Amsterdam Instrumental Activities of Daily Living questionnaire.”
By: W N Kremer Student number: 10197605 Supervised by: Sieberen van der Werf
Master thesis submitted in fulfillment of the requirements for the degree of Master of Science in Clinical Neuropsychology
Programmagroep Brein en Cognitie, Klinische Neuropsychologie, Psychology Department, Universiteit van Amsterdam
2 Table of Contents Abstract ... 3 Introduction ... 4 Methods ... 7 Participants ... 7 Procedure ... 7 Materials ... 7 Analyses ... 9 Results ... 9 Discussion ... 14 References ... 16
3 Abstract
This study investigated whether the Parkinson Disease Cognitive Functional Rating Scale (PD-CFRS) and the Amsterdam Instrumental Activities of Daily Living questionnaire (A-IADL) can distinguish between Parkinson patients with Mild Cognitive Impairment (MCI) and Parkinson patients with normal cognition. Validation of these instruments could provide a new screening instrument for identifying Parkinson patients with MCI and should aid in earlier support for patients suffering from the symptoms associated with this condition. Previous research has assumed that PD patients with MCI often are still capable of
performing ADL-activities without any problems, but will show problems on IADL activities. This assumption was tested with the aforementioned IADL measures, while the Amsterdam Linear Disability Scale (ALDS) was be used to test the assumption that ADL is not related to MCI in PD. Results provided evidence for the assumption that PD patients with MCI perform worse on IADL activities than PD patients with normal cognition. Both PD-MCI and PD-NC patients score equally on ADL tasks. Furthermore, the PD-CFRS and the A-IADL both are accurate predictors of MCI or normal cognition in PD patients. The PD-CFRS has a
sensitivity of .79 and specificity of 0.77. The A-IADL has a sensitivity of .83 and specificity of 0.73. As expected, ADL activities cannot be used to distinguish between PD patients with MCI and PD with normal cognition. The assumption often described in previous research was thus confirmed and the IADL instruments were (partially) validated.
4 Introduction
Parkinson’s disease (PD) is a degenerative disorder of the nervous system mainly affecting the nigrostriatal dopamine system (Hussl, Seppi, & Poewe, 2013). The most recognizable symptoms of this disease are movement symptoms such as bradykinesia, rest tremor, rigidity and impaired postural reflexes. These symptoms are collectively called Parkinsonism and they are the anchors of the current clinical criteria. These Parkinsonism symptoms have been found to hamper so-called activities of daily living (ADL). These activities are essential to self-care, such as dressing, grooming, bathing and feeding (Gobbens & Assen, 2014). Besides motor symptoms, PD is also associated with cognitive symptoms. In the course of the disease these symptoms might range from mild cognitive impairment (MCI) to full-blown PD associated dementia. Besides Parkinsonism, impairments in executive function, visuomotor function and verbal memory might also negatively affect more complex daily activities such as carrying out housework, financial administration, shopping or preparing meals (Aarsland et al., 2010; Levin et al., 1991; Muslimovic et al., 2005). These more complex activities are called instrumental activities of daily living (ADL; Gobbens & Assen, 2014). Both ADL and I-ADL represent functional independence and quality of life (QoL) and several (PD-specific) ratings scales have been developed to assess these concepts (Weisscher et al., 2009; Sikkes et al., 2012; Kulisevsky et al., 2013). However, there are no validated IADL-questionnaires that assess this type of cognitive deterioration in PD patients with MCI. Availability of such an instrument might provide an effective screening instrument for identifying PD patients with MCI at an early stage, since IADL activities are affected by the cognitive symptoms
associated with these patients.
The functional limitations in daily life of PD patients have been found to be associated with the degree of cognitive impairment, severity of motor symptoms, depressive symptoms, and age at the time of diagnosis. The functional limitations associated with PD affect quality of life and may result in complete care dependence (Hobson, Holden & Meara, 1999).
Detecting these symptoms at an early stage gives caretakers the chance to offer fitting support and could therefore improve QoL and functional limitations of PD patients. A reliable and valid screening instrument will be useful in achieving this. Below, current perspectives of which symptoms cause problems in everyday life are discussed and explored.
