Assessment of Medication Optimization in Rural Kentucky Appalachian Patients With Mild Cognitive Impairment or Dementia: The AMOR Kentucky Study
Phase: NA
Conditions: Dementia, Mild Cognitive Impairment
Sponsor: Daniela Moga

Document Coversheet 
 
 Study Title: Assessment of Medication Optimization in Rural Kentucky Appalachian Patients 
With Mild Cognitive Impairment or Dementia: The AMOR Kentucky Study 
Institution/Site:  
University of Kentucky 
Document (Approval/Update) Date: 
10/12/2020 
NCT Number: 
NCT05078437 
IRB Number 
69305 
Coversheet created: 
6/12/2024 
 
 

Study overview: The current proposal includes a single arm, unblinded feasibility study of the MTM describing 
intervention in rural/underserved Kentucky Appalachian populations with MCI and/or dementia. Our well-
established experience in providing MTM deprescribing interventions to the aging population with and without 
cognitive decline has allowed us to develop routine practices of assessment of medication appropriateness 
using the MAI, as well as implementation of a multidisciplinary physician-pharmacist team targeting 
improvement in cognitive outcomes in the aging population. This approach will be carried forward through a 
telemedicine practice that is comprised of approximately 500 patient-caregiver dyads throughout rural areas of 
Appalachian Kentucky. The methods for cognitive assessment and assessment of other health related issues 
have been well-established through an initial grant from the Alzheimer’s Association in 2007 and have been in 
practice for 16 years here at UK. 
We intend to use this system and these experiences to assess medication appropriateness in 50 research 
participants over the one-year funding. In this trial, each participant will be evaluated for medication 
appropriateness, and a deprescribing intervention will be provided by our multidisciplinary team. 
Reassessment of the proposed medication changes, as well as the potential impact on cognition will be 
determined at the six-month evaluation for each of these participants. Participants will be age greater than 60 
years, with mild cognitive impairment, and/or in the early 
stages of dementia. Participants will be enrolled and 
followed for 6 months to determine the impact of the 
telemedicine-delivered deprescribing intervention in 
improving medication-related outcomes (i.e., medication 
appropriateness, number of medication/PIM) in 
rural/underserved Kentucky Appalachian populations with 
cognitive impairment and/or dementia. As secondary 
outcome measures, we will evaluate the impact of the 
deprescribing intervention on cognitive function and 
caregiver burden using validated assessment instruments 
(see description of outcome measures below).  
Study Design. This preliminary feasibility study will use an unblinded, single-arm design. See study table for 
timing of specific procedures and intervention (Table 3).  
Study population. Participants will all be enrolled from rural Appalachian referrals to the UK telemedicine 
Cognitive Clinic. All people enrolled in this clinic receive a standardized cognitive evaluation and treatment 
plan, described below. Immediately after completing their first remote visit, eligibility for participating in the 
study intervention – which comprises specific medication-focused evaluation and recommendations, also 
described below – will be assessed. Eligibility includes: (1) 60 years or older, (2) diagnosed with mild cognitive 
impairment or dementia, (3) using at least one PIM, (4) living in the community, (5) willing to participate in this 
intervention study (both the patient and the caregiver). Subjects meeting eligibility criteria will be contacted, 
informed about the study, and invited to participate. The informed consent process will be performed remotely 
with the participant and or legally authorized representative using IRB-approved protocols (see Human 
Participants Section for details).  
AMOR-KY MTM Intervention. The proposed deprescribing intervention is using a patient-centered framework 
by: (1) balancing the risks and benefits, and addressing the specific needs of each individual patient, (2) 
considering the individual patient and their caregiver’s preferences and values, and (3) empowering the patient 
and their caregiver to take responsibility and fully participate in the decision-making process as equal team 
players.28-30 The proposed MTM deprescribing intervention will be developed on an individualized basis, taking 
into account specific medications and medical conditions for each unique participant, and delivered in an 
interdisciplinary fashion by the pharmacist-physician team working closely with the patient and their caregiver.  
After enrollment, we will conduct an interview with the participant and their caregiver to collect information on 
all the medications the participant is taking, including prescription and over-the-counter medications, vitamins 
and supplements. These data will include health history, indication for treatment, duration of therapy, dose and 
mode of administration, and adherence to therapy. In addition, we will assess the potential for adverse drug 
effects by asking the participant and their caregiver to recall any side effects, unwanted reactions, or other 
problems with their medications in the last year or since the medication was initiated, whichever is shorter.31
For patients reporting adverse effects, additional information will be collected to include the name of the 
Table 3. Timeline of study events
Study procedures
Baseline evaluation
4 weeks
3 months
6 months
Complete medical
evaluation
X
X
MTM intervention
X
X
Assessment of 
medications
X
X
X
X
Assessment of 
AE/SAEs
X
X
X
Participant 
outcome measures
X
X
Caregiver outcome 
measures
X
X
Abbreviations: MTM, Medication Therapy Management 
Intervention; AE, adverse event: SAE, serious adverse event.

