MEDITERRANEAN DIET AND MAGNETIC RESONANCE IMAGING-ASSESSED BRAIN ATROPHY IN COGNITIVELY NORMAL INDIVIDUALS AT RISK FOR ALZHEIMER’S DISEASE

2014 ◽  
pp. 1-10
Author(s):  
L. Mosconi ◽  
J. Murray ◽  
W.H. Tsui ◽  
Y. Li ◽  
M. Davies ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mediterranean Diet ◽  
Brain Atrophy ◽  
Tissue Loss ◽  
Middle Temporal Gyrus ◽  
Intracranial Volume ◽  
Cross Sectional ◽  
Cognitively Normal ◽  
Lower Adherence

OBJECTIVES: Epidemiological evidence linking diet, one of the most important modifiable environmental factors, and risk of Alzheimer’s disease (AD) is rapidly increasing. Several studies have shown that higher adherence to a Mediterranean diet (MeDi) is associated with reduced risk of AD. This study examines the associations between high vs. lower adherence to a MeDi and structural MRI-based brain atrophy in key regions for AD in cognitively normal (NL) individuals with and without risk factors for AD. DESIGN: Cross-sectional study. SETTING: Manhattan (broader area). PARTICIPANTS: Fifty-two NL individuals (age 54+12 y, 70% women) with complete dietary information and cross-sectional, 3D T1-weighted MRI scans were examined. MEASUREMENTS: Subjects were dichotomized into those showing higher vs. lower adherences to the MeDi using published protocols. Estimates of cortical thickness for entorhinal cortex (EC), inferior parietal lobe, middle temporal gyrus, orbitofrontal cortex (OFC) and posterior cingulate cortex (PCC) were obtained by use of automated segmentation tools (FreeSurfer). Multivariate general linear models and linear regressions assessed the associations of MeDi with MRI measures. RESULTS: Of the 52 participants, 20 (39%) showed higher MeDi adherence (MeDi+) and 32 (61%) showed lower adherence (MeDi-). Groups were comparable for clinical, neuropsychological measures, presence of a family history of AD (FH), and frequency of Apolipoprotein E (APOE) ε4 genotype. With and without controlling for age and total intracranial volume, MeDi+ subjects showed greater thickness of AD-vulnerable ROIs as compared to MeDi- subjects (Wilk’s Lambda p=0.026). Group differences were most pronounced in OFC (p=0.001), EC (p=0.03) and PCC (p=0.04) of the left hemisphere. Adjusting for gender, education, FH, APOE status, BMI, insulin resistance scores and presence of hypertension did not attenuate the relationship. CONCLUSION: NL individuals showing lower adherence to the MeDi had cortical thinning in the same brain regions as clinical AD patients compared to those showing higher adherence. These data indicate that the MeDi may have a protective effect against tissue loss, and suggest that dietary interventions may play a role in the prevention of AD

scholarly journals Eating a Weekly Serving of Walnuts Relates to Beneficial Brain Imaging Phenotypes in a Cohort at Increased Risk of Alzheimer's Disease

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1234-1234
Author(s):  
Aleix Sala-Vila ◽  
Marta Crous-Bou ◽  
Gonzalo Sánchez-Benavides ◽  
Eider M de Arenaza-Urquijo ◽  
Marc Suárez-Calvet ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mediterranean Diet ◽  
Successful Aging ◽  
Small Vessel Disease ◽  
Gray Matter Volume ◽  
Intracranial Volume ◽  
Cross Sectional ◽  
Apoe Ε4 ◽  
Increased Risk