In previous research, Cahn and colleagues (1998) examined IADL activities in PD-patients and found executive functioning to be an independent predictor of performance of IADL activities. Motor functioning did not predict IADL activities. This suggests that
5 cognitive symptoms play a distinct role in IADL activities of Parkinson’s patients. However, at the moment there is very little research regarding the impact of cognitive dysfunction on IADL activities in PD patients. More knowledge should be gathered on this subject in order to get a better idea of which cognitive symptoms are at the root of the problems PD patients could be experiencing in everyday life.
Additional relevant research has found that IADL activities involve higher order cognitive functioning such as executive functioning, these activities are sensitive to early effects of cognitive deterioration and could be useful in early diagnosis of dementia (Aarsland et al., 2010; Levin et al., 1991; Muslimovic et al., 2005; Sikkes et al., 2011). Furthermore, previous research has shown that an early sign of dementia in PD patients includes executive dysfunction. However, there are no validated IADL-questionnaires that assess this type of cognitive deterioration in PD patients with MCI. The A-IADL scale developed by Sikkes has been validated as a screener to detect dementia in patients with Alzheimer’s Disease, but not yet in PD-patients (Sikkes et al, 2012). Many IADL activities also include motor components. This could cause extra problems for PD patients, in contrast to patients with Alzheimer’s disease. Therefore, this instrument needs to be validated specifically for PD-patients.
Another study, conducted by Kulisevky and colleague’s (2013) found the Parkinson’s Disease-Cognitive Functioning Rating Scale (PD-CFRS) to be a reliable and valid instrument to detect the influence of cognitive symptoms in PD patients on IADL activities. This
questionnaire consists of 12 questions that have to be answered by an informant that knows the patient well. This is much shorter than the A-IADL scale. Thus, if this questionnaire could provide similar specificity and sensitivity, it would provide a faster screener than the A-IADL. However, the instrument used to assess cognitive functioning in this study was the
Parkinson’s Disease-Cognitive Rating Scale (PD-CRS). This is a cognitive screening instrument created specifically for PD patients and takes approximately 20 minutes to administer (Paganobarraga et al, 2008). This means that this study did not use results of extensive neuropsychological testing batteries in order to distinguish between PD patients with MCI and those with normal cognition. The PD-CRS merely provides an indication of cognitive functioning, whereas an extensive neuropsychological testing battery offers a broader and more objective estimation of a patient’s cognitive functioning. Therefore, future research needs to check the validity of this scale with data from full and thorough
neuropsychological testing batteries.
In order to detect problems with IADL activities for PD-MCI patients, more IADL instruments need to be validated that can assess functional deterioration as a result of
6 cognitive dysfunction. This way the assumption that PD-MCI patients experience more
problems with IADL activities can be checked (Cahn et al., 1998). Secondly, validating the questionnaires for PD patients allows researchers to take into account PD motor symptoms since these might affect the cut-off value for these instruments. Validation of these
instruments will thus have practical benefits but will also contribute to the knowledge of the pathology of Parkinson’s Disease.
As discussed above, there is a lack of studies examining the impact of cognitive dysfunction on IADL in the predementia stage of patients with Parkinson’s Disease. For this reason, the goal of the current study will be to determine the influence of MCI on functional deterioration in PD patients. The secondary goal will be to validate the A-IADL and the PD-CFRS, as possible screeners to detect MCI in patients with PD, since it is important to have a valid instrument to distinguish between these patients and PD patients with normal cognition. Additionally, this will help detect PD patients that might have problems with IADL-activities. By being able to identify these patients they can be helped with problems in order to improve their quality of life (Schrag, Jahanshahi & Quinn, 2000).
In order to determine which patients have MCI, an extensive neuropsychological examination will be performed (Litvan et al., 2012). In addition, an ADL questionnaire (ALDS) will be used as a reference measure for the IADL questionnaires. The reason for this is that PD patients with MCI often are still capable of performing ADL-activities without much trouble. This questionnaire will be used to check this last assumption.