medication they suspected, a description of the symptomatology experienced, and whether they modified the 
use of the medication in question on their own or after discussing with their primary care physician.31 
Based on the data collected, the pharmacist will review the information and will prepare prioritized written 
recommendations to include the ‘problem-list’ of medications that are potentially inappropriate (based on 
indication, adverse events, drug-drug or drug-disease interaction, or as described by the Beers 2019 criteria, 
specifically focusing on medications like anticholinergics, benzodiazepines, or Z-drugs that are of importance 
to patients experiencing MCI or dementia).36,37 The pharmacist will also provide recommendations on the 
proposed action for each of these medications including: 1) discontinuation; 2) modification of therapy to switch 
to suggested safer alternative, or to change the dose; or 3) continuation of treatment due to treatment 
necessity and favorable outcomes under treatment. Where appropriate, the proposed alternatives will include 
medications listed in an adjunct to the Beers 2019 criteria as “Alternative Medications for Medications in the 
Use of High-Risk Medications in the Elderly and Potentially Harmful Drug-Disease Interactions in the Elderly 
Quality Measures”.36-38  
Following this review, the pharmacist-physician team 
will meet during case conferences to discuss all the 
problems identified and decide on final 
recommendations for discontinuation or change related 
to inappropriate medications. The final 
recommendations and their rationale, along with 
general drug information will be discussed by the 
pharmacist with the patient and their caregiver. 
Attention will be given to explaining the rationale behind 
each recommendation and allowing the patient and the 
caregiver to ask clarification questions, and to express 
concerns. The written recommendations and the 
proposed changes will be shared with the patient’s 
primary care physician who will be consulted on the 
best approach to improve the patient’s outcomes. At 4 
weeks and 3 months after the initial intervention was 
delivered, we will follow up with the participant and their 
caregiver to determine the need for additional 
evaluations by the pharmacist and/or physician. If 
necessary, the pharmacist-physician team will provide 
the following for the participant: (1) comprehensive 
medication list, updated each time there is a medication 
change; (2) monitoring for patient concerns or 
adherence issues; (3) targetted additional evaluation 
and recommendations for interim medication changes. The intervention will be administered using the existing 
tele-medicine infrastructure at UK.  
Telemedicine Evaluation Protocol. All study participants will receive the standard telemedicine evaluation for 
the UK Telemedicine Cognitive Clinic, which includes a 1-hour initial visit and a 30 minute follow up 
telemedicine evaluation (as noted above, after the first clinic visit, patients will be evaluated for eligibility for the 
“add-on” MTM intervention we seek to study, and thereafter invited to participate in this research). In the initial 
evaluation, a diagnosis is made or diagnostic testing is pursued, which may include routine laboratory blood 
