11 Mar 2002 12:31 AR AR153-10.tex AR153-10.SGM LaTeX2e(2001/05/10) P1: IKH
10.1146/annurev.publhealth.23.100901.140525
Annu. Rev. Public Health 2002. 23:213–31
DOI: 10.1146/annurev.publhealth.23.100901.140525
Copyright c
°2002 by Annual Reviews. All rights reserved
THE PUBLIC HEALTH IMPACT OF ALZHEIMER’S
DISEASE, 2000–2050: Potential Implication of
Treatment Advances
Philip D. Sloane1,2, Sheryl Zimmerman1,3,
Chirayath Suchindran4, Peter Reed1, Lily Wang4,
Malaz Boustani5, and S. Sudha6
1Cecil G. Sheps Center for Health Services Research, 2Department of Family Medicine,
3School of Social Work, 4Department of Biostatistics, 5Program on Aging, University of
North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599; 6University of North
Carolina at Greensboro, PO Box 26170, Greensboro, North Carolina 27402-6170;
Key Words public health impact, Alzheimer’s disease, Alzheimer’s care
■Abstract Recent developments in basic research suggest that therapeutic break-
throughs may occur in Alzheimer’s disease treatment over the coming decades. To
model the potential magnitude and nature of the effect of these advances, historical
data from congestive heart failure and Parkinson’s disease were used. Projections in-
dicate that therapies which delay disease onset will markedly reduce overall disease
prevalence, whereas therapies to treat existing disease will alter the proportion of cases
that are mild as opposed to moderate/severe. The public health impact of such changes
would likely involve both the amount and type of health services needed. Particularly
likely to arise are new forms of outpatient services, such as disease-specific clinics
and centers. None of our models predicts less than a threefold rise in the total number
of persons with Alzheimer’s disease between 2000 and 2050. Therefore, Alzheimer’s
care is likely to remain a major public health problem during the coming decades.
INTRODUCTION
Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by
progressive deterioration of cognitive function. It begins insidiously, with early
signs including patchy memory loss and subtle behavioral changes. The illness
gradually progresses until, often after a decade or more, the individual is unable to
speak or comprehend language, no longer controls his or her bowels, and requires
assistance with all aspects of personal care. Persons in the later stages of the illness
are often placed in nursing homes, which have become increasingly populated by
0163-7525/02/0510-0213$14.00 213
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214 SLOANE ET AL.
older persons with cognitive impairment. Since AD predominantly affects older
persons, one outcome of the graying of America during the coming decades is
likely to be a tidal wave of persons with AD.
What will be the effect on public health of AD during the coming decades?
How many people will have the disease in the future, and what will be their
service needs? This paper addresses these questions empirically by presenting and
discussing several future scenarios of AD prevalence in the United States between
2000 and 2050. Two of these scenarios have already been published—resulting
in high (12) and low (46) estimates of prevalence derived by applying current
disease patterns to future population projections. Such projections are likely to
be inaccurate, however, because recent developments in AD research suggest that
one or more therapeutic breakthroughs is likely in the coming decades (26,32, 38).
Therefore, to project the impact of potential advances in therapy, this paper applies
estimatesbasedonhistoricaldatafromtwochronicdiseasesforwhichmanagement
has changed markedly during the past five decades: congestive heart failure and
Parkinson’sdisease. Inthis manner, wediscuss afuller rangeof possibilitiesfacing
the public health system, toward the goal of better informing public debate on the
needs and priorities of health care for the elderly over the coming decades.
ALZHEIMER’S DISEASE TODAY
Etiology and Clinical Course
Thespecific causeof ADis unknown,and itmay wellbe a multifactorialsyndrome
rather than a single disease (41). Age and family history of the disease in a first-
degree relative are the strongest epidemiological risk factors for AD. Persons age
85 and older have 14 times the incidence of AD compared with persons age 65
to 69 (16a), and the relative risk of AD for those with at least one first-degree
relative with dementia is 3.5 (95% CI 2.6 to 4.6) (46a). Other putative risk factors
include head trauma, education level, number of siblings, non-suburban residence,
maternal age at birth, hypothyroidism, and apolipoprotein E4 genotype (27a,46a).
