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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


that affects QOL [3]. Simple measures of cognitive or
Alzheimer’s disease (AD) is a chronic disease that re-
functional decline are not sufficient to address the
quires care for several years and remains one the most
complexity of AD, and QOL is a useful additional dimen-
frequent disabling diseases in aging populations [1,2]. It
sion to consider as a broader outcome measure which may
is a major cause of decreased quality of life (QOL) in
represent more “clinically significant” changes or benefits
older adults, and some studies have shown that more
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,
There are conflicts of interest to disclose. personal beliefs, and the subject’s relationship with the
The contents of this article are solely the responsibility of the authors specifics of their environment [5]. Researchers [6,7] and
and do not necessarily represent the official view of the French Ministry regulatory agencies [8] emphasize the need to take into
of Health. The study sponsor had no role in the study. account patient QOL in the evaluation of new drugs but
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-
stress the need for further validation work to use it as
42-40. an end point in clinical trials. For example, little is known
E-mail address: sandrine.andrieu@univ-tlse3.fr about the natural history of QOL in AD, the determinants
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.
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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 and patient-proxy agreement because this group under-
QOL [9]. went more comprehensive evaluations than the usual care
Caregiver ratings are frequently used as part of multidi- group (as part of the intervention). The intervention had no
mensional evaluations of AD patients, in particular to mea- significant effect on any of the primary or secondary efficacy
sure patients’ functional status and neuropsychiatric measures, including QOL.
symptoms, and caregivers may also be asked to rate patients’ The study was funded by the Ministry of Health and
QOL [4]. However, because QOL is subjective and defined was approved by the Institutional Review Board and ethics
as an individual perception, it should ideally be assessed committee of Toulouse University. Written informed con-
from the subject’s own perspective [10,11], but declining sent was obtained from all patients and their caregivers.
cognitive function makes this harder to do in AD [10]. This trial was registered in clinicaltrials.gov (identifier:
Many QOL scales have been proposed in AD [12], including NCT00480220).
the QOL-AD scale which requires both the patient and care-
giver to rate the same domains of patient QOL [10]. 2.2. Measurements
Several previous studies [13–17] have reported
Patients were evaluated every 6 months in memory
discrepancies between caregiver and self reports of AD
centers in general or university hospitals.
patients’ QOL, and some have identified factors associated
with divergent ratings [15–19]. Most studies were small
2.2.1. QOL measure
scale and targeted populations coming from particular
Patient QOL was assessed by the QOL-AD scale [10], a
settings, such as residential care homes [20], or from thera-
13-item questionnaire designed to provide patient and care-
peutic trials, thus providing a selected sample with an abnor-
giver reports of the patient’s QOL which covers various do-
mally low rate of comorbidities [21,22]. Furthermore, very
mains (physical health, energy, mood, living situation,
few studies have examined longitudinal changes in patient
memory, family, marriage, friends, self as a whole, ability
and proxy QOL reports over .1 year of follow-up [18].
to do chores, ability to do things for fun, financial situation,
The primary objective of this multicentre study was to and QOL as a whole). Items are scored on a 4-point Likert
explore discrepancies between self and caregiver reports of
scale ranging from 1 (poor) to 4 (excellent). Total scores
patient QOL in a large population of well-characterized
range from 13 to 52 with higher scores indicating better
community-dwelling AD patients at baseline and during 2
QOL. As proposed by Logsdon [10], missing items were re-
years of follow-up and to determine factors associated
placed by the mean score of the remaining items if no more
with disagreement at baseline. The secondary objective
than two items were missing; otherwise, the score was
was to assess factors explaining a low level of self- or
considered missing.
caregiver-reported patient QOL at baseline.
2.2.2. Other measures
2. Methods Sociodemographic data (age, sex, educational level, and
living arrangements), time since diagnosis of dementia as
This study includes AD patients and their primary care- declared by the caregiver, comorbidities, use of support ser-
givers enrolled in the Plan de soin et d’aide dans la maladie vices, and assistance in the home (home help, supervision,
d’Alzheimer (PLASA) study, a randomized trial that tested meal delivery service, and nursing care) were recorded using
the efficacy of a standardized care plan versus usual demen- a standardized questionnaire. Number of medications used
tia care on functional decline over 2 years of follow-up. and use of anti-AD drugs (i.e., cholinesterase inhibitors,
PLASA is described in detail elsewhere [23]. N-Methyl-D-aspartate receptor antagonists) were recorded.