Previous research has shown that PD patients with MCI reported more IADL
impairment than patients with normal cognition. Therefore, it is hypothesized that PD-MCI patients will report significantly more problems on both the A-IADL and the PD-CFRS than those with normal cognition.(Pirogovsky et al., 2014; Hypothesis 1). Thus, these instruments could be used as screening instruments for detecting early signs of cognitive symptoms associated with PD. No such difference is expected for ADL tasks (Hypothesis 2).
Furthermore, in order to validate the IADL questionnaires, this study will examine which questionnaire is best able to distinguish between PD patients with MCI and PD patients with normal cognition. It is expected that both of these questionnaires (PD-CFRS & A-IADL) are good predictors of MCI or normal cognition (NC; Hypothesis 3). Additionally, it is expected that ADL measures will not be a good predictor of MCI or normal cognition when compared to IADL measures (Hypothesis 4).
7 Methods
Participants
Participants were 50 patients (ages 45-80) with the diagnosis Parkinson’s disease who agreed to participate in this study. Patients with Parkinson dementia, comorbid psychiatric or
neurological disorders were excluded. In addition, an informant had to consent to participate in this research. This informant had to be someone who spends a significant amount of time with the patient (partner/family member/close friend/caregiver) and who was capable to witness and judge the problems the patient might experience in everyday life. Patients and their informants were recruited at the Amsterdam Medical Center (AMC) and the VU medical center (VUmc). At the AMC, participants were recruited during a Deep Brain Stimulation screening. Prior to neuropsychological testing, patients were asked if they were willing to participate in this research study. At the VUmc, participants were recruited in the Parkinson outpatient clinic. Here, patients were also asked whether they were willing to participate in a research study prior to neuropsychological testing.
Procedure
For this study, patients underwent neuropsychological testing and an informant of the patient completed 3 questionnaires. The neuropsychological testing battery contained at least two tests for each of the following two domains: executive functioning, attention, memory, language and visuospatial skills. Based on the results of these tests patients were assigned to the MCI group or Normal Cognition group. This was done based on the level 2 MDS Task Force guidelines (Litvan et al., 2012).
While the patient underwent extensive neuropsychological testing, informants completed the following three questionnaires: ALDS, PD-CFRS and the A-IADL. These questionnaires assessed possible problems that patients experience in daily life. Informants were given time to fill in these questionnaires while patients were undergoing
neuropsychological testing. These tests took anywhere from 1,5 hours to 3 hours, depending on the speed of the patient. Completing the three ADL and IADL questionnaires took informants between 30 to 45 minutes.
Materials
This study used several different neuropsychological tests. The diagnosis of PD-MCI was based on neuropsychological assessments and both participating hospitals used slightly
8 different test protocols (Table 1). Each of these batteries contained at least two tests of each cognitive domain described above.
In addition to these neuropsychological tests, three questionnaires were administered: The Amsterdam Instrumental Activities of Daily Living (A-IADL), the Parkinson Disease Cognitive Functional Rating Scale (PD-CFRS) and the AMC Linear Disability Scale (ALDS). These questionnaires were completed by an informant using a tablet (iPad).
The A-IADL consists of 70 items and takes approximately 20 minutes to complete (Sikkes et al., 2012). The goal of this survey is to give a comprehensive overview of possible problems in carrying out daily activities. It employs item-response theory in order to shorten the time it takes to fill in. Sikkes et al. (2012) determined the internal consistency to be high (0.97) in a group of 206 informants of Alzheimer patients. The content validity of this survey was judged by a group of experts and a group of informants. Both of these groups agreed on the importance and relevance of the items included in the final version of the survey.
The PD-CFRS consists of 12 items and takes approximately five minutes to administer. The main goal of this survey is to detect cognitive dysfunction that is associated with Parkinson’s disease. Questions involving motor functions are minimalized in this questionnaire (Pagonabarraga, 2008). Kulisevsky and colleagues (2013) determined the PD-CFRS has an intermediate concurrent validity of 0.50 with another survey of IADL
functioning (Older Americans Resource Survey), high test-retest reliability (0.82), high inter-rater reliability (0.80) and a sufficient internal consistency (Cronbach's α = 0.79). The participants in this study were 53 PD patients without dementia and 53 control patients.
