Furey, M. L., Horwitz, B., Pietrini, P., Alexander, G. E., Mentis, M. J., Dani, A., Shetty, U., Freo, U., Rapoport, S. I., & Schapiro, M. B. (1997). Improved performance on working memory is related to regional cerebral blood flow changes induced by pharmacological modulation of the cholinergic system. NeuroImage, 5(4 PART II), S623.
Teipel, S. J., Schapiro, M. B., Alexander, G. E., Krasuski, J. S., Horwitz, B., Hoehne, C., Möller, H., Rapoport, S. I., & Hampel, H. (2003). Relation of corpus callosum and hippocampal size to age in nondemented adults with Down's syndrome. American Journal of Psychiatry, 160(10), 1870-1878.
PMID: 14514503;Abstract:
Objective: Aging in Down's syndrome is accompanied by amyloid and neurofibrillary pathology, the regional and laminar distribution of which resembles pathological changes seen in Alzheimer's disease. Previous studies using magnetic resonance imaging (MRI) demonstrated age-related atrophy of medial temporal lobe structures in nondemented older subjects with Down's syndrome, reflecting early allocortical pathology. Corpus callosum atrophy has been established as a marker of neocortical neuronal loss in Alzheimer's disease. This study investigated whether atrophy of the corpus callosum and hippocampus occurs in nondemented subjects with Down's syndrome and compared the degree of age-related atrophy between these structures. Method: Hippocampus and corpus callosum measures were obtained from volumetric T1-weighted MRI scans of 34 non-demented Down's syndrome adults (mean age=41.6 years, 17 women) and 31 healthy comparison subjects (mean age= 41.8 years, 14 women). Results: Down's syndrome subjects had smaller corpus callosum areas and hippocampal volumes relative to age-matched healthy comparison subjects, even after age and total intracranial volume were controlled. There was an age-related decrease of corpus callosum area (most prominent in posterior regions) and hippocampal volume in the Down's syndrome group. The degree of the age effect was comparable between the total corpus callosum and hippocampus, and corpus callosum size was correlated with cognitive performance in the Down's syndrome subjects. There was no correlation between age and corpus callosum or hippocampal size in the comparison group. Conclusions: Comparable decrease of corpus callosum and hippocampal size with age in nondemented subjects with Down's syndrome suggests that neocortical neuronal alterations accompany allocortical changes in the predementia phase of Down's syndrome.
Bharadwaj, P. K., Hishaw, G. A., Haws, K. A., Nguyen, L. A., Trouard, T. P., & Alexander, G. E. (2015). Evaluation of lesion probability maps for automated segmentation of MRI white matter hyperintensities in healthy aging. ..
Chen, K., Reiman, E. M., & Alexander, G. E. (2007). A Monte-Carlo simulation package, multiple comparison corrections and power estimation incorporating secondary supportive evidence. 2007 IEEE/ICME International Conference on Complex Medical Engineering, CME 2007, 907-913.
Abstract:
Various approaches have been proposed to account for the family-wise type-I errors in neuroimaging studies. This study introduces new global features as alternatives to address the multiple-comparison issue. These global features can serve as alternative brain indices whose type-I error theoretical calculations are unknown. A Monte-Carlo simulation package was used to calculate the family-wise type-I error of the newly introduced global features, as well as the conventional multiple comparison corrected p-values related to the height of the statistic (and cluster size) of interest in situations where random field theorem based p-values might be validated. In addition, this package was designed to perform statistical power analyses, taking multiple comparisons into consideration for the conventional statistics and the new global features. The behaviors of the global index type-I error thresholds as a function of the degrees of freedom (D) of t-distribution were investigated. Data from an oxygen-15 water PET study of right hand movement was used to illustrate the use of the global features and their type-I error and statistical power. With this PET example, we showed the superior statistical power of some global indices in cases where there were moderate changes over a relatively large brain volume. We believe that the global features and the calculation of type-I errors/statistical powers by the computer simulation package provide researchers alternative ways to account for multiple comparisons in neuroimaging studies. © 2007 IEEE.
Leow, A. D., Yanovsky, I., Parikshak, N., Hua, X., Lee, S., Toga, A. W., Jack Jr., C. R., Bernstein, M. A., Britson, P. J., Gunter, J. L., Ward, C. P., Borowski, B., Shaw, L. M., Trojanowski, J. Q., Fleisher, A. S., Harvey, D., Kornak, J., Schuff, N., Alexander, G. E., , Weiner, M. W., et al. (2009). Alzheimer's Disease Neuroimaging Initiative: A one-year follow up study using tensor-based morphometry correlating degenerative rates, biomarkers and cognition. NeuroImage, 45(3), 645-655.
PMID: 19280686;PMCID: PMC2696624;Abstract:
Tensor-based morphometry can recover three-dimensional longitudinal brain changes over time by nonlinearly registering baseline to follow-up MRI scans of the same subject. Here, we compared the anatomical distribution of longitudinal brain structural changes, over 12 months, using a subset of the ADNI dataset consisting of 20 patients with Alzheimer's disease (AD), 40 healthy elderly controls, and 40 individuals with mild cognitive impairment (MCI). Each individual longitudinal change map (Jacobian map) was created using an unbiased registration technique, and spatially normalized to a geometrically-centered average image based on healthy controls. Voxelwise statistical analyses revealed regional differences in atrophy rates, and these differences were correlated with clinical measures and biomarkers. Consistent with prior studies, we detected widespread cerebral atrophy in AD, and a more restricted atrophic pattern in MCI. In MCI, temporal lobe atrophy rates were correlated with changes in mini-mental state exam (MMSE) scores, clinical dementia rating (CDR), and logical/verbal learning memory scores. In AD, temporal atrophy rates were correlated with several biomarker indices, including a higher CSF level of p-tau protein, and a greater CSF tau/beta amyloid 1-42 (ABeta42) ratio. Temporal lobe atrophy was significantly faster in MCI subjects who converted to AD than in non-converters. Serial MRI scans can therefore be analyzed with nonlinear image registration to relate ongoing neurodegeneration to a variety of pathological biomarkers, cognitive changes, and conversion from MCI to AD, tracking disease progression in 3-dimensional detail. © 2009 Elsevier Inc. All rights reserved.
