD patients and to investigate relationships between peripheral and central biomarkers.Methods
One thousand forty participants (417 amnestic MCI, 122 nonamnestic MCI, and 501 AD) from the Biomarker of AmyLoïd pepTide and AlZheimer's diseAse Risk multicenter prospective study with cognition, plasma, cerebrospinal fluid (CSF), and magnetic resonance imaging assessments were included.Results
Plasma Aβ1–42 and Aβ1–40 were lower in AD (36.9 [11.7] and 263 [80] pg/mL) than in amnestic MCI (38.2 [11.9] and 269 [68] pg/mL) than in nonamnestic MCI (39.7 [10.5] and 272 [52] pg/mL), respectively (P = .01 for overall difference between groups for Aβ1–42 and P = .04 for Aβ1–40). Globally, plasma Aβ1–42 correlated with age, Mini–Mental State Examination, and APOE ε4 allele. Plasma Aβ1–42 correlated with all CSF biomarkers in MCI but only with CSF Aβ42 in AD.Discussion
Plasma Aβ was associated with cognitive status and CSF biomarkers, suggesting the interest of plasma amyloid biomarkers for diagnosis purpose. 相似文献10.
Peng Li Lei Yu Andrew S.P. Lim Aron S. Buchman Frank A.J.L. Scheer Steven A. Shea Julie A. Schneider David A. Bennett Kun Hu 《Alzheimer's & dementia》2018,14(9):1114-1125
Introduction
Healthy physiological systems exhibit fractal regulation (FR), generating similar fluctuation patterns in physiological outputs across different time scales. FR in motor activity is degraded in dementia, and the degradation correlates to cognitive decline. We tested whether degraded FR predicts Alzheimer's dementia.Methods
FR in motor activity was assessed in 1097 nondemented older adults at baseline. Cognition was assessed annually for up to 11 years.Results
Participants with an FR metric at the 10th percentile in this cohort had a 1.8-fold Alzheimer's disease risk (equivalent to the effect of being ～5.2 years older) and 1.3-fold risk for mild cognitive impairment (equivalent to the effect of being ～3.0 years older) than those at the 90th percentile. Consistently, degraded FR predicted faster cognitive decline. These associations were independent of physical activity, sleep fragmentation, and stability of daily activity rhythms.Discussion
FR may be a useful tool for predicting Alzheimer's dementia. 相似文献11.
Background
In spite of their extensive use, the ecological relevance of tasks dedicated to assessing real-world decision-making in a laboratory setting remains unclear.Objectives
Our study aimed to evaluate the relationship between decision-making and behavioral competency and awareness of limitations.Methods
A total of 20 patients with Alzheimer's disease (AD), 20 with amnestic mild cognitive impairment (aMCI) and 20 healthy controls (HC) were assessed for decision-making using the Iowa Gambling Task (IGT). Behavioral competency was evaluated by the Patient Competency Rating Scale (PCRS), which requires each participant and a relative to answer the same 30 questions on participant's competency and to rate each item, while awareness of limitations was evaluated by subtracting the self-rated score from the relative-rated score.Results
Using the median-split approach, the proportion of disadvantageous decision-makers was higher in both the MCI and AD groups than in HC (P = 0.02 and P = 0.03, respectively), with no differences between clinical groups. The percentage of participants with poorer behavioral competency was also higher in the MCI and AD than in the HC (self-rated: P = 0.025 and P = 0.01, respectively; relative-rated: P = 0.008 and P = 0.008, respectively), again with no differences between MCI and AD. All groups were comparable in awareness. For all participants, disadvantageous decision-making was associated with both reduced behavioral competency and poor awareness of limitations (OR: 3.47, P = 0.03 and OR: 5.4, P = 0.004, respectively).Conclusion
Our findings support the ecological relevance of the IGT. Behavioral competency integrity and awareness of limitations are both associated with advantageous decision-making profiles. 相似文献12.
《Alzheimer's & dementia》2019,15(10):1322-1332
IntroductionThe low mild cognitive impairment (MCI) to cognitively normal (CN) reversion rate in the Alzheimer's Disease Neuroimaging Initiative (2-3%) suggests the need to examine reversion by other means. We applied comprehensive neuropsychological criteria (NP criteria) to determine the resulting MCI to CN reversion rate.MethodsParticipants with CN (n = 641) or MCI (n = 569) were classified at baseline and year 1 using NP criteria. Demographic, neuropsychological, and Alzheimer's disease biomarker variables as well as progression to dementia were examined across stable CN, reversion, and stable MCI groups.ResultsNP criteria produced a one-year reversion rate of 15.8%. Reverters had demographics, Alzheimer's disease biomarkers, and risk-of-progression most similar to the stable CN group and showed the most improvement on neuropsychological measures from baseline to year 1.DiscussionNP criteria produced a reversion rate that is consistent with, albeit modestly improved from, reversion rates in meta-analyses. Reverters’ biomarker profiles and progression rates suggest that NP criteria accurately tracked with underlying pathophysiologic status. 相似文献
13.
