Alzheimer's disease (AD) is a major health problem facing this country. The destruction of brain tissue in this degenerative disease likely begins decades before the onset of clinical symptoms. Identification of preclinical markers for AD would be extremely valuable for both intervention and treatment. Recent work suggests that decrements in cognition and changes on neuroimaging in asymptomatic individuals may identify those who go on to develop AD.
The aim of this project is to study both cognition and structural and functional neuroimaging longitudinally in a sample of adults who are at increased risk for development of AD and contrast these findings with those of a matched control group. Specifically we will examine cognitive performance on tests of memory and learning, generalized and regional brain measures from conventional MRI and changes in activation with a memory fMRI paradigm. In a small subsample, we will investigate activation changes using olfactory fMRI. In addition, participants will be referred to NIH for assay of amyloid in cerebral spinal fluid. Participants, all at least 50 years of age, will include adult offspring (N=100) of autopsy-confirmed AD cases who are members of multiplex families with extensively characterized pedigrees, currently enrolled in a genetic study of AD, and adults matched for age and gender (N=100) who are presently followed in a study of normal aging. Approximately equal numbers of males and females will be enrolled. All participants will be evaluated twice, three years apart to examine change over time on these measures. In addition, all participants will be typed on two genetic markers (APOE, Alpha2 Macroglobulin) for correlation of allele status with the above measures. The results of this study will provide information on the identification of preclinical markers for late-onset AD. It is hoped that the findings here will prove of significant value as future interventions for Alzheimer's disease are developed. In addition, the proposed studies will provide valuable data for planned long-term longitudinal studies of persons at-risk for AD.
| Li, Shanshan; Eloyan, Ani; Joel, Suresh et al. (2012) Analysis of group ICA-based connectivity measures from fMRI: application to Alzheimer's disease. PLoS One 7:e49340 |
| Carass, Aaron; Cuzzocreo, Jennifer; Wheeler, M Bryan et al. (2011) Simple paradigm for extra-cerebral tissue removal: algorithm and analysis. Neuroimage 56:1982-92 |
| Chen, Min; Carass, Aaron; Bogovic, John et al. (2011) Distance Transforms in Multi Channel MR Image Registration. Proc SPIE Int Soc Opt Eng 2011: |
| Caffo, Brian S; Crainiceanu, Ciprian M; Verduzco, Guillermo et al. (2010) Two-stage decompositions for the analysis of functional connectivity for fMRI with application to Alzheimer's disease risk. Neuroimage 51:1140-9 |
| Thambisetty, Madhav; Wan, Jing; Carass, Aaron et al. (2010) Longitudinal changes in cortical thickness associated with normal aging. Neuroimage 52:1215-23 |
| Cuzzocreo, Jennifer L; Yassa, Michael A; Verduzco, Guillermo et al. (2009) Effect of handedness on fMRI activation in the medial temporal lobe during an auditory verbal memory task. Hum Brain Mapp 30:1271-8 |
| Yousem, D M; Yassa, M A; Cristinzio, C et al. (2009) Intelligence and medial temporal lobe function in older adults: a functional MR imaging-based investigation. AJNR Am J Neuroradiol 30:1477-81 |
| Yassa, Michael A; Verduzco, Guillermo; Cristinzio, Catherine et al. (2008) Altered fMRI activation during mental rotation in those at genetic risk for Alzheimer disease. Neurology 70:1898-904 |
| DuBois Bowman, F; Caffo, Brian; Bassett, Susan Spear et al. (2008) A Bayesian hierarchical framework for spatial modeling of fMRI data. Neuroimage 39:146-56 |
| Bazin, Pierre-Louis; Cuzzocreo, Jennifer L; Yassa, Michael A et al. (2007) Volumetric neuroimage analysis extensions for the MIPAV software package. J Neurosci Methods 165:111-21 |
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