Dement Geriatr Cogn Disord 2014;37:366–375 DOI: 10.1159/000350800 Accepted: March 12, 2013 Published online: February 18, 2014
© 2014 S. Karger AG, Basel 1420–8008/14/0376–0366$39.50/0 www.karger.com/dem
Original Research Article
Diagnostic Validity of the Alzheimer’s Disease Functional Assessment and Change Scale in Mild Cognitive Impairment and Mild to Moderate Alzheimer’s Disease R.M. Manero a, b M. Casals-Coll c G. Sánchez-Benavides c O.N. Rodríguez-de los Reyes m M. Aguilar f D. Badenes f J.L. Molinuevo d A. Robles g M.S. Barquero h C. Antúnez j C. Martínez-Parra k A. Frank-García i M. Fernández l R. Blesa e J. Peña-Casanova a, c for the NEURONORMA Study Team a
Service of Neurology and Section of Behavioral Neurology and Dementias, Hospital del Mar, b Universitat Autònoma de Barcelona, c Behavioral Neurology Group, Institut Hospital del Mar d’Investigació Mèdica, d Service of Neurology, Hospital Clínic, and e Service of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, f Service of Neurology, Hospital Mútua de Terrassa, Terrassa, g Service of Neurology, Hospital Clínico Universitario, Santiago de Compostela, h Service of Neurology, Hospital Clínico San Carlos, and i Department of Neurology, Hospital Universitario La Paz, Madrid, j Service of Neurology, Hospital Virgen Arrixaca, Murcia, k Service of Neurology, Hospital Virgen Macarena, Sevilla, and l Service of Neurology, Hospital de Cruces, Bilbao, Spain; m Service of Psychiatry, Hospital Regional de Alta Especialidad de Ciudad Victoria, Ciudad Victoria, Mexico
Key Words Alzheimer’s disease · Mild cognitive impairment · Activities of daily living · Functional assessment · Reliability · Validity Abstract Background: The Alzheimer’s Disease Functional Assessment and Change Scale (ADFACS) is a functional assessment instrument widely used in clinical research. Aims: To test the diagnostic and concurrent validity of the Spanish version of this scale and to describe the functional deficit pattern for mild cognitive impairment (MCI) and Alzheimer’s disease (AD) dementia. Methods: The ADFACS, the Interview for Deterioration in Daily Living Activities in Dementia (IDDD), and the Mini Mental State Examination (MMSE) were administered to 146 control subjects (CS) and 165 patients (67 MCI and 98 AD). Nonparametric tests were used to compare the diagnostic groups. Cronbach’s α and correlations with the MMSE and the IDDD
R.M.M. and M.C.-C. have contributed equally to this work. Jordi Peña-Casanova Section of Behavioral Neurology and Dementias, Hospital del Mar IMIM, Biomedical Research Park Building Carrer Dr. Aiguader 88, ES–08003 Barcelona (Spain) E-Mail jpcasanova @ parcdesalutmar.cat
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© 2014 S. Karger AG, Basel www.karger.com/dem
Manero et al.: Diagnostic Validity of the Alzheimer’s Disease Functional Assessment and Change Scale in Mild Cognitive Impairment and Mild to Moderate Alzheimer’s Disease
were calculated. Sensitivity, specificity and predictive values were studied. Results: The ADFACS had a high internal consistency (α = 0.95). Three cutoff points of 1, 4, and 17 were provided to separate CS and MCI patients, MCI and mild AD patients, and mild AD and moderate AD patients, respectively. The ADFACS strongly correlated with functional (IDDD, 0.927) and cognitive (MMSE, 0.747) measures. A similar pattern of dysfunction, but in different grades, was found for the MCI and AD groups. Conclusion: The ADFACS is a reliable, valid, and sensitive instrument to assess functional abilities; it is useful in dementia assessment for elderly populations. © 2013 S. Karger AG, Basel
Introduction
Dementia is a growing health concern in many aging societies as the number of people who suffer from it continues to rise. The most prevalent pathology that causes dementia is Alzheimer’s disease (AD). According to Alzheimer’s Disease International, an evidence-based Delphi consensus on dementia estimated that there were 24.3 million people with dementia in 2001, and the number of people affected is expected to double every 20 years [1]. As a result, there is a strongly growing interest in the diagnosis of dementia. AD diagnosis is associated with a progressive impairment of cognition and social or occupational functioning [2]. Thus, cognitive disorders arising in the course of the disease result in limitations in the patient’s ability to carry out activities of daily living (ADL). Complex tasks such as telephoning, handling medications or housekeeping, so-called instrumental activities of daily living (IADL), are the first to be affected. Some authors have considered, since the 1990s, that a group of advanced ADL, related with control of social and physical environments, should be set apart from IADL [3]. The advanced ADL would be affected before the IADL. Basic activities of daily living (BADL), which include grooming, feeding, and toileting, become affected in later stages of the disease. As dementia progresses, the patient becomes increasingly dependent on help from others. The establishment of diagnostic criteria for the intermediate stage between normal aging and dementia, so-called mild cognitive impairment (MCI), is controversial. Initial diagnostic criteria required that functional abilities remain intact in MCI in order to distinguish MCI from dementia [4]. However, ADL deteriorate while progressing from MCI to dementia, and recent data suggest that subjects with MCI show impaired IADL but not BADL [5]. There are several scales designed to assess functional abilities in dementia. They can be administered to the subject or an external source. The IADL scale of Lawton and Brody [6], the Blessed Dementia Rating Scale [7], and the Interview for Deterioration of Daily Living Activities in Dementia (IDDD) [8] are commonly used tools in moderate to severe stages of dementia. Other scales such as the Disability Assessment for Dementia [9], the Functional Assessment Questionnaire [10], and the Bayer Activities of Daily Living Scale [11] include items about advanced ADL which can be useful in early cognitive impairment diagnosis [12]. The Alzheimer’s Disease Functional Assessment and Change Scale (ADFACS) [13] is a 16-item instrument based on IADL and BADL scales widely used in clinical research [14, 15], which have been modified to reflect functional impairment in mild to moderate AD. The 6 BADL and 5 of the 10 IADL items were directly adapted from the scale described by Lawton and Brody [6], which included instrumental items from the IADL scale [16, 17] and basic items from the Physical Self-Maintenance Scale [18]. The remaining IADL items were adapted from the following tools: the ADL inventory of the AD Cooperative Study [19], the Clinical Dementia Rating scale [20, 21], and the Dementia Rating Scale [7]. The ADFACS assessment is informant-based.