Dementia severity was evaluated based on assessments of
2.1. Subjects cognition (MMSE) [25], function (activities of daily living
[ADL] [26], instrumental activities of daily living [IADL]
Briefly, a total of 1131 AD patients and their caregivers
[27]), and behavioral disorders (neuropsychiatric inventory
were recruited in a French nationwide network of 50 mem-
[NPI]) [28]. Nutritional status was evaluated with the mini
ory centers. To be included, subjects had to meet the
nutritional assessment (MNA) [29], and caregiver burden
following inclusion criteria: diagnosis of probable or
was evaluated using the Zarit Burden Interview [30].
possible AD according to the National Institute of Neurolog-
ical and Communicative Disorders and Stroke and the Alz-
2.3. Data analysis
heimer’s Disease and Related Disorders Association
criteria [24], mini-mental status examination (MMSE) [25] Baseline mean total scores and individual domain scores
score between 12 and 26, community-dwelling, looked after were calculated for patient- and caregiver-rated QOL when a
by a well-identified informal caregiver, and not participating score was available for both members of the dyad.
in any other research program. In the present analysis, we To address the extent of agreement between patient
included only the 574 patients randomly assigned to the and caregiver reports, Spearman and intraclass correla-
intervention group to be able to study the determinants of tion coefficients (ICCs) were computed for each item at
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S. Andrieu et al. / Alzheimer’s & Dementia 12 (2016) 427-437 429

baseline. Correlations between total scores were also (OR) and 95% confidence intervals (CIs) for significant
evaluated via the Pearson correlation coefficient and the variables. Model fit was examined using the Hosmer-
ICC. Differences between mean patient and caregiver Lemeshow goodness-of-fit test [32]. Subjects with
scores for total QOL-AD score and individual domains missing data for any of the variables included in the
were tested using paired Student’s t-tests or nonpara- models were excluded from this analysis.
metric Wilcoxon tests. All P values were based on two-sided tests and were
Baseline patient and caregiver characteristics of dyads in considered statistically significant at P , .05. Analyses
agreement for the total QOL-AD score were compared with were conducted using SAS 9.1 software (SAS Institute
those of dyads in which patient and caregiver scores were not Inc., Cary, NC, USA).
in agreement. Disagreement was separated into caregivers
who scored lower and caregivers who scored higher than 3. Results
their patient. Statistical significance was assessed with
Fisher (analysis of variance) or Kruskal-Wallis tests for 3.1. Population characteristics
quantitative variables and c2 tests for qualitative variables. At baseline, the 574 patients had a mean age of 79.6 years
Variables with a P value of ,.2, and patient age and sex, (standard deviation [SD], 5.9) and 66.6% were women. On
were entered into a multivariate multinomial logistic regres- average, they had been diagnosed with AD for 1.22 years
sion model, and a backward stepwise selection procedure (1.44). Their mean MMSE score was 19.5 (3.9), and
was used to identify factors that were significantly and inde- 76.5% were treated with cholinesterase inhibitors or mem-
pendently associated with disagreement (underestimation or antine before inclusion in the study. Most patients showed
overestimation of patient QOL by caregivers compared with limitations in more than two IADLs (64.2%) and 45.1%
self-ratings). had at least one basic ADL limitation. Behavioral disorders
Prospective changes over time in self- and caregiver- were frequent in this population, with 93.8% subjects pre-
reported patient QOL were analyzed using a three-level senting at least one NPI symptom (mean NPI score was
repeated measures linear-mixed regression model with 17.7 [16.4]).
random intercept and random linear slope to account for A third (32.6%) of patients lived at home alone. Care-
the within-subject correlations due to repeated observations givers were mostly female (66.2%) with a mean age of
and correlations within clusters (centers) [31]. We took into 64.1 years (13.7). They were mainly the spouse (47.2%) or
account all available data during follow-up (i.e., until the end child (44.6%) of the patient.
of the study or until the participant dropped out, was institu-
tionalized, or there was a change in the caregiver).
