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Articles
by
Joyce Suhy |
Total Records (
4 ) for
Joyce Suhy |
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Christopher Carlson
,
Wahiba Estergard
,
Joonmi Oh
,
Joyce Suhy
,
Clifford R. Jack
,
Eric Siemers
and
Jerome Barakos
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Background
Cerebral vasogenic edema (VE) has been reported to occur during antiamyloid immunotherapy. VE may be associated with central nervous system pathology with bloodbrain barrier disruptions; however, less is known about the prevalence of naturally occurring VE in patients with Alzheimers disease (AD).
Methods
Fluid-attenuated inversion recovery imaging sequences were obtained from four ongoing multicenter, randomized, double-blind, placebo-controlled, phase 3 trials in patients with mild-to-moderate AD. The first set of baseline scans was from patients in volumetric magnetic resonance imaging addenda in the Interrupting Alzheimer's Dementia by EvaluatiNg Treatment of Amyloid PaThologY (IDENTITY) studies examining semagacestat, a γ-secretase inhibitor (cohort 1, n = 621). The second set of baseline scans was from the EXPanding alzhEimer's Disease InvestigaTIONs (EXPEDITION) studies examining solanezumab, an anti-Aβ monoclonal antibody (cohort 2, n = 2141). Readers were blinded to patient-identifying information and future treatment. A third set of baseline scans was from the first 700 patients who underwent protocol-specified magnetic resonance imaging before randomization in the EXPEDITION studies (cohort 3). The analysis used three neuroradiologists: two performed independent primary interpretations and the third was the adjudicator. Readers were blinded to patient information, treatment, protocol, and time point.
Results
Four cases of asymptomatic VE were detected at baseline/screening. Two VE cases were due to underlying extra-axial mass lesions. The third VE case was associated with numerous microhemorrhages in keeping with cerebral amyloid angiopathy-related inflammation or Aβ-related angiitis. The final VE case demonstrated localized sulcal fluid-attenuated inversion recovery imaging hyperintensity. No VE was detected in cohort 3 by readers blinded to patient baseline status.
Conclusions
VE seems to be rare at baseline in patients with AD in clinical trials, 2 of 2762 associated with AD. Additional cohorts should be evaluated to support these findings. |
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Michael W. Weiner
,
Carl Sadowsky
,
Judith Saxton
,
Robert K. Hofbauer
,
Stephen M. Graham
,
ung Yun Yu
,
Shaoyi Li
,
Hai-An Hsu
,
Joyce Suhy
,
Moshe Fridman
and
James L. Perhach
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Background
This study was designed to assess changes in brain volume and cognitive abilities in memantine-treated patients with Alzheimers disease (AD) by using an exploratory, single-arm, delayed-start design.
Methods
Cholinesterase inhibitor-treated patients with AD (N = 47; Mini-Mental State Examination score range: 1523) were enrolled in an observational lead-in period (weeks: 124), followed by an open-label period of add-on memantine treatment (weeks: 2548). The patients underwent magnetic resonance imaging at weeks 0 (baseline), 24 (immediately before memantine initiation), and 48 (endpoint), and a battery of neuropsychological tests at weeks 0, 24, 28, 36, and 48. The primary outcome measure was the annualized rate of change (%) in total brain volume (TBV) between the two study periods. Data were analyzed using paired t-tests.
Results
There were no statistically significant differences in the rates of change in TBV, ventricular volume, or left hippocampal volume between the study periods; however, the memantine treatment period was associated with a significantly slower right hippocampal atrophy (−5.5% ± 12.0% vs −10.8% ± 7.2%; P = .038). Memantine treatment was also associated with superior performances on the Boston Naming Test (P = .034) and the Trail Making Test, Part B (P = .001), but also with a higher number of errors (i.e., repetitions and intrusions) on the California Verbal Learning Test. Memantine was found to be safe and well tolerated.
