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Alzheimer’s & Dementia 12 (2016) 427-437

Featured Article

Assessing Alzheimer’s disease patients’ quality of life: Discrepancies

between patient and caregiver perspectives
Sandrine Andrieua,b,*, Nicola Coleya,b, Yves Rollanda,c, Christelle Canteta,c,
Catherine Arnauda,b, Sophie Guyonneta,c, Fati Nourhashemia,c, Alain Granda,b, Bruno Vellasa,c,
and the PLASA group1
a
Inserm-Toulouse University UMR1027, Toulouse, France
b
CHU Toulouse, Department of Epidemiology and Public Health, Toulouse, France
c
Gerontopole, CHU Toulouse, Department of Geriatric Medicine, Toulouse, France

Abstract Introduction: Quality of life (QOL) is an important dimension to consider in Alzheimer’s disease
(AD), but few large-scale studies have analyzed self and caregiver reports of patient QOL.
Methods: Patient QOL was evaluated in a cohort of 574 AD patients with the QOL-AD scale over
2 years.
Results: Caregiver reports of patient QOL were lower at baseline than self reports. Older patient age
was associated with overestimation of QOL by caregivers, whereas neuropsychiatric inventory score
and caregiver burden were associated with underestimation. Activities of daily living limitation,
depressive symptoms, and caregiver burden were systematically associated with poorer QOL,
whereas caregiver relationship and apathy were associated with poorer QOL only for self reports
or caregiver reports, respectively. Cognitive function and professional care were not associated
with QOL. Self-rated patient QOL did not change over time, whereas disease severity markers and
caregiver-rated patient QOL declined.
Discussion: It is important to assess both self and caregiver ratings when assessing patient QOL.
Ó 2016 The Alzheimer’s Association. Published by Elsevier Inc. All rights reserved.

Keywords: Alzheimer’s disease; Quality of life; QOL-AD; Caregivers; Proxy report; Longitudinal