Abstract Objectives There is increasing evidence on the brain benefits of nut consumption. Magnetic resonance imaging (MRI) enables the detection of brain changes associated with neurodegenerative and vascular diseases. In middle-aged cognitively unimpaired subjects at increased risk of Alzheimer's disease (AD), we searched for cross-sectional associations between nut consumption and MRI-assessed brain phenotypes, including white matter hyperintensities (WMH, a marker of cerebral small vessel disease that confers increased risk of AD and stroke) and topographic patterns of gray matter volume (GMv). Methods We performed high-resolution structural MRI in 382 participants from the ALFA study (ALzheimer and FAmilies) cohort, which is enriched by family history of sporadic AD and APOE-ε4 carriership, the most prevalent genetic risk factor for AD. We assessed nut consumption by a food-frequency questionnaire containing five items related to nuts. WMH volume was normalized by intracranial volume (TIV) and rank-transformed. For WMH, we conducted univariate models with two factors: nut consumption (<1 and ≥1 serving/week) and being APOE-ε4 homozygote (yes/no), and their interaction, adjusting for age, gender, hypertension, hypercholesterolemia, and adherence to Mediterranean Diet. We also explored whether nut consumption related to differences in GMv using a voxel-based morphometry analysis corrected by age, gender, number of APOE-ε4 alleles, hypertension, hypercholesterolemia, adherence to Mediterranean Diet, and TIV. Results 187 participants reported nut consumption of ≥1 serving/week, 148 of whom disclosed walnut consumption. Nut (or walnut) consumption of ≥1 serving/week related to a significantly lower WMH volume (P ≤ 0.035, both). We found no statistically significant nut × APOE-ε4 interactions. Participants reporting consumption of ≥1 walnut serving/week showed significantly greater GMv in areas including the anterior/middle cingulate cortex, which is relevant for cognition and has been associated with successful aging. Conclusions Nut (in particular walnut) consumption relates to beneficial phenotypes of both cerebral vasculature and regional GMv. Funding Sources Instituto de Salud Carlos III, Spain; “la Caixa” Foundation; California Walnut Commission.

Influence of White Matter Hyperintensities on Baseline and Longitudinal Amyloid-β in Cognitively Normal Individuals

2021 ◽  
pp. 1-11
Author(s):  
Fennie Choy Chin Wong ◽  
Seyed Ehsan Saffari ◽  
Chathuri Yatawara ◽  
Kok Pin Ng ◽  
Nagaendran Kandiah ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Executive Function ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Amyloid Β ◽  
Intracranial Volume ◽  
Linear Regression Models ◽  
Cognitively Normal

Background: The associations between small vessel disease (SVD) and cerebrospinal amyloid-β1-42 (Aβ1-42) pathology have not been well-elucidated. Objective: Baseline (BL) white matter hyperintensities (WMH) were examined for associations with month-24 (M24) and longitudinal Aβ1-42 change in cognitively normal (CN) subjects. The interaction of WMH and Aβ1-42 on memory and executive function were also examined. Methods: This study included 72 subjects from the Alzheimer’s Disease Neuroimaging Initiative. Multivariable linear regression models evaluated associations between baseline WMH/intracranial volume ratio, M24 and change in Aβ1-42 over two years. Linear mixed effects models evaluated interactions between BL WMH/ICV and Aβ1-42 on memory and executive function. Results: Mean age of the subjects (Nmales = 36) = 73.80 years, SD = 6.73; mean education years = 17.1, SD = 2.4. BL WMH was significantly associated with M24 Aβ1-42 (p = 0.008) and two-year change in Aβ1-42 (p = 0.006). Interaction between higher WMH and lower Aβ1-42 at baseline was significantly associated with worse memory at baseline and M24 (p = 0.003). Conclusion: BL WMH was associated with M24 and longitudinal Aβ1-42 change in CN. The interaction between higher WMH and lower Aβ1-42 was associated with poorer memory. Since SVD is associated with longitudinal Aβ1-42 pathology, and the interaction of both factors is linked to poorer cognitive outcomes, the mitigation of SVD may be correlated with reduced amyloid pathology and milder cognitive deterioration in Alzheimer’s disease.

