This is an application for a K23 award for Dr. Winston Chiong, a behavioral neurologist at the University of California, San Francisco. This K23 award will provide Dr. Chiong with the support necessary to accomplish the following goals: (1) to become expert at patient-oriented research in dementia;(2) to conduct behavioral and functional MRI investigations of decision-making in aging and in patients with Alzheimer's disease and frontotemporal dementia;(3) to characterize real-world decision-making errors in Alzheimer's disease and frontotemporal dementia using semi-structured informant interviews;(4) to apply tools and frameworks derived from neuroeconomics in interpreting patients'behaviors;(5) to apply new analytic techniques to functional MRI in dementia;and (6) to develop an independent research career. To achieve these goals, Dr. Chiong has assembled a mentoring team with two co-primary mentors. Dr. Howard Rosen is a behavioral neurologist who directs the UCSF State of California Alzheimer's Care Center and co-directs the UCSF Behavioral Neurology Training Program;and Dr. Mark D'Esposito is a behavioral neurologist and neuroscientist who directs the Henry H. Wheeler Jr. Brain Imaging Center at UC Berkeley. The mentoring team includes two collaborators: Dr. Joel Kramer, a neuropsychologist at UCSF with experience in measuring behavioral change in dementia;and Dr. Ming Hsu, a neuroeconomist at UC Berkeley with expertise in applying economic models to neural data. Finally, consultant Dr. John Neuhaus is a statistician who will assist in biostatistical analysis ad training. Financial decision-making errors can have disastrous consequences for patients and their families, and are among the earliest symptomatic indicators of dementia. Understanding the neural bases of these errors in dementia will therefore aid in early diagnosis, risk prediction harm prevention, and devising interventions to improve decision-making. Recent work in the neuroscience of decision-making provides a framework for understanding such errors in terms of decision-making biases, such as framing effects that distort financial judgment. Dr. Chiong's research will use a variety of techniques to study how decision-making biases and risk- taking are affected by aging and by Alzheimer's disease and frontotemporal dementia, two illnesses with very different effects on behavior and judgment. At a behavioral level, Dr. Chiong will use an established neuroeconomic task to assess framing effects and risk sensitivity in aging and in early disease.
(Aim 1) At a neural level, he will use functional MRI to assess how large-scale neural network perturbations in these diseases affect financial decision-making.
(Aim 2) And at a clinical level, he will use informant interviews within a neuroeconomic framework to characterize the financial decision-making errors that patients make in the real world.
(Aim 3) These studies will advance our understanding of this important early symptom in dementia, setting the stage for future investigations of its significance in early diagnosis, and for behavioal and policy interventions to improve decision-making.

Public Health Relevance

The proposed research is relevant to public health because financial decision-making errors are more common in older adults than in younger adults, and are among the first symptomatic indicators of early Alzheimer's disease and other dementias. These errors can have devastating consequences for older adults and their families. Investigating the underlying neural bases of these errors in aging and early dementia will guide future efforts at early diagnosis, risk prediction, preventing serious losses, and devising interventions to support decision-making.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Mentored Patient-Oriented Research Career Development Award (K23)
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National Institute on Aging Initial Review Group (NIA)
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Phillips, John
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Chiong, Winston (2018) Challenges in Communicating and Understanding Predictive Biomarker Imaging for Alzheimer Disease. JAMA Neurol 75:18-19
Chiong, Winston; Leonard, Matthew K; Chang, Edward F (2018) Neurosurgical Patients as Human Research Subjects: Ethical Considerations in Intracranial Electrophysiology Research. Neurosurgery 83:29-37
Feldman, William B; Kim, Anthony S; Chiong, Winston (2017) Trends in Recruitment Rates for Acute Stroke Trials, 1990-2014. Stroke 48:799-801
Feldman, William B; Kim, Anthony S; Chiong, Winston (2017) Response by Feldman et al to Letter Regarding Article, ""Trends in Recruitment Rates for Acute Stroke Trials, 1990-2014"". Stroke 48:e145
Possin, Katherine L; Merrilees, Jennifer; Bonasera, Stephen J et al. (2017) Development of an adaptive, personalized, and scalable dementia care program: Early findings from the Care Ecosystem. PLoS Med 14:e1002260
Huang, Ivy A; Neuhaus, John M; Chiong, Winston (2016) Racial and Ethnic Differences in Advance Directive Possession: Role of Demographic Factors, Religious Affiliation, and Personal Health Values in a National Survey of Older Adults. J Palliat Med 19:149-56
Chiong, Winston; Wood, Kristie A; Beagle, Alexander J et al. (2016) Neuroeconomic dissociation of semantic dementia and behavioural variant frontotemporal dementia. Brain 139:578-87
Feldman, William B; Kim, Anthony S; Josephson, S Andrew et al. (2016) Effect of waivers of consent on recruitment in acute stroke trials: A systematic review. Neurology 86:1543-51
Chiong, Winston; Kim, Anthony S; Huang, Ivy A et al. (2014) Inability to consent does not diminish the desirability of stroke thrombolysis. Ann Neurol 76:296-304
Chiong, Winston; Kim, Anthony S; Huang, Ivy A et al. (2014) Testing the presumption of consent to emergency treatment for acute ischemic stroke. JAMA 311:1689-91