1. Introduction than the disease itself, it is its disability-related impact

Alzheimer’s disease (AD) is a chronic disease that re-
quires care for several years and remains one the most
frequent disabling diseases in aging populations [1,2]. It
is a major cause of decreased quality of life (QOL) in
older adults, and some studies have shown that more
There are conflicts of interest to disclose.
The contents of this article are solely the responsibility of the authors
and do not necessarily represent the official view of the French Ministry
of Health. The study sponsor had no role in the study.
1
See acknowledgments for the list of the PLASA study group members.
*Corresponding author. Tel.: 133-5-61-14-59-50; Fax: 133-5-62-26-
42-40.
E-mail address: sandrine.andrieu@univ-tlse3.fr
http://dx.doi.org/10.1016/j.jalz.2015.09.003
1552-5260/Ó 2016 The Alzheimer’s Association. Published by Elsevier Inc. All rights reserved.
that affects QOL [3]. Simple measures of cognitive or
functional decline are not sufficient to address the
complexity of AD, and QOL is a useful additional dimen-
sion to consider as a broader outcome measure which may
represent more “clinically significant” changes or benefits
to the patient and caregiver [4]. QOL is a broad concep-
tual field, linked to physical health as well as psycholog-
ical state, level of independence, social relationships,
personal beliefs, and the subject’s relationship with the
specifics of their environment [5]. Researchers [6,7] and
regulatory agencies [8] emphasize the need to take into
account patient QOL in the evaluation of new drugs but
stress the need for further validation work to use it as
an end point in clinical trials. For example, little is known
about the natural history of QOL in AD, the determinants
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428 S. Andrieu et al. / Alzheimer’s & Dementia 12 (2016) 427-437
of high and low QOL, or the effects of medication on
QOL [9].
Caregiver ratings are frequently used as part of multidi-
mensional evaluations of AD patients, in particular to mea-
sure patients’ functional status and neuropsychiatric
symptoms, and caregivers may also be asked to rate patients’
QOL [4]. However, because QOL is subjective and defined
as an individual perception, it should ideally be assessed
from the subject’s own perspective [10,11], but declining
cognitive function makes this harder to do in AD [10].
Many QOL scales have been proposed in AD [12], including
the QOL-AD scale which requires both the patient and care-
giver to rate the same domains of patient QOL [10].
Several previous studies [13–17] have reported
discrepancies between caregiver and self reports of AD
patients’ QOL, and some have identified factors associated
with divergent ratings [15–19]. Most studies were small
scale and targeted populations coming from particular
settings, such as residential care homes [20], or from thera-
peutic trials, thus providing a selected sample with an abnor-
mally low rate of comorbidities [21,22]. Furthermore, very
few studies have examined longitudinal changes in patient
and proxy QOL reports over .1 year of follow-up [18].
The primary objective of this multicentre study was to
explore discrepancies between self and caregiver reports of
patient QOL in a large population of well-characterized
community-dwelling AD patients at baseline and during 2
years of follow-up and to determine factors associated
with disagreement at baseline. The secondary objective
was to assess factors explaining a low level of self- or
caregiver-reported patient QOL at baseline.
2. Methods
This study includes AD patients and their primary care-
givers enrolled in the Plan de soin et d’aide dans la maladie
d’Alzheimer (PLASA) study, a randomized trial that tested
the efficacy of a standardized care plan versus usual demen-
tia care on functional decline over 2 years of follow-up.
PLASA is described in detail elsewhere [23].
2.1. Subjects
Briefly, a total of 1131 AD patients and their caregivers
were recruited in a French nationwide network of 50 mem-
ory centers. To be included, subjects had to meet the
following inclusion criteria: diagnosis of probable or
possible AD according to the National Institute of Neurolog-
ical and Communicative Disorders and Stroke and the Alz-
heimer’s Disease and Related Disorders Association
criteria [24], mini-mental status examination (MMSE) [25]
score between 12 and 26, community-dwelling, looked after
by a well-identified informal caregiver, and not participating
in any other research program. In the present analysis, we
included only the 574 patients randomly assigned to the
intervention group to be able to study the determinants of
QOL and patient-proxy agreement because this group under-
went more comprehensive evaluations than the usual care
group (as part of the intervention). The intervention had no
significant effect on any of the primary or secondary efficacy
measures, including QOL.
The study was funded by the Ministry of Health and
was approved by the Institutional Review Board and ethics
committee of Toulouse University. Written informed con-
sent was obtained from all patients and their caregivers.
This trial was registered in clinicaltrials.gov (identifier:
NCT00480220).
2.2. Measurements
Patients were evaluated every 6 months in memory
centers in general or university hospitals.
2.2.1. QOL measure
Patient QOL was assessed by the QOL-AD scale [10], a
13-item questionnaire designed to provide patient and care-
giver reports of the patient’s QOL which covers various do-
mains (physical health, energy, mood, living situation,
memory, family, marriage, friends, self as a whole, ability
to do chores, ability to do things for fun, financial situation,
and QOL as a whole). Items are scored on a 4-point Likert
scale ranging from 1 (poor) to 4 (excellent). Total scores
range from 13 to 52 with higher scores indicating better
QOL. As proposed by Logsdon [10], missing items were re-
placed by the mean score of the remaining items if no more
than two items were missing; otherwise, the score was
considered missing.
2.2.2. Other measures
Sociodemographic data (age, sex, educational level, and
living arrangements), time since diagnosis of dementia as
declared by the caregiver, comorbidities, use of support ser-
vices, and assistance in the home (home help, supervision,
meal delivery service, and nursing care) were recorded using
a standardized questionnaire. Number of medications used
and use of anti-AD drugs (i.e., cholinesterase inhibitors,
N-Methyl-D-aspartate receptor antagonists) were recorded.
Dementia severity was evaluated based on assessments of
cognition (MMSE) [25], function (activities of daily living
[ADL] [26], instrumental activities of daily living [IADL]
[27]), and behavioral disorders (neuropsychiatric inventory
[NPI]) [28]. Nutritional status was evaluated with the mini
nutritional assessment (MNA) [29], and caregiver burden
was evaluated using the Zarit Burden Interview [30].
2.3. Data analysis
Baseline mean total scores and individual domain scores
were calculated for patient- and caregiver-rated QOL when a
score was available for both members of the dyad.
To address the extent of agreement between patient
and caregiver reports, Spearman and intraclass correla-
tion coefficients (ICCs) were computed for each item at
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S. Andrieu et al. / Alzheimer’s & Dementia 12 (2016) 427-437
baseline. Correlations between total scores were also
evaluated via the Pearson correlation coefficient and the
ICC. Differences between mean patient and caregiver
scores for total QOL-AD score and individual domains
were tested using paired Student’s t-tests or nonpara-
metric Wilcoxon tests.
Baseline patient and caregiver characteristics of dyads in
agreement for the total QOL-AD score were compared with
those of dyads in which patient and caregiver scores were not
in agreement. Disagreement was separated into caregivers
who scored lower and caregivers who scored higher than
their patient. Statistical significance was assessed with
Fisher (analysis of variance) or Kruskal-Wallis tests for
quantitative variables and c2 tests for qualitative variables.
Variables with a P value of ,.2, and patient age and sex,
were entered into a multivariate multinomial logistic regres-
sion model, and a backward stepwise selection procedure
was used to identify factors that were significantly and inde-
pendently associated with disagreement (underestimation or
overestimation of patient QOL by caregivers compared with
self-ratings).
Prospective changes over time in self- and caregiver-
reported patient QOL were analyzed using a three-level
repeated measures linear-mixed regression model with
random intercept and random linear slope to account for
the within-subject correlations due to repeated observations
and correlations within clusters (centers) [31]. We took into
account all available data during follow-up (i.e., until the end
of the study or until the participant dropped out, was institu-
tionalized, or there was a change in the caregiver).
Determinants of poorer self- and caregiver-reported pa-
tient QOL at baseline were assessed using two separate
analyses. In the absence of established cut-offs, a low
level of QOL was defined as the lowest quartile, corre-
sponding to a score ,31.0 for patient reports and
27.1
for caregiver reports. First, in a bivariate analysis, baseline
differences between subjects with a poorer level of QOL
and subjects with higher QOL were tested using t-tests
for continuous variables and c2 tests for categorical vari-
ables. Variables were eligible for inclusion in the multi-
variate analysis if they were associated with a low level
of QOL in bivariate analyses with P
.20. For the multi-
variate analysis, a series of logistic regression models
were performed. Our initial hypothesis was that after tak-
ing into account the severity of the disease, caregiver
characteristics would influence the patient’s level of
QOL. Thus, for both patient- and caregiver-rated patient
QOL, we first modeled the association between a poorer
level of QOL and patient characteristics (model 1). We
then performed an analysis including only caregiver char-
acteristics (model 2). Finally, we fit a global model which
included both patient and caregiver characteristics that
were significantly associated with QOL in models 1
and 2 (model 3). We used a backward stepwise selection
procedure to retain the factors independently associated
with the level of QOL. We present adjusted odds ratios
429
(OR) and 95% confidence intervals (CIs) for significant
variables. Model fit was examined using the Hosmer-
Lemeshow goodness-of-fit test [32]. Subjects with
missing data for any of the variables included in the
models were excluded from this analysis.
All P values were based on two-sided tests and were
considered statistically significant at P , .05. Analyses
were conducted using SAS 9.1 software (SAS Institute
Inc., Cary, NC, USA).
3. Results
3.1. Population characteristics
At baseline, the 574 patients had a mean age of 79.6 years
(standard deviation [SD], 5.9) and 66.6% were women. On
average, they had been diagnosed with AD for 1.22 years
(1.44). Their mean MMSE score was 19.5 (3.9), and
76.5% were treated with cholinesterase inhibitors or mem-
antine before inclusion in the study. Most patients showed
limitations in more than two IADLs (64.2%) and 45.1%
had at least one basic ADL limitation. Behavioral disorders
were frequent in this population, with 93.8% subjects pre-
senting at least one NPI symptom (mean NPI score was
17.7 [16.4]).
A third (32.6%) of patients lived at home alone. Care-
givers were mostly female (66.2%) with a mean age of
64.1 years (13.7). They were mainly the spouse (47.2%) or
child (44.6%) of the patient.
3.2. Agreement between self and caregiver reports of
patient QOL at baseline
At baseline, 93.0% of patients (n 5 534) provided a self-
rating of their QOL, and 91.6% of caregivers (n 5 526) pro-
vided a proxy rating of their patient’s QOL. This resulted in
501 dyads (87.3%) with total scores for both self- and
caregiver-reported QOL. Caregiver reports of patient QOL
were significantly lower than patient self-reports for the total
mean QOL-AD score (31.03 [5.35] vs. 34.54 [5.29];
P , .001), and for all items except living situation
(Table 1). The mean difference between caregiver and pa-
tient total scores (3.51) was .0.5 SD (of the caregiver’s
score), which is a widely recognized definition of clinically
meaningful difference in QOL [33].
Correlations between AD patients and caregiver scores
for the individual items and for the total score were low
(Spearman/Pearson correlations between 0.10 and 0.53; in-
traclass correlations between 0.08 and 0.49; Table 1).
For total QOL-AD scores, 50% of caregivers underesti-
mated patient QOL compared with self-ratings, whereas
12% of caregivers overestimated patient QOL, and 38%
agreed with patient ratings (Fig. 1). Agreement for individ-
ual items of the QOL-AD scale ranged from 41% to 56%
of dyads, and caregivers were more likely to underestimate
rather than overestimate patient QOL, as compared with
self-ratings, for all items.
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430 S. Andrieu et al. / Alzheimer’s & Dementia 12 (2016) 427-437