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Dement Geriatr Cogn Disord 2014;37:366–375 DOI: 10.1159/000350800
© 2014 S. Karger AG, Basel www.karger.com/dem
Manero et al.: Diagnostic Validity of the Alzheimer’s Disease Functional Assessment and Change Scale in Mild Cognitive Impairment and Mild to Moderate Alzheimer’s Disease
Literature on the ADFACS validation is, at present, nonexistent. As a result, the present paper proposes the following 3 aims: (a) to test the diagnostic validity of the ADFACS by establishing the sensitivity and specificity of cutoff points between healthy controls and MCI patients, MCI and mild AD patients, and mild AD and moderate AD patients for clinical purposes; (b) to test the concurrent validity of this scale in a Spanish clinical population by determining its relationship with the Mini Mental State Examination (MMSE) [22] and another functional measure, i.e. the IDDD [8], and (c) to describe the functional deficit pattern for each diagnostic group. Materials and Methods Subjects A total of 311 subjects (178 females and 133 males) were recruited and assessed, with a mean age of 73.4 years (SD 7.0) and a mean education of 8.1 years (SD 4.9). Participants were classified by diagnostic group: 146 control subjects (CS), 67 MCI patients and 98 AD patients. In addition, subjects were classified using the Global Deterioration Scale (GDS) [23], which is an instrument utilized to grade the severity in dementia. The GDS describes 7 stages from healthiness to severe dementia. Our CS can then be classified into GDS stages 1 or 2, which describe healthy people with no objective cognitive deterioration and either with or without subjective complaints. Stage 3 of the GDS is usually considered equivalent to MCI, GDS stage 4 is for mild dementia, 5 for moderate dementia, 6 for severe dementia and 7 for very severe dementia. In our study, AD subjects are classified as having mild or moderate dementia (GDS stages 4 and 5). Study controls were identified as normal based on criteria established by the NEURONORMA project [24], a study that provided norms for neuropsychological tests to be applied in subjects over 49 years old. Recruitment criteria, sociodemographics, and characteristics of the control sample have been reported in a previous paper [24]. Baseline enrolment took place in 2004–2007, from urban sources. A matching process was employed to balance the diagnostic groups in terms of age and education. One hundred forty-six individuals were selected from the 356 subjects making up the NEURONORMA control sample. Patients were diagnosed with MCI following IPA-WHO (International Psychogeriatric AssociationWorld Health Organization) [25] criteria: (a) no age restriction (in our project, the subjects had to be at least 50 years old); (b) decline of cognitive capacity affirmed by the patient and/or informant; (c) gradual decline and of a minimal duration of 6 months; (d) any of the following cognitive functions could be affected: memory and learning, attention and concentration, thinking, language or visuospatial functioning; (e) neuropsychological performance more than 1 standard deviation below the age and education norms in well-standardized neuropsychological tests; (f) the disorder does not have sufficient intensity to establish the diagnosis of dementia, nor does delirium exist; (g) there are no cerebral, systemic, or psychiatric processes that could explain the symptoms, and (h) a score >21 on the Spanish version of the MMSE [26] adjusted for age and education, and a GDS [23] score of 3. In our study, the test selected as neuropsychological test was the abbreviated Barcelona Test [27], which assesses each of the cognitive functions that can be affected in MCI, such as memory and learning, attention and concentration, thinking, language, or visuospatial functioning. The AD group was composed following the criteria of the NINCDS/ADRDA [28] and the Diagnostic and Statistical Manual for Mental Disorders, ed 4 [29]. MCI and AD recruitment was enhanced with patients who visited the participant centers. AD subjects were assigned by clinical status at GDS 4 (n = 68) and GDS 5 (n = 30). GDS 4 individuals were considered to belong to the mild AD group, and GDS 5 ones to the moderate AD group. Figure 1 shows the sample flow diagram. All participants were required to have an informant who knew them well and could answer questions about their cognition, function, and health. The relationships of the informants to the participants were spouse or significant other, adult offspring, other family member, or friend. The participants did not receive financial reimbursement or any other compensation for their participation. Ethical approval for the study was granted by the Research Ethics Committee of the Municipal Institute of Medical Care of Barcelona, Spain, and by the various participating centers. The study was conducted in accordance with the Declaration of Helsinki [30] and its subsequent amendments, and the European Union regulations concerning medical research.
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© 2014 S. Karger AG, Basel www.karger.com/dem
Manero et al.: Diagnostic Validity of the Alzheimer’s Disease Functional Assessment and Change Scale in Mild Cognitive Impairment and Mild to Moderate Alzheimer’s Disease
Neuronorma sample (n = 535)
Normative sample
Pathological sample (n = 179) Enrolment
CS (n = 356)
MCI (n = 79)
AD (n = 100)
Validation sample (n = 328) Included (matching enrolment) CS (n = 149)
MCI (n = 79)
AD (n = 100)
Not included (n = 207)
ADFACS validation sample (n = 311) Completing ADFACS and analyzed CS (n = 146)
MCI (n = 67)
AD (n = 98)
Missing (n = 17)
Fig. 1. Sample flow diagram.
Study Scale The ADFACS [13] is a specific scale for the functional assessment of people with AD. It is based on an interview with an informant with day-to-day knowledge about the subject and asks about the ability to perform BADL and IADL. A number of specific descriptions of performance levels for each item is offered, and the caregiver is asked to identify the one that most accurately describes the patient’s performance during the 3 weeks prior to the interview. The scale consists of 16 items for the assessment of ADL, i.e. 6 items for BADL (toileting, feeding, dressing, personal hygiene and grooming, personal ambulation, and bathing), and 10 items for IADL (ability to use the telephone, performing household tasks, using household appliances, handling money, shopping, preparing food, ability to get around, ability to perform leisure activities, handling personal mail, and ability to understand situations or explanations). The ADFACS offers two partial scores (for IADL and BADL) and a total one. IADL items are scored from 0 to 4: 0 = no impairment, 1 = mild impairment, 2 = moderate impairment, 3 = severe impairment and 4 = nonassessable, with a range from 0 to 30. BADL items are scored from 0 to 5: 0 = no impairment, 1 = mild impairment, 2 = moderate impairment, 3 = severe impairment, 4 = very severe impairment and 5 = nonassessable, with a range from 0 to 24. In each part, the ‘nonassessable’ answer is substituted by an estimation from the average of the responded items. The total score (IADL + BADL) ranges from 0 to 54 (from best to worst). The score reflects the cognitive incapacity to carry out the activities. The ADFACS was originally in English. It was later translated into Spanish within a sequence of forward and backward translations as described in previous multicenter studies [31–33].
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3.0
CS MCI Mild AD
2.5
Moderate AD
2.0
1.5
1.0
0.5
0 1
2
3
4
5
6
7
8
9
10
1
2
3
CS
0.02
0.01
0
0.04
0.01
MCI
0.15
0.07
0.13
Mild AD
0.71
0.92
Mod. AD
1.56
CS/MCI
* * * * * *
5
6
0
0.01
0.01
0
0
0
0
0
0.39
0.17
0.08
0.22
0.20
0.22
0.18
0
0
0
0
0
0
0
0.01
0.84
1.79
1.17
0.89
1.19
1.15
1.25
0.78
0.01
0.04
0
0.12
0.13
0.12
0.04
1.83
2.05
2.77
2.54
1.95
1.97
1.92
2.34
1.67
0.40
* * * * *
* * * * * *
* * * * * *
* * * * * *
* * * * * *
* * * * * *
* * * * * *
* * * * * *
* * * * * *
0.47
0.93
1.03
0.37
1.03
*
*
* *
* *
*
* *
* *
* *
* * * * *
IADL
CS/mild AD CS/mod. AD MCI/mild AD MCI/mod. AD Mild AD/mod. AD
4 BADL
*
* *
Fig. 2. Means in each ADFACS item distributed according to the diagnostic groups. The scale consists of 16 items for the assessment of ADL; i.e. 10 items for IADL [ability to use the telephone (1), performing household tasks (2), using household appliances (3), handling money (4), shopping (5), preparing food (6), ability to get around (7), ability to perform leisure activities (8), handling personal mail (9), and ability to understand situations or explanations (10)], and 6 items for BADL [toileting (1), feeding (2), dressing (3), personal hygiene and grooming (4), personal ambulation (5), and bathing (6)]. * = Significant difference in post hoc pairwise comparison after correction for multiple comparisons (p < 0.0083).
Data Management and Statistical Analysis Basic descriptive analyses included the mean and standard deviation of sociodemographic variables and the ADFACS score of each diagnostic group (CS, MCI, mild AD, and moderate AD). ANOVA and a post hoc analysis (Scheffé) were conducted to examine group differences in the sociodemographic variables of interest. χ2 tests were applied to study differences in gender among the groups. Due to the nonnormal distribution of the data group differences in the ADFACS total score, IADL and BADL subscores and item-by-item comparisons were analyzed by means of nonparametric tests (Kruskal-Wallis). Subsequent Mann-Whitney U tests were applied for pairwise comparisons, with the application of a Bonferroni correction for multiple comparisons to adjust for the increase in the alpha error (an initial p value threshold of significance was set to 0.05 and then divided by the number of comparisons 0.05/6 = 0.0083). In all other statistical analyses, the significance threshold was set at 0.05. Scale reliability was determined by using Cronbach’s α index in order to obtain a measure of internal consistency. Spearman’s correlation coefficient was used to assess the ADFACS concurrent validity by determining its relationship with the MMSE and the IDDD. To determine the diagnostic validity, the following parameters were calculated: sensitivity, specificity, positive and negative predictive values, and the receiver operating characteristic curve analysis for optimal cutoff point attainment. A larger area under the curve indicated improved diagnostic performance. The data analysis was performed using SPSS v.12.0 and R statistical software v.2.7.
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Table 1. Sociodemographic characteristics of the sample
Groups
n
Mean age ± SD, years
Mean education ± SD, Females, years %
CS MCI AD
146 67 98
72.70 ± 6.90 72.93 ± 6.36 74.67 ± 7.57
8.52 ± 5.15 7.96 ± 4.64 7.68 ± 4.68
54.1 53.7 64.3
Total
311
73.37 ± 7.04
8.14 ± 4.90
57.2
There were no differences in sociodemographic variables among the groups (p > 0.05).