FINANCIAL MANAGEMENT SKILLS IN AGING, MCI AND DEMENTIA: CROSS SECTIONAL RELATIONSHIP TO 18F-FLORBETAPIR PET CORTICAL Β-AMYLOID DEPOSITION

2019 ◽  
pp. 1-9
Author(s):  
S. Tolbert ◽  
Y. Liu ◽  
C. Hellegers ◽  
J.R. Petrella ◽  
M.W. Weiner ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
At Risk ◽  
Amyloid Deposition ◽  
Cross Sectional ◽  
Cognitively Normal ◽  
Financial Capacity ◽  
Cohen’S D ◽  
Β Amyloid ◽  
Cohen's D

Background: There is a need to more fully characterize financial capacity losses in the preclinical and prodromal stages of Alzheimer’s disease (AD) and their pathological substrates. Objectives: To test the association between financial skills and cortical β-amyloid deposition in aging and subjects at risk for AD. Design: Cross-sectional analyses of data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI-3) study conducted across 50 plus sites in the US and Canada. Setting: Multicenter biomarker study. Participants: 243 subjects (144 cognitively normal, 79 mild cognitive impairment [MCI], 20 mild AD). Measurements: 18F-Florbetapir brain PET scans to measure global cortical β-amyloid deposition (SUVr) and the Financial Capacity Instrument Short Form (FCI-SF) to evaluate an individual’s financial skills in monetary calculation, financial concepts, checkbook/register usage, and bank statement usage. There are five sub scores and a total score (range of 0–74) with higher scores indicating better financial skill. Results: FCI-SF total score was significantly worse in MCI [Cohen’s d= 0.9 (95%CI: 0.6-1.2)] and AD subjects [Cohen’s d=3.1(CI: 2.5-3.7)] compared to normals. Domain scores and completion times also showed significant difference. Across all subjects, higher cortical β-amyloid SUVr was significantly associated with worse FCI-SF total score after co-varying for age, education, and cognitive score [Cohen’s f2=0.751(CI: 0.5-1.1)]. In cognitively normal subjects, after covarying for age, gender, and education, higher β -amyloid PET SUVr was associated with longer task completion time [Cohen’s f2=0.198(CI: 0.06-0.37)]. Conclusion: Using a multicenter study sample, we document that financial capacity is impaired in the prodromal and mild stages of AD and that such impairments are, in part, associated with the extent of cortical β-amyloid deposition. In normal aging, β-amyloid deposition is associated with slowing of financial tasks. These data confirm and extend prior research highlighting the utility of financial capacity assessments in at risk samples.

scholarly journals Open Access Series of Imaging Studies (OASIS): Cross-sectional MRI Data in Young, Middle Aged, Nondemented, and Demented Older Adults

2007 ◽  
Vol 19 (9) ◽  
pp. 1498-1507 ◽  
Author(s):  
Daniel S. Marcus ◽  
Tracy H. Wang ◽  
Jamie Parker ◽  
John G. Csernansky ◽  
John C. Morris ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Magnetic Resonance ◽  
Open Access ◽  
Intracranial Volume ◽  
Resonance Imaging ◽  
Imaging Studies ◽  
Cross Sectional ◽  
Data Set

The Open Access Series of Imaging Studies is a series of magnetic resonance imaging data sets that is publicly available for study and analysis. The initial data set consists of a cross-sectional collection of 416 subjects aged 18 to 96 years. One hundred of the included subjects older than 60 years have been clinically diagnosed with very mild to moderate Alzheimer's disease. The subjects are all right-handed and include both men and women. For each subject, three or four individual T1-weighted magnetic resonance imaging scans obtained in single imaging sessions are included. Multiple within-session acquisitions provide extremely high contrast-to-noise ratio, making the data amenable to a wide range of analytic approaches including automated computational analysis. Additionally, a reliability data set is included containing 20 subjects without dementia imaged on a subsequent visit within 90 days of their initial session. Automated calculation of whole-brain volume and estimated total intracranial volume are presented to demonstrate use of the data for measuring differences associated with normal aging and Alzheimer's disease.

scholarly journals Spatial Relationships between Molecular Pathology and Neurodegeneration in the Alzheimer’s Disease Continuum