3.2. Agreement between self and caregiver reports of
Determinants of poorer self- and caregiver-reported pa-
patient QOL at baseline
tient QOL at baseline were assessed using two separate
analyses. In the absence of established cut-offs, a low At baseline, 93.0% of patients (n 5 534) provided a self-
level of QOL was defined as the lowest quartile, corre- rating of their QOL, and 91.6% of caregivers (n 5 526) pro-
sponding to a score ,31.0 for patient reports and 27.1 vided a proxy rating of their patient’s QOL. This resulted in
for caregiver reports. First, in a bivariate analysis, baseline 501 dyads (87.3%) with total scores for both self- and
differences between subjects with a poorer level of QOL caregiver-reported QOL. Caregiver reports of patient QOL
and subjects with higher QOL were tested using t-tests were significantly lower than patient self-reports for the total
for continuous variables and c2 tests for categorical vari- mean QOL-AD score (31.03 [5.35] vs. 34.54 [5.29];
ables. Variables were eligible for inclusion in the multi- P , .001), and for all items except living situation
variate analysis if they were associated with a low level (Table 1). The mean difference between caregiver and pa-
of QOL in bivariate analyses with P  .20. For the multi- tient total scores (3.51) was .0.5 SD (of the caregiver’s
variate analysis, a series of logistic regression models score), which is a widely recognized definition of clinically
were performed. Our initial hypothesis was that after tak- meaningful difference in QOL [33].
ing into account the severity of the disease, caregiver Correlations between AD patients and caregiver scores
characteristics would influence the patient’s level of for the individual items and for the total score were low
QOL. Thus, for both patient- and caregiver-rated patient (Spearman/Pearson correlations between 0.10 and 0.53; in-
QOL, we first modeled the association between a poorer traclass correlations between 0.08 and 0.49; Table 1).
level of QOL and patient characteristics (model 1). We For total QOL-AD scores, 50% of caregivers underesti-
then performed an analysis including only caregiver char- mated patient QOL compared with self-ratings, whereas
acteristics (model 2). Finally, we fit a global model which 12% of caregivers overestimated patient QOL, and 38%
included both patient and caregiver characteristics that agreed with patient ratings (Fig. 1). Agreement for individ-
were significantly associated with QOL in models 1 ual items of the QOL-AD scale ranged from 41% to 56%
and 2 (model 3). We used a backward stepwise selection of dyads, and caregivers were more likely to underestimate
procedure to retain the factors independently associated rather than overestimate patient QOL, as compared with
with the level of QOL. We present adjusted odds ratios 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 self-ratings, and NPI total score (OR, 1.02; 95% CI, 1.00–
agreement 1.04) and higher caregiver burden (low-moderate burden:
OR, 1.67; 95% CI, 1.02–2.72; moderate-severe burden:
Significant differences between dyads in agreement for OR, 1.99; 95% CI, 0.93–4.23) were significantly associated
the total QOL-AD score and those in which patient and care- with underestimation of QOL by caregivers compared with
giver scores were not in agreement were observed for both patient self-ratings (Table 2).
patient (IADL, ADL, MNA, one-leg balance, and NPI total
score and certain items) and caregiver (level of subjective
3.4. Two-year changes in patient- and caregiver-reported
burden) characteristics (Table 2). In the multivariate multi-
patient QOL
nomial logistic regression model, older patient age (OR,
1.08; 95% CI, 1.02–1.14) was significantly associated with During the 2 years of follow-up, 43 patients died and 127
overestimation of QOL by caregivers compared with patient 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 We observed discrepancies between caregiver and self
were also more likely to live with a spouse at baseline and ratings of patient QOL at baseline and during 2-years of
their caregivers reported significantly lower levels of burden follow-up in a population of community-dwelling AD pa-
at baseline. tients who were evaluated every 6 months.