Table 2. Mean scores (and standard deviation) of the ADFACS, IDDD and MMSE
CS
MCI
Mild AD
Moderate AD
Significant differences in pairwise comparison
ADFACS Total IADL BADL
0.10 (0.40) 0.10 (0.40) 0.00 (0.00)
1.85 (1.93) 1.82 (1.94) 0.03 (0.17)
11.16 (5.23) 10.70 (4.84) 0.47 (1.08)
24.83 (6.53) 20.60 (4.63) 4.23 (3.34)
all pairs all pairs all pairs except CS-MCI, CS-mild AD and MCI-mild AD
IDDD Total CA PC
33.26 (0.76) 17.25 (0.72) 16.00 (0.08)
35.72 (2.40) 17.25 (0.72) 16.09 (0.38)
44.77 (6.23) 28.19 (5.80) 16.58 (1.07)
59.00 (10.17) 37.58 (4.90) 21.41 (6.17)
MMSE
28.31 (1.71)
25.60 (2.22)
21.15 (4.12)
18.20 (3.09)
all pairs all pairs all pairs except CS-MCI, CS-mild AD and MCI-mild AD all pairs
CA = Complex activities; PC = personal care.
Results
Table 1 shows sociodemographic characteristics of the sample. All groups were similar in age and education (ANOVA tests: p > 0.05). Besides this, correlational results between these sociodemographic variables and the ADFACS scores were very weak (r < 0.2). Females made up approximately 57% of the sample, and there were no differences among the groups in the proportion of males/females (p > 0.05). With respect to the number of subjects, the groups were heterogeneous; the CS group was the largest (146 subjects) and the moderate AD the smallest (30 subjects). Table 2 shows mean scores and standard deviations for the scales for each group. The means of each ADFACS item, distributed according to the diagnostic groups, and the results of pairwise analyses are shown in figure 2. Significant differences among the diagnostic groups were observed when a mean comparison was calculated to separately analyze the ADFACS total score, the IADL score and the BADL score. When a pairwise comparison was applied, significant differences were found amongst all groups in the ADFACS total score (p < 0.0001), and IADL score (p < 0.0001). Regarding the BADL score, all differences were significant (p < 0.0001) with the exception of 3 cases: CS-MCI (p = 0.991), CS-mild AD (p = 0.052), and MCI-mild AD (p = 0.172). The same pattern was observed in IDDD analysis (table 2). A good internal reliability was found with a Cronbach’s α of 0.95. Spearman correlation analysis showed a very strong relationship between the scores of the ADFACS and
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DOI: 10.1159/000350800
Manero et al.: Diagnostic Validity of the Alzheimer’s Disease Functional Assessment and Change Scale in Mild Cognitive Impairment and Mild to Moderate Alzheimer’s Disease
Table 3. Cutoff points, sensitivity and specificity values and PPV and NPV Cutoff Sen Spe J points
PPV at different prevalence rates
NPV at different prevalence rates
5% 10% 15% 20% 25% 30% 40% 50%
5% 10% 15% 20% 25% 30% 40% 50%
CS-MCI
1
0.70 0.92 0.63 0.33 0.51 0.62 0.70 0.76 0.80 0.86 0.90
0.98 0.96 0.95 0.92 0.90 0.88 0.82 0.75
MCI-mild AD
4
0.93 0.86 0.80 0.27 0.43 0.55 0.63 0.70 0.75 0.92 0.90
0.99 0.99 0.98 0.98 0.97 0.96 0.95 0.92
Mild ADmoderate AD
17
0.90 0.85 0.75 0.24 0.40 0.52 0.60 0.67 0.72 0.80 0.86
0.99 0.99 0.98 0.97 0.96 0.95 0.93 0.90
1.0
1.0
0.8
0.8
0.8
0.6
0.6
0.6
0.4
0.4 0.2
0.2 0
Sensitivity
1.0
Sensitivity
Sensitivity
PPV = Positive predictive value; NPV = negative predictive value; Sen = sensitivity; Spe = specificity; J = Youden index.
0
0.2 0.4 0.6 0.8 1 – specificity
a
0
1.0
b
0.4 0.2
0
0.2 0.4 0.6 0.8 1 – specificity
0
1.0
0
0.2 0.4 0.6 0.8 1 – specificity
1.0
c
Fig. 3. Receiver operating characteristic curves for CS-MCI (a), MCI-mild AD (b), and mild AD-moderate AD (c) discrimination.
the IDDD (r = 0.927). When a separate analysis of BADL and IDDD personal care and IADL and IDDD complex activities was made between the two scales, strong relationships were also found (r = 0.746 and 0.926, respectively). The scores of the ADFACS and MMSE also showed a strong relationship between each other (r = –0.747). Figure 3 illustrates receiver operating characteristic curves plotted for CS/MCI, MCI/mild AD, and mild AD/moderate AD discrimination. The areas under the curve obtained were 0.826, 0.960, and 0.956, respectively. Table 3 presents cutoff points, their associated sensitivity and specificity values, and positive and negative predictive values for different prevalence rates. Cutoff values were selected on the basis of the Youden index. Discussion
This study describes the performance of a group of MCI and AD patients and a control sample on the ADFACS, and presents data concerning the diagnostic and concurrent validity of this functional scale for clinical use. The results showed a good diagnostic validity to identify the consecutive AD stages and strong correlations with the IDDD scale and the MMSE test demonstrating a satisfactory concurrent validity.
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Dement Geriatr Cogn Disord 2014;37:366–375 DOI: 10.1159/000350800
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Manero et al.: Diagnostic Validity of the Alzheimer’s Disease Functional Assessment and Change Scale in Mild Cognitive Impairment and Mild to Moderate Alzheimer’s Disease
ADFACS total scores and IADL scores observed in the diagnostic groups were distributed in the expected way: the order of the means was CS > MCI > mild AD > moderate AD; all the groups were statistically different. BADL mean scores only differed in the pathologic groups and were statistically different in the following way: MCI > mild AD > moderate AD. Scores in functional skills were observed to decrease in parallel with the general decline in the course of the disease. Thus, regarding IADL, the 3 pathologic groups presented a similar pattern of dysfunction but with different grades; handling money and personal mail were the two activities most affected in each diagnostic group. Only the moderate AD group showed dependence in all BADL. A small percentage of individuals from the mild AD group did, however, present light affectation in some of these basic activities. Since dependence in basic activities is not expected in mild and moderate AD according to GDS staging, the observed scores could be explained by the way in which the items are formulated. In some items, lack of initiative is considered as dependence, and in other items, physical disability is scored as functional impairment. When an accurate analysis of each item was carried out, it was observed that the moderate AD subjects present lack of initiative and not dependence in BADL. The performance of MCI patients was significantly poorer than that of age- and educationmatched controls in most of the IADL, although means between both groups were very low and similar. The items asking for the ability to use the telephone, using household appliances, handling money, shopping, preparing food, ability to get around, ability to perform leisure activities, handling personal mail, and ability to understand situations or explanations showed statistically significant differences. On the other hand, there were no differences between MCI subjects and healthy controls regarding more basic activities. These findings are in agreement with studies showing that many MCI patients exhibit impaired IADL but not BADL [5]. Moreover, this IADL impairment observed in MCI subjects has recently been associated with amyloid burden quantified in vivo by means of Pittsburgh Compound B retention measures [34]. The 2 subscales of the ADFACS (BADL and IADL) as well as the ADFACS total score clearly differentiated between the patient groups (MCI, mild AD, and moderate AD) and the CS. The BADL subscale, however, did not differentiate MCI from CS. The only subscale able to achieve this separation was the IADL one. This significant difference between CS and MCI in the complex activities items, and between MCI and mild AD in IADL as well as in BADL makes the ADFACS a useful tool for the detection of the early stages of the disease. The scale is also good at discriminating between the stages mild and moderate AD. Nevertheless, a multidisciplinary diagnosis is always necessary, and a cognitive, behavioral and clinical analysis is essential to explore AD. The cutoff point proposed for the ADFACS to discriminate between healthy controls and MCI was 1 (sensitivity 0.70; specificity 0.92). This cutoff point has a low power of discrimination which could be explained by two facts. The first is that the characterization of the groups was very restrictive. Thus, when MCI, which had some very subtle dysfunction, was compared exclusively with healthy controls, the differences were very poor due to the proximity of the score means between these groups. The second is that the scale contains very few advanced ADL items able to discriminate the groups mentioned. For the discrimination of MCI and mild AD, the cutoff point proposed was 4 (sensitivity 0.93; specificity 0.87). With the same inconvenience of proximity of the score means between these groups, this cutoff point distinguishes selectively between demented and nondemented subjects and rightly describes the progression to mild AD stage. It is important to emphasize that these cutoff points were suggested for the ADFACS total score. In order to differentiate between mild AD and moderate AD a cutoff point of 17 was proposed because it presented the best sensitivity and specificity according to the Youden index.
