Executive functioning and attention post-stroke:

location and side of stroke and its association with 3, 6 and 15

months performances on the Stroop and Trail Making Test.

I.J.D. van der Wal

ANR: 53 86 83

First Supervisor: Dr. R.E. Nieuwenhuis - Mark

Second Supervisor: Drs. A.H.M. van Boxtel

Master thesis Medical Psychology

University of Tilburg

Augustus 2009

2

Abstract

Background The prevalence of cognitive impairment after stroke is high. Often executive functioning

and attention are affected. Executive functioning measured in the acute phase post-stroke predicts

cognitive functioning in the long term and may be influenced by side and location of a stroke.

Objectives The current study aims to assess whether executive functioning and attention measured

three months post stroke improve over time and if this improvement is dependent on the side (left or

right) and location (cortical or subcortical) of a stroke. Method 26 patients with a first ever stroke

were tested at three, six and fifteen months post stroke. The participants underwent a

neuropsychological assessment which included the Trail Making Test and Stroop. Medical information

for each participant was also collected. Results No effects emerged for the TMT. An interaction

effect of side and location of stroke on errors made on Stroop 2 emerged, with cortical right

sided stroke patients having a better performance than subcortical right sided and subcortical

left sided stroke patients have a better performance than cortical left sided. A main effect of

side of stroke was found for errors made on Stroop 1, with left sided stroke patients having a

better performance that right sided. There is a linear interaction effect of time and side of

stroke for Stroop 3, with right sided performance improving over time and left sided

worsening over time. Performances on the TMT and Stroop did not change over time, except

performances on the Stroop Interference and errors made on the 3rd Stroop card. They

improved over 3 to 15 months post-stroke. Conclusions There is almost no difference in TMT

and Stroop performances between the 4 groups. There is almost no improvement over 15

months except on Stroop cards that measure divided attention and mental flexibility. The

improvement is not related to a combination effect of side and location of stroke.

Improvement is related to side of stroke for one aspect of de Stroop: right sided improved

more than left sided. One can conclude that there is no statistical beneficial effect of

combining location and side of stroke in predicting the recovery course of patients.

Keywords: Stroke – Location – Side – Executive functioning - Attention

3

Samenvatting

Achtergrond Cognitieve beperkingen komen veelvuldig voor na een CVA. Executief

functioneren en aandacht zijn vaak aangedaan. Executief functioneren, gemeten in de acute

fase na een CVA, voorspelt cognitief functioneren over lange tijd en wordt mogelijk

beïnvloed door kant en locatie van een CVA. Doel De huidige studie heeft als doel om te

bepalen of executief functioneren en aandacht, gemeten 3 maanden na een CVA, verbeteren

over de tijd en of deze verbetering afhankelijk is van de kant (links of rechts) en locatie

(corticaal of subcorticaal) van een CVA. Methode 26 patiënten die voor het eerst een CVA

door hebben gemaakt, werden getest op 3, 6 en 15 maanden na hun CVA. De deelnemers

ondergingen een neuropsychologisch onderzoek, met onder andere de Trail Making Test en

Stroop. Medische informatie, van elke deelnemer, werd ook verzameld. Resultaten Er

werden geen effecten op de TMT gevonden. Er werd een interactie effect van kant en locatie

van een CVA gevonden op het aantal fouten wat gemaakt werd op de Stroop 2. Daarbij lieten

subcoricale linker CVA patiënten de beste resultaten zien, gevolgd door corticale rechter,

corticale linker en als laatste subcorticale rechter CVA patiënten. Een hoofdeffect werd

gevonden tussen kant en het aantal fouten wat gemaakt werd op de Stroop 1, met linker kant

CVA patiënten hadden een beter score dan rechter kant CVA patiënten. Tevens was er een

interactie effect tussen kant en tijd op de Stroop kaart 3. De resultaten van linker kant CVA

patiënten verslechterde over de tijd, rechter kan nam de prestatie toe. Er werd geen

verandering in resultaten op de TMT en Stroop geobjectiveerd over de 15 maanden heen,

behalve voor de resultaten op de Stroop Interferentie en aantal fouten die gemaakt worden

op de 3e kaart van de Stroop. Deze resultaten verbeterde tussen de 3 en 15 maanden.