Table 1
Differences between patient and caregiver ratings of patient QOL at baseline (based on complete patient-caregiver pairs for each domain)
Complete Patient score, Caregiver Difference,
Domain pairs, n (%) mean (SD) score, mean (SD) mean (SD) Correlation* ICC
y
Physical health 563 (98.1) 2.61 (0.67) 2.51 (0.75) 0.10 (0.88) 0.2647 0.2488
Energy 563 (98.1) 2.52 (0.73) 2.12 (0.80) 0.40 (0.93)z 0.2664 0.2580
Mood 563 (98.1) 2.55 (0.66) 2.34 (0.70) 0.21 (0.82)z 0.2743 0.2810
Living situation 563 (98.1) 2.97 (0.61) 2.93 (0.62) 0.04 (0.81) 0.1444 0.1239
Memory 562 (97.9) 1.84 (0.70) 1.34 (0.52) 0.51 (0.83)z 0.1003 0.0841
Family 562 (97.9) 3.18 (0.74) 2.89 (0.79) 0.28 (0.90)z 0.2678 0.3086
Marriage 521 (90.8) 2.99 (0.69) 2.71 (0.75) 0.28 (0.72)z 0.5279 0.4884
Friends 518 (90.2) 2.91 (0.71) 2.71 (0.79) 0.21 (0.87)z 0.3346 0.3075
Self as a whole 546 (95.1) 2.54 (0.67) 2.32 (0.84) 0.21 (0.91)z 0.2627 0.2633
Ability to do chores 533 (92.9) 2.66 (0.74) 2.29 (0.87) 0.37 (0.95)z 0.3081 0.2926
Ability to do things for fun 518 (90.2) 2.39 (0.79) 1.91 (0.80) 0.48 (0.93)z 0.3098 0.3140
Finances 541 (94.3) 2.71 (0.69) 2.56 (0.86) 0.14 (0.99)y 0.1707 0.1896
Life as a whole 550 (95.8) 2.64 (0.70) 2.29 (0.75) 0.35 (0.92)z 0.2059 0.1992
QOL-AD score 501 (87.3) 34.54 (5.29) 31.03 (5.35) 3.51 (5.90)z 0.3849 0.3675
Abbreviations: QOL, quality of life; SD, standard deviation; ICC, intraclass correlation coefficient; AD, Alzheimer’s disease.
*Spearman correlation coefficients for individual items; Pearson correlation coefficient for total score. P values are ,.05 for all correlation coefficients.
y
Two-sided Student paired t-test/nonparametric Wilcoxon test P , .01.
z
Two-sided Student paired t-test/nonparametric Wilcoxon test P , .001.

