Author ORCID Identifier

Date Available


Year of Publication


Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation




Pharmaceutical Sciences

First Advisor

Dr. Daniela Claudia Moga


Preventable and unintended consequences of medication use occur in more than 25% of ambulatory and hospitalized patients, and nearly half of long-term care patients. Unfortunately, many medications used to treat common health conditions in older adults (such as anxiety, behavioral disturbances, incontinence, insomnia, depression, and pain) have also been linked to cognitive impairment and decline. Recently, substantial efforts to investigate medications and medication classes that may be associated with cognitive impairment and decline in older adults have been undertaken. Unfortunately, studies have used a wide variety of different tools to define “potentially inappropriate medication” (PIM) use, and no published literature has consistently associated a particular medication appropriateness tool with cognitive outcomes, leaving clinicians and patients without a much-needed approach to deprescribing for preservation of cognitive function. Given the national focus on prevention of cognitive decline, the vast pool of available PIM measurement tools, and the variety of ways in which to consider exposure to PIMs, there is a need to determine which tool (if any) identifies PIMs most strongly associated with cognitive decline. Without widespread consensus as to what measure of PIM use is the best to use when studying the aptitude of medications to cause cognitive decline, clinicians will not have the tools they need to improve outcomes for their patients. As the world awaits further developments that may one day produce an effective treatment (or even cure) for the terrible brain-destroying disease of dementia, we can take steps today to improve medication therapy that may dampen its horrific impact on the lives of older adults and their loved ones.

In this work, we set out to examine the issue of measuring medication appropriateness to target cognitive outcomes with the intent of informing future research and clinical practice. While the gold-standard in evidence generation remains randomized placebo-controlled clinical trials, we have seen that even the most rigorously performed trials are not useful to generate evidence if there is not a consistent meaning to "inappropriate medication." Groundwork must laid to provide crucial validation and consensus to the measurement of medication appropriateness in light of cognition, and then it must be applied to numerous prospective research endeavors in order to provide a synthesized evidence-base for how medications should be managed to ensure appropriate use in older adults wishing to preserve cognition.

In the first section, we have provided a historical context for the importance of medication management, described the current state of affairs in the US and around the world, and provided an overview of the available tools that have been used to measure medication appropriateness with a perspective toward cognition.

Section two will utilize a number of these tools to estimate prevalence of potentially inappropriate medication use in various populations of American older adults.

The next section will use various methodological techniques and data sources to explore how some of these tools may or may not be associated with cognitive decline in older adults. We will define both PIM use and cognitive decline in a variety of ways to determine the effect varying definitions may have on new evidence generation.

Finally, we will explore how the findings provided in this work may be applied to clinical practice, future research endeavors, and governmental policies.

Digital Object Identifier (DOI)