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1.
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2.
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3.
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
4.
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5.
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6.
Shahzad Ahmad Christian Bannister Sven J. van der Lee Dina Vojinovic Hieab H.H. Adams Alfredo Ramirez Valentina Escott-Price Rebecca Sims Emily Baker Julie Williams Peter Holmans Meike W. Vernooij M. Arfan Ikram Najaf Amin Cornelia M. van Duijn 《Alzheimer's & dementia》2018,14(7):848-857
Introduction
Exploring the role of Alzheimer's disease (AD) implicated pathways in the predementia phase may provide new insight for preventive and clinical trials targeting disease specific pathways.Methods
We constructed weighted Genetic risk scores, first based on 20 genome-wide significant AD risk variants and second clustering these variants within pathways. Risk scores were investigated for their association with AD, mild cognitive impairment, and brain magnetic resonance imaging phenotypes including white matter lesions, hippocampal volume, and brain volume.Results
The risk score capturing endocytosis pathway was significantly associated with mild cognitive impairment (P = 1.44 × 10?4). Immune response (P = .016) and clathrin/AP2 adaptor complex pathway (P = 3.55 × 10?3) excluding apolipoprotein E also showed modest association with white matter lesions but did not sustain Bonferroni correction (P = 9.09 × 10?4).Discussion
Our study suggests that the clinical spectrum of early AD pathology is explained by different biological pathways, in particular, the endocytosis, clathrin/AP2 adaptor complex, and immune response pathways, that are independent of apolipoprotein E (APOE). 相似文献7.
The rapidly increasing prevalence of cognitive impairment and Alzheimer’s disease has the potential to create a major worldwide healthcare crisis. Structural MRI studies in patients with Alzheimer’s disease and mild cognitive impairment are currently attracting considerable interest. It is extremely important to study early structural and metabolic changes, such as those in the hippocampus, entorhinal cortex, and gray matter structures in the medial temporal lobe, to allow the early detection of mild cognitive impairment and Alzheimer’s disease. The microstructural integrity of white matter can be studied with diffusion tensor imaging. Increased mean diffusivity and decreased fractional anisotropy are found in subjects with white matter damage. Functional imaging studies with positron emission tomography tracer compounds enable detection of amyloid plaques in the living brain in patients with Alzheimer’s disease. In this review, we will focus on key findings from brain imaging studies in mild cognitive impairment and Alzheimer’s disease, including structural brain changes studied with MRI and white matter changes seen with diffusion tensor imaging, and other specific imaging methodologies will also be discussed. 相似文献
8.
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9.
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
10.
11.
Takeshi Iwatsubo Atsushi Iwata Kazushi Suzuki Ryoko Ihara Hiroyuki Arai Kenji Ishii Michio Senda Kengo Ito Takeshi Ikeuchi Ryozo Kuwano Hiroshi Matsuda Chung-Kai Sun Laurel A. Beckett Ronald C. Petersen Michael W. Weiner Paul S. Aisen Michael C. Donohue 《Alzheimer's & dementia》2018,14(8):1077-1087
Introduction
We conducted Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI) and compared the basic characteristics and progression profiles with those of ADNI in North America.Methods
A total of 537 Japanese subjects with normal cognition, late amnestic mild cognitive impairment (LMCI), or mild Alzheimer's disease (AD) were enrolled using the same criteria as ADNI. Rates of changes in representative cognitive or functional measures were compared for amyloid positron emission tomography- or cerebrospinal fluid amyloid β(1–42)-positive LMCI and mild AD between J-ADNI and ADNI.Results
Amyloid positivity rates were significantly higher in normal cognition of ADNI but at similar levels in LMCI and mild AD between J-ADNI and ADNI. Profiles of decline in cognitive or functional measures in amyloid-positive LMCI in J-ADNI (n = 75) and ADNI (n = 269) were remarkably similar, whereas those in mild AD were milder in J-ADNI (n = 73) compared with ADNI (n = 230).Discussion
These results support the feasibility of bridging of clinical trials in the prodromal stage of AD between Asia and western countries. 相似文献12.
