Indiana University Dementia Screening Trial: The IU CHOICE Study
Phase: NA
Conditions: Dementia, Alzheimer's Disease, Mild Cognitive Impairment
Sponsor: Indiana University

 
Indiana University Dementia Screening Trial 
 The IU CHOICE Study 
 
Study Protocol 
Version 6 
March 28, 2013 
 
CHOICE Study Team 
 
Malaz A. Boustani, MD, MPH 
 
 
 
Chris Callahan, MD 
Principal Investigator            
 
 
 
Co-Investigator 
IDND Network Director 
 
 
 
 
IU Center for Aging Research Dir 
Regenstrief Institute, Inc. Scientist 
 
 
 
Regenstrief Institute, Inc. Scientist 
IU Center for Aging Research 
 
 
 
IU Center for Aging Research 
 
Email: mboustan@iupui.edu  
 
 
 
 
 
Greg Sachs, MD  
 
 
 
 
 
Paul Dexter, MD 
Co-Investigator 
 
 
 
 
 
Co-Investigator 
Chief of Div of Gen Internal Med & Geriatrics 
 
Chief Med Information Officer WHS 
Regenstrief Institute, Inc. Scientist 
 
 
 
Regenstrief Institute, Inc. Scientist 
IU Center for Aging Research 
 
 
 
Biomedical Informatics  
 
 
 
 
 
 
 
 
 
Amie Frame, MPH  
 
 
 
 
 
 
 
 
Research Manager 
 
 
 
 
 
 
Regenstrief Institute, Inc. 
IU Center for Aging Research 
410 West 10th Street, Suite 2000 
Indianapolis, IN 46202-3012 
Phone: (317) 423-5910 
Fax: (317) 423-5653 
Email: amiframe@iupui.edu 
 
 
 
 

2 
 
 
Table of Contents 
 
A. Rationale and Study Specific Aims ......................................................................................................... 3 
B. Innovation .............................................................................................................................................. 5 
C. Background ............................................................................................................................................. 8 
D. Preliminary Studies ............................................................................................................................... 10 
E. CHOICE Trial .......................................................................................................................................... 20 
F. Inclusion/Exclusion Criteria .................................................................................................................. 35 
G. Enrollment/Randomization .................................................................................................................. 35 
H. Data Collection ..................................................................................................................................... 39 
I. 
Statistical Plan  ..................................................................................................................................... 43 
J. Limitations ............................................................................................................................................ 47 
K. Timeline ................................................................................................................................................ 48 
L. Protection of Human Subjects .............................................................................................................. 49 
M. Reporting of Unanticipated Problems & Adverse Events .................................................................... 54 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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A. Rationale and Study Specific Aims 
 
A fundamental tenet of any screening program is that it should “reduce individual and 
societal burden from specific disorders”.1,2 Screening is, by definition, applied to individuals 
without symptoms. Thus, a physician completing a cognitive assessment on a patient 
presenting with complaints of memory problems is engaged in case-finding or diagnosis.1,2 
Assessment of symptomatic individuals is not screening and is not the subject of this trial.  
Screening for some conditions among some populations has resulted in magnificent 
improvements in individual and societal burdens of diseases (e.g. colon cancer and 
cardiovascular disease, among others). However, screening can also cause harm, excess 
costs, and considerable societal controversy (e.g. mammography for some patient groups and 
prostate specific antigen testing, among others). Furthermore, not all screening is advisable at 
an individual level or at a societal level. In some conditions (e.g. depression), screening is not 
recommended unless a health care system has in place the resources and expertise needed to 
appropriately diagnose and treat positively-screened patients.3,4 According to the US Preventive 
Services Task Force, we do not have sufficient evidence of the benefits and harms of screening 
to recommend routine screening for dementia in primary care.5   
In the context of insufficient data on harms and benefits, providers already have wide 
availability of dementia screening instruments,6,7 advocacy for and against routine screening2,5,8-
12 and a downstream list of potential follow-up diagnostic testing including routine blood test 
such as thyroid stimulating hormone, as well as neuroimaging.13,14 Providers also have 
widespread availability of psychopharmacologic agents (ranging from anti-dementia drugs to 
antidepressants and antipsychotics) that are highly controversial in dementia care and 
associated with important adverse effects.15-20 Clinical trials, such as our own collaborative care 
trial, require significant practice redesign to implement and many of these redesign elements 
are not reimbursable by the Center for Medicare and Medicaid Services (CMS). Finally, 

4 
 
Alzheimer’s disease and related dementia are dreaded conditions and people are seeking 
answers.  Even though no cure is in sight, patients and families seek help in managing 
behavioral symptoms and health care decision-making.21-24 It is of little wonder that primary care 
physicians find themselves in a situation of therapeutic nihilism, cynicism, low levels of 
confidence, and frustration.25-27 Our prior explanatory trial demonstrated that primary care 
providers, given the proper resources, can improve behavioral and psychological symptoms 
associated with dementia, caregiver stress, and depression. 
The objective of this proposal is to address the question of whether the benefits 
outweigh the harms of routine screening for dementia among older adults in primary care when 
the screening program is coupled with primary care practices prepared to provide care for those 
who screen positive. All subjects will complete a screening questionnaire that includes 
screening already recommended for older adults (e.g. smoking). A random sample of these 
subjects will have a cognitive screener embedded within this larger set of screening questions.  
Thus, the control condition (no screening) means no cognitive screener. 
The proposed project will contribute important information to patient, families, providers, 
and policy-makers about the harms and benefits of routine screening for dementia. If this trial is 
successful, it will not only address the appropriateness of routine screening for dementia, it will 
also provide a template for the successful implementation of screening programs, coupled with 
diagnosis and treatment programs, that are practical for a broad range of health care systems. 
Finally, we will report data on cost and cost effectiveness. 
 
 
 
 
 
 
 
 
 

5 
 
The specific aim of the study is to conduct a pragmatic randomized clinical trial 
assessing the harms and benefits of screening for dementia, compared to no screening 
for dementia, among 4,000 typical, older adults, cared for in typical, primary care 
practices, prepared to deliver best practices dementia care. 
 
Primary Specific Aim 1: Test the impact of dementia screening on health-related quality of life 
of the patient at baseline and at 1, 6, and 12 months.  
(We hypothesis that screened subjects, compared with non-screened subjects, will have a higher health-
related quality of life as measured by the Health Utility Index (HUI) at 12 months post-screening.) 
 
Primary Specific Aim 2: Test the impact of dementia screening on the mood and anxiety 
symptoms of patient at baseline and 1, 6, and 12 months (i.e., primary potential harms).  
(We hypothesize that screened subjects will not have higher depression or anxiety at one month post-
screening (as measured by the Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder 
(GAD-7) scales) 
 
Secondary Aims: Estimate the cost effectiveness of dementia screening. 
(We hypothesize that screened subjects will have an Incremental Cost Effectiveness Ratio (ICER) below 
the maximum acceptable threshold of $100,000 per quality adjusted life year saved at 12 months.) 
 
B. Innovation 
Pragmatic 
Previous studies by our team and others have demonstrated that routine feedback of 
dementia screening scores, continuing medical education for dementia, and other passive 
educational interventions can improve rates of diagnosis, but not patient outcomes.12,28-32 We 
have shown that patients and families perceive potential harms from screening and that 
dementia screening can result in important incremental health care costs.21-23,33 Conversely, we 
and others have also already demonstrated that collaborative care, focused on non-

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pharmacologic approaches to behavioral disturbances, can improve patient outcomes under 
experimental conditions.34,35 The innovation of this trial is in moving the process upstream to 
asymptomatic, older adults, cared for in typical but prepared community-based practices, to 
document actual benefits and harms, including costs. “Asymptomatic”, in the case of cognitive 
impairment, is paradoxical in some respects, but we denote asymptomatic to mean that the 
cognitive impairment is not a presenting symptom of the patient (just as hypertension is 
asymptomatic but can be detected by screening, cognitive impairment can be detected through 
screening tests). 
 
Academic Community Partnership 
 
Moving from an explanatory trial to a pragmatic trial is much more complicated than 
simply a change in setting. Moving research to “the usual conditions in which it will be applied” 
requires an entirely different research approach.36-41 We are not new to this area. Through prior 
work, we have a running start in terms of a program (screening, diagnosis, treatment, and 
longitudinal assessment tools) and in understanding the process of adapting an intervention to 
local micro-environments.42,43 Through funding from the NIMH, we not only have experience in 
conducting implementation research in community settings, we also have experience in 
conducting pragmatic mental health services research. One hallmark of a true community-based 
participatory research is that the community partners have meaningful input into the study 
design and interpretation. A partnership is more than a venue change.   
 
Integrated Health Information Technology 
We have access to a regional health information exchange (RHIO) which we have used 
in prior research.44-71 Additionally, we have already initiated the building of research partnerships 
with the targeted community-based health care systems through prior research 

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projects.1,34,42,43,72,73  Thus, we have a track record of successful human subject recruitment at 
these sites as well as co-management of the projects.  
 
Primary Care Focus 
Most older adults are cared for in primary care and primary care is the most likely site for 
early identification and treatment of dementia. However, the typical primary care physician with 
a panel of ~2,000 patients would care for only about two dozen older adults with dementia, at 
least half of whom would be undiagnosed. Among the 300 other patients aged 65 years and 
older in this practice, 150 would suffer from at least three chronic conditions, 200 would report 
pain, 100 feeling anxious, and 63 patients would require hospitalization.74 This primary care 
provider needs an estimated 10 hours per working day to deliver all of the recommended care 
for patients with chronic conditions and an additional seven hours per day to provide preventive 
services.75 Patients with dementia in the primary care system also suffer from numerous chronic 
medical conditions, receive multiple prescriptions including psychotropic drugs, display a wide 
range of behavioral and psychological symptoms, and extensively utilize the health care 
system.46,47,76-78  Organizational and procedural changes in this care environment, that continue 
to place new demands on providers, are not only difficult, but they may have unintended 
consequences. We recognize the complexity of the primary care environment and have 
established the relationships needed to conduct research in this arena. 
The key innovation of this proposal is our inter-related capacity to conduct a pragmatic 
trial within an academic-community partnership served by health information technology 
and to focus the study in the site of care where the intervention is most likely to be applied: 
overburdened primary care practices. 
 