tests to evaluate for reversible causes of dementia and brain imaging studies (CAT scan or MRI) according to 
the AAN practice parameter on the initial workup and diagnosis of dementia (AAN practice parameter on initial 
evaluation of dementia). Details of the standard telemedicine evaluation used in this study are provided in 
Table 4. These assessment scales are ideal for telemedicine assessment providing insights into diagnosis as 
well as gait, balance and fall risk that are important outcomes of deprescribing interventions. They will serve as 
appropriate clinical diagnostic and research outcome measures supporting the proposed protocol.  
Table 4. Description of components of the standard telemedicine evaluation used in 
this proposal 
Instrument 
Description & Rationale 
Alzheimer disease 8 
questions scale 
(AD8) 
Brief 8 item screening questionnaire validated for the detection of 
MCI and/or dementia 
Past Medical History 
Includes medical/surgical/family/social history components of the 
standard clinical evaluation. Used to determine MAI and identify 
covariates 
Neuropsychiatric 
inventory (NPI) 
Used to assess behavioral and psychiatric symptoms of dementia. 
These may serve as exploratory measures and are important for 
AE/SAE issues. 
Functional 
Assessment 
Questionnaire (FAQ) 
Used to assess functional consequences of MCI/dementia. These 
may serve as exploratory measures and are important for AE/SAE 
issues. 
Kokmen Short Test 
of Mental Status 
(KSTMS) 
Global assessment of cognitive function that allows cross 
comparisons between other commonly used global assessment 
tools such as the Folstein Mini-Mental State examination (MMSE) 
and the Montreal Cognitive Assessment (MOCA). Used to define 
cognitive state, diagnosis, and to track longitudinal change. 
5 Word Free & Cued 
Recall Test 
Memory test that assesses learning, free-delayed recall, and recall 
augmented by category and choice cuing. Used to define memory 
components, assist with diagnosis, and to track longitudinal change. 
Category Fluency 
(animal naming) 
Number of animals one can name in 60 seconds. Semantic fluency 
measure used to assess verbal capacity that has been shown to 
high predictive ability for early clinical cognitive decline and for 
tracking longitudinal change. 
Phonemic Fluency 
(letter fluency) 
Number of words starting with the letter “S” one can name in 60 
seconds. Phonemic fluency measure used to assess verbal capacity 
that has been shown to high predictive ability for early clinical 
cognitive decline and for tracking longitudinal change. 
Physical 
Examination 
Extraocular movements, AMRs (alternating motion rates) in all 4 
extremities, Praxis in all 4 extremities, Gait and postural stability, 
Frontal release signs (glabellar, snout, palmomental). 
Clinical Dementia 
Rating (CDR) scale 
The CDR is a fundamental staging system for MCI and dementia 
stage determination including both global as well as sum of box 
scores spanning 6 domains of cognition and function. Scores will 
allow determinations of inappropriate medication use and success of 
the intervention as well as serving as a covariate in the secondary 
and exploratory and outcome measures described. 

