Alzheimer’s & Dementia 9 (2013) 58–62

The economics of mild cognitive impairment

Pei-Jung Lin*, Peter J. Neumann
Center for the Evaluation of Value and Risk in Health, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA, USA

Abstract Individuals with amnestic mild cognitive impairment (MCI) are at elevated risk of developing
Alzheimer’s disease (AD). Although the economic burden of AD itself is well recognized, little is
known about the direct and indirect costs associated with MCI before the onset of AD. Insufficient
data on the economic impact of MCI as well as other gaps in the knowledge base (such as estimates
of MCI progression rates and factors that drive MCI-related costs) present challenges to understanding
the burden of MCI and to modeling the cost-effectiveness of potential MCI interventions. Initiating
treatment and care management in the MCI phase could improve the health and well-being of patients
and caregivers and possibly offset certain costs. Future economic analyses should incorporate new
data, as they become available, from patient registries and linked administrative claims and electronic
medical records to better characterize the cost consequences of MCI detection and management. Such
analyses should help payers, providers, and policy makers make more informed decisions about the
costs and benefits of new tests, treatments, and other management strategies for the condition.
Ó 2013 The Alzheimer’s Association. All rights reserved.
Keywords: Alzheimer’s disease; Mild cognitive impairment; Cost-effectiveness; Cost analysis

1. Introduction [4,6–8]. In this Perspective, we consider economic issues

surrounding the amnestic subtype of MCI, focusing on the
Researchers have long recognized that Alzheimer’s dis-
US population.
ease (AD) is a slowly progressive degenerative illness that
Many payers now use economic data in addition to safety
includes a predementia period during which symptoms are
and efficacy measures for drug and medical reimbursement
mild or barely detectable [1]. Individuals in this prodromal
decisions. It is important for payers, providers, and policy
stage have been identified as having mild cognitive impair-
makers to understand the economic aspects of MCI, as
ment (MCI) [2], affecting 10% to 20% of individuals aged
they will confront invariably decisions about the costs and
65 years [3–6]. Although not all individuals with MCI
benefits of new tests, treatments, and other management
progress to full-blown AD, they are at an increased risk—
strategies for the condition. Economic data can be used to
as many as 15% develop AD or related dementias each
improve efficiencies and to inform management decisions,
year [7].
such as the identification of patients who would most benefit
What is new and potentially paradigm shifting are ad-
from early interventions. From a societal perspective, the
vances in neuroimaging and other diagnostics that promise
growth of older populations increases the importance of un-
early identification of AD, and the eventual prospect of
derstanding the economics of MCI. Forecasting how early
disease-modifying treatments. These developments will
treatment may influence downstream costs would enable
have profound economic as well as clinical implications. In-
better targeting of health care services throughout the AD
dividuals with MCI are often divided into two groups: those
continuum.
with amnestic MCI and those with nonamnestic MCI [2].
Memory loss is the dominant symptom of amnestic MCI,
and these patients are at elevated risk of developing AD 2. Economics of MCI: State of the field
It is well established that individuals with AD incur
higher health care costs compared with those without the dis-
*Corresponding Author: Tel.: 617-636-4616; Fax: 617-636-5560. ease [9–15], despite great variation in the magnitude of
E-mail address: plin@tuftsmedicalcenter.org specific estimates [16]. Moreover, AD imposes substantial
1552-5260/$ - see front matter Ó 2013 The Alzheimer’s Association. All rights reserved.
http://dx.doi.org/10.1016/j.jalz.2012.05.2117
 P.-J. Lin and P.J. Neumann / Alzheimer’s & Dementia 9 (2013) 58–62
physical and psychological burden on caregivers, as well as
high indirect costs (unpaid caregiver time, lost caregiver pro-
ductivity) [10,17]. It is also well documented that costs of
AD increase with advanced stages in which patients have
worse Mini-Mental State Examination (MMSE) scores
[18], more functional impairment [19], and behavioral
symptoms [20].