Conclusie Er is bijna geen verschil tussen TMT en Stroop resultaten tussen de vier groepen.

Er vindt bijna geen verbetering plaats in 15 maanden, behalve op de Stroop kaarten die

verdeelde aandacht en mentale flexibiliteit meten. De verandering van resultaten is niet

afhankelijk van een interactie tussen kant en locatie van een CVA. Verbetering over de tijd op

executief functioneren en aandacht, gemeten met de Stroop, was wel afhankelijk van kant van

een CVA: rechter kant verbeterde meer dan linker kant CVA patiënten. Men kan concluderen

4

dat het combineren van kant en locatie van een CVA geen statistisch behulpzaam effect heeft

op het voorspellen van het herstel van cognitief functioneren na een CVA.

Keywords: CVA – Locatie – Kant – Executief functioneren - Aandacht

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Acknowledgements

This research project was supported by Tilburg University, the Netherlands. I

thank dr. R. Mark and drs. A. van Boxtel for their advise, dr. P. de Kort for

providing access to his patient population, drs. G. Nefs for the data collection

at the TweeSteden Hospital, and finally drs. M. van Rijsbergen for the data

collection at the St. Elisabeth Hospital and her advise and help coordinating

this study.

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Introduction

Stroke and cognitive impairment

In The Netherlands, about 41.000 patients suffer a stroke each year [1]. The

prevalence of cognitive impairment after stroke is high, varying from 35.2-60.7% [2-

6]. Cognitive domains reported to be the most likely impaired are memory, mental

speed, attention and executive functioning. Executive functioning measured in the

acute phase post-stroke predicts cognitive functioning in the long term [7] and may

be influenced by side [7, 8] and location [7-9] of a stroke. Being able to predict

cognitive functioning is useful for clinicians to improve discharge decision,

programming of rehabilitation strategies, and better prepare patients for the

problems they can be presented with in daily life. The current study will take a closer

look at the recovery course of executive function and attention post-stroke. Also, it is

explored if the recovery course is different between the four subgroups: right sided

cortical, left sided cortical, right sided subcortical and left sided subcortical stroke

patients.

Side and location of stroke

Research shows that cognitive functioning is dependent on side and location of the

stroke [2-4, 7, 10, 12]. Hemispheric side of stroke seems to have implications for

general cognitive functioning [3, 11], but research is ambiguous on this topic [13, 14].

Research that did find lateralization, showed in general that stroke on the left side of

the brain implicated a lower score on all cognitive domains [2, 11, 12]. Not only side

of stroke but also location of stroke has its implications on cognitive impairment after

stroke. It is reported that a left sided, cortical stroke is associated with a higher

cognitive impairment than a right sided, cortical stroke (measured 3 weeks [7]and 3

7

months [8] post-stroke). No such discrepancy was found between left and right sided

subcortical strokes [7]. It was also found that patients with Subcortical Ischemic

Vascular Disease (a small vessel disease that is characterised by extensive cerebral

white matter lesions and lacunar infarcts in deep grey and white matter structures

[15]) 3 months post stroke, showed more executive dysfunction than other stroke

patients [9, 16]. This suggests that location of the stroke (cortical or subcortical) may

in turn determine a patients’ cognitive impairment profile. Specific research on the

cognitive profile of cortical or subcortical stroke is scarce, while research on other

diseases, affecting the brain either cortically or subcortically, is more common. This

research indicates a different cognitive impairment profile for subcortical diseases

like Parkinson’s disease and Lewy Body Disease in comparison to cortical diseases

like Alzheimer’s Disease [17-19]. A specific cognitive impairment profile of the

subcortical-type was found by Janvin et. al. [19] whereby their Parkinson’s and Lewy

Body Disease patients showed executive, visuoconstructive and attention

impairment and relatively good memory, assessed using the Dementia Rating Scale.