In addition, between one and two percent of cases demonstrate an autosomal
dominant genetic pattern with nearly complete penetrance (7). During the past
decade a number of advances have been made in understanding the biochemical
nature of the disease. Current thinking is that several biochemical mechanisms
may contribute to neuronal degeneration, with final pathways involving both the
cleavage of βamyloid precurser protein to form βamyloid (a major component of
senile plaques), and abnormal processing and accumulation of tau protein (a major
component of neurofibrillary tangles) (38,41). In addition, small and large vessel
cerebrovascular disease can cause dementia syndromes that often are difficult to
distinguish from, and can occur concurrently with, AD (7).
Thedisease canbecharacterized bythreephases: aprolonged preclinical phase,
in which subtle signs are detectable but the diagnosis cannot be established; a mild
symptomatic period, where patients suffer memory loss, impaired judgment, and
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IMPACT OF ALZHEIMER’S DISEASE 215
Figure 1 General model of the course of Alzheimer’s disease and other chronic diseases.
decreasing ability to carry out everyday activities such as shopping, cooking, and
grooming [stage 1 on the Clinical Dementia Rating Scale (CDR) (22)]; and a
moderate/severe period, in which patients require 24-hour supervision and are in-
creasingly impaired in basic functional areas such as locomotion, speech, ability to
maintaincontinence,feeding,andhydration(23,33).Figure1providesaschematic
overviewof thecourse ofAD; thisschema can beapplied tomost chronicdiseases.
The rate of progression of untreated cases of AD varies among individuals. On
average, about one quarter of people progress each year from mild (CDR stage 1)
to moderate disease (CDR stage 2) (9,25). In addition, multiple longitudinal stud-
ies have identified an average annual decline of 3.5 points on Mini-Mental State
Examination (a 30-point scale) and 7–9 points on the Alzheimer’s Disease Assess-
ment Scale (a 70-point scale) (43).
Current and Projected Prevalence
Obtaining accurate assessment of the current and projected prevalence of AD is a
challengebecausethereisnodefinitivediagnostictestandbecausemanyofitssigns
andsymptoms aresharedby severalotherforms ofcognitivedecline anddementia.
Other factors that contribute to the difficulty of determining the prevalence of
AD include the absence of a formal reporting system for diagnosed cases and
misrepresentation of disease prevalence due to unrecognized cases. Therefore,
existing prevalence rates vary widely.
A conservative (low) estimate for the current and future prevalence of AD was
provided by the U.S. General Accounting Office (GAO) (46). Based on a meta-
analysis integrating estimates from 18 studies of Alzheimer’s disease prevalence,
theGAO publishedage-specific,five-yearprevalenceratesfor allcasesandmoder-
ate/severe AD. A more liberal (high) estimate of the current and future prevalence
of AD was provided by Evans et al. (12). They estimated prevalence by age, in
ten-year intervals, based on a community study of 3623 adults over age 65 in
East Boston, MA. While the study provided age-specific rates for Alzheimer’s
disease, stage-specific rates were provided only for cognitive impairment. There-
fore, we estimated stage-specific rates by applying the cognitive impairment stag-
ing ratios to the number of estimated cases of AD. This calculation was based
on an assumption that, although there are more cases of cognitive impairment
than AD, the relative proportions of cases at various disease stages would be
equivalent.
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216 SLOANE ET AL.
These methods estimated that there were between 2.17 and 4.78 million cases
of AD in the United States in 2000, of which between 44 (12) and 57 (46) percent
had moderate or severe disease. To calculate the possible range of the total number
of AD cases over the next 50 years, assuming no significant change in disease
epidemiology, we applied both the liberal and conservative rates to the middle
series Census estimates for age-specific populations (45). Table 1 displays these
projections. They indicate that, if no scientific advances alter the incidence and
progression of AD, between 7.98 and 12.95 million people in the United States
will be suffering from the illness by the year 2050, a fourfold increase from the
current prevalence.
