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Articles by Michael Weiner
Total Records ( 3 ) for Michael Weiner
  Beth Kuczynski , Elizabeth Targan , Cindee Madison , Michael Weiner , Yu Zhang , Bruce Reed , Helena C. Chui and William Jagust
  Background Studies show that white matter hyperintensities, regardless of location, primarily affect frontal lobe metabolism and function. This report investigated how regional white matter integrity (measured as fractional anisotropy [FA]) relates to brain metabolism, to unravel the complex relationship between white matter changes and brain metabolism. Objective To elucidate the relationship between white matter integrity and gray matter metabolism using diffusion tensor imaging and fluorodeoxyglucose-positron emission tomography in a cohort of 16 subjects ranging from normal to demented (age, >55 years). Methods Mean FA values from white matter regions underlying the medial prefrontal, inferior-lateral prefrontal, parietal association, and posterior temporal areas and the corpus callosum were regressed with glucose metabolism (by positron emission tomography), using statistical parametric mapping (P < 0.005; voxel cluster, >100). Regional cerebral glucose metabolism was the primary outcome measure. According to our hypothesis, those hypometabolic cortical regions affected by Alzheimer's disease would correlate with a lower FA of associated tracks. Results Our data show inter-regional positive correlations between FA and gray matter metabolism for the prefrontal cortex, temporal, and parietal regions. Our results suggest that left prefrontal FA is associated with left temporal and parietal metabolism. Further, left posterior temporal FA correlated with left prefrontal metabolism. Finally, bilateral parietal FA correlated with bilateral temporal metabolism. Conclusions These regions are associated with cognitive processes affected in Alzheimer's disease and cerebrovascular disease, suggesting a link with white matter degeneration and gray matter hypometabolism. Therefore, cortical function and white matter degeneration are related in aging and dementia.
  Clifford R. Jack , Frederik Barkhof , Matt A. Bernstein , Marc Cantillon , Patricia E. Cole , Charles DeCarli , 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 , Reisa Sperling , Joyce Suhy , Paul M. Thompson , Michael Weiner and Norman L. Foster
  Background The promise of Alzheimer‘s 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 Alzheimer‘s 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 Alzheimer‘s Disease Centers–Alzheimer‘s 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 (Alzheimer‘s 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.
  Nicola Coley , Sandrine Andrieu , Mark Jaros , Michael Weiner , Jesse Cedarbaum and Bruno Vellas
  Background Clinical measures continue to be used as primary endpoints for disease-modifying trials for Alzheimer‘s disease (AD). Currently, two co-primary endpoints must be specified, which measure cognitive and functional impairments. Generally, the Alzheimer‘s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) is one of the co-primary endpoints, but high variability in this measure results in large sample sizes. We evaluated the psychometric properties of the Clinical Dementia Rating-Sum of Boxes (CDR-SB) to assess its suitability as a single primary endpoint as an alternative to the traditional co-primary approach. Methods Internal consistency, structural and convergent validity, and 2-year internal and external responsiveness of the CDR-SB were assessed in 667 very mild to moderate (global Clinical Dementia Rating, 0.5–2) AD patients from the REAL.FR (Reseau sur la Maladie d'Alzheimer Francais) study. Results The CDR-SB showed good internal consistency (Cronbach‘s alpha = 0.88), and acceptable structural (separate ”cognitive“ and ”functional“ factors) and convergent validity. Variability in mean changes over time was low, leading to excellent internal responsiveness (effect size = 1.2; standardized response mean = 1.17 at 2 years) and smaller sample sizes as compared with the ADAS-Cog. External responsiveness was acceptable when compared with ”clinically meaningful“ changes on the Activities of Daily Living scale but only borderline acceptable when compared with the ADAS-Cog and Instrumental Activities of Daily Living. Levels of missing data and floor/ceiling effects were low. Conclusions The CDR-SB measures cognitive and functional impairment simultaneously, and has excellent 2-year internal responsiveness. This makes it a promising candidate as a sole primary endpoint for AD trials, although more work is required to determine the clinical relevance of CDR-SB changes, and its usefulness as an endpoint at other disease stages.
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