3.3. Factors associated with patient and caregiver
agreement
Significant differences between dyads in agreement for
the total QOL-AD score and those in which patient and care-
giver scores were not in agreement were observed for both
patient (IADL, ADL, MNA, one-leg balance, and NPI total
score and certain items) and caregiver (level of subjective
burden) characteristics (Table 2). In the multivariate multi-
nomial logistic regression model, older patient age (OR,
1.08; 95% CI, 1.02–1.14) was significantly associated with
overestimation of QOL by caregivers compared with patient
self-ratings, and NPI total score (OR, 1.02; 95% CI, 1.00–
1.04) and higher caregiver burden (low-moderate burden:
OR, 1.67; 95% CI, 1.02–2.72; moderate-severe burden:
OR, 1.99; 95% CI, 0.93–4.23) were significantly associated
with underestimation of QOL by caregivers compared with
patient self-ratings (Table 2).
3.4. Two-year changes in patient- and caregiver-reported
patient QOL
During the 2 years of follow-up, 43 patients died and 127
dropped out for other reasons. Patients who remained in the

Fig. 1. Percentage (of complete pairs) of patient-caregiver dyads in agreement or disagreement for individual items and total score of the QOL-AD scale at
baseline. Abbreviation: QOL-AD, quality of life-Alzheimer’s disease.
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Table 2
Factors associated with disagreement between self and caregiver ratings of patient quality of life for the total score of the QOL-AD scale at baseline (unadjusted and multivariate analyses)
Unadjusted analysis Multivariate (adjusted) analysis*
Agreement Patient score , caregiver Patient score . caregiver OR (95% CI), patient score OR (95% CI), patient score
Characteristics (n 5 189) score (n 5 62) score (n 5 250) P , caregiver score P . caregiver score P
Patient characteristics
Age, mean (SD), y 78.9 (5.6) 79.7 (7.2) 79.6 (5.7) .416 1.08 (1.02–1.14) .012 1.03 (0.99–1.07) .109
Gender, women, n (%) 127 (67.2) 38 (61.3) 166 (66.4) .687
Educational level .077
Elementary or no formal, n (%) 49 (25.9) 15 (24.2) 54 (21.7)
Primary school certificate, n (%) 73 (38.6) 22 (35.5) 110 (44.2)
Secondary education, n (%) 34 (18.0) 10 (16.1) 58 (23.3)
Tech/high school certificate or higher, n (%) 33 (17.5) 15 (24.2) 27 (10.8)
Years since diagnosis, mean (SD) 1.2 (1.5) 1.1 (1.3) 1.3 (1.4) .295

S. Andrieu et al. / Alzheimer’s & Dementia 12 (2016) 427-437

Use of AD medication, n (%) 150 (79.4) 43 (69.4) 192 (76.8) .269
Number of other medications, mean (SD) 4.0 (2.2) 4.0 (2.4) 4.2 (2.5) .656
MMSE score, mean (SD) 19.6 (3.9) 20.3 (4.0) 19.5 (3.9) .387
Limitation in 1 ADL, n (%) 69 (36.5) 21 (33.9) 122 (48.8) .013
Limitation in .2 IADLs, n (%) 80 (44.2) 29 (47.5) 138 (56.6) .036
MNA score
23.5, n (%) 45 (24.7) 16 (27.6) 86 (36.0) .040
NPI total score, mean (SD) 13.4 (13.4) 12.2 (13.0) 21.0 (17.6) ,.001 0.99 (0.96–1.01) .331 1.02 (1.00–1.04) .022
Living arrangements .453
Living alone, n (%) 64 (33.9) 19 (30.7) 73 (29.2)
With spouse, n (%) 107 (56.6) 36 (58.1) 139 (55.6)
Other, n (%) 18 (9.5) 7 (11.3) 38 (15.2)
Abnormal one-leg balance, n (%) 67 (35.5) 15 (24.2) 101 (40.9) .046
Autonomy allowance, n (%) 30 (16.0) 5 (8.2) 50 (20.0) .080
Caregiver characteristics
Age, mean (SD), y 64.3 (13.9) 66.7 (13.1) 64.6 (13.8) .472
Gender, women, n (%) 119 (63.0) 37 (59.7) 169 (67.6) .396
Relationship with patient, n (%) .927
Spouse 93 (49.2) 34 (54.8) 126 (50.4)
Child 80 (42.3) 23 (37.1) 106 (42.4)
Other 16 (8.5) 5 (8.1) 18 (7.2)
Subjective level of burden, ZBI, n (%) ,.001
Absent to low (score 0–20) 92 (53.8) 37 (63.8) 82 (36.3) 1 1
Low to moderate (score 21–40) 61 (35.7) 12 (20.7) 102 (45.1) 0.63 (0.29–1.38) .248 1.67 (1.02–2.72) .040
Moderate to severe (score .40) 18 (10.5) 9 (15.5) 42 (18.6) 1.79 (0.64–5.00) .269 1.99 (0.93–4.23) .075
Abbreviations: QOL, quality of life; AD, Alzheimer disease; OR, odds ratio; CI, confidence interval; SD, standard deviation; MMSE, mini-mental status examination (scores range from 0 to 30, with higher
scores indicating better function); ADL, activities of daily living (scores range from 0 to 6, with higher score indicating better function, dichotomized as 0 vs. 1 limitation); IADL, instrumental activities of daily
living (scores range from 0 to 8, with higher scores indicating better function, dichotomized as 0 vs. .2 limitations); MNA, mini nutritional assessment (score range from 0 to 30, with higher score in better
nutritional status, with a score
23.5 indicating that the patient is at risk of malnutrition or is malnourished); NPI, neuropsychiatric inventory (score range from 0 to 144, with higher score indicating more severe
symptoms); ZBI, Zarit Burden Interview (scores range from 0 to 88, with higher scores indicating higher levels of burden, scores
20 represent low-or-no burden; scores of 21–40 represent low-to-moderate
burden, and scores .40 represent moderate-to-severe burden).
NOTE. Global P values in the final model were: Patient age (P 5 .031); NPI total score (P 5 .007); and caregiver burden (P 5 .027). Bold text indicates P ,.05.
*Adjusted odds ratios are shown for variables that remained in the final multivariate multinomial model. Variables with a P value of ,.2, and patient age, sex, and level of education, were entered into the initial
model, and a backward stepwise selection procedure was used to identify factors that were significantly and independently associated with underestimation or overestimation of patient QOL by caregivers
compared with self-ratings. Variables that did not remain in the final model (following backward stepwise selection) were level of education, level of functional autonomy (IADL, ADL), nutritional status