Silvia Rios-Romenets Hugo Lopez Liliana Lopez Liliana Hincapie Amanda Saldarriaga Lucia Madrigal Francisco Piedrahita Alex Navarro Juliana Acosta-Uribe Laura Ramirez Margarita Giraldo Natalia Acosta-Baena Sebastián Sánchez Claudia Ramos Claudia Muñoz Ana Baena Diana Alzate Paula Ospina Francisco Lopera 《Alzheimer's & dementia》2017,13(5):602-605
14.
Antoine Leuzy Elena Rodriguez-Vieitez Laure Saint-Aubert Konstantinos Chiotis Ove Almkvist Irina Savitcheva My Jonasson Mark Lubberink Anders Wall Gunnar Antoni Agneta Nordberg 《Alzheimer's & dementia》2018,14(5):652-663
Introduction
Cross-sectional findings using the tau tracer [18F]THK5317 (THK5317) have shown that [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) data can be approximated using perfusion measures (early-frame standardized uptake value ratio; ratio of tracer delivery in target to reference regions). In this way, a single PET study can provide both functional and molecular information.Methods
We included 16 patients with Alzheimer's disease who completed follow-up THK5317 and FDG studies 17 months after baseline investigations. Linear mixed-effects models and annual percentage change maps were used to examine longitudinal change.Results
Limited spatial overlap was observed between areas showing declines in THK5317 perfusion measures and FDG. Minimal overlap was seen between areas showing functional change and those showing increased retention of THK5317.Discussion
Our findings suggest a spatiotemporal offset between functional changes and tau pathology and a partial uncoupling between perfusion and metabolism, possibly as a function of Alzheimer's disease severity. 相似文献15.
Shoichi Sasaki 《Alzheimer's & dementia》2018,14(12):1615-1622
Introduction
The objective of this study was to examine the prevalence of the coexistence of parkinsonism in patients with mild cognitive impairment (MCI) or mild Alzheimer's disease (AD).Methods
Outpatients were evaluated with Mini–Mental State Examination, Clinical Dementia Rating Scale, NIA-AA criteria, MRI, and 123I-IMP SPECT (3D-SSP). Parkinsonism in patients diagnosed with MCI (Mini–Mental State Examination ≥24, n = 63) or mild AD (Mini–Mental State Examination 20–23, n = 43) was examined using the Unified Parkinson's Disease Rating Scale–III and 123I-FP-CIT dopamine transporter SPECT.Results
One hundred six patients (60–97 years) were enrolled. Fifty-six patients (52.8%) were diagnosed as having concomitant parkinsonism with rigidity and resting tremor and dopamine transporter reduction in the basal ganglia. The mean (SD) age (n = 56) was 80.6 (6.1) years, significantly older than patients without parkinsonism [77.6 (7.0) years, n = 50] (P < .05). The mean (SD) UPDRS–III score was 5.8 (2.4).Conclusion
The prevalence rate of the coexistence of mild parkinsonism in MCI or mild AD may be higher than previously recognized. 相似文献16.
Sanna-Kaisa Herukka Anja Hviid Simonsen Niels Andreasen Ines Baldeiras Maria Bjerke Kaj Blennow Sebastiaan Engelborghs Giovanni B. Frisoni Tomasz Gabryelewicz Samantha Galluzzi Ron Handels Milica G. Kramberger Agnieszka Kulczyńska Jose Luis Molinuevo Barbara Mroczko Agneta Nordberg Catarina Resende Oliveira Markus Otto Gunhild Waldemar 《Alzheimer's & dementia》2017,13(3):285-295
This article presents recommendations, based on the Grading of Recommendations, Assessment, Development, and Evaluation method, for the clinical application of cerebrospinal fluid (CSF) amyloid-β1–42, tau, and phosphorylated tau in the diagnostic evaluation of patients with mild cognitive impairment (MCI). The recommendations were developed by a multidisciplinary working group and based on the available evidence and consensus from focused group discussions for 1) prediction of clinical progression to Alzheimer's disease (AD) dementia, 2) cost-effectiveness, 3) interpretation of results, and 4) patient counseling. The working group recommended using CSF AD biomarkers in the diagnostic workup of MCI patients, after prebiomarker counseling, as an add-on to clinical evaluation to predict functional decline or conversion to AD dementia and to guide disease management. Because of insufficient evidence, it was uncertain whether CSF AD biomarkers outperform imaging biomarkers. Furthermore, the working group provided recommendations for interpretation of ambiguous CSF biomarker results and for pre- and post-biomarker counseling. 相似文献
17.