The ALDS consists of 77 items that assess level of functioning in everyday life and since it employs item-response theory to present the items, it takes approximately 5 minutes to complete this questionnaire (Weisscher et al., 2007). In order to validate this instrument, Weisscher and colleagues (2007) recruited 132 patients with recently diagnosed Parkinson’s Disease. Construct validity was assessed by examining whether the ALDS discriminated between patients with severe PD motor symptoms and moderate PD motor symptoms. This proved to be the case. Patients with more severe PD motor symptoms were significantly more disabled than those with moderate or mild PD motor symptoms. Additionally, they found high internal consistency reliability (0.95).
9 Table 1:
Neuropsychological Testing Battery Vrije Universiteit Medical Center (VUmc) & Amsterdam Medical Center (AMC)
Cognitive Domain Location Neuropsychological Test Attention and
concentration VUmc Trail Making Test A, Stroop Color Word Test – Card II AMC Trail Making Test A, Stroop Color Word Test -- Card II
Memory VUmc
15-Words test, Visual Association Test, Rey Complex Figure Test - Delayed Recall
AMC 15-Words test, Rivermead Behavioural Memory Test – Stories Language VUmc Boston Naming Test, Category Fluency – Animals
AMC
Boston Naming Test, Wechsler Adult Intelligence Scale-IV Similarities
Executive Function VUmc Trail Making Test B, Stroop Color Word Test - Card III AMC Trail Making Test B, Stroop Color Word Test - Card III
Visuospatial skills VUmc
Rey Complex Figure Test - Copy, Visual Object and Space Perception Battery - Position Discrimination
AMC
Groninger Intelligence Test - Puzzle Pieces, Judgement of Line Orientation
Analyses
In order to test the first two hypotheses a MANOVA will be conducted with diagnosis (MCI vs NC) and location (AMC vs VUmc) as categorical independent variables, IADL & ADL (PD-CFRS, A-IADL and ALDS) as dependent variables. Since patients are recruited from two separate locations it will be checked whether there are any significant differences in test results between the two. Assumptions for this analysis will be checked using SPSS.
The third and fourth hypotheses will be tested by constructing Receiver Operating Curves for each IADL and ADL instrument. Sensitivity and specificity will be determined at the optimal cut-off point for each instrument.
Results
A total of 53 PD patients participated in this study. The study population consisted of 24 PD-MCI patients and 26 PD-NC patients. 3 participants were excluded from this research since
10 they received a dementia diagnosis from the hospital. Unfortunately, due to technical
difficulties while measuring the ALDS score, 17 of the patients seen are missing values. A software update resolved this issue for patients tested at a later time. Preliminary testing revealed that there were no significant differences in age, education or gender between PD-MCI patients and PD-NC patients (see Table 2).
Table 1:
Descriptive Statistics of Parkinson’s Disease Patients participating in a Validation Study
PD-MCI patients (n=24) PD-NC patients (n=26) p
Age (years) 65.5 ± 6.41 62.19 ± 7.96 0.12a
Men (%) 83.3 61.5 0.09b
Education (Verhage coding) 5.04 ± 1.08 5.5 ± 0.99 0.12a
PD-CFRS 6.59 ± 4.92 2.94 ± 4.15
A-IADL 54.61 ± 6.21 60.31 ± 5.86
ALDS (n=33) 79 ± 13.99 (n=15) 76.78 ± 19.21 (n=18)
Note: Values are expressed as mean ± SD, or percentage of subjects (%). Verhage coding ranges from 1 = lower level than elementary school or did not finish elementary school to 7 = college educated individual. PD-MCI = Parkinson’s Disease patients diagnosed with Mild Cognitive Impairment. PD-NC = Parkinson’s Disease patients with normal cognition. PD-CFRS = Parkinson Disease Cognitive Functional Rating Scale. A-IADL = Amsterdam Instrumental Activities of Daily Living questionnaire. ALDS = Amsterdam Linear Disability Scale.