 
 

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C. Background 
 
 
There were an estimated 5 million cases of dementia in the U.S. in 2000 and this 
number may grow to 18.5 million by the year 2050.79,80 According to the Global Burden of 
Disease estimates for the 2003 World Health Report, dementia contributed to11% of years lived 
with disability in people aged 60 years and older; more than cancer, stroke and cardiovascular 
disease.81,82 Currently, Medicare beneficiaries with dementia account for 34% of Medicare 
spending, even though they constitute only 13% of the beneficiaries aged 65 and older. By 
2050, Medicare will be spending over $1 trillion on beneficiaries with this syndrome.81,83,84  Most 
older adults with dementia receive their medical care in primary care settings, yet most primary 
care physicians care for less than two dozen older adults with dementia.33,74,78,85 Researchers 
and policy-makers consistently document suboptimal quality and poor outcomes among older 
adults with dementia receiving the usual care of generalist physicians.33,48,86,87 Beginning in 
January 2011, CMS started covering the costs of an annual wellness visit for Medicare 
beneficiaries that included detection of cognitive impairment.88 Yet, the US Preventive Services 
Task Force could not identify sufficient data to recommend for or against routine screening for 
dementia;5 patients and caregivers report concerns about potential harms from screening;21-24 
and most primary care practices are not prepared to follow-up positive screening with 
appropriate diagnosis, education, and management strategies.26-31,89,90 In the top quartile of 
research priorities in 2010, the Institute of Medicine recommended research to “Compare the 
effectiveness and costs of alternative detection and management strategies for dementia in 
community-dwelling individuals.”91 
 
Patients, families, policymakers, and researchers are understandably seeking a cure for 
Alzheimer’s disease and related dementias. In 2011, President Obama signed legislation 
approving the National Alzheimer’s Project Act to increase funding for research on prevention 
and treatment strategies. Multiple agencies within the Department of Health and Human 

9 
 
Services, including CMS and the NIH, have identified Alzheimer’s disease and related 
dementias as a top priority for research. While seeking a cure is the ultimate goal, we must also 
recognize that millions of Americans already have dementia and many more will develop 
dementia over the coming decades even if new prevention strategies are identified.79 Experts 
agree that we must prepare the health care system to provide hands-on care for millions of 
older Americans with dementia. This proposal makes the assumption, backed by our research 
and that of others, that early recognition of dementia could improve patient and caregiver 
outcomes, even if there are no cures, and even if there is only minimally effective (and 
sometimes dangerous) pharmacologic options for treatment of symptoms. This is true because 
randomized controlled trials have shown that nonpharmacologic approaches, either alone or in 
combination with pharmacologic approaches, can improve patient and caregiver outcomes, alter 
use of nursing home care, or reduce the use of harmful medications. Thus, a contention that 
screening for dementia is not useful because providers have nothing to offer, is not supported 
by the existing literature. 34,35  What remains highly controversial is the value, including harms 
and benefits, of screening populations of asymptomatic, older adults for dementia in an attempt 
to identify the disease at its earliest manifestations. Data clearly shows that early recognition of 
treatment of vascular risk factors, even in their asymptomatic manifestation, improves patient 
outcomes. Such data is not available for dementia. 
 
The proposed project will contribute important information to patient, families, providers, 
and policy-makers about the harms and benefits of routine screening for dementia. If this trial is 
successful, it will not only address the appropriateness of routine screening for dementia, it will 
also provide a template for the successful implementation of screening programs, coupled with 
diagnosis and treatment programs, that are practical for a broad range of health care systems. 
Finally, we will report data on cost and cost effectiveness. 
 
 

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D. Preliminary Studies 
 
We have a longstanding commitment to improving the care of older adults with dementia 
in primary care. This preliminary studies section describes (a) our experience in conducting 
clinical trials among older adults with dementia; (b) responsible use of data in the RHIO; (c) our 
initial work in understanding the benefits and harms of dementia screening from the patient’s 
and caregiver’s perspective; (d) estimates of potential cost savings with more effective 
management of dementia; and (e) initial efforts to adopt new models of care to real-world 
practices and demonstrate their financial sustainability. 
 
Primary Care Clinical Trial Experience 
 
In the early 1990s, our study team completed an extensive screening program of 4,000 
older adults who were approached during their regularly scheduled primary care appointments.  
The program was designed to assess the prevalence of cognitive impairment, depressive 
symptoms, suicidal ideation, and alcohol abuse.48,54-56,92 Less than 25% of patients with 
moderate-severe cognitive impairment had dementia recorded as a diagnosis; depression and 
problem drinking were similarly under-diagnosed. We coupled these screening data with clinical 
practice data from the Indiana Network for Dementia Care (INPC) (at that time known as the 
Regenstrief Medical Record System).49,60,61,66 We then followed this cohort of older adults for up 
to seven years to study the association between cognitive impairment and mortality.45 Cognitive 
impairment, measured at baseline, was a significant predictor of early mortality, even when 
controlling for comorbid conditions. These early observational studies provided the foundation 
for later intervention clinical trials in primary care.  More recently, we reported the mortality 
experience of this cohort at 15 years.44 
 
We were part of the design team and one of the clinical sites for the IMPACT trial of late 
life depression among primary care patients.93,94 Over two years, 1,800 older adults with major 
depression or dysthymia were recruited with 250 recruited from the Indiana site. Half of the 

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subjects were randomly assigned to a collaborative stepped care program where a depression 
clinical nurse specialist worked with the patient’s regular primary care provider to treat 
depression using antidepressant medications and Problem Solving Treatment in Primary Care. 
The intervention was specifically designed to coordinate care for depression with the patient’s 
regular primary care provider. Intervention patients were significantly more likely to receive 
guideline-level care, recover from depression, and to report improvement in physical function, 
health-related quality of life, and satisfaction with care.93 We learned a great deal from the 
conduct of this study and used this experience to conceptualize a study of collaborative care for 
dementia in primary care. 
 
In 2000, our research team designed a collaborative, primary care intervention based on 
published treatment guidelines for the recognition and treatment of Alzheimer’s disease.34 The 
program included a screening and diagnosis program and a randomized controlled clinical trial. 
Dementia was diagnosed according to ICD-10 criteria by an expert consensus panel using a 
process that mirrored the diagnostic scheme of the Alzheimer’s Disease Cooperative Studies 
group.33 We completed a controlled clinical trial of 153 older adults with Alzheimer disease and 
their caregivers who were randomized by physician to receive collaborative care versus 
augmented usual care.5 Both study groups completed a counseling visit with an advanced 
practice nurse who provided education about Alzheimer’s disease and a referral to community 
resources. Over the following year, intervention patients received care management by an 
interdisciplinary team led by a nurse practitioner working with the patient’s family caregiver.95 In 
addition to consideration for treatment with cholinesterase inhibitors, the team used standard 
protocols to identify, monitor, and treat behavioral and psychological symptoms of dementia 
(BPSD). The guidelines stressed non-pharmacologic management. Outcome measures 
included the instruments of the Alzheimer’s Disease Cooperative Studies group: 
Neuropsychiatric Inventory (NPI), Activities of Daily Living (ADL), and the Resource Use Scale.  
Study procedures assured that enrolled patients received an adequate dose and duration of the 

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treatment and we monitored the fidelity of the intervention, patient contacts, and patient 
outcomes using a web-based tracking system. 
 
Initiated by caregivers’ reports, 89% of intervention patients triggered at least one 
protocol for BPSD with a mean of four (4) per patient from a total of eight (8) possible. These 
results highlight the clinical observation that primary care patients with Alzheimer’s disease are 
indeed highly symptomatic. Intervention patients were more likely to receive cholinesterase 
inhibitors (79.8% v. 55.1%, p = 0.002) and antidepressants (45.2% v. 27.5%, p=0.03). There 
were no group differences in prescriptions for antipsychotics or sedative-hypnotics. Intervention 
subjects were more likely to rate their primary care as very good or excellent (82.8% v. 55.9%, p 
= 0.002). Intervention patients had significantly fewer BPSD at 12 months (mean difference -5.6, 
p = 0.011) as measured by the NPI. Intervention caregivers also reported significant 
improvements in distress and depression at 12 months. These improvements in behavioral 
symptoms are among the largest reported in the literature. This explanatory trial establishes 
that, under experimental conditions, the care of patients with dementia can be improved with 
interventions that can be deployed in primary care given sufficient practice redesign and 
resources. 
 
In 2007, we updated the USPSTF review with a focus on identifying practical and 
accurate dementia screeners suitable to the primary care systems. Among the 29 dementia 
screening instrument studies included, we found 12 instruments with promising performance 
and practical implementation (less than seven minutes of administration time).6 Rather than 
identifying one best instrument, our review suggested that the clinician’s strategy should simply 
be to pick one tool based on the population they cared for, with an awareness of how 
educational level, race, and age affect scoring, and then consider adding one or two others for 
special situations as needed. In addition to the brief screeners, we found a number of 
comprehensive instruments that evaluated multiple domains of cognition, thus having the 
potential to increase accuracy at the cost of increased administration time. We also identified 

13 
 
screening tests that could be useful in special situations. For example, the Telephone Interview 
for Cognitive Status (TIC) and MIS-T (Memory Impairment Screen – telephone version) could 
be useful for brief telephone based screeners outside the pressured atmosphere of the primary 
care visit, a critical feature for ensuring screening can occur feasibly in a broad range of 
healthcare delivery settings. Based on this review, we selected the MIS-T as the instrument of 
choice to be used within the diverse primary care clinics of our recruitment sites.96 The MIS-T is 
a quick test of recall ability (4 minutes to perform) and has a high accuracy for dementia 
diagnosis with a positive LR ranging from 11 to 33 (95%, CI 15 to 72) and negative LR of 0.08 
(95%, CI 0.02 to 0.3).97-99 
 
Responsible Use of Data from the Regional Health Information Exchange (RHIO)  
 
The proposed pragmatic trial will rely heavily on data routinely collected and stored in 
“Indiana Network for Patient Care (INPC), the RHIO in central Indiana. A full review of our prior 
work using the INPC, and its predecessor, the Regenstrief Medical Record System, is beyond 
the scope of this review of preliminary work. Over the past 20 years, we have used these data 
to describe patterns and cost of care for older adults across the entire urban public health 
system52, described emergency department use67, medication use68, patterns of care for 
dementia, depression, alcohol abuse, and other geriatric syndromes.33,48,54,56,70,92 We have 
described mortality outcomes of older adults with cognitive impairment and depression44,45, and 
explored treatment of older adults with advanced cancer.71 We have an excellent track record of 
using these epidemiologic data to design, implement, and test interventions to improve the care 
of older adults.   
 
We have also combined data from the RHIO with Medicare claims data as well as 
Medicaid, MDS, and OASIS data.46,69 To our knowledge, this dataset represented the first time 
these databases, which span the continuum of care, have been combined. In an ongoing NIMH-
funded study, we are using these data to describe the patterns of health services use over a 10-

14 
 
year period among older adults with lifelong serious mental illness. In a recent paper, we used 
these data to map transitions in care over five years among a cohort of older adults with 
prevalence and incident dementia. Compared to subjects never diagnosed (n=2,674), older 
adults with prevalent (n=524) or incident dementia (n=999) had greater Medicare (11.4% v. 
44.7% v. 44.8%, p=<.0001) and Medicaid (1.4% v. 21.0% v. 16.8%, p<.0001) nursing facility 
use, greater hospital (51.2% v. 76.2% v. 86.0%, p< .0001) and home health use (27.3% v. 
55.7% v. 65.2%, p< .0001), more transitions in care per person in year of follow-up (1.4 v. 2.6 v. 
2.7, p<.0001), and more mean total transitions (3.8 v. 11.2 v. 9.2, p<.0001).  Among the 1,523 
subjects with dementia, 74.5% of transitions to nursing facilities were transfers from hospitals. 
Among transitions from nursing facilities, the conditional probability was 41.0% for a return 
home without home health care, 10.7% for home health care, and 39.8% for a hospital transfer. 
Among subjects with dementia with a ≤30-day re-hospitalization, 45% had been discharged to 
nursing facilities from the index hospitalization. At time of death, 46% of subjects with dementia 
were at home, 35% in the hospital, and 19% in a nursing facility. Thus, we found that patients 
with dementia live and frequently die in community settings. Nursing facilities are part of a 
dynamic network of care characterized by frequent transitions. This study again demonstrates 
the fundamental role of primary care in the longitudinal care of older adults with dementia. 
 