431
(MNA), receipt of autonomy allowance, and one-leg balance.
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432 S. Andrieu et al. / Alzheimer’s & Dementia 12 (2016) 427-437

study were significantly younger and had better cognitive, 4. Discussion

functional, and neuropsychiatric scores at baseline, as
well as higher self- and caregiver-reported QOL. They
were also more likely to live with a spouse at baseline and
their caregivers reported significantly lower levels of burden
at baseline.
Mean patient self-reported QOL remained stable over
the 2 years of follow-up, (34.55 [standard error, 0.48] at
baseline and 34.50 [0.51] at 2 years, P 5 .857), whereas
mean caregiver-reported patient QOL decreased from
30.75 (0.36) to 28.64 (0.40) (P , .001; Table 3). In this
period, there was significant progression of disease
severity, as measured by cognitive, functional, and behav-
ioral measures (Table 3).
3.5. Factors associated with a low level of QOL at
baseline
Table 4 shows patient and caregiver characteristics asso-
ciated with poorer patient QOL at baseline. The results of the
multivariate logistic regression models adjusted for covari-
ates showed that several factors linked to AD severity
were associated with QOL, regardless of who (patient or
caregiver) made the assessment; having at least one basic
ADL limitation and the presence of depressive symptoms
according to the NPI were both associated with poorer
QOL. The level of subjective caregiver burden was also
independently associated with poorer QOL whether it was
self rated or caregiver rated.
Furthermore, caregivers tended to rate QOL lower for fe-
male patients compared with male patients; and for self-
reported QOL, patients cared for by their children were
more likely to declare poorer QOL than those cared for by
their spouses. The presence of apathy was independently
associated with poorer QOL for caregiver-reported scores
only. Neither the level of cognitive impairment nor the num-
ber of comorbidities was associated with patient QOL. The
use of support services or home assistance was also not asso-
ciated with the level of QOL.
We observed discrepancies between caregiver and self
ratings of patient QOL at baseline and during 2-years of
follow-up in a population of community-dwelling AD pa-
tients who were evaluated every 6 months.
In cross-sectional analyses, we found that caregivers sys-
tematically underestimated patient QOL compared with pa-
tient self-ratings for the total QOL-AD score and for most of
the domains covered by the scale. This result is consistent
with previous findings reported in the literature [13–17].
Discrepancies between patient and caregiver ratings at
baseline were not associated with patient cognitive or
functional status, nor with the patient-caregiver relationship.
However, increasing frequency and severity of neuropsychi-
atric symptoms, and a higher level of caregiver burden, were
significantly and independently associated with underesti-
mation of patient QOL by caregivers compared with self-
ratings. Caregivers may consider the effects of burden and
neuropsychiatric symptoms (which may affect them more
than the patient) on their own QOL when rating those of
the patient. Our results are consistent with recent findings
from smaller studies demonstrating an association between
caregiver psychosocial well-being (particularly level of
burden and depression) and discrepancies in patient QOL
ratings [15–19] and confirm that this association remains
even after adjustment for numerous patient characteristics
(including living alone) in a population of patients who
were exclusively community dwelling. An original finding
of our study was that increasing patient age was associated
with overestimation of patient QOL by caregivers
compared with patients, suggesting that they may take into
account age in their ratings.
During the 2 years of follow-up, there was a progressive
worsening of dementia in the AD patients included in this
study, based on cognitive, functional, and behavioral as-
sessments. Despite this worsening, mean self-rated patient
QOL did not change during this time, whereas caregiver
ratings of patient QOL significantly declined. This finding