Mean patient self-reported QOL remained stable over In cross-sectional analyses, we found that caregivers sys-
the 2 years of follow-up, (34.55 [standard error, 0.48] at tematically underestimated patient QOL compared with pa-
baseline and 34.50 [0.51] at 2 years, P 5 .857), whereas tient self-ratings for the total QOL-AD score and for most of
mean caregiver-reported patient QOL decreased from the domains covered by the scale. This result is consistent
30.75 (0.36) to 28.64 (0.40) (P , .001; Table 3). In this with previous findings reported in the literature [13–17].
period, there was significant progression of disease Discrepancies between patient and caregiver ratings at
severity, as measured by cognitive, functional, and behav- baseline were not associated with patient cognitive or
ioral measures (Table 3). 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
3.5. Factors associated with a low level of QOL at
significantly and independently associated with underesti-
baseline
mation of patient QOL by caregivers compared with self-
Table 4 shows patient and caregiver characteristics asso- ratings. Caregivers may consider the effects of burden and
ciated with poorer patient QOL at baseline. The results of the neuropsychiatric symptoms (which may affect them more
multivariate logistic regression models adjusted for covari- than the patient) on their own QOL when rating those of
ates showed that several factors linked to AD severity the patient. Our results are consistent with recent findings
were associated with QOL, regardless of who (patient or from smaller studies demonstrating an association between
caregiver) made the assessment; having at least one basic caregiver psychosocial well-being (particularly level of
ADL limitation and the presence of depressive symptoms burden and depression) and discrepancies in patient QOL
according to the NPI were both associated with poorer ratings [15–19] and confirm that this association remains
QOL. The level of subjective caregiver burden was also even after adjustment for numerous patient characteristics
independently associated with poorer QOL whether it was (including living alone) in a population of patients who
self rated or caregiver rated. were exclusively community dwelling. An original finding
Furthermore, caregivers tended to rate QOL lower for fe- of our study was that increasing patient age was associated
male patients compared with male patients; and for self- with overestimation of patient QOL by caregivers
reported QOL, patients cared for by their children were compared with patients, suggesting that they may take into
more likely to declare poorer QOL than those cared for by account age in their ratings.
their spouses. The presence of apathy was independently During the 2 years of follow-up, there was a progressive
associated with poorer QOL for caregiver-reported scores worsening of dementia in the AD patients included in this
only. Neither the level of cognitive impairment nor the num- study, based on cognitive, functional, and behavioral as-
ber of comorbidities was associated with patient QOL. The sessments. Despite this worsening, mean self-rated patient
use of support services or home assistance was also not asso- QOL did not change during this time, whereas caregiver
ciated with the level of QOL. 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) 427-437 435

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

References [19] Zhao H, Novella JL, Drame M, Mahmoudi R, Barbe C, di Pollina L,


et al. Factors associated with caregivers’ underestimation of quality
of life in patients with Alzheimer’s disease. Dement Geriatr Cogn Dis-
[1] Aguero-Torres H, Fratiglioni L, Guo Z, Viitanen M, von Strauss E,
ord 2012;33:11–7.
Winblad B. Dementia is the major cause of functional dependence
[20] Hoe J, Hancock G, Livingston G, Orrell M. Quality of life of people
in the elderly: 3-year follow-up data from a population-based study.
with dementia in residential care homes. Br J Psychiatry 2006;
Am J Public Health 1998;88:1452–6.
188:460–4.
[2] Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M,
[21] Aisen PS, Schafer KA, Grundman M, Pfeiffer E, Sano M, Davis KL,
et al. Global prevalence of dementia: A Delphi consensus study. Lan-
et al. Effects of rofecoxib or naproxen vs placebo on Alzheimer disease
cet 2005;366:2112–7.
progression: A randomized controlled trial. JAMA 2003;289:2819–26.
[3] Netuveli G, Wiggins RD, Hildon Z, Montgomery SM, Blane D. Func-
[22] Wlodarczyk JH, Brodaty H, Hawthorne G. The relationship between
tional limitation in long standing illness and quality of life: Evidence
quality of life, mini-mental state examination, and the instrumental ac-
from a national survey. BMJ 2005;331:1382–3.
tivities of daily living in patients with Alzheimer’s disease. Arch Ger-
[4] Banerjee S, Smith SC, Lamping DL, Harwood RH, Foley B, Smith P,
ontol Geriatr 2004;39:25–33.
et al. Quality of life in dementia: More than just cognition. An analysis
[23] Nourhashemi F, Andrieu S, Gillette-Guyonnet S, Giraudeau B,
of associations with quality of life in dementia. J Neurol Neurosurg
Cantet C, Coley N, et al. Effectiveness of a specific care plan in pa-
Psychiatry 2006;77:146–8.
tients with Alzheimer’s disease: Cluster randomised trial (PLASA
[5] WHO World Organization Group. Development of the WHOQOL:
study). BMJ 2010;340:c2466.
