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Articles by Nick C. Fox
Total Records ( 4 ) for Nick C. Fox
  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.
  Gloria C. Chiang , Philip S. Insel , Duygu Tosun , Norbert Schuff , Diana Truran- Sacrey , Sky T. Raptentsetsang , Paul M. Thompson , Eric M. Reiman , Clifford R. Jack , Nick C. Fox , William J. Jagust , Danielle J. Harvey , Laurel A. Beckett , Anthony Gamst , Paul S. Aisen , Ron C. Petersen and Michael W. Weiner
  Background The majority of studies relating amyloid pathology with brain volumes have been cross-sectional. Apolipoprotein ɛ4 (APOE ɛ4), a genetic risk factor for Alzheimer‘s disease, is also known to be associated with hippocampal volume loss. No studies have considered the effects of amyloid pathology and APOE ɛ4 together on longitudinal volume loss. Methods We evaluated whether an abnormal level of cerebrospinal fluid beta-amyloid (CSF Aβ) and APOE ɛ4 carrier status were independently associated with greater hippocampal volume loss over 1 year. We then assessed whether APOE ɛ4 status and CSF Aβ acted synergistically, testing the significance of an interaction term in the regression analysis. We included 297 participants: 77 cognitively normal, 144 with mild cognitive impairment (MCI), and 76 with Alzheimer‘s disease. Results An abnormal CSF Aβ level was found to be associated with greater hippocampal volume loss over 1 year in each group. APOE ɛ4 was associated with hippocampal volume loss only in the cognitively normal and MCI groups. APOE ɛ4 carriers with abnormal CSF Aβ in the MCI group acted synergistically to produce disproportionately greater volume loss than noncarriers. Conclusion Baseline CSF Aβ predicts progression of hippocampal volume loss. APOE ɛ4 carrier status amplifies the degree of neurodegeneration in MCI. Understanding the effect of interactions between genetic risk and amyloid pathology will be important in clinical trials and our understanding of the disease process.
  Manja Lehmann , Josephine Barnes , Gerard R. Ridgway , Natalie S. Ryan , Elizabeth K. Warrington , Sebastian J. Crutch and Nick C. Fox
  Background Posterior cortical atrophy (PCA) is a neurodegenerative condition predominantly associated with Alzheimer‘s disease (AD) pathology. Cross-sectional imaging studies have shown different atrophy patterns in PCA patients compared with typical amnestic Alzheimer‘s disease (tAD) patients, with greatest atrophy commonly found in posterior regions in the PCA group, whereas in the tAD group, atrophy is most prominent in medial temporal lobe regions. However, differential longitudinal atrophy patterns are not well understood. Methods This study assessed longitudinal changes in brain and gray matter volumes in 17 PCA patients, 16 tAD patients, and 18 healthy control subjects. Both patient groups had symptom durations of approximately 5 years. Results Progressive gray matter losses in both PCA and tAD patients were relatively widespread throughout the cortex, compared with control subjects, and were not confined to areas related to initial symptomatology. A multivariate classification analysis revealed a statistically significant group separation between PCA and tAD patients, with 72.7% accuracy (P < .01). Conclusion Progression from an initially focal presentation to a more global pattern suggests that these different clinical presentations of AD might converge pathologically over time.
  Bradley T. Wyman , Danielle J. Harvey , Karen Crawford , Matt A. Bernstein , Owen Carmichael , Patricia E. Cole , Paul K. Crane , Charles DeCarli , Nick C. Fox , Jeffrey L. Gunter , Derek Hill , Ronald J. Killiany , Chahin Pachai , Adam J. Schwarz , Norbert Schuff , Matthew L. Senjem , Joyce Suhy , Paul M. Thompson , Paul M. Thompson and Clifford R. Jack
  The Alzheimer‘s 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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