Understanding the Patient and Caregiver Perspective 
 
Over the past six years, we used the Health Belief Model (HBM) as the theoretical 
framework for the development of an instrument to capture the public perceived benefits of 
dementia screening, the PRISM-PC questionnaire.21-23,100 We completed the PRISM-PC 
questionnaire on more than 500 patients aged 65 years and older attending several primary 
care clinics in Indianapolis who had no documented history of dementia or other illness 
such as depression, schizophrenia, or bipolar disorder. Approximately 13% of this group of 
older adults screened positive for the presence of cognitive impairment. The majority of subjects 

15 
 
had positive attitudes of dementia screening such as that 65% to 90% felt that dementia 
screening would provide them with the opportunity to plan their future finance and health care, 
advance directive, to participate in research, and motivate them to have a healthier life style. 
Few older adults perceived a negative impact of dementia screening on their emotional health 
or their independence. These findings suggest that the process of dementia screening may 
improve the quality of life not only for patients with unrecognized dementia but also for older 
adults with screen negative results, including at minimum the assurance of the absence of 
significant cognitive impairment. However, older adults did report concerns about potential 
harms including suffering from depression or anxiety, loss of driving privileges, difficulty 
obtaining long-term health insurance, and worries that people would treat them differently.21-
23,100 
 
Estimating Economic Impact 
 
To investigate the current and future economic impact of the collaborative dementia care 
management program in primary care settings, we developed a model to evaluate the net 
benefits for CMS of applying the collaborative dementia care program early via a routine 
screening in primary care. We used data from the collaborative dementia care trial, the 
dementia screening and diagnosis study, the USPSTF systematic review, and North Carolina 
public health impact of dementia forecasting study.1,33,34,79 We used cost terminology suggested 
by Gold et al.101 Direct formal costs included those costs in which a Medicare payment will be 
made for the services (e.g., physician visits, medications, hospital care, paid home care, and 
long-term care services); direct informal costs were the hourly wage of a worker who would 
need to be hired to provide the same care that an unpaid caregiver is providing; and finally cost 
estimates for different time periods were inflated by the Medical Care component of the 
Consumer Price Index (CPI).  After estimating the per capita total annual costs, we generated 
aggregate estimates of dementia prevalence over the period 2010 - 2050. The per-patient costs 

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were multiplied by the national prevalence weight to extrapolate the sample costs to population 
size for calculation of the total direct aggregated healthcare cost. 
 
The model predicts that total direct annual savings with the early implementation of the 
collaborative dementia care intervention among unrecognized dementia patients relative to 
usual care model are $4 billion dollars in 2010, $22 billion dollars in 2025, and $29 billion dollars 
in 2050. We further developed modified projections based on three scenarios: The discovery of 
a medical therapeutic that would reduce dementia incidence rate by 50%; the discovery of an 
intervention that would delay institutionalization by 12 months; and the discovery of therapeutics 
that would lead to reduction in dementia incidence rate and delay institutionalization. Compared 
to the baseline projections, the projected saving ranged from $24 billion in 2011 to $50 billion in 
2050 under any of the three scenarios. Our forecasting study demonstrated that at varying rates 
of effectiveness and in constant dollars, early implementation of the collaborative dementia care 
intervention via a routine screening in primary care, is cost effective for CMS with direct annual 
savings ranging from four billion dollars in 2010 to $29 billion dollars in 2050.102  
 
Initial Efforts to Adopt New Models of Care to Real-World Practices 
 
Through funding from the NIMH “Interventions and Practice: Research Infrastructure 
Program (IP-RISP R24), we have been building the infrastructure for an academic-community 
research partnership. The specific aims of the Indianapolis IP-RISP were to (1) foster an 
academic community-provider partnership that supports a research culture focused on the 
practical implementation and evaluation of novel mental health services for older adults; and (2) 
conduct and evaluate mental health services and implementation science pilot projects that 
address the quality improvement priorities of the community partner and their patients. Although 
the entire project is composed of eight different pilot projects, two are of particular interest to this 
proposal. The first was to create an integrated medical record to support clinical care for primary 
care patients who were also cared for in the local Community Mental Health Center. Records 

17 
 
had been previously kept in two different silos for these two different sites of care. The project is 
important to the current proposal because it taught us that technical barriers are often minor 
compared to cultural and legal barriers and resistance due to fear of change. The second 
project was to implement a collaborative care model for older adults with depression, cognitive 
impairment, or both and also integrate the care of cardiovascular disease. Manuscripts 
describing the success of this major implementation science project were published in Aging 
and Mental Health (2011).42,43 This second project is particularly important to the current 
proposal because we developed three infrastructure components to facilitate adoption of the 
collaborative care in primary care.   
 
The first component is the Healthy Aging Brain Care (HABC) Monitor.  Funded through a 
combination of the IP-RISP, the NIA IU Roybal Center, and industry, we developed a novel new 
caregiver “blood pressure cuff” for dementia, suitable for routine use in primary care.103 This 
HABC Monitor will assist with one of the main tenets of chronic care which is longitudinal 
tracking of patient outcomes. The HABC Monitor has excellent psychometric properties and is a 
practical measure of behavioral and psychological symptoms of dementia.103 The second 
component is the electronic medical record for aging brain care or eMR-ABC.  In order to 
efficiently deliver the various components of the collaborative care model, we developed a web-
based program management platform called eMR-ABC. The platform of the eMR-ABC includes 
a set of processes and software such as:   
 
Flexible and secure access to platform from multiple locations and by various clinical 
users; 
 
Manual, web-based, and optically scanned solutions to capture self/caregiver reported 
functional, behavioral, psychological, and cognitive symptoms;  
 
Decision support to deliver personalized, pharmacological and non-pharmacological 
care protocols;  

18 
 
 
Tracking process of care coordination tasks delivered by the care coordinators;  
 
Monitor patients’ and their caregivers’ biopsychosocial needs;   
 
Monitor population-based outcomes to guide overall program performance;   
 
Integration capacity with other informatics tools such as the Indiana Network for Patient 
Care (INPC) ; and 
 
Easy interface to move data from the eMR-ABC to analyzable datasets and potential 
merging with other datasets. 
 
 
The third component is a manual to assist practices in replicating the collaborative care 
management program. Through funding from the NIMH and other local and federal funding, we 
have developed the prototype for an implementation manual. The implementation or “replication 
manual” is based on a combination of the original collaborative care clinical trial and the field 
experience we gained through our initial local implementation efforts. We first adapted our 
original collaborative care model to improve its long-term adoptability by an urban public 
hospital.42,43  Capitalizing on the substantial interest in the US on the patient-centered medical 
home and reducing 30-day re-hospitalizations, we re-conceptualized our collaborative care 
model as the Aging Brain Care Medical Home. This new program was adapted to target older 
adults with dementia or depression who had been recently hospitalized by providing 
collaborative care in the home setting immediately following hospitalization discharge. In a 
recent publication, we described a structured set of activities that laid the foundation for a new 
partnership with the health care system and the lessons learned in implementing this new care 
model. We used the reflective adaptive process as a relationship building framework that 
recognizes primary care practices as complex adaptive systems.104-106 This framework allows for 
local adaptation of the protocols and procedures developed in the clinical trials. Tailored care for 
individual patients was facilitated through a care manager working in collaboration with a 

19 
 
primary care physician and supported by specialists in a memory care clinic as well as by 
information technology resources.   
 
Building on the success of this project, we received funding from the Regenstrief 
Institute to begin development of a replication manual to facilitate the wider dissemination of this 
care model.  A few summary pages from this existing manual are depicted in the picture at right. 
The manual provides information to primary care practices on how to set up a functional model 
of best practices for the care of older adults with dementia or depression. We emphasize that 
any screening 
program would 
need to have in 
place the capacity 
to provide 
education, 
diagnosis, and care 
for screen positive 
patients and their 
family caregivers.  
This replicable 
manual not only 
provides 
instructions that are 
consistent with 
treatment 
guidelines13,14, it 
also provides 

20 
 
written materials to assist in caregiver education and support. 
 
Through this summary of our preliminary studies we hope to establish our preparedness 
for the successful completion of this pragmatic clinical trial of dementia screening in 
primary care. 
 
 
E. CHOICE Trial  
 
 
We are proposing to enroll 4,000 adults, aged 65 and older, attending 10 primary care 
clinics in Indianapolis; these clinics are representative of two large health care systems: 
Wishard Health Services (WHS) and IU Health (IUH). We will randomize older adults at ratio of 
1:1 into “no screening” or “screening” groups. Subjects randomized into the screening group 
who have a positive screening would be further referred into a dementia diagnostic assessment 
and counseling and management program. Our outcomes will be measured at baseline, 1, 6 
and 12 months. Using data from our local Regional Health Information Exchange, the Indiana 
Network for Patient Care (INPC), we will collect health care utilization data of our samples; and 
monitor new diagnosis, diagnostic testing, and prescribed treatments and referrals. The flow 
diagram for the proposed study is depicted below. 
 

21 
 
6000  Primary care patients aged ≥65 yrs; no dementia or MCI diagnosis; no severe mental illness
4000 Pts consent  for and complete baseline data collection (HUI + PHQ-9 + GAD-7 + MOS)
Randomized; ratio 1 to 1
2000 Pts into No screening 
2000 Pts into Screening with MIS-T
1700 Pts screen negative on MIS-T
300 Pts screen  positive on MIS-T
200 proceed to diagnosis program
100 Pts receive diagnosis of 
Normal or MCI
100 Pts receive diagnosis of Dementia and 
are managed by dementia care program 
100 Pts refuse evaluation
HUI: Health Utility Index; PHQ-9: Patient Health Questionnaire-9; GAD-7:  General Anxiety Disorder screener; MOS: Medical Outcome Study;  MIS-T: Memory Impairment 
Screen-telephone version; MCI: Mild Cognitive Impairment; HER-electronic health record.
Telephone-based re-evaluation at 1, 6, and 12 months (HUI + PHQ-9 + GAD-7 + MOS); EHR data acquisition
 
 
 
Subject Recruitment 
 
 
Established in 1999, the Indiana University Practice Based Research Network (IU-
PBRN) consists of 17 primary care centers affiliated with Wishard Health Services and Indiana 
University Health.73 These two systems serve a diverse population of insured and uninsured 
patients throughout Indianapolis. More than 110 primary-care physicians practice at these sites. 
These physicians treat approximately 100,000 patients per year in more than 300,000 visits 
annually. Using the INPC data repository, IU-PBRN effectively uses informatics tools to 
streamline patient recruitment and follow-up.73 Since its inception, the IU-PBRN has screened 
more than 45,000 primary care patients, enrolling more than 17,000 subjects into more than 75 
studies.  The study team has been utilizing the IU-PBRN since its inception and the successful 
completion of these projects, described in the Preliminary Studies section, are a testament to 

22 
 
the effectiveness of the IU-PBRN.  The IU-PBRN achieved this success through the following 
informatics innovations. 
 