Cognitive impairment profile of a cortical-type was exhibited by most (67%)

moderate Alzheimer Dementia patients, characterized by relatively more impaired

memory performances and better performances on executive, visuo-construction and

attention [19]. These results suggest that executive functioning and attention were

more impaired among subcortical disease patients, compared to cortical disease

patients [17-19]. Since these two cognitive domains differ between the cognitive

profile of subcortical and cortical disease, the current study focused on executive

functioning and attention.

8

Executive functioning and attention

Executive function is defined as “mental processes involved in goal-directed

behavior”, encompassing a wide array of subfunctions related to attention, will,

planning and effective performance [20]. Executive functioning is a global term and is

measured by many different neuropsychological tests. Attention refers to “several

different capacities or processes that are related to aspects of how the organism

becomes receptive of stimuli and how it may begin processing incoming or attended-

to excitation” [21]. It contains four aspects: selective, sustained, divided and

alternating attention [20].

Stroop and the Trail Making Test

The Stroop test [22] and Trail Making Test (TMT) [23] are often used to

assess executive functioning (Stroop in [9, 10, 18, 24-26]; TMT in [7, 9, 10, 13, 24-

29]) and attention [4, 10, 22-24]. However, the Stroop does not purely measure

executive functioning or attention, the Stroop also measures working memory [10, 25]

and language [10].

The TMT [23] consists of scanning and visuomotor tracking, divided

attention, and cognitive flexibility and has two parts. During part A, the subject must

draw lines to connect consecutively numbered circles one to 25. In part B the subject

must connect consecutively numbered (1-13) and lettered circles (A-L) by alternating

between these two. Both tasks have to be completed as quickly as possible. Reaction

time in seconds is recorded on each trial. A large difference in time between both

parts (TMT B/A ratio) is an indication for problems in divided attention. This ratio

[9, 28], time to complete both trails [4, 9, 26-28] and errors made [4, 26] are the

variables of interest.

9

The Stroop Colour Word test [10, 22, 20] is a measure of selective attention

and interference susceptibility. It contains three trials of 100 items with the colours

yellow, green, blue and red. During trial one, the subject reads the words ‘yellow’,

‘green’, ‘blue’, and ‘red’ printed in black ink. During trail two, the subject reads the

colour names of coloured patches. Finally, during trail three, the subject reads the

name of the colour of the ink in which a colour name is printed. The print ink is a

different colour than the colour name (colour-word interference trial). The test is

based on the finding that it takes longer to complete trial three compared too one or

two. The variables of interest are the time needed to complete each of the three

subtests [9, 26], the interference score (time trail 3 subtracted from time trail 2) [9, 10]

and errors made [9, 10, 26].

Executive functioning measured with the Stroop and Trail Making Test

Previous research, investigating the difference between a subcortical and cortical

cognitive profile, focussing on executive functioning and attention measured with

the TMT, find different results [4, 9, 28]. While Hochstenbach et al. [4] found no

effect of subcortical or cortical stroke on TMT performance (time and errors, assessed

2.3 and 27.7 months post-stroke), Jokinen et. al. [9] found that at 3 months post-

stroke TMT B/A ratio significantly differed between Subcortical Ischemic Vascular

Disease patients and other stroke patients. The time on TMT B and B/A ratio also

differed between patients with Subcortical Ischemic Changes (SIC) and without SIC

[28]. Patients with subcortical diseases had lower scores on the TMT time [24, 26] and

TMT B/A ratio [29] and errors [26] than healthy subjects.

Different performances based on location of stroke, were found for executive

functioning and attention as measured with the Stroop. Stroop performances were

worse for patients with a subcortical disease compared to other stroke types [9] or

10

Alzheimer disease (Lewy Body Disease patients performed worse than Alzheimer

Disease patients [18]. Patients with subcortical disease also had lower scores on the

Stroop time [25, 26], interference [25] and errors [26] compared to healthy subjects.

Previous research, investigating the difference between a left and right sided

stroke patients’ cognitive profile, focussing on executive functioning and attention

measured with the TMT and Stroop, find no differences in the cognitive profile [4, 10,

14]. Hochstenbach et. al. [4] found that side of stroke did not effect performances on

TMT, Max [14] concurred with these finding in children with a stroke. Stroop

interference was also not affected by side of stroke [10, 14].