Table 3
Two-year changes in disease severity parameters and self- and caregiver-reported patient QOL with linear mixed model (n 5 574)
Baseline, 12 mo, 24 mo, Slope*, 12 mo, Slope*, 24 mo,
Parameter mean (SE) mean (SE) mean (SE) mean (SE) mean (SE) P
Patient characteristics
Basic activities of daily living (ADL score) 5.35 (0.06) 4.79 (0.07) 4.21 (0.09) 20.56 (0.04) 21.15 (0.06) ,.001
Instrumental activities of daily living 4.26 (0.17) 3.18 (0.17) 2.40 (0.18) 21.08 (0.08) 21.86 (0.11) ,.001
(IADL/8 score)
Cognitive function (mini-mental status 19.44 (0.19) 17.90 (0.23) 15.75 (0.29) 21.54 (0.15) 23.69 (0.23) ,.001
examination score)
Behavioral disturbances (NPI score) 18.26 (1.20) 19.05 (1.17) 19.85 (1.26) 0.80 (0.39) 1.59 (0.77) .040
Self-reported QOL score 34.55 (0.48) 34.52 (0.48) 34.50 (0.51) 20.02 (0.13) 20.05 (0.25) .857
Caregiver evaluations
Subjective burden (ZBI score) 24.14 (0.92) 26.62 (0.93) 29.10 (1.06) 2.48 (0.35) 4.95 (0.70) ,.001
Caregiver-reported QOL score 30.75 (0.36) 29.70 (0.35) 28.64 (0.40) 21.05 (0.14) 22.11 (0.28) ,.001
Abbreviations: QOL, quality of life; SE, standard error; ADL, activities of daily living; IADL, instrumental activities of daily living; NPI, neuropsychiatric
inventory; ZBI, Zarit Burden Interview.
*Slope estimated from the mixed model.
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Table 4
Patient and caregiver characteristics associated with poorer self- or caregiver-reported patient QOL at baseline
Self-reported patient QOL, n 5 534 Caregiver-reported patient QOL, n 5 526
Lowest quartile Quartiles 1–3 Lowest quartile Quartiles 1–3
(QOL-AD (QOL-AD Adjusted OR (QOL-AD (QOL-AD Adjusted OR
Characteristics score ,31) score 31) (95% CI)y P score
27.1) score .27.1) (95% CI)z P
Patient characteristics
Age, mean (SD), y 79.3 (6.2) 79.5 (5.8) 79.5 (5.2) 79.4 (6.1)
Gender, women, n (%) 92 (70.2) 262 (65.0) 104 (75.9)* 244 (62.7)* 2.0 (1.2–3.4) .010
Educational level, n (%)
Elementary or no formal 27 (20.6) 97 (24.1) 37 (27.0) 92 (23.8)
Primary school certificate 60 (45.8) 163 (40.6) 56 (40.9) 155 (40.1)
Secondary education 22 (16.8) 87 (21.6) 31 (22.6) 73 (18.9)
Tech/high school certificate or higher 22 (16.8) 55 (13.7) 13 (9.5) 67 (17.3)

S. Andrieu et al. / Alzheimer’s & Dementia 12 (2016) 427-437

Time elapsed since diagnosis, mean (SD), y 1.5 (1.5)* 1.2 (1.4)* 1.5 (1.5)* 1.1 (1.4)*
Number of medications, mean (SD) 4.1 (2.2) 4.1 (2.4) 4.2 (2.4) 4.1 (2.3)
Use of AD medication, n (%) 109 (83.2)* 299 (74.2)* 108 (78.8) 297 (76.4)
MMSE score, mean (SD) 19.0 (3.8) 19.8 (3.9) 18.6 (3.9)* 19.9 (3.8)*
Limitation in at least one ADL, n (%) 74 (56.5)* 158 (39.2)* 2.0 (1.3–3.1) .002 87 (63.5)* 141 (36.3)* 2.0 (1.2–3.3) .005
Limitation in at least three IADLs, n (%) 76 (59.4)* 184 (48.9)* 84 (64.1)* 172 (46.6)*
MNA score
23.5, n (%) 44 (36.1) 118 (30.5) 49 (37.4) 107 (28.8)
History of osteoarthritis, n (%) 18 (13.7) 53 (13.2) 28 (20.4)* 47 (12.1)*
Behavioral symptoms, NPI items, n (%)
Delusions 24 (18.5) 85 (21.1) 41 (29.9)* 65 (16.8)*
Hallucinations 13 (10.0) 38 (9.4) 16 (11.7) 36 (9.3)
Agitation 50 (38.5) 161 (40.0) 69 (50.4)* 137 (35.3)*
Depression 76 (58.9)* 178 (44.3)* 1.8 (1.1–2.8) .012 91 (66.4)* 163 (42.2)* 2.3 (1.4–3.7) ,.001
Anxiety 73 (56.2) 194 (48.1) 81 (59.1)* 183 (47.2)*
Elation/euphoria 9 (6.9) 50 (12.4) 12 (8.8) 47 (12.1)
Apathy 89 (68.5)* 224 (55.7)* 108 (78.8)* 194 (50.1)* 2.3 (1.3–4.0) .003
Disinhibition 28 (21.7) 81 (20.1) 42 (30.9)* 67 (17.3)*
Irritability 56 (43.1) 181 (44.9) 75 (54.7)* 155 (40.0)*
Aberrant motor behavior 29 (22.5) 96 (23.9) 39 (28.9) 81 (20.9)
Sleep 33 (26.6) 90 (22.9) 43 (32.6)* 81 (21.5)*
Appetite and eating disorder 52 (40.3)* 112 (27.9)* 52 (38.2)* 105 (27.1)*
Living arrangements, n (%)
Living alone 46 (35.1) 122 (30.3) 45 (32.9) 122 (31.4)
With spouse 67 (51.2) 229 (56.8) 67 (48.9) 221 (56.8)
Other 18 (13.7) 52 (12.9) 25 (18.3) 46 (11.8)
Caregiver characteristics
Age, mean (SD), y 62.1 (13.2)* 65.2 (13.9)* 61.8 (14.6)* 65.6 (13.3)*
Gender, women, n (%) 90 (68.7) 258 (64.0) 92 (67.2) 250 (64.3)
Relationship with patient, n (%) * *
Spouse 53 (40.5) 209 (51.9) 1 — 56 (40.9) 205 (52.7)
Child 65 (49.6) 166 (41.2) 1.8 (1.1–2.8) .015 70 (51.1) 154 (39.6)
Other 13 (9.9) 28 (6.9) 2.0 (0.9–4.4) .111 11 (8.0) 30 (7.7)
Subjective level of burden, ZBI, n (%) * * * *
Absent to low (score 0–20) 43 (36.1) 173 (49.3) 1 — 22 (18.6) 197 (56.1) 1 —

433
(Continued )
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434 S. Andrieu et al. / Alzheimer’s & Dementia 12 (2016) 427-437

confirms results from smaller studies of trajectories of self-

,.001
,.001

Adjusted odds ratios for poorer quality of life are shown for variables that remained in the final multivariate logistic regression model following the stepwise selection procedure. For caregiver-rated