Centralized Electronic Data Management:  
 
Before a study is operationalized, data managers extract from INPC a list of eligible 
patients based on the study’s inclusion criteria (e.g. patients cared for in the targeted primary 
care practice, over the age of 65, and without a diagnosis of dementia). Once an eligible list of 
patients has been extracted, it is provided to the clinicians, who must authorize the study to 
approach their patients for potential participation. Letters are sent to those patients informing 
them of the study and the appointments records are queried to determine when the patients are 
next due for appointments. Lists of patients with upcoming appointments are then generated to 
develop a weekly list of the patients eligible for the study. This electronic list is accessed via the 
intranet by the IU-PBRN research assistants, who subsequently enter recruitment information 
into the database about all patients contacted. The data manager then merges the data into a 
master database that is used to generate future lists. IU-PBRN has established a study 
monitoring system that uses the above-mentioned master database to upload enrollment dates 
into the electronic medical record. The electronic medical records contain the dates of 
enrollment and discharge from the project for each patient. This allows the data managers to 
establish date ranges for clinical data among enrolled patients. It allows them to know when 
patients have completed or have been removed from a study as they may be available for 
recruitment into other studies. 
 
Electronic Data Collection 
 
At the start of a new study, an electronic data extraction is performed to generate a list of 
potential subjects from the INPC. Patients are then automatically excluded if they have 
previously indicated an unwillingness to participate in future trials. IU-PBRN generates a 

23 
 
customized list of patients for each physician. The treating physician indicates whether IU-
PBRN should approach a patient for enrollment in the study. Eligible patients will be approached 
by research assistants (RAs) at their next scheduled appointment. The patient’s preference and 
any initial screening information are recorded at this session using portable computers. 
Electronic data management ensures that patients’ and physicians’ preferences are stored, 
retrieved, and delivered to minimize inconvenience to both parties and to maximize the 
efficiency of the RAs. We will use the IU-PBRN experience and research recruitment 
infrastructure to identify older adults for RAs to approach for potential participation into our 
pragmatic dementia screening trial. 
 
Not all inclusion and exclusion criteria can be reliably assessed through the INPC data 
available to the IU-PBRN.  A final determination of the subject’s eligibility is made during the 
face-to-face encounter in clinic with the IU-PBRN RA.  We will exclude any subject who: 
 
 
are a permanent resident of a nursing facility; 
 
have a serious mental illness such as bipolar disorder or schizophrenia as 
determined by the presence of related ICD-9  codes indicative of such an illness; or 
 
have a pre-existing diagnosis of dementia or cognitive impairment  
 
 
The list of inclusion and exclusion criteria will be given to the PBRN coordinator to 
arrange for subject contact during their next primary care visit. Based on our previous dementia 
related studies in the targeted primary care systems22,33,34,100,107, we anticipate approaching 
6,000 older adults to enroll 4,000.  Rolling enrollment will take place over 30 months with an 
approximate monthly enrollment rate of 130 subjects. As outlined in the figure above, we 
anticipate that the dementia collaborative care program will manage 100 subjects with 
dementia. They will also counsel 100 subjects regarding the future impact and management of 
their diagnosis of mild cognitive impairment and assure them that their cognition is normal 

24 
 
despite their positive screening results. The entire 4,000 subjects will be followed for 12 months. 
Across the various primary care practices, we will have access to more than 12,000 adults aged 
65 and older. From our prior screening studies, we know that the prevalence of screening 
positive for possible dementia is 13-15% and of these, 50% will have dementia on subsequent 
diagnostic assessments. Although we have designed this study as a pragmatic trial, we will be 
requesting that patients sign informed consent for participation in the project. 
Telephone Recruitment: 
 
We will also employ a telephone version of the informed consent process to allow for 
potential recruitment of previously identified eligible patients via the INPC that were not 
approached in clinic by the ResNet team due to time and prioritization restraints. We will obtain 
a list of the eligible participants that were not approached from the PBRN Program Manager on 
a regular basis. These participants will be contacted for participation by telephone by study 
research assistants. We will also utilize the same telephone consenting process to recruit 
subjects attending the IU Health Arnett primary care clinics. Eligible patients from the IU Health 
Arnett primary care clinics will be identified by the treating physician and a list generated for the 
study research team.  
 Screening Process 
 
Both subjects who are randomized into the non-screening arm of the study and those 
who are randomized into the screening arm will complete a set of standardized questions about 
successful aging, preventive health measures, and lifestyle behaviors. This is to invest the 
patients randomized into the non-screening arm of the study in the project, minimize the 
potential excess focus on cognitive screening alone, and to remove any impressions among the 
“non-screened” group that they missed out on an important health screen. We have not pre-
specified the content of this screener because it will be designed based on ongoing data 
collection in the two targeted health care systems. This is consistent with our approach to 
embed the project, whenever possible, into ongoing or emergent activities. Examples of 

25 
 
questions to include in this control questionnaire might include: smoking, physical activity, 
influenza vaccination, or seat belt use for example. At the time of this questionnaire, enrolled 
subjects will also complete the baseline study assessment described later in this proposal. 
 
Through the systematic review described in the Preliminary Studies section, we have 
identified a screening instrument that meets the following criteria: 1) demonstrated validity in 
primary care settings; 2) requires less than five minutes to administer; and 3) has a positive 
likelihood ratio (LR) of 5 or higher. Based on our systematic evidence review for the literature 
that was published in JAMA in 200778, we selected the Memory Impairment Screen Telephone 
version (MIS-T)96 as the screening instrument. The MIS-T takes only four minutes to complete 
with excellent inter-rater reliability, has been validated in multiple primary care and community 
samples, and has a positive LR of 33.6,96-99 The MIS-T has a total score from 0 point to 8 points. 
A cut-score < 5 has 86% sensitivity and 91% specificity for dementia with a positive predictive 
value of 72% and negative predictive value of 96% in a setting with a dementia prevalence of 
15%.6,96-99  The MIS-T will be administered by the study research assistants after the subject 
consents to be enrolled in the study and randomized into the screening arm of the study. 
 
Subjects who are randomized into the screening arm of the trial and score less than 5 
points on the MIS-T will be referred to the collaborative dementia care program for a 
subsequent diagnostic assessment, counseling and management. We are not expecting the 
primary care practice to complete this next step. Among the 300 patients who will score less 
than 5 on the MIS-T (15% positive screening rate), we anticipate that approximately 100 (a 
refusal rate of 33%) will refuse follow-up diagnostic assessment, 100 subjects will not be 
diagnosed with dementia despite their positive screening results, and 100 subjects will be 
diagnosed with dementia.  
Why not simply rely on the primary care practice to deliver the Collaborative Care Program? 
 
Given that this is a pragmatic trial, reviewers might question whether the provision of the 
collaborative care program moves this project too close to an explanatory design. Our research team did 

26 
 
discuss this decision in assessing our design via the PRECIS tool. Three issues guided our decision-
making. First, we know from prior research that simple provision of screening data or treatment guidelines 
has little impact on patient outcomes.  Second, we know from prior research on depression screening that 
screening harms outweigh benefits if the clinical practice is not prepared to evaluate and treat the patients 
who screen positive. Third, we already know the collaborative care program is more effective than usual 
care under experimental conditions. The collaborative care program patients, referred to in the current 
proposal, are exemplary of the practical application of the collaborative care.34,42,43 
 
 
The Collaborative Dementia Care Program 
 
The goal of the program is to assist primary care clinicians in achieving the 
recommended standard of care in the diagnosis and management of older patients with 
dementia. Much of the intervention, facilitated by an Advanced Practice Nurse as the care 
coordinator, is targeted to co-manage or support the practice behavior of primary care clinicians, 
enhance self-management skills of both the care-recipient and the informal caregiver, and 
maximize the coping behavior of the patient and the informal caregiver. By design, the program 
planned protocols lead to individualized and patient-centered profiles of actual interventions for 
individual patients and their informal caregivers. The program has four main phases: the initial 
assessment phase, the plan of care development phase, the second home visit phase, and the 
follow-up phase.  
 
The initial assessment: The care coordinator conducts a demographic and medical information 
interview, reviews medication lists and discharge plans if the patient is currently hospitalized or 
is post-hospitalization, gathers and reviews any diagnostic testing and brain imaging results with 
the primary intention of identifying any reversible and co-morbid conditions, and schedules an 
initial home visit with the patient and the patient’s informal caregiver. After completing a pre-

27 
 
home visit interview, the care coordinator travels to and conducts a face-to-face initial 
assessment at the patient’s and/or informal caregiver’s residence or preferred location. At the 
patient’s home, the care coordinator conducts a brief cognitive assessment; biopsychosocial 
needs assessment of patient and informal caregiver, and medication reconciliation. The 
program uses standardized assessment tools including: The Healthy Aging Brain Care Monitor 
(HABC-M).108 If there is no available or identified caregiver, the care coordinator attempts to 
identify a caregiver and complete the caregiver questions at a later date either by phone or in 
person. The care coordinator documents the initial and follow up visits using care coordination 
software called the eMR-ABC.  
 
The Plan of Care Development Phase: This phase is designed to facilitate the creation of an 
individualized care plan with an emphasis on 
coordinating care with the patient’s primary care 
provider. This phase begins after the first home visit and 
concludes with the second home visit by the care 
coordinator. After consultation and coordination with the 
program geriatrician and primary care physician, the 
care coordinator rules in or out the diagnosis of 
dementia and its subtypes, and finalizes the 
individualized care plan with the primary care physician. 
Complex patients or patients with diseases that may 
benefit from specialty care, may be recommended for 
specialty evaluation and co-management. If necessary, 
the patient will be referred for a more extensive cognitive 
and mental health evaluation at the local memory care practice. This decision would be jointly 
reached by the program geriatrician (Dr. Sachs) and the patient’s primary care provider. Finally, 
Program Services and Protocols 
 Self-Management /Caregiver 
Skills Enhancement 
 Support Group Participation 
 Informal Telephone Support 
 Problem Solving Training 
 Reducing Anticholinergic 
Medications 
 Prescribing FDA-Approved 
Medications 
 Managing High Vascular Burden 
 Monitoring and Supporting of 
Caregiver’s Emotional and 
Physical Health 
 Managing Transitional Care 
 Managing Acute Care Problems 
 Root-Cause Analysis of Re-
Hospitalization or Re-
Emergency Room Visit 
 Care Prioritization 

28 
 
the care coordinator will schedule a second face-to-face home visit with the patient and the 
informal caregiver within 2-4 weeks of the initial home visit. 
 
The Second Home Visit Phase: The care coordinator discusses the individualized care plan; 
explains the diagnosis, the natural history, and the prognosis of dementia; implements 
appropriate care protocols; reviews, explains, and distributes the corresponding educational 
handouts for both the patient and the informal caregiver; and connects patients and informal 
caregivers to in-home services and community resources as needed.  
 