Rationale and current status. Int J Ment Health 1994;23:24–56.
[24] McKhann G, Drachman D, Folstein M, Katzman R, Price D,
[6] Vellas B, Andrieu S, Sampaio C, Coley N, Wilcock G. Endpoints for
Stadlan EM. Clinical diagnosis of Alzheimer’s disease: Report of
trials in Alzheimer’s disease: A European task force consensus. Lancet
the NINCDS-ADRDA Work Group under the auspices of Department
Neurol 2008;7:436–50.
of Health and Human Services Task Force on Alzheimer’s Disease.
[7] Trinh NH, Hoblyn J, Mohanty S, Yaffe K. Efficacy of cholinesterase
Neurology 1984;34:939–44.
inhibitors in the treatment of neuropsychiatric symptoms and func-
[25] Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A prac-
tional impairment in Alzheimer disease: A meta-analysis. JAMA
tical method for grading the cognitive state of patients for the clinician.
2003;289:210–6.
J Psychiatr Res 1975;12:189–98.
[8] EMEA. European Medicines Agency. Committee for Medicinal Prod-
[26] Katz S, Ford AB, Moskowitz RW, Jackson BA, Jaffe MW. Studies of
ucts for Human Use (CHMP) draft guideline on medicinal products for
illness in the aged. The index of ADL: A standardized measure of bio-
the treatment of Alzheimer’s disease and other dementias. Doc.
logical and psychosocial function. JAMA 1963;185:914–9.
Ref. CPMP/EWP/553/95 Rev. 1 2007; Available from: http://www.
[27] Lawton MP, Brody EM. Assessment of older people: Self-maintaining
ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/
and instrumental activities of daily living. Gerontologist 1969;
2009/09/WC500003565.pdf.
9:179–86.
[9] Banerjee S. Commentary on “Health economics and the value of ther-
[28] Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA,
apy in Alzheimer’s disease.” Quality of life in dementia: Development
Gornbein J. The neuropsychiatric inventory: Comprehensive assess-
and use of a disease-specific measure of health-related quality of life in
ment of psychopathology in dementia. Neurology 1994;44:2308–14.
dementia. Alzheimers Dement 2007;3:166–71.
[29] Guigoz Y, Vellas B, Garry PJ. Assessing the nutritional status of the
[10] Logsdon RG, Gibbons LE, McCurry SM, Teri L. Assessing quality of
elderly: The mini nutritional assessment as part of the geriatric evalu-
life in older adults with cognitive impairment. Psychosom Med 2002;
ation. Nutr Rev 1996;54(1 Pt 2):S59–65.
64:510–9.
[30] Zarit SH, Reever KE, Bach-Peterson J. Relatives of the impaired
[11] Scholzel-Dorenbos CJ, Ettema TP, Bos J, Boelens-van der Knoop E,
elderly: Correlates of feelings of burden. Gerontologist 1980;
Gerritsen DL, Hoogeveen F, et al. Evaluating the outcome of interven-
20:649–55.
tions on quality of life in dementia: Selection of the appropriate scale.
[31] Singer JD. Using SAS PROC MIXED to fit multilevel models, hierar-
Int J Geriatr Psychiatry 2007;22:511–9.
chical models, and individual growth models. J Educ Behav Stat 1998;
[12] Ready RE, Ott BR. Quality of life measures for dementia. Health Qual
23:323–55.
Life Outcomes 2003;1:11.
[32] Hosmer DW, Lemeshow S. Applied logistic regression. 2nd ed. New
[13] Jonsson L, Andreasen N, Kilander L, Soininen H, Waldemar G,
York, NY: John Wiley & Sons; 2000. 118.