In contrast, the economic literature on MCI is relatively
sparse [21–24]. This is in part because of the lack, until
recently, of well-defined criteria for characterizing this
symptomatic transition phase between normal aging and
AD [1]. Before their formal AD diagnosis, individuals
may begin using more health care services [23] and accruing
higher expenditures [22] compared with those without the
condition. One analysis found, for example, that the excess
primary care costs of incident AD cases in the year before
diagnosis were $1167 (85% higher compared with control
cases) for men and $239 (26% higher) for women among
Medicare enrollees in New York (New York) in 1996 [22].
Although studies have suggested poor cost-effectiveness
of imaging tests, such as positron emission tomography, in
the diagnosis of AD (especially in the absence of effective
disease-modifying agents for AD [25,26]), detection in the
MCI phase could reflect reasonable value on cost-
effectiveness grounds. A recent United Kingdom–based
simulation model showed that although assessment of
early-stage AD (which was assumed to include a visit to
a general practitioner, two specialist visits, laboratory tests,
and a magnetic resonance imaging [MRI] or computed to-
mography scan) had significant up-front costs, identifying
patients in this stage could produce downstream cost savings
($3100 per patient, with an additional $5300 in savings at-
tributable to reductions in caregiver time) and health benefits
compared with no early assessment [27]. These findings are
consistent with another recent simulation model of the po-
tential benefits of early AD detection followed by treatment
in the United States [28], indicating that early assessment
may reduce costs, particularly if it targets resources to those
individuals most likely to benefit from intensive workup and
follow-up.
3. Gaps in the knowledge base
3.1. Epidemiology of MCI
Epidemiological studies can provide information on MCI
incidence and prevalence rates, which are needed for esti-
mates of the economic burden at the population level. Sev-
eral longitudinal studies have shown that individuals with
amnestic MCI are at higher risk for developing AD [4,6–
8], and that AD progresses more slowly in the early stages
of the condition [29,30]. However, even within the
restrictive definition of (amnestic) MCI, there exists
considerable heterogeneity in the prognosis and the
disease progression with respect to patient characteristics.
Moreover, estimates about the course of MCI vary across
studies and populations [8]. This is in part because the
59
slow and uneven progression of the condition makes it chal-
lenging to identify a threshold for conversion between nor-
mal aging, MCI, and AD [31]. Currently, the diagnosis of
MCI cannot be made by a laboratory test, but requires the
judgment of a clinician based on symptoms defined by clin-
ical, cognitive, and functional criteria. Yet, measurements
used to define an individual’s conversion from MCI to AD
can be subjective [32]. A survey of 420 American Academy
of Neurology members showed that some respondents be-
lieved MCI would be too difficult to diagnose accurately
or reliably, and a diagnosis would cause unnecessary worry
among patients and families [33]. In addition, studies com-
monly use measures of cognitive function to define the con-
dition, but the rate of cognitive decline may be highly
dependent on the precise tool used [34].
Although a variety of physiological and clinical measures
have been used to define MCI, practical markers for predict-
ing progression to AD have yet to be identified. A multicen-
ter longitudinal study using data from the Alzheimer’s
Disease Neuroimaging Initiative (ADNI) [35] suggested
that MCI patients who had abnormal results on both 18F-flu-
orodeoxyglucose positron emission tomography and epi-
sodic memory tests were 11.7 times more likely to develop
AD over a 2-year follow-up period, compared with subjects
who had normal results on both measures [36]. Another
ADNI-based analysis indicated that both cerebrospinal fluid
(CSF) biomarkers and Spatial Pattern of Abnormalities for
Recognition of Early AD at baseline were sensitive in pre-
dicting conversion to AD; however, many MCI patients
who were nonconverters also had abnormal baseline CSF
and Spatial Pattern of Abnormalities for Recognition of
Early AD results. One study that included 148 outpatients
with MCI demonstrated that combining multiple disease
markers (informant report of functioning, olfactory identifi-
cation, verbal memory, MRI hippocampal volume, and MRI
entorhinal cortex volume) was more accurate (sensitivity:
85%, specificity: 90%) in predicting the conversion from
MCI to AD during a 3-year follow-up period than the com-
bination of age and MMSE (sensitivity: 39%, specificity:
90%) [37]. To date, researchers have not validated the panel
of early disease markers in large representative samples.