The Follow-Up Phase: It includes interaction with the patient or the caregiver via face-to-face 
home or clinic visit, phone contact, email, fax or mail. The minimum amount of contact during 
this time will be once monthly for the first three months and once every three months thereafter. 
During these interactions, the care coordinator will answer any questions generated from 
previous visits; collect patient and informal caregiver feedback; reconcile medications and 
review medication adherence; have the informal caregiver complete the HABC Monitor to trigger 
the use of specific care protocols; and facilitate the informal caregiver’s participation in the 
Support Program. Throughout the duration of the follow-up phase, the team will continue to 
work with the patient, the informal caregiver, and the patient’s primary care provider to monitor, 
implement, and adjust as necessary the individualized care plan. The program care services 
and protocols already developed and fields tested include: 
 
1) Self-Management/Caregiver Skills Enhancement: Prior to this second home visit, the care 
coordinator prepares the various relevant materials to enhance patient self-management or 
caregiver skills. These materials (the Patient or Caregiver Care Manual) can include: 
information on legal and financial planning with referrals made to elder law specialists and legal 
services programs in the community; specific behavioral interventions techniques to help 

29 
 
manage, reduce or avoid patient problem behaviors; and/or coping strategies to ensure the 
caregivers’ emotional and physical health remain intact. These materials are provided to the 
patient or the caregiver via various face-to-face or home counseling sessions. If the patient’s or 
caregiver’s needs are particularly complex, the counseling can take place over more than one 
face-to-face and/or telephone sessions. 
 
2) Support Group Participation:  In collaboration with the Central Indiana Alzheimer’s 
Association, the program will organize a monthly support group, facilitated by the care 
coordinator, and located at the Indianapolis Senior Center. While support groups are available 
in the metropolitan area through the Alzheimer’s Association (AA), the program support group 
will be specifically designed to give the dyads tailored information to meet their needs within 
WHS and IU Health systems. While mandatory participation is difficult to enforce, the team will 
encourage participation by stressing the importance of the support group for the overall health 
of both the patient and the caregiver. The support group meets on the fourth Friday of each 
month at the local senior center for two hours. In cases that the dyad cannot make the support 
group due to access and distance, the team will write a pro-active prescription to connect the 
dyad with their local AA that specifies the type of support needed from the local Alzheimer 
Association, such as belonging to a monthly support group, provision of particular educational 
materials, or case management. The team will obtain permission from the caregiver/patient to 
be proactively contacted by their local Alzheimer Association.  
 
3) Informal Telephone Support: The dyads will have access to telephone consultation by the 
care team. The telephone contact can be initiated by the spouse or any other family member 
participating in the patient’s care. Offering access to the care team empowers the informal 
caregiver to try different interventions more readily.   
 

30 
 
4) Problem Solving Process: Using data collected from the structured caregiver interview or 
during face-to-face visits, the care team, in coordination with the primary care provider, uses 
standardized problem solving protocols to manage any behavioral and psychological symptoms 
related to dementia. The care team educates the caregiver on implementing these protocols 
and monitors the success of such implementation via face-to-face or telephone follow-up 
interactions. 
  
5) Reducing the Anticholinergic Cognitive Burden: Using the Anticholinergic Cognitive Burden 
Scale (ACBS), developed by our Aging Brain group, the care team reviews the over-the-counter 
and prescribed medications taken by the patient and coordinates with the primary care clinician 
to identify the presence of any anticholinergic medication in efforts to balance their benefits and 
harms.109,110 
  
6) Prescribing FDA-Approved Medications: The care team, in coordination with the primary care 
provider, prescribes and discusses the indications, benefits and expectations of using FDA-
approved medications for dementia. 
  
7) Managing High Vascular Burden: The care team will review the current vascular burden of 
the patient and work with the primary care provider on reducing such a burden using both 
pharmacological and non-pharmacological interventions.   
 
8) Monitoring and Support of the Caregiver’s Emotional and Physical Health: The care team will 
use the HABC Monitor to monitor the cognitive, functional, behavioral and psychological 
symptoms of patients and  caregiver stress (see supportive tools below).  
 

31 
 
9) Managing Transitional Care: The care coordinator conducts a home visit within 72 hours of 
hospital discharge to reconcile discharge medications and counsel and support the dyad to 
carry out any post-hospital care plans.    
 
10) Managing Acute Care Problems:  There are times when a patient will call the ABC team with 
an acute care problem and seek direction. To avoid a potentially unnecessary ED visit, the care 
team may make a home visit, inform the primary care physician, and manage the problem 
accordingly.  
 
11) Root-Cause Analysis of Re-Hospitalization or Re-Emergency Room Visit: Within one week 
of the re-admission event date, the care team will interview the patient, the caregiver, and the 
clinical team to determine the appropriateness of the re-admission and brainstorm about 
possible underlying causes for preventable re-admission. In addition, the team will review the 
medical records and try to identify a list of potential triggers for preventable re-admission failure. 
The team will review the failure case within a week of the event date.  
 
12) Care Prioritization: Under circumstances where patients have significant needs that exceed 
the capacity of the clinical program, the care team will utilize set guidelines to prioritize 
addressing these needs to ensure  the most vulnerable patients (those who require a hospital or 
emergency department visit followed by those who require post-hospital or emergency 
department transitional care) receive timely care coordination by the care team including a 
home visit within 72 hours of discharge from a hospital or emergency department. 
 
13) Discharge Criteria: The care team will discharge the patient and caregiver if they meet any 
of the following criteria: 1) patient expires; 2) patient and/or family/caregiver decline to continue 
in the program; 3) primary care provider requests patient discharge from the program; 4) patient 

32 
 
transitions to another health care system or move outside Marion County; or 5) patient’s living 
situation/environment becomes unsafe for patient and/or staff and therefore requires long-term 
skilled nursing home care. 
 
The Support Tools of the Collaborative Dementia Care Program 
 
1) The Mobile Office: The “Mobile Office” concept enhances the opportunity for the care team to 
see patients and caregivers in a variety of settings that are most conducive for their physical, 
emotional and psychological comfort, thus allowing for conducting a biopsychosocial needs 
assessment, care coordination, information gathering, or support for self-management 
education. The mobile office sites 
may include any of the primary 
care clinics; the patient’s home; 
the Center for Senior Health; any 
of the specialty clinics at Wishard 
or IU Health; or areas in the 
community, including the 
caregiver’s place of employment. 
 
2) The Care Coordination Support Software: In order to efficiently deliver the various 
components of any collaborative coordination care model, we developed and implemented a 
web-based care coordination software called eMR-ABC. This software includes the following 
functions: 1) flexible and secure access to the platform from multiple locations and by various 
users; 2) manual, web-based, and optically scanned solutions to capture patient centered 
outcomes such as functional, behavioral, psychological, and cognitive symptoms; 3) decision 
support to deliver personalized pharmacological and non-pharmacological care protocols; 4) a 

33 
 
tracking process of care coordination tasks delivered by the care coordinator; 5) monitoring 
patients and caregiver responses to care protocols; 6) monitoring population-based outcomes to 
guide the overall program performance; 7) integration capacity with other informatics tools such 
as the local electronic medical record and regional health information exchange; and 8) an easy 
interface to move data from the eMR-ABC to analyzable datasets. The Advanced Practice 
Nurse will have access to the eMR-ABC via a laptop with wireless air card connection. 
   
3) The Healthy Aging Brain Care (HABC) Monitor: The team will use the HABC Monitor to 
monitor the cognitive, functional, 
behavioral and psychological 
symptoms of patients and the 
caregiver stress. The HABC 
monitor is comprised of 32 items 
tapping the previous four 
constructs.103 While the total HABC 
Monitor score is helpful to measure 
change over time, each question 
also indicates a specific care area where help or coping strategies might be indicated. The 
HABC Monitor also includes questions on dangerous behaviors such as falls, home safety, and 
automobile driving. When these functional, cognitive, behavioral, psychological, or psychiatric 
conditions (for either the patient or the caregiver) are identified, the care team will work with the 
primary care clinician and other providers to begin initial pharmacological and non-
pharmacological management. This may also include working with the caregiver’s primary care 
provider. Consistent with current recommendations, protocols for patient management 
emphasize non-pharmacologic treatment at the outset.  
 

34 
 
A patient who screened positive for cognitive impairment but found to have no dementia 
by the subsequent assessment, will continue to be referred for an annual cognitive 
assessment with the local memory care practice at WHS or IU Health.   
 
Assuring Adherence to our Intervention: 
 
The director of the clinical core (Dr. Sachs) will meet with the Advanced Practice Nurse 
on a weekly basis to review the performance of the program, its fidelity and any complicated 
care using the electronic reports generated by the care coordination support software (eMR-
ABC). The eMR-ABC will provide Dr. Sachs with a weekly report of the performance of the care 
coordinator in regards to the adherence of delivering specific protocols.  
  
The Usual Care Control Groups: 
 
The 2,000 subjects who would be randomized into the “no screening group” will continue 
to receive their usual care, including a referral to the local memory care practices if their primary 
care provider suspects the presence of a cognitive problem at any time during the study follow-
up. 
 
 
Overview of Data Sources  
 
Construct 
Source of data 
Specific 
variables/Instruments 
Social, Demographic, 
Advance care planning 
Study Survey 
MOS, age, gender, race, 
education, income, living situation, 
marital status, and advance care 
planning 
Health Related Quality of 
Life, Mood and Anxiety 
Study Survey 
HUI, PHQ-9, GAD-7 
Health Care Utilization 
Indiana Network for Patient Care records for the 
4000 subjects 
ER episode, location 
Hospital episode, location 
Inpatient diagnoses (ICD9 codes) 
Length of stay 
Co-morbidity 
Indiana Network for Patient Care records for the 
4000 subjects 
ICD-9 codes for the 10 common 
chronic diseases 

35 
 
Medication Use 
Indiana Network for Patient Care records for the 
4000 subjects 
Psychotropics 
Care Processes 
eMR-ABC and INPC 
Visits to memory care practice. 
Collaborative dementia care team 
visit. 
Visits with HABC monitor 
Protocols delivered by the care 
team 
 
 
 
F. Inclusion/Exclusion Criteria 
 
Inclusion criteria include: 
 
adults age 65 and older; 
 
at least one office visit to their primary care physician within the previous year;  
 
no previous diagnosis of dementia or memory problem as determined by ICD-9 codes or 
the presence of prescription for anti-dementia medications (cholinesterase inhibitors or 
memantine); 
 
ability to consent to participate in the study; and 
 
ability to communicate in English 
 
Exclusion criteria include: 
 
adults who are a permanent resident of a nursing facility;  
 
a serious mental illness such as bipolar disorder or schizophrenia as determined by the 
presence of related ICD-9    codes indicative of such an illness; or 
 
a pre-existing diagnosis of dementia or cognitive impairment  
 

36 
 
G. Enrollment/Randomization 
 
 
Clinical Settings and Population 
 
The proposed study will be conducted in 
multiple primary care clinics affiliated with Wishard 
Health Services and Indiana University Health in 
Indianapolis, IN that provide medical care for a diverse, 
urban population of older adults. We have a long-
standing research partnership with WHS and a growing 
relationship with IU Health. It is only in the last year that IU Health came into existence through 
a new collaboration between the IU School of Medicine and a statewide health care system 
formerly known as Clarian Health.  
 
