Sensory and Perceptual Measures as Biomarkers of Alzheimer's Disease Pathology

点击翻译按钮获取中文摘要

 DESCRIPTION (provided by applicant): 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.