Seok Woo Moon Ivo D. Dinov Alen Zamanyan Ran Shi Alex Genco Sam Hobel Paul M. Thompson Arthur W. Toga Alzheimer's Disease Neuroimaging Initiative 《Psychiatry investigation》2015,12(1):125-135
Objective
This article investigates subjects aged 55 to 65 from the Alzheimer''s Disease Neuroimaging Initiative (ADNI) database to broaden our understanding of early-onset (EO) cognitive impairment using neuroimaging and genetics biomarkers.Methods
Nine of the subjects had EO-AD (Alzheimer''s disease) and 27 had EO-MCI (mild cognitive impairment). The 15 most important neuroimaging markers were extracted with the Global Shape Analysis (GSA) Pipeline workflow. The 20 most significant single nucleotide polymorphisms (SNPs) were chosen and were associated with specific neuroimaging biomarkers.Results
We identified associations between the neuroimaging phenotypes and genotypes for a total of 36 subjects. Our results for all the subjects taken together showed the most significant associations between rs7718456 and L_hippocampus (volume), and between rs7718456 and R_hippocampus (volume). For the 27 MCI subjects, we found the most significant associations between rs6446443 and R_superior_frontal_gyrus (volume), and between rs17029131 and L_Precuneus (volume). For the nine AD subjects, we found the most significant associations between rs16964473 and L_rectus gyrus (surface area), and between rs12972537 and L_rectus_gyrus (surface area).Conclusion
We observed significant correlations between the SNPs and the neuroimaging phenotypes in the 36 EO subjects in terms of neuroimaging genetics. However, larger sample sizes are needed to ensure that the effects will be detectable for a reasonable false-positive error rate using the GSA and Plink Pipeline workflows. 相似文献18.
Stefan J. Teipel Enrica Cavedo Simone Lista Marie-Odile Habert Marie-Claude Potier Michel J. Grothe Stephane Epelbaum Luisa Sambati Geoffroy Gagliardi Nicola Toschi Michael D. Greicius Bruno Dubois Harald Hampel 《Alzheimer's & dementia》2018,14(9):1126-1136
Introduction
Cognitive change in people at risk of Alzheimer's disease (AD) such as subjective memory complainers is highly variable across individuals.Methods
We used latent class growth modeling to identify distinct classes of nonlinear trajectories of cognitive change over 2 years follow-up from 265 subjective memory complainers individuals (age 70 years and older) of the INSIGHT-preAD cohort. We determined the effect of cortical amyloid load, hippocampus and basal forebrain volumes, and education on the cognitive trajectory classes.Results
Latent class growth modeling identified distinct nonlinear cognitive trajectories. Education was associated with higher performing trajectories, whereas global amyloid load and basal forebrain atrophy were associated with lower performing trajectories.Discussion
Distinct classes of cognitive trajectories were associated with risk and protective factors of AD. These associations support the notion that the identified cognitive trajectories reflect different risk for AD that may be useful for selecting high-risk individuals for intervention trials. 相似文献19.
David S. Knopman Samantha Budd Haeberlein Maria C. Carrillo James A. Hendrix Geoff Kerchner Richard Margolin Paul Maruff David S. Miller Gary Tong Maria B. Tome Melissa E. Murray Peter T. Nelson Mary Sano Niklas Mattsson David L. Sultzer Thomas J. Montine Clifford R. Jack Hartmuth Kolb Eric Siemers 《Alzheimer's & dementia》2018,14(4):563-575
The Alzheimer's Association's Research Roundtable met in November 2017 to explore the new National Institute on Aging and the Alzheimer's Association Research Framework for Alzheimer's disease. The meeting allowed experts in the field from academia, industry, and government to provide perspectives on the new National Institute on Aging and the Alzheimer's Association Research Framework. This review will summarize the “A, T, N System” (Amyloid, Tau, and Neurodegeneration) using biomarkers and how this may be applied to clinical research and drug development. In addition, challenges and barriers to the potential adoption of this new framework will be discussed. Finally, future directions for research will be proposed. 相似文献
20.
David A. Drachman Thomas W. Smith Bassam Alkamachi Kevin Kane 《Alzheimer's & dementia》2017,13(12):1389-1396