2020 ◽  
Vol 31 (1) ◽  
pp. 1-14
Author(s):  
Leonardo Iaccarino ◽  
Renaud La Joie ◽  
Lauren Edwards ◽  
Amelia Strom ◽  
Daniel R Schonhaut ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Pathology ◽  
Fdg Pet ◽  
Imaging Modality ◽  
Clinical Trial Design ◽  
Great Majority ◽  
Intracranial Volume ◽  
Spatial Relationships ◽  
Cognitively Normal

Abstract A deeper understanding of the spatial relationships of β-amyloid (Aβ), tau, and neurodegeneration in Alzheimer’s disease (AD) could provide insight into pathogenesis and clinical trial design. We included 81 amyloid-positive patients (age 64.4 ± 9.5) diagnosed with AD dementia or mild cognitive impairment due to AD and available 11C-PiB (PIB), 18F-Flortaucipir (FTP),18F-FDG-PET, and 3T-MRI, and 31 amyloid-positive, cognitively normal participants (age 77.3 ± 6.5, no FDG-PET). W-score voxel-wise deviation maps were created and binarized for each imaging-modality (W > 1.64, P < 0.05) adjusting for age, sex, and total intracranial volume (sMRI-only) using amyloid-negative cognitively normal adults. For symptomatic patients, FDG-PET and atrophy W-maps were combined into neurodegeneration maps (ND). Aβ-pathology showed the greatest proportion of cortical gray matter suprathreshold voxels (spatial extent) for both symptomatic and asymptomatic participants (median 94–55%, respectively), followed by tau (79–11%) and neurodegeneration (41–3%). Amyloid > tau > neurodegeneration was the most frequent hierarchy for both groups (79–77%, respectively), followed by tau > amyloid > neurodegeneration (13–10%) and amyloid > neurodegeneration > tau (6–13%). For symptomatic participants, most abnormal voxels were PIB+/FTP+/ND− (median 35%), and the great majority of ND+ voxels (91%) colocalized with molecular pathology. Amyloid spatially exceeded tau and neurodegeneration, with individual heterogeneities. Molecular pathology and neurodegeneration showed a progressive overlap along AD course, indicating shared vulnerabilities or synergistic toxic mechanisms.

scholarly journals Lifestyle and vascular risk effects on MRI-based biomarkers of Alzheimer’s disease: a cross-sectional study of middle-aged adults from the broader New York City area

BMJ Open ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. e019362 ◽  
Author(s):  
Lisa Mosconi ◽  
Michelle Walters ◽  
Joanna Sterling ◽  
Crystal Quinn ◽  
Pauline McHugh ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
New York ◽  
Insulin Sensitivity ◽  
Cortical Thickness ◽  
Vascular Risk ◽  
Middle Aged ◽  
Cross Sectional ◽  
Cognitively Normal ◽  
Middle Aged Adults

ObjectiveTo investigate the effects of lifestyle and vascular-related risk factors for Alzheimer’s disease (AD) on in vivo MRI-based brain atrophy in asymptomatic young to middle-aged adults.DesignCross-sectional, observational.SettingBroader New York City area. Two research centres affiliated with the Alzheimer’s disease Core Center at New York University School of Medicine.ParticipantsWe studied 116 cognitively normal healthy research participants aged 30–60 years, who completed a three-dimensional T1-weighted volumetric MRI and had lifestyle (diet, physical activity and intellectual enrichment), vascular risk (overweight, hypertension, insulin resistance, elevated cholesterol and homocysteine) and cognition (memory, executive function, language) data. Estimates of cortical thickness for entorhinal (EC), posterior cingulate, orbitofrontal, inferior and middle temporal cortex were obtained by use of automated segmentation tools. We applied confirmatory factor analysis and structural equation modelling to evaluate the associations between lifestyle, vascular risk, brain and cognition.ResultsAdherence to a Mediterranean-style diet (MeDi) and insulin sensitivity were both positively associated with MRI-based cortical thickness (diet: βs≥0.26, insulin sensitivity βs≥0.58, P≤0.008). After accounting for vascular risk, EC in turn explained variance in memory (P≤0.001). None of the other lifestyle and vascular risk variables were associated with brain thickness. In addition, the path associations between intellectual enrichment and better cognition were significant (βs≥0.25 P≤0.001), as were those between overweight and lower cognition (βs≥-0.22, P≤0.01).ConclusionsIn cognitively normal middle-aged adults, MeDi and insulin sensitivity explained cortical thickness in key brain regions for AD, and EC thickness predicted memory performance in turn. Intellectual activity and overweight were associated with cognitive performance through different pathways. Our findings support further investigation of lifestyle and vascular risk factor modification against brain ageing and AD. More studies with larger samples are needed to replicate these research findings in more diverse, community-based settings.