Wishard Health Services (WHS) is responsible for the care of medically-indigent patients 
who live in Marion County, Indiana as well as those who are uninsured or under-insured. WHS 
provides care for about 20% of the population of Indianapolis. Fifty percent of its patients are 
African American and approximately 10% are Hispanic. 
Recognizing the importance of the community’s access 
to care, WHS developed a network of community 
health centers throughout the Indianapolis area as 
shown in the figure to the right. Underscoring WHS’s 
standing in the local community, Marion County voters 
approved a new WHS facility. This new $750 million 
facility is on schedule and on budget and will be 
opened in less than two years. The new, modern and 
efficient $1.2 million square-foot facility will equip the 
hospital with 327 inpatient beds, 17 operating rooms, four interventional labs, 12 labor and 

37 
 
delivery rooms, an emergency department with 90-treatment rooms, a 20-bed clinical decision 
unit, more than 200 exam rooms, one of two Adult Level I trauma centers in Indiana, and the 
region’s only adult burn center. The outpatient care building, which links functionally and 
operationally to the hospital, will offer 110 exam rooms in a clinical setting and serve as the 
point of entry to the hospital for most visitors and non-emergency patients.  
 
The partnership between WHS and faculty scientists in the IU Geriatrics Program and 
the Center for Aging Research has a history that spans more than 20 years. Within this 20-year 
history are multiple examples of repeated cycles of moving research to the bedside and bringing 
the bedside to research. Our programs have been inspired by, co-developed and evaluated by 
the clinicians providing care to older adults. In this regard, WHS has been the living laboratory 
for innovative, explanatory clinical trials for vulnerable elders with dementia, late life depression, 
delirium in need of end-of-life care, among others. In addition, WHS was our community partner 
in the academic-community research partnership development program, funded by the NIMH 
(IP-RISP R24), that focused on mental illness among older adults. 
 
The newly formed “Indiana University Health” (IUH), is one of the largest health care 
systems in the United States and is Indiana’s largest and most comprehensive healthcare 
system.  It is comprised of three hospitals in Indianapolis and seventeen hospitals statewide. 
The system includes hospital-based physician practices, outpatient centers, and pharmacy and 
home care services. Through its new partnership with Indiana University School of Medicine 
(IUSOM), the nation's second largest medical school and a global leader in medical education 
and research, IU Health is uniquely positioned to participate in innovative pragmatic research 
trials. As an academic health center, IU Health and IUSOM work in partnership to train 
physicians, blending breakthrough research and treatments with the highest quality of patient 
care. Research conducted by IUSOM faculty gives IU Health physicians and patients access to 
the most cutting edge and comprehensive treatment options. 

38 
 
 
We view WHS as a longstanding partner in explanatory research who will now 
collaborate with us in pragmatic research; we also view IU Health as a potential statewide site of 
pragmatic research. WHS represents the nations many urban, public hospitals and associated 
community health centers while IU Health represents the growing number of very large 
integrated health care systems. Between the two health care systems, we have access to a 
broad range of diversity in older adult patients as well as a large population of dual-eligible 
(Medicare and Medicaid), older adults. WHS cares for a population of approximately 12,000 
older adults (60% African-American) in nine primary care practices whereas IU Health cares for 
approximately 36,000 older adults (13% African-American) in 19 primary care practices. The 
Indiana Hispanic population is growing rapidly, but it is dominated by younger adults. 
Consequently, the population of Hispanic older adults in both health care systems is less than 
2%. 
 
As already mentioned, both of these health care systems are served by a regional health 
information exchange. In 1995, with support from the AHRQ, the National Library of Medicine, 
the National Cancer Institute, and the Regenstrief Institute, IU researchers created the first 
regional health information technology network called the Indiana Network for Patient Care 
(INPC).49,64-66 The INPC is a regional health information exchange that integrates clinical 
information from the five major health care systems in Indianapolis in support of medical care.49 
These five health care systems provide INPC with laboratory results, emergency department 
data, inpatient and outpatient encounter data, coded diagnoses and procedures, radiology 
reports, hospital discharge summaries, operative notes, pathology reports, medication records, 
and electrocardiogram reports, among many other data elements. These five participating 
systems operate fifteen hospitals and more than 100 clinics and day surgery facilities that 
account for over 95% of all beds, hospitalizations, and emergency department visits in the 
Indianapolis metropolitan area (which has a population of 1.5 million). Together, they have 
165,878 inpatient admissions, 450,000 emergency visits, and 2.7 million outpatient visits per 

39 
 
year. INPC also carries data from the Marion County Health Department; the Indiana State 
Department of Health; Indiana Medicaid; and RxHub, a national consortium of pharmacy benefit 
managers.49 The INPC’s rich clinical repository is organized by patient and medical record data 
and segregated into separate files by institutional source, but the data about one patient from 
many institutions can be viewed as a single virtual medical record, and clinicians can review a 
patient’s record in a variety of video screens and hard-copy formats. 
 
With initial focus in support of quality improvement, INPC is also beginning to serve 
biomedical research. In a recent clinical trial,34,51 we used INPC data to track utilization across 
the five health care systems in support of analyses examining the impact of new models of care 
on older adults health care utilization. These data were made available after appropriate 
approvals from the INPC Privacy Board which includes representative from all five health care 
systems and the Regenstrief Institute. Our study team has a track record in the responsible use 
of these data and in their appropriate data management and analysis. 
 
Randomization 
 
We will use a central, computer generated, web-based, randomization scheme to assign 
individual patients rather than providers or clinics to treatment conditions to minimize the effects 
of unmeasured case mix differences and clinic-level clustering. We estimate that the risk for 
‘spillover’ from having participating clinics treat both intervention and usual care patients is likely 
to be small.34,51,72 If anything, patient-based randomization will conservatively bias the results in 
favor of usual care.  
 
H. Data Collection  (We will use face-to-face or telephone interviews for our data collections) 
  
Health Related Quality of Life (HRQOL) 
 
The primary outcome measure will be the HRQOL measured at baseline, 1, 6 and 12 
months among the entire 4,000 enrollees. We will use the 15-item Health Utility Index (HUI) to 

40 
 
determine the subject’s HRQOL.111 The HUI is a generic, utility-based HRQOL instrument 
applied in patients with a wide range of medical conditions.111,112 It has eight attributes: Vision, 
hearing, speech, ambulation, dexterity, emotion, cognition and pain. The individual health 
domain scores range from 0.00 (maximum impairment) to 1.00 (no impairment) and the multi-
attribute (HUI index) scores, a multiplicative function of individual attribute levels, range from 
0.36 to 1.00 with anchors 0.00 = dead and 1.00 = perfect health. Naglie et al found that test-
retest reliability exceeded the standard for adequate reliability of 0.70 in those with mild 
dementia (ICC = 0.75).113 Dr. Barbara Vickrey recently published a paper that provides new 
evidence regarding the construct validity (including responsiveness) of the HUI in community-
based subjects with dementia.112 The mean HUI multi-attribute utility score for 408 primary care 
patients with dementia was 0.54 (SD = 0.23) and the mean one year change was -0.30 among 
240 dementia patients who remained in their own home after one year of receiving dementia 
care program whereas the mean one year change was -0.76 among 29 dementia patients who 
moved into a skilled nursing home facility.112  
 
Mood and Anxiety Outcomes 
 
We will use the Patient Health Questionnaire–9 (PHQ-9)114-116 and Generalized Anxiety 
Disorder Scale (GAD-7)117,118 to determine the impact of screening on our subjects’ mood and 
anxiety at baseline, 1,6, and 12 months. We have used both instruments in various primary 
care-based research studies including our dementia collaborative care trial.34,51,93,114-118 The 
PHQ-9 is a nine-item depression scale with a total score from 0 to 27 and the GAD-7 is a seven-
item anxiety scale with a total score from 0 to 21. Both of these scales are derived from the 
Patient Health Questionnaire; have good internal consistency and test–retest reliability; as well 
as convergent, construct, criterion, procedural and factorial validity for the diagnosis of major 
depression and general anxiety disorder.114-118 In our previous primary care studies, the mean 

41 
 
PHQ-9 scores ranged from 3.8 (SD = 5.1) to 4.4 (SD = 5.6) and the mean GAD scores ranged 
from 2.7 (SD = 3.2) to 3.2 (SD= 3.5).34,114-118  
 
For any subject who expresses thoughts/tendencies of self-harm (a positive response of 1, 2, or 
3 to question 9 on the PHQ-9), the Research Assistant will notify the Study Coordinator. The 
Study Coordinator will keep a detailed log of these events and will be responsible for notifying 
the subject’s primary care provider immediately.   
 
Health Care Utilization 
 
We will obtain consent at enrollment from all subjects for permission to review their medical 
records. We will then use the Indiana Network for Patient Care (a fully operational Health 
Information Exchange) to identify any episode of ambulatory or acute care that occurred within 
the following 12 months of enrollment date. We will structure continuous variables that describe 
the number of ambulatory and/or acute care episodes. Furthermore, we will structure additional 
variables that describe a potentially preventable hospital admission (preventable 
hospitalization).76 Preventable hospitalizations will include any hospitalization for an ICD-9 
based disease that is considered an ambulatory care sensitive condition where the condition 
itself or its course can be mitigated through optimal outpatient management.  
 
Other Data Collection 
Social and Demographic 
 
Patient age, gender, race, education, income, living situation, and marital status will be 
collected, along with social support as measured by the five-item Medical Outcome Study 
(MOS) social support instrument.119  The five-item MOS social support instrument was derived 
from the Medical Outcome Study (5 = worst to 25 = best). It has a minimum factor loading of 
0.738 with Cronbach’s alpha of 0.859.119 The five-item MOS instrument includes having 

42 
 
someone to confide in or talk to about problems, to get together with for relaxation, to help with 
daily chores if sick, to turn to for suggestions about how to manage personal problems, and to 
love and make feel wanted.119,120  
 
Common Chronic Conditions 
 
Using the Indiana Network for Patient Care, we will evaluate all 4,000 subjects for the 
presence of ten common chronic diseases detected by ICD-9 codes in the year prior to 
enrollment: arthritis, congestive heart failure (CHF), coronary artery disease (CAD), cancer, 
chronic obstructive pulmonary disease (COPD), diabetes, stroke, hypertension, kidney disease, 
and liver disease. These conditions were chosen based on their high prevalence in our older 
adult population.33,47 
 
Medication Use 
 
 Prescription records for all patients enrolled in the study will be reviewed using the 
Indiana Network for Patient Care to evaluate the use of psychotropic medications such as 
anticholinergics, antidepressants, anxiolytics and antipsychotics. These psychotropic 
medications will be categorized based on the American Hospital Formulary Service system 
criteria into anti-dementia (including cholinesterase inhibitors or memantine), antipsychotics, 
antidepressants, and anxiolytics.121 
 
Care Processes 
 
 We will use the web-based tracking system (eMR-ABC) and INPC to monitor multiple 
processes of dementia care measures for both the control and the intervention groups including 
all patient contacts by the local memory care or primary care practices, the referral to local 
Alzheimer disease support groups, the use of home health services, and assessment of the 
level of participation of patients and caregivers in the collaborative care intervention program.   