Taking this research into account, one can conclude that subcortical disease

may have a negative effect on TMT and Stroop performances and one can hypothese

that subcortical disease affects TMT and Stroop scores more negatively than cortical

disease. Previous studies do not find an effect of side of stroke on TMT and Stroop

performances, but these studies did not look at the effect of side of stroke in

combination with location of stroke. Nys et. al. [7] did show lateralization on

executive functioning in combination with location of stroke (left cortical stroke had

lower executive functioning performances than right cortical stroke patients) but did

not use the Stroop or TMT. The current study combines location and side of stroke

and perhaps by combining them a difference in performance on the TMT and Stroop

may be found.

Recovery over time

Stroke has an effect on cognitive functioning as indicated above, yet, little is known

about the extent and recovery over time of cognitive functioning. A number of

studies have investigated recovery after stroke, most of them focused on general

cognitive recovery [3, 6, 7, 13, 31, 32] over a relatively short period after stroke,

11

usually 3 to 6 months [9, 33]. Long-term improvement in general cognitive function

does occur [4], as does executive functioning 10 [5] and 15 months post-stroke [34].

Attention measured by TMT errors and time performances also improve over 2 years

post-stroke [4]. Improvement on the TMT is related to side of stroke: left sided stroke

had a lower improvement on the TMT B and B errors made than right sided stroke

patients [4]. Performance on the Stroop also improves over time (tested 21 days and

6-10 months after stroke) [5].

These results suggest that Stroop and TMT performances appear to improve over

time, and at least for the TMT, this improvement is dependent on side of stroke.

There is little research on differences on improvement over time of TMT

performances associated with location of stroke, or of Stroop performances

associated with either side or location of stroke.

Clinical implication

Side and location of stroke are diagnosed in the acute phase after stroke. They may

influence and predict the recovery on cognitive functioning after stroke. Research

found that neuropsychological testing at an early stage to 2 years after stroke showed

a stable profile with respect to abnormalities on the different tasks [11], thereby

implicating that cognitive evaluation in the early phase post-stroke has predictive

value for cognitive functioning in the long-term. Longitudinal research found that

cognitive impairment identified in a early phase post-stroke (3 months), predicts

functional impairment in the long term (4 years [4]). Executive functioning measured

within 3 weeks post-stroke is a good predictor of cognitive impairment and attention

is a good predictor of functional impairment 6 to 10 months post-stroke [5].

However, little is known about the recovery of executive functioning and attention

measured with the TMT and Stroop in the long term and the influence of side and

12

location of stroke. Measuring executive functioning and attention with the TMT and

Stroop in an early phase after stroke and using side an location of stroke to predict its

course of recovery may give clinicians an indication what to expect for a patient on

cognitive performance and functional outcomes and thus be able to accurately

identify those patients who are at risk of this impairment. This is important because

even small cognitive deficits have an influence on rehabilitation [35]. Knowing the

course of recovery could improve discharge decision, programming of rehabilitation

strategies, and better prepare patients for the problems they can be presented with in

daily life.

Current study

The aim of the current study was twofold:

1. To compare the performances on TMT and Stroop between left/right sided

and cortical/subcortical stroke patients and their effect on the recovery

course.

2. To delineate a 15 months post-stroke profile of TMT and Stroop performances

and explore if executive functioning and attention performances improve

over time.

The hypotheses were as follows:

By looking at the interaction effect of side and location of stroke, a

discrepancy on TMT and Stroop performances is expected between the four groups.

Performances will be more impaired among subcortical [9, 18], left sided [7] stroke

patients compared to cortical [9, 18], and right sided [7] stroke patients.

There will be a significant interaction effect of side, location and time.

Previous research found more improvement for right sided stroke patients than left

13

sided [4]. However, no other research studied the improvement of TMT or Stroop

performances in relation to side or location of stroke. Therefore, hypotheses about

the direction of improvement for location of stroke can not be made.

Although cognitive functioning in the long-term stays stable for most patients

[4, 36] and only few improve (from 7.8 % to 18%) [5, 36, 37], both attention [4] and

executive functioning [5] improved significantly post-stroke. It is to be expected that

performances in the current study will show a small but significant improvement

over 15 months.