scholarly journals Alzheimer’s pathology targets distinct memory networks in the ageing brain

Brain ◽  
2019 ◽  
Vol 142 (8) ◽  
pp. 2492-2509 ◽  
Author(s):  
Anne Maass ◽  
David Berron ◽  
Theresa M Harrison ◽  
Jenna N Adams ◽  
Renaud La Joie ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Functional Mri ◽  
Memory Function ◽  
Memory Task ◽  
Amyloid Β ◽  
Functional Specificity ◽  
Cross Sectional ◽  
Cognitively Normal

Abstract Alzheimer’s disease researchers have been intrigued by the selective regional vulnerability of the brain to amyloid-β plaques and tau neurofibrillary tangles. Post-mortem studies indicate that in ageing and Alzheimer’s disease tau tangles deposit early in the transentorhinal cortex, a region located in the anterior-temporal lobe that is critical for object memory. In contrast, amyloid-β pathology seems to target a posterior-medial network that subserves spatial memory. In the current study, we tested whether anterior-temporal and posterior-medial brain regions are selectively vulnerable to tau and amyloid-β deposition in the progression from ageing to Alzheimer’s disease and whether this is reflected in domain-specific behavioural deficits and neural dysfunction. 11C-PiB PET and 18F-flortaucipir uptake was quantified in a sample of 131 cognitively normal adults (age: 20–93 years; 47 amyloid-β-positive) and 20 amyloid-β-positive patients with mild cognitive impairment or Alzheimer’s disease dementia (65–95 years). Tau burden was relatively higher in anterior-temporal regions in normal ageing and this difference was further pronounced in the presence of amyloid-β and cognitive impairment, indicating exacerbation of ageing-related processes in Alzheimer’s disease. In contrast, amyloid-β deposition dominated in posterior-medial regions. A subsample of 50 cognitively normal older (26 amyloid-β-positive) and 25 young adults performed an object and scene memory task while functional MRI data were acquired. Group comparisons showed that tau-positive (n = 18) compared to tau-negative (n = 32) older adults showed lower mnemonic discrimination of object relative to scene images [t(48) = −3.2, P = 0.002]. In a multiple regression model including regional measures of both pathologies, higher anterior-temporal flortaucipir (tau) was related to relatively worse object performance (P = 0.010, r = −0.376), whereas higher posterior-medial PiB (amyloid-β) was related to worse scene performance (P = 0.037, r = 0.309). The functional MRI data revealed that tau burden (but not amyloid-β) was associated with increased task activation in both systems and a loss of functional specificity, or dedifferentiation, in posterior-medial regions. The loss of functional specificity was related to worse memory. Our study shows a regional dissociation of Alzheimer’s disease pathologies to distinct memory networks. While our data are cross-sectional, they indicate that with ageing, tau deposits mainly in the anterior-temporal system, which results in deficits in mnemonic object discrimination. As Alzheimer’s disease develops, amyloid-β deposits preferentially in posterior-medial regions additionally compromising scene discrimination and anterior-temporal tau deposition worsens further. Finally, our findings propose that the progression of tau pathology is linked to aberrant activation and dedifferentiation of specialized memory networks that is detrimental to memory function.

scholarly journals Brainstem Volumetric Integrity in Preclinical and Prodromal Alzheimer’s Disease