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Manero et al.: Diagnostic Validity of the Alzheimer’s Disease Functional Assessment and Change Scale in Mild Cognitive Impairment and Mild to Moderate Alzheimer’s Disease
Concerning external validity, very strong correlations were found with the IDDD scale. Strong correlations were also observed when IADL and complex activities and BADL and personal care were compared between the two scales. In the present study, the MMSE and the ADFACS total score correlation was strong (r = –0.747). Several studies present evidence of the relationship between ADL and neuropsychological performance. A recent review of studies with older people found that executive functions explain at least three times as much of the variance in IADL as memory [35]. In addition, a recent meta-analysis of studies of people with AD has linked executive function with declining skills and abilities in ADL, suggesting that executive dysfunction may contribute significantly to functional difficulties [36]. In agreement with this findings, higher impairments in multiple-domain MCI than singledomain amnestic MCI have been reported [37]. Future investigations will determine the relationship between the ADFACS and executive functions, specifically between the IADL subscale and this cognitive domain. It will also be useful to verify differences in the scale according to the sex variable since some activities are typically performed by women. To summarize, the ADFACS showed adequate diagnostic validity to differentiate between MCI and mild AD, and mild AD and moderate AD, with 4 and 17 as cutoff points for clinical use, respectively. At the same time, the ADFACS demonstrated a very satisfactory concurrent validity when correlations with other functional and cognitive scales were made. In addition, a similar pattern but with different levels of dysfunction was described for the three pathologic groups suggesting a lineal continuum in AD.
References 1 2
3 4 5 6 7 8 9 10 11 12
Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, Hall K, Hasegawa K, Hendrie H, Huang Y, Jorm A, Mathers C, Menezes PR, Rimmer E, Scazufca M, Alzheimer’s Disease International: Global prevalence of dementia: a Delphi consensus study. Lancet 2005;366:2112–2117. McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carillo MC, Thies B, Weintraub S, Phelps CH: The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on AgingAlzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011;7:263–269. Reuben DB, Laliberte L, Hiris J, Mor V: A hierarchical exercise scale to measure function at the advanced activities of daily living (AADL) level. J Am Geriatr Soc 1990;38:855–861. Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E: Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 1999;56:303–308. Perneczky R, Pohl C, Sorg C, Hartmann J, Tosic N, Grimmer T, Heitele S, Kurz A: Impairment of activities of daily living requiring memory or complex reasoning as part of the MCI syndrome. Int J Geriatr Psychiatry 2006;21: 158–162. Lawton MP, Brody EM: Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 1969;9:179–186. Blessed G, Tomlinson BE, Roth M: The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Br J Psychiatry 1968;114:797–811. Teunisse S, Derix MM, van Crevel H: Assessing the severity of dementia: patient and caregiver. Arch Neurol 1991;48:274 – 277. Gelinas I, Gauthier L, McIntyre M, Gauthier S: Development of a functional measure for persons with Alzheimer’s disease: the disability assessment for dementia. Am J Occup Ther 1999;53:471–481. Pfeffer RI, Kurosaki TT, Harrah CH, Chance JM, Filos S: Measurement of the functional activities in older adults in the community. J Geront 1982;37:323–329. Hindmarch I, Lehfeld H, de Jongh P, Erzigkeit H: The Bayer Activities of Daily Living Scale (B-ADL). Dement Geriatr Cogn Disord 1998;9:20–26. Sánchez-Benavides G, Manero RM, Quiñones-Úbeda S, de Sola S, Quintana M, Peña-Casanova J: Spanish version of the Bayer Activities of Daily Living Scale in mild cognitive impairment and mild Alzheimer disease: discriminant and concurrent validity. Dement Geriatr Cogn Disord 2009;27:572–578.
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13 14 15 16 17 18 19 20 21 22 23 24
25 26 27 28 29 30 31 32
33
34 35 36 37
Mohs RC, Doody RS, Morris JC, Ieni JR, Rogers SL, Perdomo CA, Pratt RD, for the ‘312’ Study Group: A 1-year, placebo-controlled preservation of function survival study of donepezil in AD patients. Neurology 2001;57: 481–488. Molinuevo JL, Berthier ML, Rami L: Donepezil provides greater benefits in mild compared to moderate Alzheimer’s disease: implications for early diagnosis and treatment. Arch Gerontol Geriatr 2011;52:18–22. Román GC, Wilkinson DG, Doody RS, Black SE, Salloway SP, Schindler RJ: Donepezil in vascular dementia: combined analysis of two large-scale clinical trials. Dement Geriatr Cogn Disord 2005;20:338–344. Barrabee P, Barrabee E, Finesinger J: A normative social adjustment scale. Am J Psychiatry 1955;117:120–124. Phillips LG: Human Adaptation and Its Failures. New York, Academic Press, 1968. Lowenthal MF: Lives in Distress. New York, Basic Books, 1964. Galasko D, Bennett D, Sano M, Ernesto C, Thomas R, Grundman M, Ferris S: An inventory to assess activities of daily living for clinical trials in patients with Alzheimer’s disease. Alzheimer Dis Assoc Disord 1997;11:S33– S39. Berg L, Miller JP, Baty J, Rubin EH, Morris JC, Figiel G: Mild senile dementia of the Alzheimer type. 4. Evaluations of intervention. Ann Neurol 1992;31:242–249. Morris JC: The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology 1993;43:2412– 2414. Folstein MF, Folstein SE, McHugh PR: ‘Mini- Mental State’: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–198. Reisberg B, Ferris SH, de Leon MJ, Crook T: The Global Deterioration Scale for assessment of primary degenerative dementia. Am J Psychiatry 1982;139,1136–1139. Peña-Casanova J, Blesa R, Aguilar M, Gramunt-Fombuena N, Gómez-Ansón B, Oliva R, Molinuevo JL, Robles A, Barquero MS, Antúnez C, Martínez-Parra C, Frank-García A, Fernández M, Alfonso V, Sol JM, for the Neuronorma Study Team: Spanish Multicenter Normative Studies (NEURONORMA project): methods and sample characteristics. Arch Clin Neuropsychol 2009;24:307–319. Levy R: Aging-associated cognitive decline. Working Party of the International Psychogeriatric Association in collaboration with the World Health Organization. Int Psychogeriatr 1994;6:63–68. Blesa R, Pujol M, Aguilar M, Santacruz P, Bertrán-Serra I, Hernández G, Sol JM, Peña-Casanova J, NORMACODEM Group: Clinical validity of the ‘mini-mental state’ for Spanish speaking communities. Neuropsychologia 2001;39:1150–1157. Peña-Casanova J: Programa integrado de exploración neuropsicológica. Test Barcelona-revisado. Barcelona, Masson, 2005. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM: Clinical diagnosis of Alzheimer’s disease. Report of the NINCDS-ADRDA work group under the auspices of the Department of Human Services Task Force on Alzheimer’s disease. Neurology 1984;34:939–944. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, ed 4. Washington, American Psychiatric Association, 1994. World Medical Association declaration of Helsinki: recommendations guiding physicians in biomedical research involving human subjects. JAMA 1997;277:922–923. Erzigkeit H, Lehfeldt H, Peña-Casanova J, Bieber F, Yekrangi-Hartmenn C, Rupp M, Rappard F, Arnold K, Hindmarch I: The Bayer-Activities of Daily Living Scale (B-ADL): results from a validation study in three European countries. Dement Geriatr Cogn Disord 2001;12:348–358. Verhey FR, Huppert FA, Korten EC, Houx P, de Vugt M, van Lang N, DeDeyn PP, Saerens J, Neri M, de Vreese L, Peña-Casanova J, Böhm P, Stoppe G, Fleischmann U, Wallin A, Hellström P, Middelkoop H, Bollen W, Klinkenberg EL, Derix MM, Jolles J: Cross-national comparisons of the Cambridge Cognitive Examination-revised. The CAMCOG-R. Age Ageing 2003;32:534–540. Verhey FR, Houx P, Van Lange N, Huppert F, Stoppe G, Saerens J, Böhm P, de Vreese L, Nordlund A, DeDeyn PP, Neri M, Peña-Casanova J, Wallin A, Bollen E, Middelkoop H, Nargeot MC, Puel M, Fleischmann UM, Jolles J: Cross-national comparison and validation of the Alzheimer’s Disease Assessment Scale: results from the European Harmonization Project for Instruments in Dementia (EURO-HARPID). Int J Geriatr Psychiatry 2004; 19:41–50. Marshall GA, Olson LE, Frey MT, Maye J, Becker JA, Rentz DM, Sperling RA, Johnson KA: Instrumental activities of daily living impairment is associated with increased amyloid burden. Dement Geriatr Cogn Disord 2011;31: 443–450. Royall DR, Lauterbach EC, Kaufer D, Malloy P, Coburn KL, Black KJ: The cognitive correlates of functional status: a review from the Committee on Research of the American Neuropsychiatric Association. J Neuropsychiatry Clin Neurosci 2007;19:249–265. Martyr A, Claire L: Executive function and activities of daily living in Alzheimer’s disease: a correlational metaanalysis. Dement Geriatr Cogn Disord 2012;33:189–203. Yeh YC, Lin KN, Chen WT, Lin CY, Chen TB, Wang PN: Functional disability profiles in amnestic mild cognitive impairment. Dement Geriatr Cogn Disord 2011;31:225–232.