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Method

Participants

The subjects for this study consists of stroke patients discharged home from the stoke

unit of the St.-Elisabeth Hospital in Tilburg. Patients were included and contacted if

they had suffered an ischemic stroke or intracerebral haemorrhage. Patients were

excluded using the criteria described underneath:

� were diagnosed with a transient ischemic attack (TIA);

� were diagnosed before with a stroke;

� had a pre-existing psychiatric or neurological disorder;

� had a pre-existing cognitive impairment, including any type of dementia

(based on a score >0.5 on the Clinical Dementia Rating Scale);

� had a disturbed consciousness at time of evaluation;

� had a poor comprehension of the Dutch language;

Subjects were included if they signed an informed consent to participate. A total of

110 subjects participated in the baseline measurement, 81 participated in the follow-

up at 6 months and 37 participants remained in the follow-up at 15 months (see

Table 1 for flow-chart). Only 26 participants completed their 3, 6 and 15 months

measurements and were included in the analyses of the current study.

The demographic, stroke and medical characteristics which were collected are

presented in appendix I. The sample consisted of 17 (65.4 %) males and 9 (34.6 %)

females, with a mean age of 65.46 years (st.d. 10.41; range 47-82). Education level

ranged from less than 8 years primary school to full academic training: 4 participant

with low education level, 14 with average and 8 with high education. Most of the

participants had a partner (N=20, 76.9%), while 3 participants (11.5 %) were

widowed, 2 had a life partner (7.7) and 1 divorced (3.7%). Concerning stroke

characteristics, all participants had suffered an ischemic stroke and it was their first

15

stroke. According to medical records, 11 (42.3 %) patients had a stroke located in the

right and 15 (57.7 %) in the left hemisphere. In 8 (30.8 %) of the cases, the stroke had

damaged cortical regions, while 18 (69.2 %) participants had experienced a stroke

subcortically. Comorbidity was relatively low, except for hypertension (n = 17; 65.4

%) and lipid disorders (n = 17; 65.4 %). Aspirin, statins and diuretics were used most

often by 21 (80.8%), 19 (73.1%) and 12 (46.2%) of the participants, respectively.

Procedure

Two and a half months after their stroke, patients received a letter in which it was

explained that they will be asked to participate in a study. Information about the

study was included. One week after they had received the letter, a medical

psychology intern contacted the patients by phone and explained the study again

and asked them if they were willing to participate in the study. Patients were invited

to the hospital for the assessment. If mobility was a problem, patients were assessed

at their home (a total of 3 (3,85%) assessments took place at home). The first

assessment (T0) took approximately 1.5 hours, carried out by the medical

psychology intern and comprised an interview to collect demographic information

(see Appendix I), a battery of questionnaires and a neuropsychological examination

(see Table 2).

Six months after stroke (T1), patients that were assessed at 3 months post-stroke,

were contacted for a follow-up. The exact same procedure as the assessment at 3

months post-stroke was used to collect the data. 15 Months post-stoke (T2) patients

were contacted again and identically assessed.

16

Clinical data

Some clinical data was collected from the digital medical file of the patients. At

baseline, clinical information was collected from medical records (see Appendix I).

Data regarding stroke subtype (ischemic / hemorrhagic), stroke location (left / right;

supratentorial / infratentorial), number of stroke (first ever; prior event), co-

morbidity, and medication use was noted. Stroke location was based on the

evaluation of computed tomography scans by the attending neurologist during the

initial hospital admission.

Instruments

Patients were assessed cognitively with a broad neuropsychological test battery.

Instruments that were used in the study are described in Table 2. Further

information about the tests and questionnaires used in this study can be found in

Appendix II. The neuropsychological tests were presented in 3 different sequence

orders across subjects in an attempt to control for possible fatigue effects (see

Appendix III). Patients are randomly assigned to one of these sequences. Due to

(time) constrictions of the tests, not all tests have the same rank order position. Thus,

despite randomisation, fatigue may play a larger role in some tests than in others.

