Goal: The applicant wishes to pursue an academic career as a researcher, clinician, and teacher in geriatric neuropsychology, with particular expertise regarding the boundaries of normal versus abnormal cognitive aging. The applicant's prior experience as a researcher has resulted in a variety of publications examining normal and abnormal cognition in relation to brain structural and metabolic indices. However, the applicant is eager to advances his knowledge in these areas at a more fundamental, theoretical level. Likewise, as a clinician, the applicant has evaluated a wide spectrum of neurologic and psychiatric disorders but wish to further refine my diagnostic acumen. Finally, the applicant has imparted statistical analysis, database-management, and manuscript- preparation skills to residents, interns, medical students, and work- study students; however, He would like now to increase his sophistication in these areas, especially in the context of a classroom mode of instruction. The applicant will receive mentorship and classroom instruction by local experts in each of the above areas, as well as instruction on diagnostic issues by an eminent investigator external to my institution. To refine and expand his repertoire of skills, he will continue his ongoing academic activities, as well as receive classroom instruction in neuroanatomy, neuroradiology, biometry, biomedical engineering, computer science, and experimental psychology. Research Project: Brain structure and cognition in elderly with APOE e4. A specific research project is outlined exploring relationships between apolipoprotein E (APOE) e4, magnetic resonance imaging (MRI) abnormalities, and neuropsychological performance in subjects with age- associated memory impairment and a family history of dementia, complied with age- and sex-matched cognitively normal controls with a family history of dementia. in particular, work will be directed toward elucidating the relationship between APOE isoforms(e2,e3, and e4), hippocampal findings on MRI, and impairment of memory. Results: The proposed training experiences will enhance his skills as a researcher, clinician, and teacher in geriatric neuropsychology. The research project will further refine these skills in practice, provide important information on APOE and other risk factors for brain alterations associated with aging, and provide preliminary data for subsequent research and grant applications, e.g., future longitudinal work. In short, this award will help to establish the applicant as an independent researcher and refine his capacities to assist others both as a clinician and a teacher.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Clinical Investigator Award (CIA) (K08)
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Study Section
Mental Disorders of Aging Review Committee (MDA)
Program Officer
Chavez, Mark
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Duke University
Schools of Medicine
United States
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Skotko, Brian G; Rubin, David C; Tupler, Larry A (2008) H.M.'s personal crossword puzzles: understanding memory and language. Memory 16:89-96
Tupler, Larry A; Krishnan, K Ranga R; Greenberg, Daniel L et al. (2007) Predicting memory decline in normal elderly: genetics, MRI, and cognitive reserve. Neurobiol Aging 28:1644-56
Tupler, Larry A; De Bellis, Michael D (2006) Segmented hippocampal volume in children and adolescents with posttraumatic stress disorder. Biol Psychiatry 59:523-9
Greenwood, Robert S; Tupler, Larry A; Whitt, J Kenneth et al. (2005) Brain morphometry, T2-weighted hyperintensities, and IQ in children with neurofibromatosis type 1. Arch Neurol 62:1904-8
Vythilingam, Meena; Charles, H Cecil; Tupler, Larry A et al. (2003) Focal and lateralized subcortical abnormalities in unipolar major depressive disorder: an automated multivoxel proton magnetic resonance spectroscopy study. Biol Psychiatry 54:744-50
Tupler, Larry A; Krishnan, K Ranga R; McDonald, William M et al. (2002) Anatomic location and laterality of MRI signal hyperintensities in late-life depression. J Psychosom Res 53:665-76
Kim, Dennis M; Xanthakos, Stavra A; Tupler, Larry A et al. (2002) MR signal intensity of gray matter/white matter contrast and intracranial fat: effects of age and sex. Psychiatry Res 114:149-61