Nygaard H, et al. Patient- and proxy-reported utility in Alzheimer dis-
[33] Norman GR, Sloan JA, Wyrwich KW. Interpretation of changes in
ease using the EuroQoL. Alzheimer Dis Assoc Disord 2006;20:49–55.
health-related quality of life: The remarkable universality of half a
[14] Yasuda N, Zimmerman S, Hawkes WG, Gruber-Baldini AL, Hebel JR,
standard deviation. Med Care 2003;41:582–92.
Magaziner J. Concordance of proxy-perceived change and measured
[34] Bosboom PR, Alfonso H, Almeida OP. Determining the predictors of
change in multiple domains of function in older persons. J Am Geriatr
change in quality of life self-ratings and carer-ratings for community-
Soc 2004;52:1157–62.
dwelling people with Alzheimer disease. Alzheimer Dis Assoc Disord
[15] Schulz R, Cook TB, Beach SR, Lingler JH, Martire LM,
2013;27:363–71.
Monin JK, et al. Magnitude and causes of bias among family care-
[35] Clare L, Woods RT, Nelis SM, Martyr A, Markova IS, Roth I, et al.
givers rating Alzheimer disease patients. Am J Geriatr Psychiatry
Trajectories of quality of life in early-stage dementia: Individual var-
2013;21:14–25.
iations and predictors of change. Int J Geriatr Psychiatry 2014;
[16] Zucchella C, Bartolo M, Bernini S, Picascia M, Sinforiani E. Quality
29:616–23.
of life in Alzheimer disease: A comparison of patients’ and caregivers’
[36] Tatsumi H, Nakaaki S, Torii K, Shinagawa Y, Watanabe N, Murata Y,
points of view. Alzheimer Dis Assoc Disord 2015;29:50–4.
et al. Neuropsychiatric symptoms predict change in quality of life of
[17] Huang HL, Weng LC, Tsai YH, Chiu YC, Chen KH, Huang CC, et al.
Alzheimer disease patients: A two-year follow-up study. Psychiatry
Predictors of self- and caregiver-rated quality of life for people with
Clin Neurosci 2009;63:374–84.
dementia living in the community and in nursing homes in northern
[37] Pearlin LI, Schooler C. The structure of coping. J Health Soc Behav
Taiwan. Int Psychogeriatr 2015;27:825–36.
1978;19:2–21.
[18] Conde-Sala JL, Turro-Garriga O, Garre-Olmo J, Vilalta-Franch J, Lo-
[38] Whitehouse PJ, George D. Banking on stories for healthier cognitive
pez-Pousa S. Discrepancies regarding the quality of life of patients
ageing. Lancet 2009;373:1166–7.
with Alzheimer’s disease: A three-year longitudinal study. J Alz-
[39] Scholzel-Dorenbos CJ, van der Steen MJ, Engels LK, Olde
heimers Dis 2014;39:511–25.
Rikkert MG. Assessment of quality of life as outcome in dementia
Documentodescargadodesdehttp://articlesservice.es/AsofarmaNeurociencias/AsofarmaNeurocienciasel24-04-2016.Copiaparausopersonal, seprohbela transmisin de este documento por cualquier m

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

and MCI intervention trials: A systematic review. Alzheimer Dis As- [42] Selwood A, Thorgrimsen L, Orrell M. Quality of life in dementia—A
soc Disord 2007;21:172–8. one-year follow-up study. Int J Geriatr Psychiatry 2005;20:232–7.
[40] Grand A, Grand-Filaire A, Bocquet H, Clement S. Caregiver stress: A [43] Gow AJ, Whiteman MC, Pattie A, Whalley L, Starr J, Deary IJ. Life-
failed negotiation? A qualitative study in South West France. Int J Ag- time intellectual function and satisfaction with life in old age: Longi-
ing Hum Dev 1999;49:179–95. tudinal cohort study. BMJ 2005;331:141–2.
[41] Wetzels RB, Zuidema SU, de Jonghe JF, Verhey FR, Koopmans RT. [44] Hoe J, Katona C, Roch B, Livingston G. Use of the QOL-AD for
Determinants of quality of life in nursing home residents with demen- measuring quality of life in people with severe dementia—the
tia. Dement Geriatr Cogn Disord 2010;29:189–97. LASER-AD study. Age Ageing 2005;34:130–5.