Abstract
Clinical trials of Alzheimer’s disease (AD) traditionally use rating scales, such as neuropsychological tests, and disability scales as outcome measures. However, their intrinsic measurement variability, the slow disease progression, and the low efficacy of the drugs developed so far have led to trial designs with hundreds of subjects per treatment arm. The development of imaging markers with proven sensitivity to disease progression has recently paved the way for their use as outcome measures in clinical trials. The use of imaging measures has the double advantage of decreasing the number of subjects per treatment arm whilst also providing a direct measure of the degree of disease modification induced by the “active” molecules. A number of magnetic resonance (MR)-based markers have been developed for clinical trials of AD, all of which have their own strengths and weaknesses. Here, the most often used techniques, which could easily be exported to the study of neurodegeneration in clinical trials of multiple sclerosis, are reviewed.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Laakso MP, Partanen K, Riekkinen P et al (1996) Hippocampal volumes in Alzheimer’s disease, Parkinson’s disease with and without dementia, and in vascular dementia: an MRI study. Neurology 46:678–681
Laakso MP, Soininen H, Partanen K et al (1998) MRI of the hippocampus in Alzheimer’s disease: sensitivity, specificity, and analysis of the incorrectly classified subjects. Neurobiol Aging 19:23–31
Jack CR, Jr, Petersen RC, Xu YC et al (1999) Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment. Neurology 52:1397–1403
Jack CR, Jr, Petersen RC, Xu Y et al (2000) Rates of hippocampal atrophy correlate with change in clinical status in aging and AD. Neurology 55:484–489
Fox NC, Freeborough PA (1997) Brain atrophy progression measured from registered serial MRI: validation and application to Alzheimer’s disease. J Magn Reson Imaging 7:1069–1075
Ashburner J, Csernansky JG, Davatzikos C et al (2003) Computer-assisted imaging to assess brain structure in healthy and diseased brains. Lancet Neurol 2:79–88
Ashburner J, Friston KJ (2000) Voxel-based morphometry: the methods. Neuroimage 14:805–821
Thompson PM, Mega MS, Toga AW (2000) Disease-specific brain atlases. In: Toga AW, Mazziotta JC (eds) Brain mapping: the disorders. Academic Press, San Diego, CA, pp 131–177
Freeborough PA, Fox NC, Kitney RI (1997) Interactive algorithms for the segmentation and quantitation of 3-D MRI brain scans. Comput Methods Programs Biomed 53:15–25
Chetelat G, Landeau B, Eustache F et al (2005) Using voxel-based morphometry to map the structural changes associated with rapid conversion in MCI: a longitudinal MRI study. Neuroimage 27:934–946
Thompson PM, Toga AW (1996) A surface-based technique for warping 3-dimensional images of the brain. IEEE Trans Med Imaging 15:1–16
Thompson PM, Hayashi KM, de Zubicaray G et al (2003) Dynamics of gray matter loss in Alzheimer’s disease. J Neurosci 23:994–1005
Vidal CN, Rapoport JL, Hayashi KM et al (2006) Dynamically spreading frontal and cingulate deficits mapped in adolescents with schizophrenia. Arch Gen Psychiat 63:25–34
Smith SM, De Stefano N, Jenkinson M, Matthews PM (2001) Normalized accurate measurement of longitudinal brain change. J Comput Assist Tomogr 25:466–475
Resnick SM, Goldszal AF, Davatzikos C et al (2000) One-year age changes in MRI brain volumes in older adults. Cereb Cortex 10:464–472
Davatzikos C, Resnick SM (1998) Sex differences in anatomic measures of interhemispheric connectivity: correlations with cognition in women but not in men. Cereb Cortex 8:635–640
Fox NC, Black RS, Gilman S et al (2005) Effects of Aβ immunization (AN1792) on MRI measures of cerebral volume in Alzheimer disease. Neurology 64:1563–1572
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2007 Springer-Verlag Italia
About this chapter
Cite this chapter
Frisoni, G.B. (2007). Alzheimer’s Disease. In: Filippi, M., Rovaris, M., Comi, G. (eds) Neurodegeneration in Multiple Sclerosis. Topics in Neuroscience. Springer, Milano. https://doi.org/10.1007/978-88-470-0391-0_13
Download citation
DOI: https://doi.org/10.1007/978-88-470-0391-0_13
Publisher Name: Springer, Milano
Print ISBN: 978-88-470-0390-3
Online ISBN: 978-88-470-0391-0
eBook Packages: MedicineMedicine (R0)