PROJECT SUMMARY
Growing emphasis on the early diagnosis and treatment of Alzheimer’s disease and related dementias (ADRD)
increases the demand for providers to make informed care decisions. Most of the care for people recently
diagnosed with ADRD falls on primary care physicians (PCPs), as frontline providers for older adults. Many of
the clinical decisions PCPs must make to care for patients with ADRD are not currently supported by robust
evidence. Given the heterogeneity of ADRD, we cannot rely on randomized trials to provide evidence for
clinical decisions across the range of conditions and unique patient/family considerations. Unclear guidelines
on treatment strategies lead to large inconsistencies in how patients are treated, potentially causing harm and
exacerbating health inequities. There is a large and growing need for evidence on best practices in early
dementia care using accessible, timely data, and rigorous methods. This F31 career development proposal is
designed to prepare the candidate for a career focused on this critical area, delivering much-needed evidence
to guide common clinical decisions to provide the best possible care for individuals with early ADRD. The
research plan evaluates three important clinical decisions commonly encountered by PCPs caring for patients
experiencing cognitive decline. Aim 1 will evaluate whether referral to dementia specialty care delays onset of
patient frailty using electronic health record (EHR) data from University of California, San Francisco (UCSF)
primary care clinics. The candidate will use both traditional observational methods and an instrumental variable
analysis with physician preference for referral as an instrument. Aim 2 investigates whether prescriptions of an
antidementia drug (memantine) are associated with incident frailty using both traditional observational methods
and an emulated target trial design analysis using UCSF EHR data. Finally, many conditions, including urinary
tract infections (UTIs), are not specific to patients with ADRD but are more common among older adults with
cognitive decline. In the context of emerging cognitive declines, inappropriate UTI management (especially if
drug resistant) may be especially harmful. In Aim 3, we will examine whether early treatment of UTIs caused
by drug-resistant E. coli is associated with reduced risk of incident ADRD and patient frailty using EHR data
from UCSF and the San Francisco safety net public healthcare system. This proposal will demonstrate use of
EHR data to evaluate the efficacy of current and future innovations in dementia care across diverse patients,
with the goal of contributing to informed clinical guidelines for PCPs. This research will directly contribute to the
NIA’s goal to provide evidence to delay ADRD progression. Guided by an interdisciplinary and expert
mentorship team, the proposed training will enhance the candidate’s knowledge of clinical care for ADRD,
advanced causal inference and econometric methods, and clinical informatics. Facilitated by the supportive
training environment at UCSF, executing this F31 research and training plan will prepare the candidate to
succeed in a career as an independent translational researcher in dementia epidemiology.
