The objective of this proposal is to support the candidate's development into an independent clinical researcher. The outlined training plan will equip the applicant with the necessary skills to conduct patientoriented research with specific didactic training in biostatistics, neuroanatomy, behavioral neurology, and the ethical and responsible conduct of basic and clinical research. The overall goal of this project is to determine whether functional brain alterations in attention and memory systems may better elucidate early vulnerable brain regions in MCI patients at risk for cognitive decline. It remains poorly understood why some MCI patients progress to dementia, exhibiting selective vulnerability of cognitive-specific brain regions, while others remain stable or even improve. Alterations in brain activation have been exclusively assessed using episodic memory tasks. This approach remains limited in scope as many MCI patients exhibit pronounced deficits in both attention/executive function and memory domains. To accomplish this goal, our proposal will focus on a functional MRI paradigm of attention and memory in which subjects must first maintain focus during an anticipation period (attention) and then encode and recognize a visually-presented stimulus (memory). We will investigate the differential, task-specific activation of select brain regions in MCI patients and healthy controls. In addition, the neural response during the attention and memory phases will be compared to brain atrophy and cognitive performance. The goal of Aim 1 is to characterize alterations in neural activity during an attention and memory paradigm and assess the relationship between functional and structural MR! in MCI patients. The goal of Aim 2 is to measure the association between traditional neuropsychological tests of attention and memory and functional brain activation. The long-term objectives of this research are to investigate fluctuations in underlying neural networks of attention and memory in a large-scale, longitudinal study of MCI and healthy controls. In future research, we would collect multiple timepoints of fMRI and cognitive data and investigate changes in the underlying BOLD signal as cognition declines, improves, or remains stable. This will improve our understanding of the relationship between the BOLD signal and cognition. Ultimately, this will allow us to determine the utility of early neural fluctuations as a biomarker of those with or at risk for cognitive decline.

Public Health Relevance

Although there are great advances being made on understanding AD and other dementias, there are still no effective methods available for early diagnosis. The identification of MCI patients who are likely to suffer from further cognitive decline is a critical, public health issue, but no effective biomarkers have yet been identified. Functional MRI is a promising new method for in vivo investigation of early neural changes in those with or at risk for cognitive decline.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01AG034175-04
Application #
8278564
Study Section
National Institute on Aging Initial Review Group (NIA)
Program Officer
Hsiao, John
Project Start
2009-07-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
4
Fiscal Year
2012
Total Cost
$122,850
Indirect Cost
$9,100
Name
University of California San Francisco
Department
Neurology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Zanto, Theodore P; Pa, Judy; Gazzaley, Adam (2014) Reliability measures of functional magnetic resonance imaging in a longitudinal evaluation of mild cognitive impairment. Neuroimage 84:443-52
Pa, Judy; Dutt, Shubir; Mirsky, Jacob B et al. (2014) The functional oculomotor network and saccadic cognitive control in healthy elders. Neuroimage 95:61-8
Pa, Judy; Berry, Anne S; Compagnone, Mariana et al. (2013) Cholinergic enhancement of functional networks in older adults with mild cognitive impairment. Ann Neurol 73:762-73
Pa, Judy; Possin, Katherine L; Wilson, Stephen M et al. (2010) Gray matter correlates of set-shifting among neurodegenerative disease, mild cognitive impairment, and healthy older adults. J Int Neuropsychol Soc 16:640-50