43 
 
 
Advanced Care Planning (ACP) 
 
We will measure the subjects’ advanced care planning including having power attorney for 
health care and/or financial affairs, having a living will, and having life and additional insurance 
policies at baseline and 12 months. Advocates for dementia screening, even in the absence of 
highly effective anti-dementia drugs, argue that screening would offer patients a window of 
opportunity to complete ACP while most still have the capacity to do so. We are unaware of any 
data documenting that participation in a screening program for dementia or any other serious 
illness is associated with greater participation in ACP.     
 
Dementia Recognition 
 
We will determine the recognition of dementia by searching the Indiana Network for 
Patient Care databases for any ICD-9 code indicative of dementia or Alzheimer disease at 
hospital admission, discharge, or during the 12-month period following enrollment into the study.  
 
I. Statistical Plan 
 
 
The outcome measures for this study are HRQOL (HUI multi-attribute utility score), 
mood (PHQ-9) and anxiety levels (GAD-7) obtained at baseline, 1, 6, and 12 months. To verify 
the comparability of the randomized groups, patients’ baseline characteristics between the 
screened and no screening groups will be compared using t-tests for continuous variables and 
chi-square tests for categorical variables. We will carefully examine the distributions of 
continuous variable and use alternative approaches such as transformation or nonparametric 
methods in cases of violation to the normal distribution assumption. We will also examine the 
frequency distribution of all categorical variables and adopt exact inference procedures in cases 
of zero or small cell size. We will compare the baseline characteristics between subjects with 
missing outcomes due to death or refusal at 12 months to subjects who completed the follow-up 

44 
 
to detect potential violation to the missing at random assumption. Further sensitivity analyses 
will be performed using various methods of imputation or a full parametric likelihood approach 
assuming various patterns of missing data.122   
 
Primary Aim tests the hypothesis that subjects in the dementia screening group will have 
higher health-related quality of life compared those in the no screening group. We will compare 
mean measures of health-related quality of life levels in the “screening” group to the “no 
screening” group using analysis of covariance (ANCOVA) while including baseline measures as 
covariates. We will first conduct the ANCOVA models separately for outcomes obtained at 12 
months while adjusting for baseline measures. We will then use the mixed effect models to 
examine whether the difference between the two groups changes over time using repeated HUI 
measures as the dependent variables, group, time, interaction between group and time as 
independent variables while controlling for other baseline covariates. All analyses will be 
conducted using SAS 9.3 (SAS Institute, Carey, North Carolina). For the patients who do not 
complete the 12 month surveys for health-related quality of life, they will be excluded from the 
analyses followed by sensitivity analyses on missing data described below.  
 
Secondary Aim 1 compares depression and anxiety levels at 1 month post dementia screening 
between screened subjects and subjects in the no screening group. ANCOVA models will be 
used to compare PHQ-9 and GAD-7 obtained at 1 month between the screening and no 
screening groups adjusting for patients’ characteristics and baseline measures.  
 
Secondary Aim 2 estimates the cost effectiveness of the dementia screening program in 
comparison to the “no screening”. This economic evaluation will be conducted from the societal 
and payer perspectives, including the direct medical care costs, caregiver and patient time and 
transportation costs, and the effect on quality of life for patients and caregivers.123 Costs will be 

45 
 
divided into fixed and variable costs and by the screening, initial assessment phase and the 
follow-up phase of treatment. Total medical care utilization costs will be estimated for the control 
and screening groups from healthcare utilization and reimbursement data captured by the 
Indiana Network for Patient Care (INPC) during the trial.  Prescription drug use will also be 
obtained from the INPC healthcare administrative database. The cost analysis will capture the 
extent to which screening, early diagnosis and coordinated care of patients with Alzheimer’s 
disease affects medical care costs associated with dementia and co-morbid conditions such as 
diabetes, made worse by failure to manage dementia. Activity costing will be utilized to estimate 
the costs necessary to implement and operate the screening and collaborative dementia care 
management program and the usual care for dementia patients. Patient and caregiver time, 
staff time, fringe benefits, overhead costs, and materials will be logged by staff using the eMR-
ABC software and assessed for the 12 month follow-up period. Included are waiting time, time 
with patients, time in meetings, lab services, telephone calls and mailings to participants. 
Excluded are costs associated with research. Transportation costs will be estimated from data 
on distance from home to clinic. Health care contacts will be dated and checked to avoid double 
counting via claims and activity costing methods.  
 
Prescription drugs will be valued at the median wholesale price. A dispensing fee will be 
added for each 100 doses. Unit wage costs and fringe benefits will be standardized applying 
median values paid to personnel in the region; wage data collected from the health care system 
partners.  
 
Costs will be accumulated during the trial based on the probability of survival each 
month times the monthly cost of care for survivors to address censoring.124 Effects and costs will 
be discounted at a 3% annual rate for the two-year trial period. The incremental CE ratio 
(ICER), will compare the no screening and less resource intensive usual care treatment strategy 
(UC) with the screening coupled with the more intensive treatment intervention (the 

46 
 
collaborative dementia care program) using the following formulas for (1) dementia patients 
(AP) and (2) Dementia patients plus their caregivers (CG). 
 
 
 
 
Uncertainty in the cost-effectiveness ratios and 95 percent confidence intervals will be 
assessed with 1,000 bootstrap samples. The outcome of each sample will be expressed as a 
scatter plot of incremental costs and effects generated from the bootstrap samples, reflecting 
the uncertainty arising from the model parameters. Results will also be displayed using net 
benefit analysis and cost-effectiveness acceptability curves (CEAC).125 There is controversy 
about the appropriate ceiling ratio for health benefits.126 Garber et al have recommended that a 
value of twice the median annual per capita income will result in efficient resource allocation.126  
The effects on ICERs of alternative unit cost estimates for care-giver time value and overhead 
cost rate for the screening and coordinated care management will be examined in a series of 
one-way and multi-way sensitivity analyses. The ceiling ratio λ will be varied from $30,000 to 
$150,000 per QALY for the CEAC analysis. The cost-effectiveness hypothesis will be tested 
against the $100,000 per QALY maximum willingness to pay norm.   
 
Statistical Power, derived from sample size estimate, is used to test the primary hypothesis 
that subjects in the screening group will have higher health related quality of life than the no 
screening group. Previous randomized trials comparing collaborative care to usual care in 
demented patients have stated effect size of 0.4 being clinically significant.34,35 Considering that 
the majority of patients in the screening group or the no screening group are not demented, the 
observable effect size between these two groups will be a combined effect size measure in the 
non-demented subjects and in those demented subjects receiving the collaborative dementia 
care program.  
(1) 
(2) 
𝐼𝐶𝐸𝑅𝐴𝑃= [𝐶𝑂𝑆𝑇HABC − 𝐶𝑂𝑆𝑇UC] ÷ [𝑄𝐴𝐿𝑌HABC − 𝑄𝐴𝐿𝑌UC] 
𝐼𝐶𝐸𝑅𝐴𝑃+𝐶𝐺= [𝐶𝑂𝑆𝑇HABC − 𝐶𝑂𝑆𝑇UC] ÷ [𝑄𝐴𝐿𝑌HABC − 𝑄𝐴𝐿𝑌UC] 
 

47 
 
 
Assuming 85% sensitivity of screening instrument and 15% prevalence of dementia in 
this patient population, to achieve 80% power to detect a significance effect size of 0.094 
between the screening group and the no screening group at α=0.05 level (two-sided), and 
allowing 10% of patients with missing follow-up outcomes at 12 months, we need to enroll at 
least 3951 patients into the study. The effect size of 0.094 between the screening group and the 
no screening group reflects a difference of 0.40 SD between demented patients in the 
collaborative dementia care program and demented patients who were not screened and a 
difference of 0.06 SD in the majority of patients who are not demented in either group. We 
demonstrate in the table below that our planned sample size of 4,000 will have sufficient power 
to detect significant differences between the “screen” group and the “no screen” group under 
various scenarios assuming varying degrees of efficacy measures for the collaborative 
dementia care program and for the screening only subjects.  
 
 
 
Estimated power with a total sample size of 4,000 comparing primary outcome measures 
between the screening group and the no screening group (two-sided at α=0.05) allowing 10% of 
patients with missing outcomes at 12 months. 
 Effect size  of collaborative care  
in demented subjects 
Effect size  
In non-demented subjects 
Observable 
Effect Size 
Power Estimate 
0.3 
0.07 
0.091 
77.9 
 
0.08 
0.100 
85.1 
0.4 
0.07 
0.102 
86.4 
 
0.08 
0.110 
91.0 
 

48 
 
For the Secondary Aims, given the sample size of 4000, we will have greater than 95% power to 
test the equivalence levels in PHQ-9 and GAD-7 at 1 month assuming equivalence differences 
of 0.6 (SD=5.1) on PHQ-9 and 0.5 (SD=3.2) on GAD-7based on our previous studies in primary 
care patients. 34,51,93,114-118   
 
J. Limitations  
 
The proposed study has some limitations. The major limitation is its short duration of four 
years including 30 months of recruitment and one year of follow-up. Dementia is a chronic 
condition that worsens over time. While one year of observation will provide time to monitor 
changes in the outcomes selected for this trial, it does not provide a long enough observation 
window for more distal outcomes such as nursing home placement or mortality. From prior 
studies, we know that one year of follow-up data is sufficient to detect the impact of the 
collaborative dementia care program on screened detected patients with dementia. In our 
clinical trial of the collaborative dementia care program, we were able to identify a clinically 
relevant effect within 12 months.  
 
 
Perhaps the largest threat to the study as proposed is enrollment. The research 
infrastructures available for our study and the extensive experience of our investigators in 
enrolling similar large and vulnerable populations, greatly increases our likelihood of success in 
recruiting 4,000 subjects within 30 months. In addition, we have contingency plan to double our 
recruitment number by using additional Indiana University affiliated primary care clinics with 
access to more than 30,000 older adults aged 65 and older.  
 
Finally, the generalizability of our collaborative care program and our urban and minority 
dominant population might be considered a limitation. However, we are testing our intervention 
in a very challenging patient population, so that if it is successful, it would only enhance one’s 
confidence in the likelihood of success in health systems and settings that are not as resource 
constrained as our target WHS and IU Health.    

49 
 
 
K.  Time Line  
 
Following the study planning phase, we will spend additional 30 months recruiting our 
target sample size and 42 months to collect our 12 months outcomes. In the last six months we 
will analyze the data and start working on disseminating our study findings. The progress of our 
proposed project during this planning phase will be monitored by assuring the timing 
accomplishment of the following milestones: 
 
1. Organize an annual meeting of the data safety and monitoring board for the trial within the 
first quarter of each year starting with the planning year. 
2. Recruit a total of 1,660 subjects by the end of the second year. 
3. Produce a report that describes the baseline characteristics of the first 1,000 subjects 
enrolled in the trial by the end of the first quarter of year 3. 
4. Recruit a total of 3,220 subjects by the end of year 3. 
5. Complete our target recruitment of 4,000 subjects by the end of second quarter of year 4. 
6. Produce a report that describes the baseline characteristic of the entire cohort by the end of 
the fourth year. 
7. Produce a report that describes the results of the analysis for the secondary aim (one month 
mod and anxiety symptoms) of the implementation phase by the end of first quarter of year 
five. 
8. Produce a report that describes the results of the analysis for the primary aim (HRQOL at one 
year) and Secondary aim (Cost effectiveness) of the implementation phase by the end of 
third quarter of year five. 
9. Disseminate the results of our study in a peer review journal, at a national meeting and on our 
own website by the end of year 5.  
 

