Alexander, G. E., Boyes, R. G., Gunter, J. L., Frost, C., Janke, A. L., Yeatman, T., Hill, D. L., Bernstein, M. A., Thompson, P. M., Weiner, M. W., Schuff, N., Killiany, R. J., Decarli, C., Jack, C. R., & Fox, N. C. (2008). Intensity non-uniformity correction using N3 on 3-T scanners with multichannel phased array coils. Neuroimage.
Study as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI) project;Your Role: Co-author involved in the study design, analysis, and critical review of manuscript;Full Citation: Boyes RG, Gunter JL, Frost C, Janke AL, Yeatman T, Hill DL, Bernstein MA, Thompson PM, Weiner MW, Schuff N, Alexander GE, Killiany RJ, Decarli C, Jack CR, & Fox NC; for the ADNI study. (2008). Intensity non-uniformity correction using N3 on 3-T scanners with multichannel phased array coils. Neuroimage, 39, 1752-62.;Other collaborative: Yes;Specify other collaborative: Multi-institutional collaborative study as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI), including UCSF, Mayo Clinic, University College London, UCLA, Boston University, and UC Davis;
Teipel, S. J., Alexander, G. E., Schapiro, M. B., Möller, H., Rapoport, S. I., & Hampel, H. (2004). Age-related cortical grey matter reductions in non-demented Down's syndrome adults determined by MRI with voxel-based morphometry. Brain, 127(4), 811-824.
PMID: 14985261;Abstract:
Ageing in Down's syndrome is accompanied by amyloid and neurofibrillary pathology the distribution of which replicates pathological features of Alzheimer's disease. With advancing age, an increasing proportion of Down's syndrome subjects >40 years old develop progressive cognitive impairment, resembling the cognitive profile of Alzheimer's disease. Based on these findings, Down's syndrome has been proposed as a model to study the predementia stages of Alzheimer's disease. Using an interactive anatomical segmentation technique and volume-of-interest measurements of MRI, we showed recently that non-demented Down's syndrome adults had significantly reduced hippocampus, entorhinal cortex and corpus callosum sizes with increasing age. In this study, we applied the automated and objective technique of voxel-based morphometry, implemented in SPM99, to the analysis of structural MRI from 27 non-demented Down's syndrome adults (mean age 41.1 years, 15 female). Regional grey matter volume was decreased with advancing age in bilateral parietal cortex (mainly the precuneus and inferior parietal lobule), bilateral frontal cortex with left side predominance (mainly middle frontal gyrus), left occipital cortex (mainly lingual cortex), right precentral and left postcentral gyrus, left transverse temporal gyrus, and right parahippocampal gyrus. The reductions were unrelated to gender, intracranial volume or general cognitive function. Grey matter volume was relatively preserved in subcortical nuclei, periventricular regions, the basal surface of the brain (bilateral orbitofrontal and anterior temporal) and the anterior cingulate gyrus. Our findings suggest grey matter reductions in allocortex and association neocortex in the predementia stage of Down's syndrome. The most likely substrate of these changes is alterations or loss of allocortical and neocortical neurons due to Alzheimer's disease-type pathology.
Pietrini, P., Furey, M. L., Dani, A., Alexander, G. E., Mentis, M. J., Freo, U., Rapoport, S. I., & Schapiro, M. B. (1997). Brain synaptic efficiency is preserved in early but not in late stages of Alzheimer's disease: A PET-FDG stimulation study. NeuroImage, 5(4 PART II), S344.
Johnson, S. C., Schmitz, T. W., Moritz, C. H., Meyerand, M. E., Rowley, H. A., Alexander, A. L., Hansen, K. W., Gleason, C. E., Carlsson, C. M., Ries, M. L., Asthana, S., Chen, K., Reiman, E. M., & Alexander, G. E. (2006). Activation of brain regions vulnerable to Alzheimer's disease: The effect of mild cognitive impairment. Neurobiology of Aging, 27(11), 1604-1612.
PMID: 16226349;PMCID: PMC2627778;Abstract:
This study examined the functionality of the medial temporal lobe (MTL) and posterior cingulate (PC) in mild cognitive impairment amnestic type (MCI), a syndrome that puts patients at greater risk for developing Alzheimer disease (AD). Functional MRI (fMRI) was used to identify regions normally active during encoding of novel items and recognition of previously learned items in a reference group of 77 healthy young and middle-aged adults. The pattern of activation in this group guided further comparisons between 14 MCI subjects and 14 age-matched controls. The MCI patients exhibited less activity in the PC during recognition of previously learned items, and in the right hippocampus during encoding of novel items, despite comparable task performance to the controls. Reduced fMRI signal change in the MTL supports prior studies implicating the hippocampus for encoding new information. Reduced signal change in the PC converges with recent research on its role in recognition in normal adults as well as metabolic decline in people with genetic or cognitive risk for AD. Our results suggest that a change in function in the PC may account, in part, for memory recollection failure in AD. © 2005 Elsevier Inc. All rights reserved.
Woods, A. J., Cohen, R., Marsiske, M., Alexander, G. E., Czaja, S. J., & Wu, S. (2017). Augmenting cognitive training in older adults (The ACT Study): Design and Methods of a Phase III tDCS and cognitive training trial. Contemporary clinical trials, 65, 19-32.
Adults over age 65 represent the fastest growing population in the US. Decline in cognitive abilities is a hallmark of advanced age and is associated with loss of independence and dementia risk. There is a pressing need to develop effective interventions for slowing or reversing the cognitive aging process. While certain forms of cognitive training have shown promise in this area, effects only sometimes transfer to neuropsychological tests within or outside the trained domain. This paper describes a NIA-funded Phase III adaptive multisite randomized clinical trial, examining whether transcranial direct current stimulation (tDCS) of frontal cortices enhances neurocognitive outcomes achieved from cognitive training in older adults experiencing age-related cognitive decline: the Augmenting Cognitive Training in Older Adults study (ACT).