23.5 indicating that the patient is at risk of malnutrition or is malnourished); NPI, neuropsychiatric inventory (score range from 0 to 144 with higher score indicating more severe symptoms); ZBI, Zarit Burden

Adjusted odds ratios for poorer quality of life are shown for variables that remained in the final multivariate logistic regression model following the stepwise selection procedure. For self-rated QOL analyses,
Interview (scores range from 0 to 88, with higher scores indicating higher levels of burden, scores
20 represent low-or-no burden; scores of 21–40 represent low-to-moderate burden, and scores .40 represent
Abbreviations: QOL, quality of life; AD, Alzheimer disease; OR, odds ratio; CI, confidence interval; MMSE, mini-mental status examination (scores range from 0 to 30 with higher scores indicating better
function); ADL, activities of daily living (scores range from 0 to 6 with higher score indicating better function, dichotomized as 0 vs. 1 limitation); IADL, instrumental activities of daily living (scores range from
0 to 8 with higher scores indicating better function, dichotomized as 0 vs. .2 limitations); MNA, mini nutritional assessment (score range from 0 to 30, with higher score in better nutritional status, with a score

QOL, model 3 initially included patient sex, limitations in ADL, behavioral troubles (delusion, depression, and apathy), caregiver-patient relationship, and the level of subjective burden experienced by
rated QOL over time in community-dwelling patients with
P dementia [18,34–36]. It is important to understand this
increasing discrepancy between the caregiver and the
7.2 (3.6–14.4)
patient and to consider which QOL assessment must be

model 3 initially included limitations in ADL, behavioral troubles (depression, elation/euphoria), caregiver-patient relationship, and the level of subjective burden experienced by the caregiver.
Adjusted OR

3.8 (2.1–6.7)
(95% CI)z

taken into account in the evaluation of the patient’s

situation. The lack of change in patients’ self-reported
QOL over time could be caused by patients having reduced
abilities to judge their own difficulties due to increased
Caregiver-reported patient QOL, n 5 526

cognitive impairment. It has been suggested that only pa-

Quartiles 1–3

score .27.1)

tients with an MMSE score .10 can reliably report their

119 (33.9)
35 (10.0)
(QOL-AD

own QOL [10]. As only 16% of patients had MMSE scores

,10 at 2 years in our study, the lack of change in patient
self-reported QOL in our study may not be primarily due
to cognitive impairment. Another explanation could be
that AD patients adapt, through coping mechanisms, to
Lowest quartile

the new difficulties that they encounter [37], and so may

score
27.1)
59 (50.0)
37 (31.4)

not perceive any QOL decline. Some initiatives that have

(QOL-AD

attempted to better understand the meaning of QOL for pa-

tients with dementia have revealed that these patients share
a need to maintain a sense of usefulness in their lives which
could contribute to their QOL [38].
.527
.006

There may also be reasons related to the caregiver which

Patient and caregiver characteristics associated with poorer self- or caregiver-reported patient QOL at baseline (Continued )

could explain the differences in patient and caregiver ratings

of the patient’s QOL over time. For example, the caregiver’s
ratings may be influenced by their own expectations, mood,
Adjusted OR

1.2 (0.7–1.9)
2.3 (1.3–4.3)

burden of care, and their relationship with the patient

(95% CI)y

[10,39]. The decline of caregiver-rated patient QOL over

time, in contrast to patient self-ratings, could also suggest
a worsening of the caregiver’s perception of the patient’s sit-
uation. Such misunderstandings of the patient’s situation
Quartiles 1–3

may bring about mismanagement of the disease [40].

Self-reported patient QOL, n 5 534

score 31)
135 (38.5)
43 (12.3)
(QOL-AD

In terms of factors associated with patient QOL, our study

was in agreement with previous findings, suggesting that
functional impairment [20] and neuropsychiatric symptoms
[41,42] play an important role in determining patient QOL
but not cognitive status [42,43]. Patient age was not
Lowest quartile

associated with QOL in our study. This is in line with

score ,31)
46 (38.7)
30 (25.2)

some other studies, in particular those with relatively

(QOL-AD

homogeneous populations in terms of age [22]. We also

showed that patient QOL, whether rated by the patient or
by the caregiver, was independently affected by the level
of caregiver burden. Other studies have also found caregiver
burden, and caregiver depression, to be linked to patient
QOL [10], with a seemingly greater effect on caregiver-
ratings than on self-ratings, thus raising the issue of the
NOTE. Bold text indicates P ,.05.

direction of causality between caregiver burden and his/her

Moderate to severe (score .40)
Low to moderate (score 21–40)

rating of the patient’s QOL. Interventions aimed at

decreasing caregiver burden could provide benefits for the
moderate-to-severe burden).

caregiver, but also for the patient.

