Structural neuroimaging findings in Alzheimer’s disease: coordinate based random effect size meta-analyses of voxel-based morphometry studies

Background: The Amyloid Tau Neurodegeneration (ATN) framework was proposed to define the biological state underpinning Alzheimer’s disease (AD). Blood-based biomarkers offer a scalable alternative to the costly and invasive currently available biomarkers. Objective: In this meta-analysis we sought to assess the diagnostic performance of plasma amyloid (Aβ40, Aβ42, Aβ42/40 ratio), tangle (p-tau181), and neurodegeneration (total tau [t-tau], neurofilament light [NfL]) biomarkers. Methods: Electronic databases were screened for studies reporting biomarker concentrations for AD and control cohorts. Biomarker performance was examined by random-effect meta-analyses based on the ratio between biomarker concentrations in patients and controls. Results: 83 studies published between 1996 and 2020 were included in the analyses. Aβ42/40 ratio as well as Aβ42 discriminated AD patients from controls when using novel platforms such as immunomagnetic reduction (IMR). We found significant differences in ptau-181 concentration for studies based on single molecule array (Simoa), but not for studies based on IMR or ELISA. T-tau was significantly different between AD patients and control in IMR and Simoa but not in ELISA-based studies. In contrast, NfL differentiated between groups across platforms. Exosome studies showed strong separation between patients and controls for Aβ42, t-tau, and p-tau181. Conclusion: Currently available assays for sampling plasma ATN biomarkers appear to differentiate between AD patients and controls. Novel assay methodologies have given the field a significant boost for testing these biomarkers, such as IMR for Aβ, Simoa for p-tau181. Enriching samples through extracellular vesicles shows promise but requires further validation.

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Plasma Proteomic Biomarkers Relating to Alzheimer’s Disease: A Meta-Analysis Based on Our Own Studies

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.712545 ◽

2021 ◽

Vol 13 ◽

Author(s):

Liu Shi ◽

Noel J. Buckley ◽

Isabelle Bos ◽

Sebastiaan Engelborghs ◽

Kristel Sleegers ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Meta Analysis ◽

Random Effect ◽

Blood Biomarkers ◽

Gamma Chain ◽

Significant Difference ◽

The Mean ◽

Meta Analyses ◽

Complement Component 4

Background and Objective: Plasma biomarkers for the diagnosis and stratification of Alzheimer’s disease (AD) are intensively sought. However, no plasma markers are well established so far for AD diagnosis. Our group has identified and validated various blood-based proteomic biomarkers relating to AD pathology in multiple cohorts. The study aims to conduct a meta-analysis based on our own studies to systematically assess the diagnostic performance of our previously identified blood biomarkers.Methods: To do this, we included seven studies that our group has conducted during the last decade. These studies used either Luminex xMAP or ELISA to measure proteomic biomarkers. As proteins measured in these studies differed, we selected protein based on the criteria that it must be measured in at least four studies. We then examined biomarker performance using random-effect meta-analyses based on the mean difference between biomarker concentrations in AD and controls (CTL), AD and mild cognitive impairment (MCI), MCI, and CTL as well as MCI converted to dementia (MCIc) and non-converted (MCInc) individuals.Results: An overall of 2,879 subjects were retrieved for meta-analysis including 1,053 CTL, 895 MCI, 882 AD, and 49 frontotemporal dementia (FTD) patients. Six proteins were measured in at least four studies and were chosen for meta-analyses for AD diagnosis. Of them, three proteins had significant difference between AD and controls, among which alpha-2-macroglobulin (A2M) and ficolin-2 (FCN2) increased in AD while fibrinogen gamma chain (FGG) decreased in AD compared to CTL. Furthermore, FGG significantly increased in FTD compared to AD. None of the proteins passed the significance between AD and MCI, or MCI and CTL, or MCIc and MCInc, although complement component 4 (CC4) tended to increase in MCIc individuals compared to MCInc.Conclusions: The results suggest that A2M, FCN2, and FGG are promising biomarkers to discriminate AD patients from controls, which are worthy of further validation.

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Voxel-based morphometry (VBM) analysis in Alzheimer's disease an insight into heterogeneity of cerebral atrophy

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/sj.jcbfm.9591524.0338 ◽

2005 ◽

Vol 25 (1_suppl) ◽

pp. S338-S338

Author(s):

Akihiko Shiino ◽

Toshiyuki Watanabe ◽

Ichiro Akiguchi ◽

Shigehiro Morikawa ◽

Toshiro Inubushi ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebral Atrophy ◽

Voxel Based Morphometry ◽

Insight Into

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Controls-based denoising of voxel-based morphometry and multimodal imaging data improves prediction of conversion to Alzheimer’s disease

10.1055/s-0040-1708146 ◽

2020 ◽

Author(s):

D Blum ◽

C la Fougère ◽

M Reimold

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Multimodal Imaging ◽

Imaging Data ◽

Voxel Based Morphometry

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Reproducibility of Brain Volume Changes in Longitudinal Voxel-Based Morphometry Between Non-Accelerated and Accelerated Magnetic Resonance Imaging

Journal of Alzheimer s Disease ◽

10.3233/jad-210596 ◽

2021 ◽

pp. 1-10

Author(s):