50 
 
(Y1)1,2,3,4,5,6,7,8,9,10,11,12(Y2)1,2,3,4,5,6,7,8,9,10,11,12(Y3)1,2,3,4,5,6,7,8,9,10,11,12(Y4)1,2,3,4,5,6,7,8,9,10,11,12(Y5)1,2,3,4,5,6,7,8,9,10,11,12 
------------- (Study initiation) 
               ---------------------------------------------------------------------------------- (Study enrollment) 
               ----------------------------------------------------------------------------------------------------------------------------------------------------------------- (Data collection) 
                                                                                                                                                                (Data analysis)----------------------                           
L. Protection of Human Subjects 
 
Risks to the subjects 
Human subjects’ involvement and characteristics: The target population will include community-
dwelling individuals aged 65 and older who actively utilize their primary care providers with a 
minimum of one visit in the last 12 months. Most of these individuals have multiple comorbid 
conditions and approximately 6% of them will have dementia. The aims of our study require a 
face-to-face or telephone interview to assess the health-related quality of life, mood, anxiety, 
and cognition of this population. Data will also be collected from the subjects or the local INPC 
database. Elderly patients represent a vulnerable group. Our research specifically targets this 
group in an attempt to identify the benefit and harms of conducting a dementia screening, 
diagnosis, and management program and detect any potential harm that can be modified to 
improve the quality of care for these patients. 
 
Sources of material: All material to be collected is data from interviews, questionnaires, and 
electronic data abstraction. Our interviews will include informed consent processes and up to 
four sets of questionnaires collected over four time points.   
 
Potential risks: No experimental pharmacological intervention will be used in this study. On the 
contrary, the study aims to enhance recognition of dementia and provide collaborative dementia 
care management that is recommended to enhance dementia care. Although data will not be 
gathered from the patient without his or her consent, it is possible that some of the questions 
related to dementia screening and management asked of the respondents could cause anxiety.  

51 
 
The research personnel will be trained to recognize and minimize this discomfort and patients 
may discontinue participation at any time. If a respondent becomes anxious or upset, the 
principal investigator will be notified to intervene. Furthermore, patients who undergo the 
screening process and or the subsequent diagnostic assessment may end up with a dementia 
diagnosis. The impact of this diagnosis on their quality of life and care is not known and thus 
potential harms such as discrimination, loss of independence, or psychological burden may 
occur. On the other hand recognizing the presence of dementia would lead to receipt of 
appropriate and valuable treatment both pharmacologically and non-pharmacologically. Such a 
treatment may decrease the patient’s disability resulting from unrecognized or unmanaged 
dementia and enhance the patients’ adherence of medical management of other health 
conditions. Loss of confidentiality is also a risk in this type of data collection. Our data 
management and quality assurance technique has proven effective in past trials in maintaining 
confidentiality, and all study personnel have completed training in Human Subjects Research 
and HIPAA standards. 
 
Should worrisome conditions such as depression, suicidality, or other concerning clinical 
conditions be apparent during a research interview, interviewers will follow a scripted protocol to 
notify the appropriate medical personnel and the PI so that appropriate notification and clinical 
follow-up is ensured. When such concerns occur for patients while in care management, this will 
be managed as any other clinical issue would be under usual circumstances through notification 
of the appropriate primary care provider or emergency personnel depending on the severity of 
the presentation. Again, the PI and other supporting staff are available to assist if and when this 
may occur. 
 
Adequacy of protection against risks     
Recruitment and informed consent: Our proposal will be approved by the Indiana University-
Purdue University Indianapolis Institutional Review Board and the primary health centers where 

52 
 
the patients receive their care. Our study will require having informed consent from patients. 
The consent will be for the subject’s involvement in the process of collecting data from HUI, 
PHQ-9, GAD-7, the MOS social support questionnaire, administrative data extraction in a de-
identified manner and the possibility of undergoing dementia screening process if the subject is 
randomized into the screening arm of the study. 
 
Consent procedure protection against risk: This study utilizes in person methods of recruitment 
and consent. Persons who are hearing impaired or too ill to answer questions will not be asked 
to participate in an interview. Subjects will not be asked to continue with the recruitment and 
enrollment processes who cannot understand the questions being asked of them, as indicated 
by either continued non-responsive answers or by asking the interviewer to repeat more than 
three questions three times each. In addition, we have employed usual methods of determining 
capacity to consent by asking the subject to repeat in their own words a description of the study 
and their rights as a research subject. Because we are recruiting only individuals without a 
diagnosis of dementia or some other form of diagnosed cognitive impairment, we have further 
limited the risk of soliciting from individuals who lack capacity, even though we recognize up to 
6% of the sample may meet criteria for a dementia condition.   
 
Moreover, should some individuals have mild to moderate dementia, we have evidence 
from prior studies that demonstrate that such individuals often have decision-making capacity 
and are able to recognize the risk-benefit profiles of various research study scenarios.127,128 
Patients who refuse to participate in the study will not be approached again. The format and the 
procedure of data collection will be outlined in the consent form, the data will be extracted into a 
pre-designed database, and the research assistant will not collect any additional data without 
the consent of the patient and the university IRB. This process of approach and consent will 
adhere to all usual human subjects’ policies and procedures. We will use the standard 

53 
 
procedures for addressing capacity that are employed by many institutions’ human subjects 
review boards. The following questions will be employed: 
 
I just went over what participating in this study entails.  I am going to ask you a few questions just to 
make sure you understand the study before we begin.  
 
1. What would you be doing if you agree to participate in this study?  
(Examples of acceptable answers: “Take part in an interview/survey,” or “Answer questions 
about my friend or relative.”) 
  Person is able to answer this 
 
 Person is not able to answer this 
 
 
2.  What can you do or ask me to do if you are uncomfortable with a particular question in the 
survey? 
(Examples of acceptable answers: “Ask to skip the question.”  “Ask you to read another 
question.”)   
  Person is able to answer this 
 
 Person is not able to answer this 
      
 
3. What can you do if you decide after we start that you do not want to participate in the study? 
(Examples of acceptable answers: “Tell you that I do not want to answer any more questions.”)  
  Person is able to answer this 
 
 Person is not able to answer this 
 
 
For initial screening results, diagnostic determination will not be provided at that time 
except in instances where the subject asks and the results are considered normal. The 
interviewer will have a scripted response that indicates the test is not diagnostic and the results 
will be provided to the primary care provider (if the patient and/or proxy agree). They will be 
instructed that this can be discussed with that primary care provider. 
 
For those subjects who screen positive and are determined to meet criteria for dementia, 
the team will disclose the finding of new information about the patient’s health status (using 
carefully scripted protocols mindful of the potential harm that may result from disclosure of a 
stigmatizing condition) directly to the patient and the primary care physician. The principal 
investigator will be available to clarify any questions and offer any needed consultation.   
 
We make the distinction between research-obtained data (through in-person and 
telephone interviews and electronically extracted data) and clinical data (obtained through 

54 
 
ongoing care management). The latter (clinical data) will be managed using all the protocols 
that one would normally use with respect to usual clinical care and information protection 
procedures. Confidentiality with respect to research-obtained data will be protected using a 
logbook containing each participant’s unique identification number, name, and status. This 
logbook will be maintained at the data management center of the Indiana University Center for 
Aging Research. The unique identifier will be kept separate from subject identifiers and will be 
stored with a unique but otherwise meaningless identification number. All data will be double 
keyed by a data-entry professional. All telephone-acquired data gathered by computer-assisted 
telephone interviewing (CATI) will be automatically entered in a data secure method and double 
keying will not be necessary due to immediate and error free method of data entry. In addition, 
for those in care management the principal investigators will have the opportunity for feedback 
from the patient and the clinic staff to discuss any problems encountered during the data 
collection.  
 
M.  Reporting of Unanticipated Problems & Adverse Events  
 
A data safety monitoring board (DSMB) will be established and will include Drs. Barbara 
Vickrey (a neurologist), Joshua Chodosh (a geriatrician), Soo Borson (a geriatric psychiatrist), 
and a biostatistician (TBN). The DSMB will be chaired by Dr. Vickrey. The committee will meet 
at the Indiana University Center for Aging Research prior to the first patient enrollment to 
determine the nature of the DSMB report, after enrollment of the first 1000 patients and every 
six months to evaluate safety measures including overall adverse effects related to the study 
(including the potential harms from screening such as anxiety, depression), serious adverse 
events, and death after enrollment into the study. In our study an adverse event will be defined 
as any untoward medical occurrence in a subject who received study intervention without regard 
to the possibility of a causal relationship. Adverse events will be collected after the subject has 
started to receive study intervention. If a subject experiences an adverse event after screening 

55 
 
for the study but prior to randomization, the event will be reported as not related to the study 
intervention. During the study, study personnel will note any change in the condition(s) and/or 
the occurrence and nature of any adverse events.   
 
All adverse events occurring after entry into the study and until study completion will be 
recorded. An adverse event that later meets the criteria for a serious adverse event (SAE), 
between study enrollment and completion, will be reported to the local IRB as an SAE. All of the 
above safety data will be monitored throughout the course of the study in blinded fashion. If a 
death or clinical adverse event is deemed serious, unexpected, and possibly related to study 
intervention, the DSMB will be notified immediately to determine the appropriate action to take 
within the context of the event regarding blinding and reporting. Only the DSMB members will 
be unblinded in order to preserve the integrity of the data collected during this trial and minimize 
any potential for bias yet provide appropriate safety monitoring.   
 
 
Potential benefits of the proposed research to the subjects and others 
 
Although our study is collecting data to identify the benefits and harms of dementia 
screening among older adults attending primary care clinics, we anticipate some immediate 
benefit to participants at the stage of the research project following the screening results which 
may include assurance of a negative screening result or comprehensive assessment and 
management of positive screening results. Early recognition of dementia will lead to early 
enrollment in a multi-component dementia care management program that would improve the 
quality of care for dementia, reduce the burden of informal caregivers, and reduce acute care 
utilization.   
 
Importance of the knowledge to be gained  

56 
 
 
In general, this study will add more information to the scant literature about the harms 
and benefits of dementia screening in addition to the benefits of enrolling patients with dementia 
into the collaborative dementia care program early in primary care settings. The data may lead 
to a national early detection and management program for dementia as an efficient and 
beneficial method of reducing the current and future burden of dementia. We are unaware of 
any similar studies that have been or will be conducted in a diverse primary care setting. Our 
study will provide some knowledge about the specific characteristics of the residents and their 
attitudes toward dementia screening. In addition, identifying the factors associated with the 
patients’ acceptance of dementia screening, diagnosis and management program and its 
perceived harms will lead to the design of appropriate dementia screening programs that 
include individualized counseling that will decrease any potential harms of such program.