Following the Telemedicine evaluation, a tentative diagnosis will be made in relation to the research 
participant’s cognitive status, that will be used as an important covariate in the analysis. Ultimate clinical 
diagnosis and disease staging will follow currently approved National Alzheimer Coordinating Center criteria 
and guidelines.  
Outcome variables (Aims 1 and 2). 
Primary outcomes of interest
include change from baseline to the 
6 months follow-up in the
Medication Appropriateness Index
(MAI) and in number of 
medications (total number and 
number of PIM), with a focus on
medications targetted by the MTM 
deprescribing intervention. MAI rates 
each medication based on 10 
different criteria (Table 5), each of them with explicit instructions and examples to guide evaluation; the 
evaluator rates whether the particular medication is “appropriate”, “marginally appropriate”, or “inappropriate”.39
The reliability of MAI assessments made by a clinical pharmacist and a physician (i.e., internist and 
geriatrician) demonstrated high inter-rater (kappa = 0.83) and intra-rater reliability (kappa = 0.92).39 We will 
also measure the reduction in the number of potentially inappropriate medications,36 from baseline to the end 
of the study period. Secondary outcome measures will include deprescribing and caregiver assessments to 
explore the acceptability of deprescribing and caregiver burden that may be associated with inappropriate 
medication use and the correction of potential medication misuse that may be influenced through our 
interventional strategy (Table 6); these will also be 
collected at the beginning and end of the study (see 
Table 3). Additional secondary and exploratory outcome 
measures include cognitive assessments collected as 
part of the routine telemedicine cognitive assessment 
are described earlier. To assess acceptability of the 
intervention, at the last study visit, patients and 
caregivers will be surveyed using several Likert scale 
questions and will be given the opportunity to share their 
opinions of the intervention, including what they liked 
and disliked about it and what they might do differently.24
Responses to this survey will be used to inform the 
planned subsequent iteration of the study for a major 
future RCT.
Statistical Analysis Plan and Power Calculations:
Descriptive statistics will be used to describe the 
demographics of the study participants. The pre- and postintervention changes will be analyzed using the 
Wilcoxon signed-rank test. Based on previous studies using MAI as outcome of interest we calculated the 
sample size to detect a mean difference of 1.0 between baseline and follow-up assessment. We will need 34 
participants to detect this difference with 80% power at a 
significance level of 0.05 (Figure 3). This is a rather 
conservative approach as previous studies showed that 
medication reconciliation interventions can determine a 
mean MAI change ranging between 1.9 and 17,40 with our 
previous study showing a change in MAI of 3.6 after the 
intervention.24 In order to account for the potential loss to 
follow-up, we will plan to enroll 50 participants. Despite 
the use of an open label, unblinded intervention that 
precludes definitive proof of efficacy for our deprescribing 
interventions, this study will provide valuable feasibility, 
and acceptability data regarding our interventional 
strategy. The data derived will further provide estimations of intervention effect size that will enable the 
Table 6. Deprescribing and Caregiver assessments not described previously that 
extend beyond the routine telemedicine cognitive assessment.
rPATD scale
The caregiver version of the questionnaire will collect information on 
patient’s and caregiver’s attitudes and believes about deprescribing, 
information that will inform the approach in deprescribing.
Zarit’s Caregiver 
Burden Inventory
Caregiver burden may be directly impacted by inappropriate medication 
use. The Zarit Burden scale is a well validated instrument that has not 
been used previously in describing studies.
Appraisal of Self-
care Agency 
scale
“Caring for the Caregiver” is a common phrase we hear frequently. The 
assessment of self care by caregivers may be an important variable for 
study in the caregivers of persons with inappropriate medication use.

development of our planned larger scale R01 interventional study focused on remote deprescribing 
interventions in rural and underserved communities throughout distributed US populations. 
Expected results & alternative approaches. As this is a single-arm pilot study, we will not be able to 
distinguish effects of usual care from the additional MTM intervention.  However, because usual care in the 
Cognitive Clinic does not place substantial focus on medications, it is likely that any observed changes will be 
plausibly attributable to the MTM intervention, and evaluations of feasibility and acceptability will also be 
distinguishable. Relevant concerns to this study include technology and access issues that may be prohibitive 
for our rural population. This should be minimized through the availability of telemedicine in their local 
community health care facilities that afforded the initial telemedicine consultation. Should we discover such 
barriers to engagement we will leverage internal funding to provide appropriate internet connectivity and or 
devices as need to ensure the conduct of the trial is not compromised by such concerns or issues. Another 
possible barrier to the study’s conduct and execution of our planned deprescribing intervention includes issues 
in regard to coordination and acceptability of our proposed medication modifications with the rural primary care 
providers. This has not been a problem previously but maintaining close communication on our intervention 
and recommendations is needed to ensure our success. Should this prove an obstacle, further develop 
initiatives to enhance our integration and cooperativity with the rural primary care physicians that are involved 
in our participant’s care.