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Longitudinal Assessment of Patient Dependence in Alzheimer Disease
Adam M. Brickman, MA;
Aliza Riba, BA;
Karen Bell, MD;
Karen Marder, MD, MPH;
Marilyn Albert, PhD;
Jason Brandt, PhD;
Yaakov Stern, PhD
Arch Neurol. 2002;59:1304-1308.
ABSTRACT
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Background The Dependence Scale measures the amount of assistance patients with
dementia require in performing daily activities. Validity and reliability
of this scale have been demonstrated, but the progression throughout long
periods in patients with Alzheimer disease (AD) has not previously been examined.
Objective To determine the longitudinal course of patient dependence in a cohort
of prospectively followed AD patients.
Methods Two hundred thirty AD patients enrolled in the Predictors Study were
followed up prospectively at 6-month intervals for an average of 6.5 visits.
The Dependence Scale was administered to a caregiver, and patients were assessed
with the modified Mini-Mental State Examination (mMMSE) and the Blessed Dementia
Rating Scale. Dependence level and the additive sum of the Dependence Scale
items were considered for analysis.
Results Generalized estimating equations to regression analyses were used to
determine that both Dependence Scale scores and dependence level significantly
decline with time. By covarying mMMSE scores and self-care deficits factor
scores of the Blessed Dementia Rating Scale, generalized estimating equations
analysis also demonstrated that change in patient dependence was independent
of global cognitive decline and other measures of activities of daily living,
respectively.
Conclusions This study shows the validity of the Dependence Scale and demonstrated
that dependency in AD significantly declines with time independent of global
cognition and other self-care deficits. The scale is a valuable instrument
for outcomes research, efficacy trials, and behavioral research in AD.
INTRODUCTION
FUNCTIONAL DISABILITY is a defining feature of Alzheimer disease (AD).1 However, functional impairment is not a uniform construct
but is multifaceted and can be measured with various clinical instruments.
For example, traditional scales have focused on self-care needs and instrumental
activities of daily living.2-3
Others consider patient disability4 and caregiver
burden.5-6 The Dependence Scale7 was developed to assess the required amount of assistance
needed by AD patients to better understand the impact of the disease on patients
and their caregivers.
Since its introduction, the Dependence Scale has been included in several
efficacy trials for new treatments of AD,8-10
behavioral studies,11-16
and position papers.17-22
Overall, the scale has been a useful tool for characterizing functional impairment
and for examining efficacy of treatment. It has been suggested that the Dependence
Scale also has utility for examination of the functional course of AD from
mild to the most advanced stages of the disease.18
In the initial validity and reliability study, Stern et al7
demonstrated good agreement with measures of cognitive impairment and other
functional impairment scales. They further showed that the scale is organized
hierarchically, tapping into dependency needs affected both early and late
in the disease. A subset of patients enrolled in that original study were
followed up longitudinally and tested at 6-month intervals for approximately
18 months. Preliminary longitudinal analysis demonstrated excellent test-retest
reliability and provided evidence that dependency needs increase with time.
In the current study, AD patients enrolled in the Predictors Study were
followed up longitudinally at 6-month intervals for up to 10 years. Patients
were assessed with the Dependence Scale at each visit. The primary purpose
of the study was to characterize the course of patient dependency over time.
A secondary purpose was to examine the progression of patient dependence in
the context of both cognitive and other functional domains.
PARTICIPANTS AND METHODS
PARTICIPANTS
Participants (n = 230) were informants who represented patients in the
Predictors Study, which prospectively examines the course of AD. Patients
were recruited from Columbia University (n = 92), Johns Hopkins University
(n = 77), and Massachusetts General Hospital (n = 61). To be entered into
this study, patients were required to meet National Institute of Neurological
and Communicative Disorders and Stroke diagnostic criteria for probable AD1 and to demonstrate relatively mild cognitive impairment,
as indicated by a score of 30 or greater on the modified Mini-Mental State
Examination (mMMSE). Additional detailed description of inclusion and exclusion
criteria for the Predictors Study are described elsewhere.23-24
PROCEDURES
As part of the Predictors Study, AD patients are assessed prospectively
every 6 months with a standard battery of clinical and neuropsychological
tests. The Dependence Scale is administered to a reliable informant at each
visit. The scale consists of 13 items, representing a range of severity from
mild (eg, "Does the patient need frequent help finding misplaced objects?")
to moderate (eg, "Does the patient need to be watched when awake?") and severe
(eg, "Does the patient have to be fed?") levels of dependency. The scale is
designed to ascertain the current level of dependency. Table 1 gives the entire Dependence Scale. A dependence score is
derived by taking an additive sum of the 13 items. Furthermore, a 6-level
ranking of dependence is determined as follows: level 0, 0 to all items; level
1, items A, B, or C equals 1; level 2, 2 of items A, B, or C equals 1, or
A or B equals 2, or D equals 1; level 3, items E, F, or G equals 1; level
4, items H, I, or J equals 1; level 5, items K, L, or M equals 1. The 6 dependence
levels are based on responses to the Dependence Scale items and range from
no dependence to complete dependence in self-care activities. Rank levels
were created to establish dependency stages and have been used in all studies
to date that used the scale.
