This is a revised application for a K24 Midcareer Investigator Award in aging and Alzheimer's disease (AD) patient-oriented research. The candidate, Reisa A. Sperling, M.D. M.MSc., is an Associate Professor of Neurology at Harvard Medical School with a strong early track record as a productive clinical investigator and research mentor. The overarching aims of the candidate's research program are to: 1) elucidate the neural underpinnings of memory impairment in aging and early AD, 2) link the pathophysiological process of AD to the early clinical manifestations, and 3) develop sensitive imaging markers to track the progression of AD in the preclinical stages, enabling earlier intervention with disease-modifying treatments. The candidate has several ongoing NIH and foundation-funded multimodality imaging research projects in MCI and early AD, as well as a pending Program Project on aging and amyloid, which was recently very favorably reviewed. The applicant will use her funded research as a platform for the mentorship of new patient-oriented investigators and to promote a multidisciplinary research approach to the study of cognitive aging and early AD. The applicant's mentees will have the opportunity to train in functional, structural, and molecular imaging techniques, cognitive neuroscience, neuropsychological assessment of early dementia, biostatistics, and epidemiological aspects of longitudinal study design as they apply to aging and AD patient research, drawing expertise from an outstanding group of collaborators. Trainees will also be able to participate in research seminars, statistical training and imaging workshops provided by T32 and other training grants, career development and grant- writing workshops as part of the newly funded CTSA at Harvard, and didactic course work at Brigham and Women's Hospital, Massachusetts General Hospital, Massachusetts Institute of Technology, and the Harvard School of Public Health. The candidate herself will acquire additional expertise in advanced statistical and epidemiological methodology related to her ongoing research, and will expand her research into resting functional connectivity techniques as part of new research proposed for the K24 award. The K24 will be instrumental in advancing the candidate's research career in neuroimaging of early AD, and in protecting her time to mentor a new generation of investigators committed to AD patient-oriented research.

Public Health Relevance

The applicant's research program seeks to understand the cause of memory problems in older individuals, to develop imaging tools to detect the earliest signs of Alzheimer's disease (AD), and to use these imaging tools to find effective treatments for AD. The applicant will use the K24 award to expand her imaging research program and to train new investigators for clinical research careers in patient-oriented AD research.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24AG035007-03
Application #
8306146
Study Section
National Institute on Aging Initial Review Group (NIA)
Program Officer
Hsiao, John
Project Start
2010-09-15
Project End
2015-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
3
Fiscal Year
2012
Total Cost
$139,579
Indirect Cost
$10,339
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
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Sperling, Reisa; Mormino, Elizabeth; Johnson, Keith (2014) The evolution of preclinical Alzheimer's disease: implications for prevention trials. Neuron 84:608-22
Mormino, Elizabeth C; Betensky, Rebecca A; Hedden, Trey et al. (2014) Amyloid and APOE ?4 interact to influence short-term decline in preclinical Alzheimer disease. Neurology 82:1760-7
Huijbers, Willem; Mormino, Elizabeth C; Wigman, Sarah E et al. (2014) Amyloid deposition is linked to aberrant entorhinal activity among cognitively normal older adults. J Neurosci 34:5200-10
Mormino, Elizabeth C; Betensky, Rebecca A; Hedden, Trey et al. (2014) Synergistic effect of ?-amyloid and neurodegeneration on cognitive decline in clinically normal individuals. JAMA Neurol 71:1379-85
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Zoller, Amy S; Gaal, Ildiko M; Royer, Christine A et al. (2014) SIST-M-IR activities of daily living items that best discriminate clinically normal elderly from those with mild cognitive impairment. Curr Alzheimer Res 11:785-91
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Donovan, Nancy J; Amariglio, Rebecca E; Zoller, Amy S et al. (2014) Subjective cognitive concerns and neuropsychiatric predictors of progression to the early clinical stages of Alzheimer disease. Am J Geriatr Psychiatry 22:1642-51
Marshall, Gad A; Lorius, Natacha; Locascio, Joseph J et al. (2014) Regional cortical thinning and cerebrospinal biomarkers predict worsening daily functioning across the Alzheimer's disease spectrum. J Alzheimers Dis 41:719-28

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