Longer follow-up is also needed to inform the determination
of optimal predictors.
Even less is known about the progression from preclinical
presymptomatic phases to MCI [38]. Although various bio-
markers (e.g., CSF tau, brain imaging to detect b-amyloid
plaques) are being tested for detecting AD in its preclinical
presymptomatic stage, there are no established clinical diag-
nostic criteria for this very early phase of disease [38]. Ad-
vances in preclinical AD detection may enable earlier
more effective treatment and eventually guide therapy be-
fore the onset of symptoms. As knowledge accumulates
about the biomarkers’ ability to predict the timing of decline
or progression to MCI, researchers can incorporate the infor-
mation into a framework that better characterizes the earliest
stage of the disease [1,38].
60 P.-J. Lin and P.J. Neumann / Alzheimer’s & Dementia 9 (2013) 58–62
3.2. Economic impact of MCI
During MCI, patients’ everyday activities and function-
ing may not yet be compromised, although subtle changes
in memory and thinking abilities are enough to be noticed
and measured. These changes have economic consequences
[1], but the role of memory and cognition in predicting the
economic impact of MCI is not well understood. Previous
studies have used MMSE [39], Clinical Dementia Rating
(CDR) [24], and Global Deterioration Scale [40] scores
to estimate costs for mild, moderate, and severe AD.
More and better data are needed to determine the perfor-
mance of these measures in predicting the cost associated
with MCI.
Some research suggests that “patient dependence” may
be an important multidimensional predictor of cost in the
MCI phase [41–43]. Patient dependence attempts to
summarize the level of care required, that is, the need of
a patient across domains, such as cognition, function, and
behavior. Because studies of patient dependence typically
have had small sample sizes and relatively brief follow-up
periods, it remains unclear whether and how this construct
predicts the costs associated with MCI.
“Indirect” costs associated with MCI patient and care-
giver productivity are also largely understudied. As MCI
advances, the time caregivers spend to assist patients
with activities of daily living and instrumental activities
of daily living increases, as does caregiver distress and
caregiver work time lost [44,45]. Recent estimates by
the Alzheimer’s Association reported 17.4 billion hours
of unpaid care provided for AD patients in 2011, valued
at .$210 billion [17]. Although indirect costs of MCI
are likely much lower than comparable costs in AD, care-
giving burden and the resulting productivity loss should
be considered as part of the condition’s economic burden
[2,24].
3.3. Modeling the consequences of MCI interventions
One Swedish study showed that an increase of CDR score
from 0.5 (i.e., MCI) to 1.0 (i.e., mild AD) corresponded to
SEK$54,000 (US$5700) in excess costs, suggesting that de-
laying the transition to AD may result in considerable eco-
nomic benefits [24]. However, because many uncertainties
exist about the effectiveness of therapeutic agents for MCI
[46], it is unclear whether any savings generated from early
detection and treatment will offset costs associated with
more testing and therapies [24]. In addition, methodological
differences, such as the study population (e.g., patients from
memory clinics, primary care, or community settings), type
of economic model, treatment evaluated, and assumptions
about disease progression over time, warrant caution in in-
terpreting the extent of economic benefits. Research is also
needed to determine how MCI treatment would impact man-
agement of expensive comorbidities and downstream long-
term care costs (such as effects on delaying nursing home
placement).
Although there is currently no US Food and Drug Admin-
istration–approved treatment for MCI, it is important to keep
patients and caregivers well informed about what resources
and treatment options are available when symptoms become
prominent. Nonpharmacological interventions such as coun-
seling and education may promote advance care planning
and reduce family stress and misunderstanding [28,33],
and these nonhealth outcomes should be considered in
economic models for MCI.
Over the years, researchers have developed and applied
a number of decision-analytic models to characterize the
cost-effectiveness of interventions for AD. However, these
models have certain limitations. Some are Markov models,
which, although useful in characterizing how patients tran-
sition among discrete health states (e.g., mild, moderate,
and severe AD), represent relatively crude depictions of
a complex disease [47]. In addition, Markov models as-
sume a “memoryless” property (i.e., transition probabili-
ties between states are independent of the patient’s
history), which does not reflect actual experience. A sys-
tematic review of AD decision-analytic models suggested
that many of the models have defined states on the basis
of cognitive impairment, ignoring potentially important
changes in other dimensions, such as dependency and pro-
ductivity [47].