2020 ◽  
Vol 77 (4) ◽  
pp. 1579-1594 ◽  
Author(s):  
Shubir Dutt ◽  
Yanrong Li ◽  
Mara Mather ◽  
Daniel A. Nation ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Locus Coeruleus ◽  
Region Of Interest ◽  
Intracranial Volume ◽  
Cognitively Normal ◽  
Normal Individuals ◽  
Prodromal Ad ◽  
Brainstem Nuclei ◽  
Prodromal Alzheimer’S Disease

Background: Neuropathological studies have suggested the tau pathology observed in Alzheimer’s disease (AD) originates in brainstem nuclei, but no studies to date have quantified brainstem volumes in clinical populations with biomarker-confirmed mild cognitive impairment (MCI) or dementia due to AD or determined the value of brainstem volumetrics in predicting dementia. Objective: The present study examined whether MRI-based brainstem volumes differ among cognitively normal older adults and those with MCI or dementia due to AD and whether preclinical brainstem volumes predict future progression to dementia. Methods: Alzheimer’s Disease Neuroimaging Initiative participants (N = 1,629) underwent baseline MRI scanning with variable clinical follow-up (6–120 months). Region of interest and voxel-based morphometric methods assessed brainstem volume differences among cognitively normal (n = 814), MCI (n = 542), and AD (n = 273) participants, as well as subsets of cerebrospinal fluid biomarker-confirmed MCI (n = 203) and AD (n = 160) participants. Results: MCI and AD cases showed smaller midbrain volumes relative to cognitively normal participants when normalizing to whole brainstem volume, and showed smaller midbrain, locus coeruleus, pons, and whole brainstem volumes when normalizing to total intracranial volume. Cognitively normal individuals who later progressed to AD dementia diagnosis exhibited smaller baseline midbrain volumes than individuals who did not develop dementia, and voxel-wise analyses revealed specific volumetric reduction of the locus coeruleus. Conclusion: Findings are consistent with neuropathological observations of early AD-related pathology in brainstem nuclei and further suggest the clinical relevance of brainstem substructural volumes in preclinical and prodromal AD.

scholarly journals Hippocampo-Horn Percentage and Parietal Atrophy Score for Easy Visual Assessment of Brain Atrophy on Magnetic Resonance Imaging in Early- and Late-Onset Alzheimer’s Disease

2021 ◽  
pp. 1-8
Author(s):  
David Silhan ◽  
Olga Pashkovska ◽  
Ales Bartos ◽  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hip Hop ◽  
Brain Atrophy ◽  
Early Onset ◽  
Late Onset ◽  
Brain Mri ◽  
Resonance Imaging ◽  
Cognitively Normal

Background: Magnetic resonance imaging (MRI) visual scales of brain atrophy are important for differential diagnosis of dementias in routine clinical practice. Atrophy patterns in early- and late-onset Alzheimer’s disease (AD) can be different according to some studies. Objective: Our goal was to assess brain atrophy patterns in early- and late-onset AD using our recently developed simple MRI visual scales and evaluate their reliability. Methods: We used Hippocampo-horn percentage (Hip-hop) and Parietal Atrophy Score (PAS) to compare mediotemporal and parietal atrophy on brain MRI among 4 groups: 26 patients with early-onset AD, 21 younger cognitively normal persons, 32 patients with late-onset AD, 36 older cognitively normal persons. Two raters scored all brain MRI to assess reliability of the Hip-hop and PAS. Brain MRI were obtained from Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Results: The patients with early-onset AD had significantly more pronounced mediotemporal and also parietal atrophy bilaterally compared to the controls (both p <  0.01). The patients with late-onset AD had significantly more pronounced only mediotemporal atrophy bilaterally compared to the controls (p <  0.000001), but parietal lobes were the same. Intra-rater and inter-rater reliability of both visual scales Hip-hop and PAS were almost perfect in all cases (weighted-kappa value ranged from 0.90 to 0.99). Conclusion: While mediotemporal atrophy detected using Hip-hop is universal across whole AD age spectrum, parietal atrophy detected using PAS is worth rating only in early-onset AD. Hip-hop and PAS are very reliable MRI visual scales.

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