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Table 1. The Dependence Scale*
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For the purposes of this study, we used mMMSE scores obtained at each
visit to assess global level of cognitive status. The mMMSE is a modification
of the Folstein Mini-Mental State Examination25;
scores range from a minimum of 0 points to a maximum of 57. Psychometric properties
of the scale are described by Stern et al.26
Similarly, the Blessed Dementia Rating Scale (BDRS)2
was conducted at each visit to measure functional capacity. In addition to
a total score, a well-defined 4-factor model has previously been described.27 The factors include cognitive impairment, self-care
needs, personality disturbance, and apathy.
STATISTICAL ANALYSIS
The sum of the Dependence Scale items was assessed longitudinally with
generalized estimating equations (GEEs) to regression analyses with repeated
measures.28 There are several advantages to
using GEE analysis. It allows for analysis with multiple visits per participant
and corrects for the fact that the characteristics of a single individual
over time are likely to be correlated with one another. In GEE analysis, repeated
measures for each participant are clustered. Furthermore, GEE analysis takes
into account the status or changing value of covariates at each visit. Tabled
values for regression analyses involving the factor score are regression coefficients
and their SEs. The dependent measure for the GEE analysis was the sum of the
items on the Dependence Scale. To investigate whether dependency change over
time is independent of global cognition, the GEE analysis was rerun with mMMSE
score at each visit held as a covariate. Further analysis was performed with
the self-care needs factor of the BDRS score held as a covariate. For this
analysis, we wished to determine if the progression of dependency is independent
of BDRS self-care scores. This would indicate that dependency and self-care
capacity represent related but possibly distinct components of disability
in AD.
To characterize dependence change over time, cross-tabulations were
computed for dependence level and visit. This allowed us to examine the distribution
of dependence level as a function of longitudinal visit. Dependence level
was also examined with GEE analysis to characterize the average rate of change
over time.
Finally, Cox regression analysis was used to determine endorsement of
the scale items. Survival curves were generated for 3 representative scale
items, corresponding to mild ("Does the patient need frequent help finding
misplaced objects?"), moderate ("Does the patient need to be watched when
awake?"), and severe ("Does the patient have to be fed?") levels of dependence.
The 3 items were selected from 3 clearly defined subscales,7
representing mild, moderate, and severe dependence. Survival curves were plotted
to demonstrate differential progression of each of these 3 items. Results
are presented as mean ± SD.
RESULTS
At baseline, the mMMSE score was 37.72 ± 5.46, indicating a mild-to-moderate
level of cognitive impairment. Patients ranged in age from 50 to 99 years
(73.0 ± 9.2 years). Patients had, on average, 13.1 ± 3.7 years
of education, and 61% were female.
Examination of the baseline Dependence Scale revealed that the sum of
the items was 5.31 ± 2.15, indicating a mild level of patient dependency.
Similarly, most participants were rated at dependence level 2. Figure 1 displays the distribution of baseline dependence level
ratings. All patients had at least 2 semiannual longitudinal visits, with
a mean of 6.48 ± 5.13 visits.
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Figure 1. Baseline dependency level. Samples
sizes are as follows: level 0, n = 8; level 1, n = 9; level 2, n = 147; level
3, n = 56; level 4, n = 8; and level 5, n = 2.
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Results of the GEE analysis revealed that the sum of the Dependence
Scale changed significantly over time (estimated ß = 0.51 ± 0.02, P<.001), with an increase of approximately 0.5 points
per 6-month interval. A similar pattern emerged when the mMMSE score at each
visit was held as a covariate. Although mMMSE scores significantly changed
over time (estimated ß = -0.13 ± 0.01), the change in dependency
score was independent of mMMSE score (estimated ß = 0.20 ± 0.0).
The BDRS self-care covariate factor also changed significantly with time (estimated ß
= 0.70 ± 0.02, P < .001), but did not eliminate
the significant change in dependency scores (estimated ß = 0.16 ±
0.01, P<.001).
Cross-classification of dependence level with visit demonstrated that
rankings reflected progressively increased dependency with time. At baseline,
most patients were ranked at level 2. However, by visit 3, most patients were
ranked at level 3, and by visit 8, most patients were ranked at dependency
level 5. Figure 2 displays the distribution
of dependency level for 6 representative longitudinal visits. When GEE analysis
was used to examine dependence level, there was significant change over longitudinal
visits (P<.001). Consistent with the cross-classification,
the estimated ß was 0.17 ± 0.005, indicating that AD patients
in this cohort changed dependence level approximately every 3 years.
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Figure 2. Percentage distribution of dependence
level at each visit. Sample sizes are as follows: visit 0 (baseline), n =
230; visit 4, n = 155; visit 8, n = 110; visit 12, n = 87; and visit 20, n
= 1.