Ideally, future economic models for MCI (as well as for
full-blown AD) will address these limitations. The models
would have the flexibility to incorporate information on
the accuracy of early-detection diagnostics, as well as infor-
mation on the progression of MCI to AD, the effectiveness of
new treatments, and impacts on a broad array of outcomes
(cognition, function, quality of life, costs). It would be useful
if models had the granularity to reflect the pathophysiology
of MCI at a refined level of biological and clinical detail
based on trial data. An improved model would incorporate
information about the impact of potential disease-
modifying agents on various model parameters, and how
agents affect subgroups such as patients with apolipoprotein
E4 (APOE 34) and other factors [48]. Researchers can then
use the model to project how early detection and treatment
impact disease progression and health costs under a range
of assumptions.
4. Incorporating new data
Studies on AD costs typically rely on administrative
claims databases, and estimate the incremental expenditures
of treating AD patients [9,11–13,15], leaving prediagnosis
costs largely unaddressed. Major challenges exist in using
administrative data to determine the costs of MCI. For
example, MCI and mild AD cases are typically
underdiagnosed and uncoded in claims files because of
difficulties recognizing symptoms and resistance among
patients and caregivers to a dementia diagnosis [10,49]. In
addition, the US reimbursement system provides little
financial incentive for coding AD as the primary diagnosis
 P.-J. Lin and P.J. Neumann / Alzheimer’s & Dementia 9 (2013) 58–62
and instead encourages hospitals and physicians to code
comorbidities, such as aspiration pneumonia, to enhance
reimbursement. Therefore, additional data sources (e.g.,
linked administrative claims and electronic medical
records) are needed to improve case ascertainment.
Ideally, researchers can use results of memory, cognitive,
functional, and neuropsychological tests documented in
medical records to identify MCI patients.
Data sets, such as the Health and Retirement
Study–Aging, Demographics, and Memory Study [50],
linked with Medicare claims files will provide clinical de-
tail (e.g., using instruments such as the Neuropsychiatric
Inventory and CDR) to help identify affected individuals
before they have symptoms prominent enough so they ap-
pear on claims records. Researchers can use these data
sources to address questions such as the following: How
utilization components (inpatient stays, physician visits,
medications) impact health costs in the MCI stage? How
do cost drivers change as patients progress along the dis-
ease continuum? Who bears the costs associated with
MCI—Medicare, private insurance, or patients and families
themselves? For economic models of MCI treatment, ongo-
ing patient registries (e.g., the National Alzheimer’s Coor-
dinating Center Uniform Data Set [51] and the ADNI) can
supply disease progression rate estimates for patients on
current standard of care based on real-world data, and pro-
vide a baseline for comparison when new treatments be-
comes available.
5. Conclusion
Although the costs of caring for AD patients have been
studied extensively, the economic literature on MCI is rela-
tively sparse. During the MCI phase, patients may begin us-
ing more health care and incurring higher costs, but the
direct and indirect costs of treatment for individuals with
MCI as well as the rate at which patients progress to AD
have not been well characterized. Many uncertainties exist
about the potential cost-effectiveness of early detection
and therapy for MCI. Economic analyses are needed to ac-
count for the impact of interventions on increased time in
the MCI state, and consequences for patient and caregiver
productivity and the long-term cost. A new comprehensive
AD simulation model, which includes an MCI state, could
help researchers assess the economic impacts of early diag-
nosis and treatment, and to inform coverage and reimburse-
ment decisions of new interventions. The model also can
help clinicians characterize various progression scenarios,
which may assist patients and their families with disease
planning.
Acknowledgments
This work was supported by a grant from Novartis to
Tufts Medical Center. Publication was not contingent on
Novartis’ approval. We thank Usha Mallya for helpful
61
comments on an earlier version of the manuscript and Sarah
Bliss for her research assistance.
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