This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a continuing renewal of our R01 previously titled """"""""Functional MRl for Early Diagnosis of Alzheimer's Disease"""""""" (5 R01 AG013308-10). The proposed third grant cycle builds on recent findings from this project and new technologies we have developed for imaging hippocampal structure and function. Our data support the utility of combining genetic risk, structural and functional MRl to identify early manifestations of Alzheimer's disease (AD), and further suggest that brain changes may occur much earlier than previously thought in Apolipoprotein epsilon-4 (APOE-4) carriers. Recently, our group has developed new techniques in high-resolution functional MRl acquisition and analysis, and in mathematical modeling algorithms that identify structural MRl change in Alzheimer's disease subjects over very short time periods. In addition, our group has recently worked with positron emission tomography (PET) using [18F]MPPF imaging, a ligand that measures pyramidal cell density in the hippocampus (HC), entorhinal cortex and amygdala;our preliminary data show that [18F]MPPF binding is decreased in MCI and AD, and correlates with memory in healthy controls, suggesting its potential as an independent assessment of risk for AD. This grant proposes using a combination of four new imaging techniques, two structural (HC cortical thickness and HC radial atrophy), and two functional (FMRI and [18F]MPPF) in control subjects in the 40-80 range at-risk for AD and MCI patients, to determine if there are subtle longitudinal changes in HC structure and function similar to those seen in AD, in cognitively intact at-risk subjects in the late middle age to elderly range. We will recruit 60 younger (40-60) and 36 older (60+) controls, (50% of each with APOE-4), and 35 mild MCI subjects, and follow them for 21/2 years using these novel imaging measures and clinical assessments. Analyses will focus on modeling the rate of change of each measure alone and in combination, with the goal of identifying subjects at highest risk for developing AD. Diagnostic and neuropsychological evaluations will provide clinical corroboration that genotype, family history, and short-term brain changes predict cognitive decline. By combining these different measures of hippocampal structure and function, our primary goal is to develop an approach to identifying those at-risk who are more likely to develop AD, and to determine which of these novel imaging techniques provide the most optimal and independent predictors of future decline.
| Green, Shulamite A; Hernandez, Leanna M; Bowman, Hilary C et al. (2018) Sensory over-responsivity and social cognition in ASD: Effects of aversive sensory stimuli and attentional modulation on neural responses to social cues. Dev Cogn Neurosci 29:127-139 |
| Yang, Yaling; Joshi, Shantanu H; Jahanshad, Neda et al. (2017) Neural correlates of proactive and reactive aggression in adolescent twins. Aggress Behav 43:230-240 |
| Dennis, Emily L; Rashid, Faisal; Faskowitz, Josh et al. (2017) MAPPING AGE EFFECTS ALONG FIBER TRACTS IN YOUNG ADULTS. Proc IEEE Int Symp Biomed Imaging 2017:101-104 |
| Walsh, Christine M; Ruoff, Leslie; Walker, Kathleen et al. (2017) Sleepless Night and Day, the Plight of Progressive Supranuclear Palsy. Sleep 40: |
| Green, Shulamite A; Hernandez, Leanna; Bookheimer, Susan Y et al. (2017) Reduced modulation of thalamocortical connectivity during exposure to sensory stimuli in ASD. Autism Res 10:801-809 |
| Agis, Daniel; Goggins, Maria B; Oishi, Kumiko et al. (2016) Picturing the Size and Site of Stroke With an Expanded National Institutes of Health Stroke Scale. Stroke 47:1459-65 |
| Levine, Andrew J; Soontornniyomkij, Virawudh; Achim, Cristian L et al. (2016) Multilevel analysis of neuropathogenesis of neurocognitive impairment in HIV. J Neurovirol 22:431-41 |
| Flournoy, John C; Pfeifer, Jennifer H; Moore, William E et al. (2016) Neural Reactivity to Emotional Faces May Mediate the Relationship Between Childhood Empathy and Adolescent Prosocial Behavior. Child Dev 87:1691-1702 |
| Joshi, Shantanu H; Vizueta, Nathalie; Foland-Ross, Lara et al. (2016) Relationships Between Altered Functional Magnetic Resonance Imaging Activation and Cortical Thickness in Patients With Euthymic Bipolar I Disorder. Biol Psychiatry Cogn Neurosci Neuroimaging 1:507-517 |
| Ordóñez, Anna E; Loeb, Frances F; Zhou, Xueping et al. (2016) Lack of Gender-Related Differences in Childhood-Onset Schizophrenia. J Am Acad Child Adolesc Psychiatry 55:792-9 |
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