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Finally, survival analysis revealed differential endorsement of each
scale item. More than 75% of the participants endorsed items A, B, and C within
1 year of baseline. Furthermore, the number of years in which most participants
endorsed the other items generally increased with each consecutive scale item
(Table 2). Survival curves for
the 3 scale items representing mild, moderate, and severe dependence also
demonstrated varying rates of endorsement over time (Figure 3). Within 1 year of the baseline visit, 50% of the participants
endorsed the mild item ("Does the patient need frequent help finding misplaced
objects?"). Approximately 2 years following the baseline visit, 50% of participants
endorsed the moderate item ("Does the patient need to be watched when awake?").
The severe item ("Does the patient have to be fed?") was endorsed by 50% of
the participants approximately 6 years following baseline.
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Table 2. Summary of Survival Curve Analyses of the Dependence Scale*
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Figure 3. Survival curves for item C ("Does
the patient need frequent help finding misplaced objects, keeping appointments,
or maintaining health or safety?") (A), item E ("Does the patient need to
be watched or kept company when awake?") (B), and item J ("Does the patient
have to be fed?") (C).
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COMMENT
The course of patient dependency in AD was examined by analysis of the
longitudinal change in Dependence Scale scores. We demonstrated that the sum
of dependency items increases approximately one point per year. This increase
is independent of changes in both measures of global cognition and change
in BDRS scores. Similarly, we found that dependence level increases at the
rate of approximately one level per 3 years.
The findings further support the validity of the Dependence Scale. Specifically,
dependency scores reflected increased impairment with the progression of the
disease. Furthermore, the significance of change in dependency over time was
not removed when we controlled for BDRS self-care deficits. Although both
scales clearly tap into areas of functional impairment, this finding indicates
that they measure distinct but related components of disability in AD. Similarly,
the decline in patient dependency was independent of global cognition as measured
by the mMMSE. It is well established that functional and noncognitive symptoms
are poorly correlated with cognitive symptoms in AD.29-30
Thus, it is not surprising that there is a significant decline in dependency
that is not completely accounted for by a decline in global cognition. An
important implication of our findings is that patient dependency is a relevant
functional domain that should be considered in behavioral studies of AD and
new treatment trials.
Although most studies that have used the Dependence Scale have used
dependence level as a dependent measure, our study suggests an alternative
scoring. The sum of the items on the scale provides a measure more sensitive
to change than dependence level. The sum of items score might therefore be
more appropriate for short-duration clinical trials and behavioral studies.
Alternatively, the dependence level may be an appropriate
baseline covariate for similar types of research. In this vein, dependence
level serves as a staging score for patient dependency, much like the Clinical
Dementia Rating Scale31 does for overall disease
severity. Also like the Clinical Dementia Rating Scale, dependence level can
be useful for clinical characterization.
The survival curve analysis of 3 representative scale items mirrors
the finding by Stern et al7 that the Dependence
Scale taps into varying degrees of patient dependence. Specifically, we demonstrated
that the requirement of assistance of AD patients to locate misplaced objects
occurs early in the progression of the disease, whereas more time elapses
before the typical patient needs to be watched and fed. Factor analysis7 revealed that the scale assesses 3 factors: cognitive
support (items A through D); assistance, elder active (items E through I);
and assistance, elder passive (items J through M). The current study suggests
that each of the 3 factors occurs sequentially.
AUTHOR INFORMATION
Accepted for publication January 31, 2002.
Author contributions: Study concept and design (Drs Albert and Stern); acquisition of data (Ms Riba and Drs Bell, Marder, Albert, and Stern); analysis and interpretation
of data (Mr Brickman, Ms Riba, and Drs Brandt and Stern); drafting of the manuscript (Mr Brickman and Dr Stern); critical revision of the manuscript for important intellectual content (Mr Brickman, Ms Riba, and Drs Marder, Albert, Brandt, and Stern); statistical expertise (Mr Brickman and Dr Stern); obtained funding (Dr Stern); administrative,
technical, and material support (Mr Brickman, Ms Riba, and
Drs Albert and Stern); study supervision (Dr Stern).
This study was supported by National Institutes of Health (Bethesda,
Md) federal grants AG07370 and RR00645.
Corresponding author and reprints: Yaakov Stern, PhD, Gertrude H.
Sergievsky Center, Columbia University College of Physicians and Surgeons,
630 W 168th St, New York, NY 10032 (e-mail: ys11{at}columbia.edu).
From the Departments of Neurology and Psychiatry and the Gertrude H.
Sergievsky Center and Taub Alzheimer's Disease Research Center, Columbia University
College of Physicians and Surgeons, New York, NY (Mr Brickman, Ms Riba, and
Drs Bell, Marder, and Stern); Department of Psychology, Queens College, and
The Graduate Center of the City University of New York, New York (Mr Brickman);
Departments of Psychiatry and Neurology, Massachusetts General Hospital, Harvard
Medical School, Boston (Dr Albert); and Departments of Psychiatry and Behavioral
Sciences and Alzheimer's Disease Research Center, Johns Hopkins University
School of Medicine, Baltimore, Md (Dr Brandt).
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