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Original Research Article
Diagnostic Validity of the Alzheimer’s Disease Functional Assessment and Change Scale in Mild Cognitive Impairment and Mild to Moderate Alzheimer’s Disease R.M. Manero a, b M. Casals-Coll c G. Sánchez-Benavides c O.N. Rodríguez-de los Reyes m M. Aguilar f D. Badenes f J.L. Molinuevo d A. Robles g M.S. Barquero h C. Antúnez j C. Martínez-Parra k A. Frank-García i M. Fernández l R. Blesa e J. Peña-Casanova a, c for the NEURONORMA Study Team a
Service of Neurology and Section of Behavioral Neurology and Dementias, Hospital del Mar, b Universitat Autònoma de Barcelona, c Behavioral Neurology Group, Institut Hospital del Mar d’Investigació Mèdica, d Service of Neurology, Hospital Clínic, and e Service of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, f Service of Neurology, Hospital Mútua de Terrassa, Terrassa, g Service of Neurology, Hospital Clínico Universitario, Santiago de Compostela, h Service of Neurology, Hospital Clínico San Carlos, and i Department of Neurology, Hospital Universitario La Paz, Madrid, j Service of Neurology, Hospital Virgen Arrixaca, Murcia, k Service of Neurology, Hospital Virgen Macarena, Sevilla, and l Service of Neurology, Hospital de Cruces, Bilbao, Spain; m Service of Psychiatry, Hospital Regional de Alta Especialidad de Ciudad Victoria, Ciudad Victoria, Mexico
Key Words Alzheimer’s disease · Mild cognitive impairment · Activities of daily living · Functional assessment · Reliability · Validity Abstract Background: The Alzheimer’s Disease Functional Assessment and Change Scale (ADFACS) is a functional assessment instrument widely used in clinical research. Aims: To test the diagnostic and concurrent validity of the Spanish version of this scale and to describe the functional deficit pattern for mild cognitive impairment (MCI) and Alzheimer’s disease (AD) dementia. Methods: The ADFACS, the Interview for Deterioration in Daily Living Activities in Dementia (IDDD), and the Mini Mental State Examination (MMSE) were administered to 146 control subjects (CS) and 165 patients (67 MCI and 98 AD). Nonparametric tests were used to compare the diagnostic groups. Cronbach’s α and correlations with the MMSE and the IDDD
R.M.M. and M.C.-C. have contributed equally to this work. Jordi Peña-Casanova Section of Behavioral Neurology and Dementias, Hospital del Mar IMIM, Biomedical Research Park Building Carrer Dr. Aiguader 88, ES–08003 Barcelona (Spain) E-Mail jpcasanova @ parcdesalutmar.cat
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were calculated. Sensitivity, specificity and predictive values were studied. Results: The ADFACS had a high internal consistency (α = 0.95). Three cutoff points of 1, 4, and 17 were provided to separate CS and MCI patients, MCI and mild AD patients, and mild AD and moderate AD patients, respectively. The ADFACS strongly correlated with functional (IDDD, 0.927) and cognitive (MMSE, 0.747) measures. A similar pattern of dysfunction, but in different grades, was found for the MCI and AD groups. Conclusion: The ADFACS is a reliable, valid, and sensitive instrument to assess functional abilities; it is useful in dementia assessment for elderly populations. © 2013 S. Karger AG, Basel
Introduction
Dementia is a growing health concern in many aging societies as the number of people who suffer from it continues to rise. The most prevalent pathology that causes dementia is Alzheimer’s disease (AD). According to Alzheimer’s Disease International, an evidence-based Delphi consensus on dementia estimated that there were 24.3 million people with dementia in 2001, and the number of people affected is expected to double every 20 years [1]. As a result, there is a strongly growing interest in the diagnosis of dementia. AD diagnosis is associated with a progressive impairment of cognition and social or occupational functioning [2]. Thus, cognitive disorders arising in the course of the disease result in limitations in the patient’s ability to carry out activities of daily living (ADL). Complex tasks such as telephoning, handling medications or housekeeping, so-called instrumental activities of daily living (IADL), are the first to be affected. Some authors have considered, since the 1990s, that a group of advanced ADL, related with control of social and physical environments, should be set apart from IADL [3]. The advanced ADL would be affected before the IADL. Basic activities of daily living (BADL), which include grooming, feeding, and toileting, become affected in later stages of the disease. As dementia progresses, the patient becomes increasingly dependent on help from others. The establishment of diagnostic criteria for the intermediate stage between normal aging and dementia, so-called mild cognitive impairment (MCI), is controversial. Initial diagnostic criteria required that functional abilities remain intact in MCI in order to distinguish MCI from dementia [4]. However, ADL deteriorate while progressing from MCI to dementia, and recent data suggest that subjects with MCI show impaired IADL but not BADL [5]. There are several scales designed to assess functional abilities in dementia. They can be administered to the subject or an external source. The IADL scale of Lawton and Brody [6], the Blessed Dementia Rating Scale [7], and the Interview for Deterioration of Daily Living Activities in Dementia (IDDD) [8] are commonly used tools in moderate to severe stages of dementia. Other scales such as the Disability Assessment for Dementia [9], the Functional Assessment Questionnaire [10], and the Bayer Activities of Daily Living Scale [11] include items about advanced ADL which can be useful in early cognitive impairment diagnosis [12]. The Alzheimer’s Disease Functional Assessment and Change Scale (ADFACS) [13] is a 16-item instrument based on IADL and BADL scales widely used in clinical research [14, 15], which have been modified to reflect functional impairment in mild to moderate AD. The 6 BADL and 5 of the 10 IADL items were directly adapted from the scale described by Lawton and Brody [6], which included instrumental items from the IADL scale [16, 17] and basic items from the Physical Self-Maintenance Scale [18]. The remaining IADL items were adapted from the following tools: the ADL inventory of the AD Cooperative Study [19], the Clinical Dementia Rating scale [20, 21], and the Dementia Rating Scale [7]. The ADFACS assessment is informant-based.