Among the strengths of the present study are the detailed
characterization of clinical parameters by experts in AD, us-
Characteristics

the caregiver.

ing standard outcome measures which are widely used in clin-

*P , .05.

ical trials, as well as the assessment of patient QOL from both

Table 4

the patient’s and caregiver’s point of view in a large

y

community-dwelling sample. The scale we used is well

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S. Andrieu et al. / Alzheimer’s & Dementia 12 (2016) 427-437
adapted for longitudinal studies of AD patients, despite pro-
gression of disease symptoms [42], and is not overly depen-
dent on functional status, unlike some generic QOL scales.
Consequently, most of the subjects in our study were able
to self-rate their QOL. Our patients were relatively homoge-
nous in terms of age, in contrast to numerous other studies
with much variation in subject age, which can create large dif-
ferences in QOL because individuals’ expectations vary
according to the period of life [44]. However, several limita-
tions should be considered in the interpretation of our results.
Our study was based on a sample of diagnosed AD patients
with access to health care systems, rather than a representative
sample of the general population. Thus, our results may not be
generalizable to all patients with AD. The inclusion of care-
givers took place after the diagnosis of AD, and consequently
after the beginning of their caregiving activities. Further se-
lection bias may have arisen through study dropouts due to
death or institutionalization. We can hypothesize that patients
with the most stable management were overrepresented and
so perceived QOL decreased little in our cohort even though
patients’ needs increased and caregivers were more involved
in caregiving over time.
5. Conclusion
Further analyses are required to study the temporal rela-
tionship between the level of caregiver burden and patient
QOL, identify determinants of increasing patient-caregiver
disagreement about patient QOL over time, and better assess
QOL as a valuable end point to measure the impact of future
therapeutic or nontherapeutic interventions. It remains diffi-
cult to determine which type of rating (self or proxy) of AD
patients’ QOL provides the most accurate picture. However,
given the subjective nature of QOL, it is of upmost impor-
tance to take into account the patient’s own rating.
Acknowledgments
Authors’ contributions: S.A., F.N., S.G., and B.V. contrib-
uted to the conception and design. S.G., S.A., and F.N. did
the data acquisition. S.A., C.C., N.C., Y.R., and C.A. did
the data analysis and interpretation. S.A., N.C., and A.G.
did the drafting of the article. All authors contributed to
the critical review of the article and final approval of the
version to be published. B.V. obtained the funding and
contributed to the study supervision. All authors take respon-
sibility for the entire article.
The PLASA study was supported by the French Ministry of
Health grant: PHRC 02-006-01.
The authors thank H
elene Grandjean for her helpful advice
concerning the analysis and article preparation and Clarisse
Ventelon for her initial participation in this analysis.
The authors are indebted to the investigators from the
following hospitals participating in the PLASA study:
University hospital: Angers (Dr. Berrut, Dr Barre),
Bordeaux (Pr. Rainfray, Dr Harston), Brest (Dr Gentric),
435
Grenoble (Pr. Franco, Dr. Couturier), Lille (Dr Roche, Dr
Huvent), Lyon (Pr Bonnefoy), Marseille (Dr. Michel), Mont-
pellier (Pr. Jeandel), Montpellier (Pr. Touchon, Dr. Portet, Dr
Lerouge), Nice (Dr. Brocker, Dr Guerin), Nice (Pr. Robert),
Paris (Pr Teillet, Dr Lechowski), Paris (Pr. Belmin, Dr
Pariel-Madjlessi), Paris (Pr. Rigaud, Dr Latour), Paris (Pr
Verny, Dr Marquis, Dr Brihier), Paris (Pr Legrain, Dr Gir-
ard), Reims (Pr Blanchard, Dr Kack), Rennes (Pr Jouanny,
Dr Ledu), Rouen (Pr Chassagne, Dr Levasseur), and Rouen
(Pr Hannequin, Dr Dugny). General hospital: Albi (Dr Quin-
con), Ales (Dr Peju), Annecy (Dr Picot), Bar Le Duc (Dr
Tagu, Dr De Guio), Carcassonne (Dr Tannie), Carvin (Dr
Taillez), Chamb
ery (Dr Declippeleir), Champcueil (Dr Mau-
gourd, Dr Baptiste), Dieppe (Dr Pesque), Elbeuf (Dr Simon),
Grasse (Dr Ribiere), Lannemezan (Dr Bordes), Lavaur (Dr
De Pemille), Le Havre (Dr Landrin-Dutot, Dr Olivier),
Lens (Dr Senechal, Dr Fournier), Nice (Dr Giordana), N^ımes
(Dr Strubel), Niort (Dr Chaumier), Paris (Dr Durand-
Gasselin), Pau (Dr. De La Fourniere, Dr Sauvanier—Geri-
atric Unit), Plaisir (Dr Bessey, Dr Drunat), Roubaix (Dr
Forzy), Rouen (Dr Moynot, Dr Denis), Saint Dizier (Dr Au-
bertin), S
ezanne (Dr Quignard), Valenciennes (Dr Leurs),
Vannes (Dr Le Provost), Villejuif (Dr Feteanu), and Was-
quehal (Dr. Frigard, Dr Idiri).
RESEARCH IN CONTEXT
1. Systematic review: Alzheimer’s disease (AD) pa-
tients’ quality of life (QOL) is often rated by care-
givers, but such ratings are generally divergent with
self-reports. Discrepancies may be related to pa-
tient and caregiver characteristics, but previous
studies have been limited by small sample sizes,
selected study populations, and incomprehensive
patient evaluations. Furthermore, little is known
about the natural history of QOL in AD.
2. Interpretation: In our study, caregivers consistently
underestimated AD patients’ QOL compared with
that of patients themselves, and patient self-ratings
did not change over time, despite worsening of de-
mentia symptoms, although caregiver ratings
significantly declined. Patient age and neuropsychi-
atric symptoms and caregiver burden were associated
with discrepancies.
3. Future directions: Caregiver ratings of patient QOL
may be biased. Studies using solely proxy reports
of patient QOL are to be discouraged, except in se-
vere dementia. Temporal relationships between level
of caregiver burden and patient QOL and the evolu-
tion of patient–caregiver disagreement should be
further explored.
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436 S. Andrieu et al. / Alzheimer’s & Dementia 12 (2016) 427-437

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