I am currently an Assistant Research Professor at the Center for Neuroimaging in the Department of Radiology and Imaging Sciences at the Indiana University School of Medicine. My graduate and post-graduate work has focused on neuroimaging biomarkers for detection and diagnosis of Alzheimer's disease (AD) and other dementias in preclinical and prodromal stages. My long-term career goal is to become an independent investigator with a focus on developing tools for detection and diagnosis of neurodegenerative diseases such as AD. As a vehicle toward achieving my long-term career goals while expanding my knowledge and expertise, my short-term goal is to assess changes in sensory function in multiple domains in a sample of individuals with preclinical and prodromal AD to better understand the poly-sensory changes that available evidence suggests develop concurrent with and possibly precede AD pathophysiology in early stages of disease. Measures of visual function (contrast sensitivity assessed using frequency doubling technology), retinal morphology (retinal atrophy measured by optical coherence tomography), a measure of olfactory identification (University of Pennsylvania Smell Identification Test), and measures of tonal hearing and central auditory processing (pure tone audiometry; Dichotic Sentence Identification, Dichotic Digits Test, Synthetic Sentence Identification with Ipsilateral Competing Message) , will be evaluated in older adults (aged 60 or older) at risk for progression to AD due to the presence of subjective cognitive decline in the absence of psychometric deficits1 or genetic background (family AD history and/or APOE e4 allele carrier), as well as patients with amnestic mild cognitive impairment, a prodromal stage of AD, and age-matched cognitively normal healthy controls without complaints or known genetic risk. I will investigate the following specific aims: [1] test the hypothesis that combining multiple sensory modalities will provide complementary information about subtle cognitive change and predict future decline in older adults in preclinical and prodromal stages of AD; [2] test the hypothesis that multi- sensory decline in preclinical and prodromal stages of AD is driven by cerebral amyloid deposition and/or neurodegeneration to determine the stage-specificity of sensory dysfunction with regard to the current theoretical framework of AD2; [3] test the hypothesis that altered brain connectivity within sensory networks is associated with measures of multi-sensory function in preclinical and prodromal AD. The long-term goal of this research is to better understand the pathophysiology underlying sensory changes in preclinical and prodromal AD, as well as to establish sensory measures as novel, non-invasive, and inexpensive biomarkers for detecting AD neuropathology in early stages. After validation, I expect these measures will be used in clinical settings for screening and/or diagnosis to improve patient care by targeting those most likely to progress to AD for therapeutic or lifestyle intervention. Validated sensory biomarkers could also be used in trials of new AD treatments to improve screening, sample enrichment, and potentially as efficacy outcome measures.

Public Health Relevance

Non-invasive and inexpensive biomarkers for Alzheimer's disease (AD) that are sensitive to pathophysiological changes in preclinical and early prodromal stages are desperately needed for clinical research, diagnosis and screening, as well as for clinical trials of potential therapeutic treatments. Many researchers believe that effective AD treatments will need to be administered in the earliest preclinical and prodromal stages of disease. Thus, the goal of this project is to understand the pathophysiology of multimodal sensory changes in preclinical and prodromal AD and to establish measures of sensory function as sensitive screening biomarkers for AD, which can be expected to have great impact on the diagnosis and treatment of AD in early stage disease.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01AG049050-02
Application #
9120728
Study Section
Neuroscience of Aging Review Committee (NIA)
Program Officer
Hsiao, John
Project Start
2015-08-15
Project End
2020-04-30
Budget Start
2016-05-01
Budget End
2017-04-30
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
603007902
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Yan, Jingwen; Liu, Kefei; Li, Huang et al. (2018) JOINT EXPLORATION AND MINING OF MEMORY-RELEVANT BRAIN ANATOMIC AND CONNECTOMIC PATTERNS VIA A THREE-WAY ASSOCIATION MODEL. Proc IEEE Int Symp Biomed Imaging 2018:6-9
Apostolova, Liana G; Risacher, Shannon L; Duran, Tugce et al. (2018) Associations of the Top 20 Alzheimer Disease Risk Variants With Brain Amyloidosis. JAMA Neurol 75:328-341
Cong, Shan; Risacher, Shannon L; West, John D et al. (2018) Volumetric comparison of hippocampal subfields extracted from 4-minute accelerated vs. 8-minute high-resolution T2-weighted 3T MRI scans. Brain Imaging Behav 12:1583-1595
Miller, Jason E; Shivakumar, Manu K; Risacher, Shannon L et al. (2018) Codon bias among synonymous rare variants is associated with Alzheimer's disease imaging biomarker. Pac Symp Biocomput 23:365-376
Risacher, Shannon L; Farlow, Martin R; Bateman, Daniel R et al. (2018) Detection of tau in Gerstmann-Sträussler-Scheinker disease (PRNP F198S) by [18F]Flortaucipir PET. Acta Neuropathol Commun 6:114
Yan, Jingwen; Risacher, Shannon L; Shen, Li et al. (2018) Network approaches to systems biology analysis of complex disease: integrative methods for multi-omics data. Brief Bioinform 19:1370-1381
Lee, Younghee; Han, Seonggyun; Kim, Dongwook et al. (2018) Genetic variation affecting exon skipping contributes to brain structural atrophy in Alzheimer's disease. AMIA Jt Summits Transl Sci Proc 2017:124-131
Swinford, Cecily G; Risacher, Shannon L; Charil, Arnaud et al. (2018) Memory concerns in the early Alzheimer's disease prodrome: Regional association with tau deposition. Alzheimers Dement (Amst) 10:322-331
Risacher, Shannon L; Anderson, Wesley H; Charil, Arnaud et al. (2017) Alzheimer disease brain atrophy subtypes are associated with cognition and rate of decline. Neurology 89:2176-2186
Risacher, Shannon L; Tallman, Eileen F; West, John D et al. (2017) Olfactory identification in subjective cognitive decline and mild cognitive impairment: Association with tau but not amyloid positron emission tomography. Alzheimers Dement (Amst) 9:57-66

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