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Abstract
Individuals with amnestic mild cognitive impairment (MCI) are at elevated risk of developing
Alzheimers 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.
2013 The Alzheimers Association. All rights reserved.
Keywords:
1. Introduction
Researchers have long recognized that Alzheimers disease (AD) is a slowly progressive degenerative illness that
includes a predementia period during which symptoms are
mild or barely detectable [1]. Individuals in this prodromal
stage have been identified as having mild cognitive impairment (MCI) [2], affecting 10% to 20% of individuals aged
65 years [36]. Although not all individuals with MCI
progress to full-blown AD, they are at an increased risk
as many as 15% develop AD or related dementias each
year [7].
What is new and potentially paradigm shifting are advances in neuroimaging and other diagnostics that promise
early identification of AD, and the eventual prospect of
disease-modifying treatments. These developments will
have profound economic as well as clinical implications. Individuals with MCI are often divided into two groups: those
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
1552-5260/$ - see front matter 2013 The Alzheimers Association. All rights reserved.
http://dx.doi.org/10.1016/j.jalz.2012.05.2117
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59
slow and uneven progression of the condition makes it challenging to identify a threshold for conversion between normal 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 clinical, cognitive, and functional criteria. Yet, measurements
used to define an individuals conversion from MCI to AD
can be subjective [32]. A survey of 420 American Academy
of Neurology members showed that some respondents believed 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 commonly use measures of cognitive function to define the condition, 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 predicting progression to AD have yet to be identified. A multicenter longitudinal study using data from the Alzheimers
Disease Neuroimaging Initiative (ADNI) [35] suggested
that MCI patients who had abnormal results on both 18F-fluorodeoxyglucose positron emission tomography and episodic 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 predicting 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 identification, 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 combination 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 biomarkers (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 diagnostic criteria for this very early phase of disease [38]. Advances in preclinical AD detection may enable earlier
more effective treatment and eventually guide therapy before 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 information into a framework that better characterizes the earliest
stage of the disease [1,38].
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Although there is currently no US Food and Drug Administrationapproved 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 counseling 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 transition among discrete health states (e.g., mild, moderate,
and severe AD), represent relatively crude depictions of
a complex disease [47]. In addition, Markov models assume a memoryless property (i.e., transition probabilities between states are independent of the patients
history), which does not reflect actual experience. A systematic 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 productivity [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 information 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 diseasemodifying 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 [9,1113,15], 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
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