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Manero et al.: Diagnostic Validity of the Alzheimer’s Disease Functional Assessment and Change Scale in Mild Cognitive Impairment and Mild to Moderate Alzheimer’s Disease
Literature on the ADFACS validation is, at present, nonexistent. As a result, the present paper proposes the following 3 aims: (a) to test the diagnostic validity of the ADFACS by establishing the sensitivity and specificity of cutoff points between healthy controls and MCI patients, MCI and mild AD patients, and mild AD and moderate AD patients for clinical purposes; (b) to test the concurrent validity of this scale in a Spanish clinical population by determining its relationship with the Mini Mental State Examination (MMSE) [22] and another functional measure, i.e. the IDDD [8], and (c) to describe the functional deficit pattern for each diagnostic group. Materials and Methods Subjects A total of 311 subjects (178 females and 133 males) were recruited and assessed, with a mean age of 73.4 years (SD 7.0) and a mean education of 8.1 years (SD 4.9). Participants were classified by diagnostic group: 146 control subjects (CS), 67 MCI patients and 98 AD patients. In addition, subjects were classified using the Global Deterioration Scale (GDS) [23], which is an instrument utilized to grade the severity in dementia. The GDS describes 7 stages from healthiness to severe dementia. Our CS can then be classified into GDS stages 1 or 2, which describe healthy people with no objective cognitive deterioration and either with or without subjective complaints. Stage 3 of the GDS is usually considered equivalent to MCI, GDS stage 4 is for mild dementia, 5 for moderate dementia, 6 for severe dementia and 7 for very severe dementia. In our study, AD subjects are classified as having mild or moderate dementia (GDS stages 4 and 5). Study controls were identified as normal based on criteria established by the NEURONORMA project [24], a study that provided norms for neuropsychological tests to be applied in subjects over 49 years old. Recruitment criteria, sociodemographics, and characteristics of the control sample have been reported in a previous paper [24]. Baseline enrolment took place in 2004–2007, from urban sources. A matching process was employed to balance the diagnostic groups in terms of age and education. One hundred forty-six individuals were selected from the 356 subjects making up the NEURONORMA control sample. Patients were diagnosed with MCI following IPA-WHO (International Psychogeriatric AssociationWorld Health Organization) [25] criteria: (a) no age restriction (in our project, the subjects had to be at least 50 years old); (b) decline of cognitive capacity affirmed by the patient and/or informant; (c) gradual decline and of a minimal duration of 6 months; (d) any of the following cognitive functions could be affected: memory and learning, attention and concentration, thinking, language or visuospatial functioning; (e) neuropsychological performance more than 1 standard deviation below the age and education norms in well-standardized neuropsychological tests; (f) the disorder does not have sufficient intensity to establish the diagnosis of dementia, nor does delirium exist; (g) there are no cerebral, systemic, or psychiatric processes that could explain the symptoms, and (h) a score >21 on the Spanish version of the MMSE [26] adjusted for age and education, and a GDS [23] score of 3. In our study, the test selected as neuropsychological test was the abbreviated Barcelona Test [27], which assesses each of the cognitive functions that can be affected in MCI, such as memory and learning, attention and concentration, thinking, language, or visuospatial functioning. The AD group was composed following the criteria of the NINCDS/ADRDA [28] and the Diagnostic and Statistical Manual for Mental Disorders, ed 4 [29]. MCI and AD recruitment was enhanced with patients who visited the participant centers. AD subjects were assigned by clinical status at GDS 4 (n = 68) and GDS 5 (n = 30). GDS 4 individuals were considered to belong to the mild AD group, and GDS 5 ones to the moderate AD group. Figure 1 shows the sample flow diagram. All participants were required to have an informant who knew them well and could answer questions about their cognition, function, and health. The relationships of the informants to the participants were spouse or significant other, adult offspring, other family member, or friend. The participants did not receive financial reimbursement or any other compensation for their participation. Ethical approval for the study was granted by the Research Ethics Committee of the Municipal Institute of Medical Care of Barcelona, Spain, and by the various participating centers. The study was conducted in accordance with the Declaration of Helsinki [30] and its subsequent amendments, and the European Union regulations concerning medical research.
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Neuronorma sample (n = 535)
Normative sample
Pathological sample (n = 179) Enrolment
CS (n = 356)
MCI (n = 79)
AD (n = 100)
Validation sample (n = 328) Included (matching enrolment) CS (n = 149)
MCI (n = 79)
AD (n = 100)
Not included (n = 207)
ADFACS validation sample (n = 311) Completing ADFACS and analyzed CS (n = 146)
MCI (n = 67)
AD (n = 98)
Missing (n = 17)
Fig. 1. Sample flow diagram.
Study Scale The ADFACS [13] is a specific scale for the functional assessment of people with AD. It is based on an interview with an informant with day-to-day knowledge about the subject and asks about the ability to perform BADL and IADL. A number of specific descriptions of performance levels for each item is offered, and the caregiver is asked to identify the one that most accurately describes the patient’s performance during the 3 weeks prior to the interview. The scale consists of 16 items for the assessment of ADL, i.e. 6 items for BADL (toileting, feeding, dressing, personal hygiene and grooming, personal ambulation, and bathing), and 10 items for IADL (ability to use the telephone, performing household tasks, using household appliances, handling money, shopping, preparing food, ability to get around, ability to perform leisure activities, handling personal mail, and ability to understand situations or explanations). The ADFACS offers two partial scores (for IADL and BADL) and a total one. IADL items are scored from 0 to 4: 0 = no impairment, 1 = mild impairment, 2 = moderate impairment, 3 = severe impairment and 4 = nonassessable, with a range from 0 to 30. BADL items are scored from 0 to 5: 0 = no impairment, 1 = mild impairment, 2 = moderate impairment, 3 = severe impairment, 4 = very severe impairment and 5 = nonassessable, with a range from 0 to 24. In each part, the ‘nonassessable’ answer is substituted by an estimation from the average of the responded items. The total score (IADL + BADL) ranges from 0 to 54 (from best to worst). The score reflects the cognitive incapacity to carry out the activities. The ADFACS was originally in English. It was later translated into Spanish within a sequence of forward and backward translations as described in previous multicenter studies [31–33].
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3.0
CS MCI Mild AD
2.5
Moderate AD
2.0
1.5
1.0
0.5
0 1
2
3
4
5
6
7
8
9
10
1
2
3
CS
0.02
0.01
0
0.04
0.01
MCI
0.15
0.07
0.13
Mild AD
0.71
0.92
Mod. AD
1.56
CS/MCI
* * * * * *
5
6
0
0.01
0.01
0
0
0
0
0
0.39
0.17
0.08
0.22
0.20
0.22
0.18
0
0
0
0
0
0
0
0.01
0.84
1.79
1.17
0.89
1.19
1.15
1.25
0.78
0.01
0.04
0
0.12
0.13
0.12
0.04
1.83
2.05
2.77
2.54
1.95
1.97
1.92
2.34
1.67
0.40
* * * * *
* * * * * *
* * * * * *
* * * * * *
* * * * * *
* * * * * *
* * * * * *
* * * * * *
* * * * * *
0.47
0.93
1.03
0.37
1.03
*
*
* *
* *
*
* *
* *
* *
* * * * *
IADL
CS/mild AD CS/mod. AD MCI/mild AD MCI/mod. AD Mild AD/mod. AD
4 BADL
*
* *
Fig. 2. Means in each ADFACS item distributed according to the diagnostic groups. The scale consists of 16 items for the assessment of ADL; i.e. 10 items for IADL [ability to use the telephone (1), performing household tasks (2), using household appliances (3), handling money (4), shopping (5), preparing food (6), ability to get around (7), ability to perform leisure activities (8), handling personal mail (9), and ability to understand situations or explanations (10)], and 6 items for BADL [toileting (1), feeding (2), dressing (3), personal hygiene and grooming (4), personal ambulation (5), and bathing (6)]. * = Significant difference in post hoc pairwise comparison after correction for multiple comparisons (p < 0.0083).
Data Management and Statistical Analysis Basic descriptive analyses included the mean and standard deviation of sociodemographic variables and the ADFACS score of each diagnostic group (CS, MCI, mild AD, and moderate AD). ANOVA and a post hoc analysis (Scheffé) were conducted to examine group differences in the sociodemographic variables of interest. χ2 tests were applied to study differences in gender among the groups. Due to the nonnormal distribution of the data group differences in the ADFACS total score, IADL and BADL subscores and item-by-item comparisons were analyzed by means of nonparametric tests (Kruskal-Wallis). Subsequent Mann-Whitney U tests were applied for pairwise comparisons, with the application of a Bonferroni correction for multiple comparisons to adjust for the increase in the alpha error (an initial p value threshold of significance was set to 0.05 and then divided by the number of comparisons 0.05/6 = 0.0083). In all other statistical analyses, the significance threshold was set at 0.05. Scale reliability was determined by using Cronbach’s α index in order to obtain a measure of internal consistency. Spearman’s correlation coefficient was used to assess the ADFACS concurrent validity by determining its relationship with the MMSE and the IDDD. To determine the diagnostic validity, the following parameters were calculated: sensitivity, specificity, positive and negative predictive values, and the receiver operating characteristic curve analysis for optimal cutoff point attainment. A larger area under the curve indicated improved diagnostic performance. The data analysis was performed using SPSS v.12.0 and R statistical software v.2.7.
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Table 1. Sociodemographic characteristics of the sample
Groups
n
Mean age ± SD, years
Mean education ± SD, Females, years %
CS MCI AD
146 67 98
72.70 ± 6.90 72.93 ± 6.36 74.67 ± 7.57
8.52 ± 5.15 7.96 ± 4.64 7.68 ± 4.68
54.1 53.7 64.3
Total
311
73.37 ± 7.04
8.14 ± 4.90
57.2
There were no differences in sociodemographic variables among the groups (p > 0.05).