a: T-tests for independent samples b: Mann-Whitney test
Based on the first hypothesis it was expected that PD-MCI patients would score lower on IADL than PD-NC patients. To test this hypothesis a MANOVA, with diagnosis (MCI vs NC) and location (AMC vs VUmc) as categorical independent variables, IADL & ADL (PD-CFRS, A-IADL and ALDS) as dependent variables, was performed. As tested with Box’s test, the assumption of homogeneity of covariance matrices was met (p=0.32). The assumption of equality of error variances was met for the PD-CFRS & A-IADL, as tested with Levene's test (p=0.37 & p=0.07, for the PD-CFRS & A-IADL respectively). This assumption was not met for the ALDS (p=0.01). The assumption of multivariate normality was examined by assessing univariate normality of both dependent variables using a Kolmogorov-Smirnov test. This test
11 indicated univariate normality for the A-IADL (p=0.05), but not for the PD-CFRS (p<0.000) and the ALDS (p<0.000). When examining the distribution of data of the PD-CFRS, it is evident that this significant result is due to skewness of the data and a possible floor effect of this instrument. On the other hand, there is enough variance in this data to justify using a parametric test like a MANOVA (See Figure 1). Furthermore, when examining the
distribution of data of the ALDS, there is a clear indication of a non-normal distribution. For this reason the ALDS will be tested separately using a non-parametric test.
Results of the MANOVA showed that there was a significant effect of diagnosis on the score on the A-IADL but not the PD-CFRS, F(1,50)=5.00, p=0.03 and F(1,50)=2.99, p=0.09 respectively. PD-MC patients scored significantly lower than PD-NC patients on one of the IADL measures, but not on the other. The partial eta-squared for the A-IADL (η2 = .10) was of medium to large size, whereas the effect size for the PD-CFRS (η2 = .06) was of medium size. The interaction between diagnosis and location was not significant for either IADL measure, F(1,50)=0.05, p=0.83 for the PDCFRS and F(1,50)=0.01, p=0.91 for the A-IADL. This implies that the location where patients were recruited did not influence the diagnosis. These results are partially in line with the first hypothesis. However, given the p-value and the effect size, there does seem to be a trend towards significance for the PD-CFRS. Therefore, this instrument will be tested again using a non-parametric test.
In order to assess the ALDS and the PD-CFRS, a non-parametric test was used to investigate any possible differences between PD patients with MC and those with normal cognition. A Mann-Whitney test indicated that there was a significant effect of diagnosis on the score of the PD-CFRS but not on the ALDS (U=140.00, p=.001 & U=133.50, p=0.95 respectively). PD-MC patients scored significantly lower on the PD-CFRS than PD-NC patients. The eta-squared value for the PD-CFRS (η2 = .23) was of large size. There was no significant difference between these two groups for the ALDS. The eta-squared value for the PD-CFRS (η2 <.000) was of negligible size. These results are in line with the first hypothesis (PD-CFRS) and the second hypothesis (ALDS).
12
Figure 1. Distribution of data of the Parkinson’s Disease-Cognitive Functioning Rating Scale
as shown with a histogram
In order to determine specificity and sensitivity of the IADL questionnaires, (A-IADL & PD-CFRS) Receiver Operating Characteristic (ROC) Curves were made (see Figure 2 & 3). Area under the curve for both these questionnaires was compared in order to determine which test best distinguishes between PD patients with MCI and PD patients with normal cognition. Area under the curve of the A-IADL and the PD-CFRS indicate that they both classify patients into NC and MCI effectively (p=.003 and p=.001 respectively). This confirms the third hypothesis. When comparing AUC, it is apparent that the PD-CFRS has slightly more predictive value than the A-IADL (AUC=0.78 and AUC=0.75 respectively). Suggested cut-off scores were also calculated for each questionnaire. For the A-IADL a suggested cut-cut-off score below 58.85 results in a sensitivity of 0.83 and a specificity of 0.73. Patients will be labeled as having MCI when they score below this cut-off score. The suggested cut-off score for the PD-CFRS is 2.6. If a patient scores higher than this, he/she will be classified as MCI. This results in a sensitivity of 0.79 and a specificity of 0.77.