Conclusions
In this study, no difference in the rates of TBV change between the two periods was observed; however, memantine treatment was found to be associated with slowing of right hippocampal atrophy, and with improvement on one test of executive functioning as well as a test of confrontation naming ability. Trials using structural magnetic resonance imaging and a delayed-start design may be a feasible option for the assessment of treatments for AD. |
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Clifford R. Jack
,
Frederik Barkhof
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Matt A. Bernstein
,
Marc Cantillon
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Patricia E. Cole
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Charles DeCarli
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Bruno Dubois
,
Simon Duchesne
,
Nick C. Fox
,
Giovanni B. Frisoni
,
Harald Hampel
,
Derek L.G. Hill
,
Keith Johnson
,
Jean-Francois Mangin
,
Philip Scheltens
,
Adam J. Schwarz
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Reisa Sperling
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Joyce Suhy
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Paul M. Thompson
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Michael Weiner
and
Norman L. Foster
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Background
The promise of Alzheimers disease biomarkers has led to their incorporation in new diagnostic criteria and in therapeutic trials; however, significant barriers exist to widespread use. Chief among these is the lack of internationally accepted standards for quantitative metrics. Hippocampal volumetry is the most widely studied quantitative magnetic resonance imaging measure in Alzheimers disease and thus represents the most rational target for an initial effort at standardization.
Methods and Results
The authors of this position paper propose a path toward this goal. The steps include the following: (1) Establish and empower an oversight board to manage and assess the effort, (2) adopt the standardized definition of anatomic hippocampal boundaries on magnetic resonance imaging arising from the European Alzheimers Disease CentersAlzheimers Disease Neuroimaging Initiative hippocampal harmonization effort as a reference standard, (3) establish a scientifically appropriate, publicly available reference standard data set based on manual delineation of the hippocampus in an appropriate sample of subjects (Alzheimers Disease Neuroimaging Initiative), and (4) define minimum technical and prognostic performance metrics for validation of new measurement techniques using the reference standard data set as a benchmark.
Conclusions
Although manual delineation of the hippocampus is the best available reference standard, practical application of hippocampal volumetry will require automated methods. Our intent was to establish a mechanism for credentialing automated software applications to achieve internationally recognized accuracy and prognostic performance standards that lead to the systematic evaluation and then widespread acceptance and use of hippocampal volumetry. The standardization and assay validation process outlined for hippocampal volumetry was envisioned as a template that could be applied to other imaging biomarkers. |
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Bradley T. Wyman
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Danielle J. Harvey
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Karen Crawford
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Matt A. Bernstein
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Owen Carmichael
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Patricia E. Cole
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Paul K. Crane
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Charles DeCarli
,
Nick C. Fox
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Jeffrey L. Gunter
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Derek Hill
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Ronald J. Killiany
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Chahin Pachai
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Adam J. Schwarz
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Norbert Schuff
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Matthew L. Senjem
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Joyce Suhy
,
Paul M. Thompson
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Paul M. Thompson
and
Clifford R. Jack
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The Alzheimers Disease Neuroimaging Initiative (ADNI) three-dimensional T1-weighted magnetic resonance imaging (MRI) acquisitions provide a rich data set for developing and testing analysis techniques for extracting structural endpoints. To promote greater rigor in analysis and meaningful comparison of different algorithms, the ADNI MRI Core has created standardized analysis sets of data comprising scans that met minimum quality control requirements. We encourage researchers to test and report their techniques against these data. Standard analysis sets of volumetric scans from ADNI-1 have been created, comprising screening visits, 1-year completers (subjects who all have screening, 6- and 12-month scans), 2-year annual completers (screening, 1-year and 2-year scans), 2-year completers (screening, 6-months, 1-year, 18-months [mild cognitive impaired (MCI) only], and 2-year scans), and complete visits (screening, 6-month, 1-year, 18-month [MCI only], 2-year, and 3-year [normal and MCI only] scans). As the ADNI-GO/ADNI-2 data become available, updated standard analysis sets will be posted regularly. |
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