目的评估帕金森病(Parkinson’s disease,PD)患者的认知功能状态,分析帕金森病合并轻度认知功能障碍(Parkinson’s Disease with Mild Cognitive Impairment,PD-MCI)的特点。方法纳入PD患者64例,采用神经心理测试组评估其注意、视空间、执行和记忆等认知域的功能。结果本组PD患者中,认知功能正常24例(37.5%),PD-MCI 30例(46.9%),帕金森病痴呆10例(15.6%)。在PD-MCI患者中,单个认知领域轻度损害(60.0%)较多个认知域型轻度认知损害(40.0%)更常见,累及较多的认知域依次为记忆(20例,66.7%),执行(13例,43.3%),视空间(12例,36.7%)。早期PD患者PD-MCI发生率为36.4%,痴呆发生率为3.0%;中晚期PD患者PD-MCI发生率为58.1%,痴呆发生率达29.0%,两组差异有显著性(χ2=18.222,P<0.001)。PD患者的病情程度与认知功能状态呈负相关(Spearman相关系数=-0.553,P<0.001)。结论轻度认知功能障碍(mild cogni-tive impairment,MCI)在PD患者中常见,即使在疾病早期,其发生率也较高,其中单个认知领域轻度损害较多个认知域型轻度认知损害更常见。PD患者的病情越严重,认知功能状态越差。 相似文献
13.
Subjective memory complaints in Chinese subjects with mild cognitive impairment and early Alzheimer's disease 总被引：2，自引：0，他引：2
BACKGROUND: Mild cognitive impairment (MCI) represents a transitional state between normal aging and dementia. However, there is inconsistent opinion as to the validity of subjective memory complaints as a criterion for diagnosis. OBJECTIVE: This study aimed to examine the potential significance of applying a short memory questionnaire in the assessment of Chinese subjects with MCI and early dementia. METHODS: Three hundred and six ambulatory Chinese subjects were recruited. Each participant completed a short memory questionnaire. They were also assessed with the Chinese versions of the mini-mental state examination (CMMSE), Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog), category verbal fluency test (CVFT) and span tests. Severity of cognitive impairment was evaluated using the Clinical Dementia Rating (CDR); subjects with CDR 0.5 were further classified into MCI not demented (MCIND) and MCI possible incipient dementia (MCIID) depending on the subscale scores of CDR. RESULTS: An increasing frequency of memory complaints with increasing CDR was observed (Kruskal Wallis test, chi square = 21.29, df 3, p < 0.001). With a cutoff of 3 or more memory complaints, the memory questionnaire demonstrated a sensitivity of 65.3% and 70.4% in identifying subjects with incipient and early dementia respectively. Significant associations between memory complaints and most cognitive test performance were found (Spearman's correlations, p < 0.01). Logistic regression analysis revealed that educational level, the memory questionnaire, ADAS-Cog total and delayed recall scores were significant predictors of MCIID status. CONCLUSIONS: The findings suggested that a short memory questionnaire is useful in the screening of MCI, particularly in subjects who already present with subtle functioning disturbances. Subjective memory complaints were significant correlated with objective performance of memory functions, reflecting the usefulness of memory complaints in the assessment of MCI. 相似文献
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.
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16.
Rebecca A. Nebel Neelum T. Aggarwal Lisa L. Barnes Aimee Gallagher Jill M. Goldstein Kejal Kantarci Monica P. Mallampalli Elizabeth C. Mormino Laura Scott Wai Haung Yu Pauline M. Maki Michelle M. Mielke 《Alzheimer's & dementia》2018,14(9):1171-1183
Introduction
Precision medicine methodologies and approaches have advanced our understanding of the clinical presentation, development, progression, and management of Alzheimer's disease (AD) dementia. However, sex and gender have not yet been adequately integrated into many of these approaches.Methods
The Society for Women's Health Research Interdisciplinary Network on AD, comprised of an expert panel of scientists and clinicians, reviewed ongoing and published research related to sex and gender differences in AD.Results
The current review is a result of this Network's efforts and aims to: (1) highlight the current state-of-the-science in the AD field on sex and gender differences; (2) address knowledge gaps in assessing sex and gender differences; and (3) discuss 12 priority areas that merit further research.Discussion
The exclusion of sex and gender has impeded faster advancement in the detection, treatment, and care of AD across the clinical spectrum. Greater attention to these differences will improve outcomes for both sexes. 相似文献17.