Table 2. Mean scores (and standard deviation) of the ADFACS, IDDD and MMSE
CS
MCI
Mild AD
Moderate AD
Significant differences in pairwise comparison
ADFACS Total IADL BADL
0.10 (0.40) 0.10 (0.40) 0.00 (0.00)
1.85 (1.93) 1.82 (1.94) 0.03 (0.17)
11.16 (5.23) 10.70 (4.84) 0.47 (1.08)
24.83 (6.53) 20.60 (4.63) 4.23 (3.34)
all pairs all pairs all pairs except CS-MCI, CS-mild AD and MCI-mild AD
IDDD Total CA PC
33.26 (0.76) 17.25 (0.72) 16.00 (0.08)
35.72 (2.40) 17.25 (0.72) 16.09 (0.38)
44.77 (6.23) 28.19 (5.80) 16.58 (1.07)
59.00 (10.17) 37.58 (4.90) 21.41 (6.17)
MMSE
28.31 (1.71)
25.60 (2.22)
21.15 (4.12)
18.20 (3.09)
all pairs all pairs all pairs except CS-MCI, CS-mild AD and MCI-mild AD all pairs
CA = Complex activities; PC = personal care.
Results
Table 1 shows sociodemographic characteristics of the sample. All groups were similar in age and education (ANOVA tests: p > 0.05). Besides this, correlational results between these sociodemographic variables and the ADFACS scores were very weak (r < 0.2). Females made up approximately 57% of the sample, and there were no differences among the groups in the proportion of males/females (p > 0.05). With respect to the number of subjects, the groups were heterogeneous; the CS group was the largest (146 subjects) and the moderate AD the smallest (30 subjects). Table 2 shows mean scores and standard deviations for the scales for each group. The means of each ADFACS item, distributed according to the diagnostic groups, and the results of pairwise analyses are shown in figure 2. Significant differences among the diagnostic groups were observed when a mean comparison was calculated to separately analyze the ADFACS total score, the IADL score and the BADL score. When a pairwise comparison was applied, significant differences were found amongst all groups in the ADFACS total score (p < 0.0001), and IADL score (p < 0.0001). Regarding the BADL score, all differences were significant (p < 0.0001) with the exception of 3 cases: CS-MCI (p = 0.991), CS-mild AD (p = 0.052), and MCI-mild AD (p = 0.172). The same pattern was observed in IDDD analysis (table 2). A good internal reliability was found with a Cronbach’s α of 0.95. Spearman correlation analysis showed a very strong relationship between the scores of the ADFACS and
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Table 3. Cutoff points, sensitivity and specificity values and PPV and NPV Cutoff Sen Spe J points
PPV at different prevalence rates
NPV at different prevalence rates
5% 10% 15% 20% 25% 30% 40% 50%
5% 10% 15% 20% 25% 30% 40% 50%
CS-MCI
1
0.70 0.92 0.63 0.33 0.51 0.62 0.70 0.76 0.80 0.86 0.90
0.98 0.96 0.95 0.92 0.90 0.88 0.82 0.75
MCI-mild AD
4
0.93 0.86 0.80 0.27 0.43 0.55 0.63 0.70 0.75 0.92 0.90
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Mild ADmoderate AD
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0.90 0.85 0.75 0.24 0.40 0.52 0.60 0.67 0.72 0.80 0.86
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PPV = Positive predictive value; NPV = negative predictive value; Sen = sensitivity; Spe = specificity; J = Youden index.
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Fig. 3. Receiver operating characteristic curves for CS-MCI (a), MCI-mild AD (b), and mild AD-moderate AD (c) discrimination.
the IDDD (r = 0.927). When a separate analysis of BADL and IDDD personal care and IADL and IDDD complex activities was made between the two scales, strong relationships were also found (r = 0.746 and 0.926, respectively). The scores of the ADFACS and MMSE also showed a strong relationship between each other (r = –0.747). Figure 3 illustrates receiver operating characteristic curves plotted for CS/MCI, MCI/mild AD, and mild AD/moderate AD discrimination. The areas under the curve obtained were 0.826, 0.960, and 0.956, respectively. Table 3 presents cutoff points, their associated sensitivity and specificity values, and positive and negative predictive values for different prevalence rates. Cutoff values were selected on the basis of the Youden index. Discussion
This study describes the performance of a group of MCI and AD patients and a control sample on the ADFACS, and presents data concerning the diagnostic and concurrent validity of this functional scale for clinical use. The results showed a good diagnostic validity to identify the consecutive AD stages and strong correlations with the IDDD scale and the MMSE test demonstrating a satisfactory concurrent validity.
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ADFACS total scores and IADL scores observed in the diagnostic groups were distributed in the expected way: the order of the means was CS > MCI > mild AD > moderate AD; all the groups were statistically different. BADL mean scores only differed in the pathologic groups and were statistically different in the following way: MCI > mild AD > moderate AD. Scores in functional skills were observed to decrease in parallel with the general decline in the course of the disease. Thus, regarding IADL, the 3 pathologic groups presented a similar pattern of dysfunction but with different grades; handling money and personal mail were the two activities most affected in each diagnostic group. Only the moderate AD group showed dependence in all BADL. A small percentage of individuals from the mild AD group did, however, present light affectation in some of these basic activities. Since dependence in basic activities is not expected in mild and moderate AD according to GDS staging, the observed scores could be explained by the way in which the items are formulated. In some items, lack of initiative is considered as dependence, and in other items, physical disability is scored as functional impairment. When an accurate analysis of each item was carried out, it was observed that the moderate AD subjects present lack of initiative and not dependence in BADL. The performance of MCI patients was significantly poorer than that of age- and educationmatched controls in most of the IADL, although means between both groups were very low and similar. The items asking for the ability to use the telephone, using household appliances, handling money, shopping, preparing food, ability to get around, ability to perform leisure activities, handling personal mail, and ability to understand situations or explanations showed statistically significant differences. On the other hand, there were no differences between MCI subjects and healthy controls regarding more basic activities. These findings are in agreement with studies showing that many MCI patients exhibit impaired IADL but not BADL [5]. Moreover, this IADL impairment observed in MCI subjects has recently been associated with amyloid burden quantified in vivo by means of Pittsburgh Compound B retention measures [34]. The 2 subscales of the ADFACS (BADL and IADL) as well as the ADFACS total score clearly differentiated between the patient groups (MCI, mild AD, and moderate AD) and the CS. The BADL subscale, however, did not differentiate MCI from CS. The only subscale able to achieve this separation was the IADL one. This significant difference between CS and MCI in the complex activities items, and between MCI and mild AD in IADL as well as in BADL makes the ADFACS a useful tool for the detection of the early stages of the disease. The scale is also good at discriminating between the stages mild and moderate AD. Nevertheless, a multidisciplinary diagnosis is always necessary, and a cognitive, behavioral and clinical analysis is essential to explore AD. The cutoff point proposed for the ADFACS to discriminate between healthy controls and MCI was 1 (sensitivity 0.70; specificity 0.92). This cutoff point has a low power of discrimination which could be explained by two facts. The first is that the characterization of the groups was very restrictive. Thus, when MCI, which had some very subtle dysfunction, was compared exclusively with healthy controls, the differences were very poor due to the proximity of the score means between these groups. The second is that the scale contains very few advanced ADL items able to discriminate the groups mentioned. For the discrimination of MCI and mild AD, the cutoff point proposed was 4 (sensitivity 0.93; specificity 0.87). With the same inconvenience of proximity of the score means between these groups, this cutoff point distinguishes selectively between demented and nondemented subjects and rightly describes the progression to mild AD stage. It is important to emphasize that these cutoff points were suggested for the ADFACS total score. In order to differentiate between mild AD and moderate AD a cutoff point of 17 was proposed because it presented the best sensitivity and specificity according to the Youden index.
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Manero et al.: Diagnostic Validity of the Alzheimer’s Disease Functional Assessment and Change Scale in Mild Cognitive Impairment and Mild to Moderate Alzheimer’s Disease
Concerning external validity, very strong correlations were found with the IDDD scale. Strong correlations were also observed when IADL and complex activities and BADL and personal care were compared between the two scales. In the present study, the MMSE and the ADFACS total score correlation was strong (r = –0.747). Several studies present evidence of the relationship between ADL and neuropsychological performance. A recent review of studies with older people found that executive functions explain at least three times as much of the variance in IADL as memory [35]. In addition, a recent meta-analysis of studies of people with AD has linked executive function with declining skills and abilities in ADL, suggesting that executive dysfunction may contribute significantly to functional difficulties [36]. In agreement with this findings, higher impairments in multiple-domain MCI than singledomain amnestic MCI have been reported [37]. Future investigations will determine the relationship between the ADFACS and executive functions, specifically between the IADL subscale and this cognitive domain. It will also be useful to verify differences in the scale according to the sex variable since some activities are typically performed by women. To summarize, the ADFACS showed adequate diagnostic validity to differentiate between MCI and mild AD, and mild AD and moderate AD, with 4 and 17 as cutoff points for clinical use, respectively. At the same time, the ADFACS demonstrated a very satisfactory concurrent validity when correlations with other functional and cognitive scales were made. In addition, a similar pattern but with different levels of dysfunction was described for the three pathologic groups suggesting a lineal continuum in AD.
