ORCID
https://orcid.org/0000-0003-1025-3100
Language
English (en)
Date of Award
Spring 5-15-2024
Degree Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Chair and Committee
Susan L. Stark
Committee Members
Beau M. Ances, Chih-Hung Chang, Erin R. Foster, Jason Hassenstab
Abstract
Alzheimer disease (AD) is a slowly progressive neurodegenerative disorder marked by a gradual decline in cognitive functions and ability to perform daily activities. AD begins with a clinically silent period in which pathological abnormalities accumulate in the brain before cognitive impairments occur (i.e., while individuals remain cognitively normal [CN]). This stage is known as preclinical AD and can last up to two decades. It can be identified by measuring biomarkers of AD using neuroimaging or biofluid techniques. In the United States alone, it is estimated that nearly 46 million individuals are in the preclinical stage of AD and at risk of progressing to symptomatic AD. Preclinical AD offers a critical window for early detection and intervention with the highest potential for making a clinically meaningful difference on the disease’s trajectory.
Subtle impairments have been observed in preclinical AD using sensitive assessments of cognition and sensorimotor function. Little is known as to whether pathological features of preclinical AD impact daily activities, such as cognitively-focused instrumental activities of daily living (IADL; e.g., managing medications and finances). A better understanding of IADL performance in preclinical AD can lead to improved IADL assessments to screen for preclinical AD and the development of interventions to maintain IADL performance for longer into the progression of AD.
This dissertation examines complex daily tasks (i.e., cognitively-focused IADL) in preclinical AD. It aims to ascertain the appropriate assessment type to study IADL performance in preclinical AD and provide preliminary evidence to support this line of inquiry (Chapter 2); quantify the relationship between IADL performance and biomarkers of AD (Chapter 3) and the role of cognition in these relationships (Chapter 4); and explore the remote administration of a performance-based IADL assessment (Chapter 5).
We found that among CN older adults, a performance-based IADL assessment provides greater variability in scores compared to an IADL questionnaire. Next, we used a performance-based assessment to examine the relationships between IADL performance and biomarkers of AD. We found that worse IADL performance was associated with beta-amyloid protein accumulation (early-stage biomarker of preclinical AD) and neurodegeneration (late-stage biomarker of preclinical AD). We also adapted the performance-based IADL assessment to be administered remotely and findings supported its feasibility and similarity to in-person assessment.
Together, these studies provide insight into early manifestations of AD pathological burden (i.e., IADL impairment) and highlight the value of performance-based IADL assessments. Findings support that IADL impairment is associated with preclinical AD, but future longitudinal research is needed to determine how and when it fits into the trajectory of AD. Future research should also expand on these findings by incorporating additional, modifiable factors into assessments to refine our understanding of IADL performance in real-life settings and develop targeted IADL interventions for this population at risk of progressing to symptomatic AD.
DOI
https://doi.org/10.48765/bmrc-jx57
Recommended Citation
Keleman, Audrey A., "Exploring Complex Daily Tasks in Preclinical Alzheimer Disease" (2024). WUSM Theses and Dissertations – All Programs. 45.
https://digitalcommons.wustl.edu/all_etd/45