Current Public Health Impact
The clinical symptoms of AD are not limited to memory loss and other cognitive
deficits but extend to a wide spectrum of noncognitive secondary features, such
as impaired activities of daily living, depression, and challenging behavioral dis-
turbances. Assessment of overall disease impact on quality of life is challenging,
but over the last few years several self-report, proxy-report and observational tools
havebeen developedand linkedto healthoutcomes. For example, oneproxy-based
rating system that assesses behavioral engagement (participation in activities) and
subjective states (affective expression) shows increasing decline with dementia
severity (1). Another instrument, which evaluates physical condition, mood, inter-
personal relationships, ability to participate in meaningful activities, and financial
situation, has been associated with depressive symptoms and functional depen-
dence (24a). Given the impact of the disease on function and quality of life, it
is not surprising that persons with AD utilize health services at higher rates and
experience more accidents and falls than age-matched controls. As their indepen-
dence continues to decrease, persons with the disease place an increasing physical,
TABLE 1 Three estimates of the prevalence of Alzheimer’s disease, by stage, United States,
2000–2050*
Stage 2000 2005 2010 2015 2020 2025 2030 2035 2040 2045 2050
GAOaMild 0.93 1.03 1.13 1.26 1.41 1.63 1.93 2.28 2.66 2.99 3.26
Moderate/severe 1.24 1.38 1.53 1.71 1.94 2.23 2.63 3.13 3.69 4.25 4.72
All 2.17 2.41 2.67 2.97 3.35 3.86 4.55 5.41 6.35 7.24 7.98
UNCbMild 0.93 1.21 1.14 1.53 1.55 1.87 2.10 2.56 3.00 3.45 3.75
Moderate/severe 1.24 1.49 2.00 2.05 2.54 2.83 3.44 4.07 4.88 5.68 6.46
All 2.17 2.70 3.14 3.58 4.09 4.70 5.54 6.63 7.88 9.12 10.21
EvanscMild 2.69 2.83 3.10 3.58 4.16 4.83 5.44 5.85 6.13 6.37 6.65
Moderate/severe 2.08 2.25 2.51 2.86 3.23 3.70 4.24 4.81 5.33 5.85 6.29
All 4.78 5.07 5.61 6.43 7.39 8.53 9.68 10.66 11.46 12.22 12.95
*Millions of cases.
aSource: Reference (46).
bBased on applying estimated rates of transition across stages of the disease to U.S. Census projections. See text for details.
cSource: Reference (12, pp. 283–399).
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IMPACT OF ALZHEIMER’S DISEASE 217
psychological, and financial burden on family caregivers. As a result, they are fre-
quently placed in residential care/assisted living facilities, nursing homes, and
geropsychiatric hospitals.
ThereareasmanydifferentestimatesofthetotalcostofADcareasthereareesti-
matesofdiseaseprevalence.Onemid-rangeestimate,excludingcostsofmorbidity,
premature death, and lost employment income, is $38,000 per patient per year,
amounting to $65 billion nationally (1995 dollars), although estimates as much
as 50 percent lower and 50 percent higher have been proposed (11). Over time,
these costs will increase proportionate to the increase in the total size of the AD
population and the proportionate distribution of mild and moderate/severe cases.
Regardless of disease severity, most of the burden of caring for individuals with
AD is shouldered by informal caregivers, with unpaid caregiver time constituting
one half to two thirds of the total cost of care (11). The average family caregiver
spends 16.1 hours per week providing care, with increasing burden as the disease
progresses. Thus, the average time spent providing care is 5.9 hours per week for
individuals with no impairments in activities in daily living and rises to as much
as 35.2 hours per week for those with severe limitations (28).
Thelargestincrease inthecost ofcare occurs whenindividualsareinstitutional-
ized (11,17). Nursing home placement is a notable milestone in the progression of
AD because it proxies for severe disability and imposes a huge financial burden on
our health system. In 1994, the cost to Medicaid of nursing home care for persons
with AD is estimated to have exceeded $8 billion. Largely due to the costs of care
in nursing homes and other residential long-term care settings, the total cost of
caring for persons with severe AD is 2.25 times higher than for patients with mild
or moderate disease (21).
Effectiveness of Current Treatment
Until recently, treatment of AD has been entirely supportive. Management has
consisted of provision of a safe, “prosthetic” environment, education and sup-
port of family caregivers, assistance with daily activities and personal care, and
managementofbehavioralproblemsusingnonpharmacologicalstrategiesandpsy-
choactive drugs. Although these treatment strategies remain the mainstay of AD
management today (1a), drugs are increasingly being used not just for problem
behaviorsbutalso toretard thediseaseprogression. Currentpharmacologicaltreat-
ment involves one of four strategies:
■enhancing levels of the brain transmitter acetylcholine by administering
cholinesterase inhibitors,
■reducing inflammatory responses that accompany brain injury through the
use of nonsteroidal agents such as aspirin or ibuprofen,
■enhancing putative protective factors through strategies such as vitamin E
supplementation, and
■treating concomitant cardiovascular risk factors, especially hypertension.
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