References 1 2
3 4 5 6 7 8 9 10 11 12
Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, Hall K, Hasegawa K, Hendrie H, Huang Y, Jorm A, Mathers C, Menezes PR, Rimmer E, Scazufca M, Alzheimer’s Disease International: Global prevalence of dementia: a Delphi consensus study. Lancet 2005;366:2112–2117. McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carillo MC, Thies B, Weintraub S, Phelps CH: The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on AgingAlzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011;7:263–269. Reuben DB, Laliberte L, Hiris J, Mor V: A hierarchical exercise scale to measure function at the advanced activities of daily living (AADL) level. J Am Geriatr Soc 1990;38:855–861. Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E: Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 1999;56:303–308. Perneczky R, Pohl C, Sorg C, Hartmann J, Tosic N, Grimmer T, Heitele S, Kurz A: Impairment of activities of daily living requiring memory or complex reasoning as part of the MCI syndrome. Int J Geriatr Psychiatry 2006;21: 158–162. Lawton MP, Brody EM: Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 1969;9:179–186. Blessed G, Tomlinson BE, Roth M: The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Br J Psychiatry 1968;114:797–811. Teunisse S, Derix MM, van Crevel H: Assessing the severity of dementia: patient and caregiver. Arch Neurol 1991;48:274 – 277. Gelinas I, Gauthier L, McIntyre M, Gauthier S: Development of a functional measure for persons with Alzheimer’s disease: the disability assessment for dementia. Am J Occup Ther 1999;53:471–481. Pfeffer RI, Kurosaki TT, Harrah CH, Chance JM, Filos S: Measurement of the functional activities in older adults in the community. J Geront 1982;37:323–329. Hindmarch I, Lehfeld H, de Jongh P, Erzigkeit H: The Bayer Activities of Daily Living Scale (B-ADL). Dement Geriatr Cogn Disord 1998;9:20–26. Sánchez-Benavides G, Manero RM, Quiñones-Úbeda S, de Sola S, Quintana M, Peña-Casanova J: Spanish version of the Bayer Activities of Daily Living Scale in mild cognitive impairment and mild Alzheimer disease: discriminant and concurrent validity. Dement Geriatr Cogn Disord 2009;27:572–578.
375
Dement Geriatr Cogn Disord 2014;37:366–375 DOI: 10.1159/000350800
© 2014 S. Karger AG, Basel www.karger.com/dem
Manero et al.: Diagnostic Validity of the Alzheimer’s Disease Functional Assessment and Change Scale in Mild Cognitive Impairment and Mild to Moderate Alzheimer’s Disease
13 14 15 16 17 18 19 20 21 22 23 24
25 26 27 28 29 30 31 32
33
34 35 36 37
Mohs RC, Doody RS, Morris JC, Ieni JR, Rogers SL, Perdomo CA, Pratt RD, for the ‘312’ Study Group: A 1-year, placebo-controlled preservation of function survival study of donepezil in AD patients. Neurology 2001;57: 481–488. Molinuevo JL, Berthier ML, Rami L: Donepezil provides greater benefits in mild compared to moderate Alzheimer’s disease: implications for early diagnosis and treatment. Arch Gerontol Geriatr 2011;52:18–22. Román GC, Wilkinson DG, Doody RS, Black SE, Salloway SP, Schindler RJ: Donepezil in vascular dementia: combined analysis of two large-scale clinical trials. Dement Geriatr Cogn Disord 2005;20:338–344. Barrabee P, Barrabee E, Finesinger J: A normative social adjustment scale. Am J Psychiatry 1955;117:120–124. Phillips LG: Human Adaptation and Its Failures. New York, Academic Press, 1968. Lowenthal MF: Lives in Distress. New York, Basic Books, 1964. Galasko D, Bennett D, Sano M, Ernesto C, Thomas R, Grundman M, Ferris S: An inventory to assess activities of daily living for clinical trials in patients with Alzheimer’s disease. Alzheimer Dis Assoc Disord 1997;11:S33– S39. Berg L, Miller JP, Baty J, Rubin EH, Morris JC, Figiel G: Mild senile dementia of the Alzheimer type. 4. Evaluations of intervention. Ann Neurol 1992;31:242–249. Morris JC: The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology 1993;43:2412– 2414. Folstein MF, Folstein SE, McHugh PR: ‘Mini- Mental State’: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–198. Reisberg B, Ferris SH, de Leon MJ, Crook T: The Global Deterioration Scale for assessment of primary degenerative dementia. Am J Psychiatry 1982;139,1136–1139. Peña-Casanova J, Blesa R, Aguilar M, Gramunt-Fombuena N, Gómez-Ansón B, Oliva R, Molinuevo JL, Robles A, Barquero MS, Antúnez C, Martínez-Parra C, Frank-García A, Fernández M, Alfonso V, Sol JM, for the Neuronorma Study Team: Spanish Multicenter Normative Studies (NEURONORMA project): methods and sample characteristics. Arch Clin Neuropsychol 2009;24:307–319. Levy R: Aging-associated cognitive decline. Working Party of the International Psychogeriatric Association in collaboration with the World Health Organization. Int Psychogeriatr 1994;6:63–68. Blesa R, Pujol M, Aguilar M, Santacruz P, Bertrán-Serra I, Hernández G, Sol JM, Peña-Casanova J, NORMACODEM Group: Clinical validity of the ‘mini-mental state’ for Spanish speaking communities. Neuropsychologia 2001;39:1150–1157. Peña-Casanova J: Programa integrado de exploración neuropsicológica. Test Barcelona-revisado. Barcelona, Masson, 2005. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM: Clinical diagnosis of Alzheimer’s disease. Report of the NINCDS-ADRDA work group under the auspices of the Department of Human Services Task Force on Alzheimer’s disease. Neurology 1984;34:939–944. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, ed 4. Washington, American Psychiatric Association, 1994. World Medical Association declaration of Helsinki: recommendations guiding physicians in biomedical research involving human subjects. JAMA 1997;277:922–923. Erzigkeit H, Lehfeldt H, Peña-Casanova J, Bieber F, Yekrangi-Hartmenn C, Rupp M, Rappard F, Arnold K, Hindmarch I: The Bayer-Activities of Daily Living Scale (B-ADL): results from a validation study in three European countries. Dement Geriatr Cogn Disord 2001;12:348–358. Verhey FR, Huppert FA, Korten EC, Houx P, de Vugt M, van Lang N, DeDeyn PP, Saerens J, Neri M, de Vreese L, Peña-Casanova J, Böhm P, Stoppe G, Fleischmann U, Wallin A, Hellström P, Middelkoop H, Bollen W, Klinkenberg EL, Derix MM, Jolles J: Cross-national comparisons of the Cambridge Cognitive Examination-revised. The CAMCOG-R. Age Ageing 2003;32:534–540. Verhey FR, Houx P, Van Lange N, Huppert F, Stoppe G, Saerens J, Böhm P, de Vreese L, Nordlund A, DeDeyn PP, Neri M, Peña-Casanova J, Wallin A, Bollen E, Middelkoop H, Nargeot MC, Puel M, Fleischmann UM, Jolles J: Cross-national comparison and validation of the Alzheimer’s Disease Assessment Scale: results from the European Harmonization Project for Instruments in Dementia (EURO-HARPID). Int J Geriatr Psychiatry 2004; 19:41–50. Marshall GA, Olson LE, Frey MT, Maye J, Becker JA, Rentz DM, Sperling RA, Johnson KA: Instrumental activities of daily living impairment is associated with increased amyloid burden. Dement Geriatr Cogn Disord 2011;31: 443–450. Royall DR, Lauterbach EC, Kaufer D, Malloy P, Coburn KL, Black KJ: The cognitive correlates of functional status: a review from the Committee on Research of the American Neuropsychiatric Association. J Neuropsychiatry Clin Neurosci 2007;19:249–265. Martyr A, Claire L: Executive function and activities of daily living in Alzheimer’s disease: a correlational metaanalysis. Dement Geriatr Cogn Disord 2012;33:189–203. Yeh YC, Lin KN, Chen WT, Lin CY, Chen TB, Wang PN: Functional disability profiles in amnestic mild cognitive impairment. Dement Geriatr Cogn Disord 2011;31:225–232.
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