Secondly, a ROC curve was made for the ALDS scale in order to check the assumption that this test is not a good predictor of MCI or NC when compared to IADL measures (see Figure 4). The analysis confirmed this assumption. The ALDS was not an effective predictor of MCI or NC (AUC=.49, p=.96). This is in line with the fourth hypothesis.
13
Figure 2. Receiver Operating Characteristic Curve Amsterdam-Instrumental Activities of
Daily Living questionnaire
Figure 3. Receiver Operating Characteristic Curve Parkinson’s Disease-Cognitive
Functioning Rating Scale
14 Discussion
The main results of this study showed that: (1) PD-MCI patients reported more problems on IADL tasks than PD-NC patients; (2) PD-MCI patients reported an equal number of problems on ADL tasks as PD-NC patients; (3) the PD-CFRS and the A-IADL could both accurately distinguish Parkinson’s patients with and without MCI; (4) the ALDS turned out not to be an accurate predictor of MCI in Parkinson’s patients. All these results were in line with
expectations based on the hypotheses.
This study has provided evidence for the assumption made in previous research that Parkinson’s patients with MCI experience more functional deterioration in their everyday lives than PD patients with normal cognition. This difference became apparent while examining the performance of IADL tasks as assessed by the A-IADL and the PD-CFRS scale. PD-MCI patients have more trouble performing these tasks than PD-NC patients. This is owing to the fact that these tasks require patients to rely on their cognitive abilities. It seems therefore, that IADL scales are an accurate way of screening for signs of mild cognitive impairment in Parkinson patients. Results show that both the A-IADL and the PD-CFRS are well suited for this purpose.
Firstly, it should be noted that this study did have some limitations. Due to time limitations, it was only possible to gather data of 50 participants, instead of the planned 60. Additionally, quite a few values were missing for the ADL measurement. This might have skewed the results in a certain way thus affecting the results presented here. However, since these results align with evidence presented in earlier research, this is not likely. Nevertheless, future research should attempt to gather data from more patients in order to provide an accurate representation of the everyday situations PD patients face.
Secondly, in order to achieve a larger sample size, data was collected at two different academic hospitals in Amsterdam. Each hospital saw Parkinson’s patients for different purposes. By collecting data at both locations the sample would become more heterogeneous and possibly more representative of the general population. However, patients are referred to these hospitals for a certain reason. For example, patients at the AMC are there for a Deep Brain Stimulation screening. These are patients that mainly suffer from motor symptoms, and
15 not nonmotor symptoms, while the latter has been proven to negatively affect IADL (Cahn et al., 1998). A sample as such will most likely report fewer problems with IADL activities. This might have affected the comparison between the MC and NC group. Furthermore, this
selection could have resulted in a biased cut-off value as calculated with ROC curves. Therefore these results might not generalize well to the general population of PD-patients. If possible, a future study should therefore try to collect a large sample at multiple institutions with a larger variety of PD patients.
This study has confirmed a long-standing assumption that PD-MCI patients perform worse on complex daily tasks then PD-NC patients. Even though this seems like a very logical assumption, the scientific method dictates that even these logical assumptions need to be checked in order to become facts instead of assumptions. Additionally, this provides more proof for the notion that PD-MCI patients are less independent in their everyday lives than PD-NC patients.
In summary, in order to accurately track the functional deterioration observed in patients with Parkinson’s disease, it is important to have a reliable and valid instrument to screen for possible problems in daily life. This way, PD patients that are developing dementia can be offered the extra support they need in everyday life, which could help improve their quality of life (Hobson et al., 1999). For this reason, it is useful to know that the two IADL questionnaires used in this study are reliable and valid instruments that could possibly help with an early diagnosis of MCI or Parkinson’s Dementia. This is helpful in a clinical setting, but also for further research that is looking for an intervention for patients with Parkinson’s Dementia (Pirogovsky et al. 2014).
Based on the results it is recommended to use the PD-CFRS as a first choice. The reason for this is simply that this scale shorter than the A-IADL (12 and 70 items
respectively). This makes it more practical for future PD-MCI research on a bigger scale. Additionally, the results also indicated that the PD-CFRS has a good specificity and sensitivity.
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