Suzanne E. Schindler Yan Li Kaitlin W. Todd Elizabeth M. Herries Rachel L. Henson Julia D. Gray Guoqiao Wang Danielle L. Graham Leslie M. Shaw John Q. Trojanowski Jason J. Hassenstab Tammie L.S. Benzinger Carlos Cruchaga Mathias Jucker Johannes Levin Jasmeer P. Chhatwal James M. Noble John M. Ringman Anne M. Fagan 《Alzheimer's & dementia》2019,15(5):655-665
IntroductionFour less well-studied but promising “emerging” cerebrospinal fluid (CSF) biomarkers are elevated in late-onset Alzheimer disease (AD): neurogranin, synaptosomal-associated protein-25 (SNAP-25), visinin-like protein 1 (VILIP-1), and chitinase-3-like protein 1 (YKL-40).MethodsCSF neurogranin, SNAP-25, VILIP-1, and YKL-40 were measured in families carrying autosomal-dominant AD mutations.ResultsThe four emerging CSF biomarkers were significantly elevated in the mutation carriers (n = 235) versus noncarriers (n = 145). CSF SNAP-25, VILIP-1, and YKL-40 were altered very early in the AD time course, approximately 15–19 years before estimated symptom onset. All CSF biomarkers predicted important AD-related outcomes including performance on a cognitive composite, brain amyloid burden as measured by amyloid positron emission tomography, and the estimated years from symptom onset.DiscussionEarly abnormalities in CSF tTau, pTau, SNAP-25, VILIP-1, and YKL-40 suggest that synaptic damage, neuronal injury, and neuroinflammation begin shortly after the commencement of brain amyloid accumulation. 相似文献
18.
Karen Ritchie Michael Ropacki Bruce Albala John Harrison Jeffrey Kaye Joel Kramer Christopher Randolph Craig W. Ritchie 《Alzheimer's & dementia》2017,13(2):186-195
The Horizon 2020/IMI European Prevention of Alzheimer's Dementia (EPAD) project will undertake large-scale proof-of-concept trials in predementia Alzheimer's disease (AD). Within EPAD, the monitoring of cognitive trajectories in the preclinical period will constitute a central outcome measure; however, there are currently no clear guidelines as to how this should be achieved as most measures have been developed for the period around dementia diagnosis. The EPAD Scientific Advisory Group for Clinical and Cognitive Outcomes identified appropriate cognitive measures based on a literature search covering both cognitive correlates of preclinical brain changes from imaging studies and cognitive changes observed over time in nondementia population cohorts developing incident dementia. These measures were evaluated according to the following criteria: validity, coherence with biomarker changes, psychometric properties, cross-cultural suitability, availability of alternative forms, and normative data limited practice effects. The resulting consensus statement provides recommendations for both future drug trials and research into preclinical Alzheimer's disease. 相似文献
19.
Selina Mrdh 《中国神经再生研究》2013,8(8):760-766
Central coherence refers to the ability to interpret details of information into a whole.To date,the concept of central coherence is mainly used in research of autism,Asperger’s syndrome and recently in the research on eating disorders.The main purpose of the present study was to examine central coherence in patients with Alzheimer’s disease.Nine Alzheimer’s disease patients and ten age-and gender-matched control subjects,who differed significantly in neurological assessment,were shown a picture of a fire.Compared to control subjects,the Alzheimer’s disease patients described the picture in a fragmented way by mentioning details and separate objects without perceiving the context of the fire.In conclusion,patients with Alzheimer’s disease are at the weak end of central coherence,and hence suffer from a fragmented view of their surroundings.The findings have important clinical implications for the understanding of patients with Alzheimer’s diseaseand also for the possibility of caregivers to meet the Alzheimer’s disease individual in an appropriate way in the everyday care. 相似文献
20.
Annie M. Racine Tamara G. Fong Yun Gou Thomas G. Travison Douglas Tommet Kristen Erickson Richard N. Jones Bradford C. Dickerson Eran Metzger Edward R. Marcantonio Eva M. Schmitt Sharon K. Inouye 《Alzheimer's & dementia》2018,14(5):590-600