Hidemasa Takao ◽

Shiori Amemiya ◽

Osamu Abe ◽

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Magnetic Resonance ◽

Gray Matter ◽

Gray Matter Volume ◽

Elderly Subjects ◽

Voxel Based Morphometry ◽

Volume Changes ◽

Matter Volume ◽

Healthy Elderly

Background: Scan acceleration techniques, such as parallel imaging, can reduce scan times, but reliability is essential to implement these techniques in neuroimaging. Objective: To evaluate the reproducibility of the longitudinal changes in brain morphology determined by longitudinal voxel-based morphometry (VBM) between non-accelerated and accelerated magnetic resonance images (MRI) in normal aging, mild cognitive impairment (MCI), and Alzheimer’s disease (AD). Methods: Using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) 2 database, comprising subjects who underwent non-accelerated and accelerated structural T1-weighted MRI at screening and at a 2-year follow-up on 3.0 T Philips scanners, we examined the reproducibility of longitudinal gray matter volume changes determined by longitudinal VBM processing between non-accelerated and accelerated imaging in 50 healthy elderly subjects, 54 MCI patients, and eight AD patients. Results: The intraclass correlation coefficient (ICC) maps differed among the three groups. The mean ICC was 0.72 overall (healthy elderly, 0.63; MCI, 0.75; AD, 0.63), and the ICC was good to excellent (0.6–1.0) for 81.4%of voxels (healthy elderly, 64.8%; MCI, 85.0%; AD, 65.0%). The differences in image quality (head motion) were not significant (Kruskal–Wallis test, p = 0.18) and the within-subject standard deviations of longitudinal gray matter volume changes were similar among the groups. Conclusion: The results indicate that the reproducibility of longitudinal gray matter volume changes determined by VBM between non-accelerated and accelerated MRI is good to excellent for many regions but may vary between diseases and regions.

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IC-P-020: A voxel-based morphometry study of volumetric MRI in familial Alzheimer's disease

Alzheimer s & Dementia ◽

10.1016/j.jalz.2012.05.052 ◽

2012 ◽

Vol 8 (4S_Part_1) ◽

pp. P17-P18

Author(s):

David Cash ◽

Gerard Ridgway ◽

Natalie Ryan ◽

Kirsi Kinnunen ◽

Tom Yeatman ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Voxel Based Morphometry ◽

Volumetric Mri ◽

Familial Alzheimer’S Disease ◽

Familial Alzheimer's Disease

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Comparison of effects of different dietary interventions on cognitive function in Alzheimer’s disease: protocol for systematic review and network meta-analysis

BMJ Open ◽

10.1136/bmjopen-2020-042997 ◽

2021 ◽

Vol 11 (1) ◽

pp. e042997

Author(s):

Lili Chen ◽

Xinhua Xu ◽

Huizhen Cao ◽

Hong Li

Keyword(s):

Systematic Review ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Function ◽

Risk Of Bias ◽

Evaluation Framework ◽

Controlled Trials ◽

Cochrane Central Register ◽

Dietary Interventions ◽

Meta Analyses

IntroductionAlzheimer’s disease (AD) is the most common neurodegenerative disease and is characterised by cognitive impairment. Non-pharmacological treatments such as diet therapy have been widely investigated in studies on AD. Given the synergistic effects of nutrients present in foods, considering overall dietary composition rather than focusing on a single nutrient may be more useful for evaluating the relationship between diet and AD cognition. The present study aimed to assess the efficacy of different dietary interventions (eg, ketogenic and Mediterranean diets) on cognitive function in patients with AD in a systematic review and pairwise and network meta-analyses of randomised controlled trials or clinical trials.Methods and analysisTwo reviewers will independently conduct searches of PubMed, Cochrane Central Register of Controlled Trials, Embase, CINAHL, PsycINFO and China National Knowledge Infrastructure databases. Data will be extracted from selected studies and risk of bias will be assessed using the revised Cochrane risk-of-bias tool, and evidence quality will be assessed according to the Grading of Recommendations, Assessment, Development and Evaluation framework. The primary outcome of interest is cognitive function in patients with AD; secondary outcomes include biochemical biomarkers of AD and oxidative stress and/or inﬂammatory biomarkers in cerebrospinal fluid or plasma. For each outcome, random-effects pairwise and network meta-analyses will be carried out to determine the pooled relative effect of each intervention relative to every other intervention.Ethics and disseminationAs this study is based solely on published literature, no ethics approval is required. The research will be published in a peer-reviewed journal.

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Influence of Educational Attainment on Cognition-Based Intervention Programs for Persons with Mild Alzheimer’s Disease

Journal of the International Neuropsychological Society ◽

10.1017/s135561771600014x ◽

2016 ◽

Vol 22 (5) ◽

pp. 577-582 ◽

Cited By ~ 4

Author(s):

Israel Contador ◽

Bernardino Fernández-Calvo ◽

Francisco Ramos ◽

Javier Olazarán

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Decline ◽

Effect Size ◽

Study Groups ◽

Total Sample ◽

Cognitive Intervention ◽

Potential Effect ◽

Cognitive Status ◽

Disease Assessment

AbstractObjectives: This research retrospectively analyzed the effect of education on cognitive interventions carried out in patients with mild Alzheimer’s disease (AD). Methods: The total sample consisted of 75 patients with mild AD receiving treatment with cholinesterase inhibitors. The participants were divided into two groups: cognitive intervention (IG; n=45) and waiting list (WLG; n=30). Patients in the IG received either the Big Brain Academy (n=15) or the Integrated Psychostimulation Program (n=30) during 12 weeks. The influence of education on intervention effect was analyzed comparing mean change scores of the two study groups in the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog), stratified by educational level. The potential effect of age, sex, cognitive status, and type of intervention was examined using post hoc stratification analyses. Results: Higher education was associated with faster cognitive decline in the WLG (effect size=0.51; p<.01). However, cognitive evolution was not influenced by education in the IG (effect size=0.12; p=.42). Conclusions: Our results suggest that cognitive intervention might delay accelerated cognitive decline in higher educated individuals with mild AD. (JINS, 2016, 23, 1–6)

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