Design

The present study uses a repeated measures design with multiple dependent

variables. There was no control group included due to practical reasons and time

constraints. Patients’ performances were compared to their own performances over

time, therefore functioning as their own control group. Individual test performances

are also compared between subjects.

17

Statistical analysis

Research indicated that parametric tests are robust for the violation of the

assumptions of parametric statistics: i.e. normally distributed, homogeneity of

variance, interval or ratio data, and independence. Therefore, only parametric tests

were used, even though most of the data was not normally distributed. Most of the

data on the instruments are interval (see Table 3). Due to the fact that research is

ambiguous on the effect of side, location and time, all tests will be two-tailed. A p-

value of less than 0.05 is considered to indicate statistical significance. All analyses

are performed with SPSS Statistics 16.

When comparing the four groups based on side and location of stroke on

demographic and clinical variables, ANOVA, X² tests and the Kruskal-Wallis test

were used.

To test for the influence of side and location of stroke on cognitive

functioning over time, a MANOVA for repeated measures was applied for data of

the 26 participants who participated at T0, T1 and T2. In this model, location

(cortical, subcortical) and side (right, left) were used as between-subjects variables

and Time (T0, T1, T2) as within-subjects variable. As dependent variables, TMT-A

raw score, TMT-B raw score, TMT Interference B/A ratio, TMT A errors, TMT B

errors, Stroop card 1 raw score, Stroop card 2 raw score, Stroop card 3 raw score,

Stroop Interference T-score, Stroop 1 errors, Stroop 2 errors and Stroop 3 errors were

used.

18

Results

Comparison of participants on demographic and clinical variables

There were no significant differences found between the 4 groups (right cortical,

right subcortical, left cortical and left subcortical stroke) and medical characteristics,

medication and demographic variables, except for the medication ACE inhibitors

(X2=8.702; p=0.034) (see Table 4). It is not expected that ACE inhibitors have an effect

on cognitive functioning, therefore it is expected that this difference will not have an

influence on the performance on the TMT or Stroop.

Effect of side and location of stroke on TMT and Stroop performances

Table 5 shows the mean scores and their standard deviations for all the

neuropsychological tests for the 4 groups. The MANOVA for repeated measures

revealed no significant interaction for the between-subjects factors ‘location’ and

‘side’ for any scores on the tests as described in table 6, except for errors made on the

Stroop 2 [(F1, 18) = 10.18, p=0.005)]. This indicates that there is a difference between

the 4 groups and their errors made on the Stroop 2 (see Figure 1). The effect size for

the group variable (partial eta squared = 0.361) can be classified as a large effect

using Cohen’s criterion [38]. The performances are as follows: cortical right sided

stroke patients have a better performance than subcortical right sided and subcortical

left sided stroke patients have a better performance than cortical left sided.

All main effects were non-significant as well, except on the Stroop 1. There is

a between subjects main effect for side of stroke on Stroop 1 errors [(F 1,18)= 10.175,

p= 0.005, η2= 0.361] (see Figure 2). This figure shows that left sided stroke patients

improve in their performance and stabilize after 6 months. Right sided stroke

patients make the same amount of errors at T0 and T1 and then there performance

19

drops. There is almost a significant between subjects main effect for location of stroke

on TMT B/A ratio [(F 1,21)= 1.967, p= 0.087, η2= 0.133] (see Figure 3). As the figure

shows, subcortical stroke patient had a more impaired performance on the TMT B/A

ratio, compared too cortical stroke patients.

Effect of side and location of stroke on the recovery course of TMT and Stroop performances

A MANOVA for repeated measures (Table 7) was conducted and the within-

subjects effects were investigated to indicate the main and interaction effect of

location and side of stroke on cognitive functioning three, six and fifteen months post

stroke. Twelve dependent variables were used: TMT A-B, errors A and B and B/A

ratio, Stroop card 1-2-3 and Interference T-scores as well as errors on card 1-2-3.

Location and side were between-group independent variables, while timing of

assessment (three, six and fifteen months post stroke) was a within-group factor. For

the TMT and Stroop performances, the interaction effect of location, side of stroke

and time did not reach statistical significance. This indicates that there was no

difference in the recovery course of TMT or Stroop performances over 15 months

post-stroke, between the 4 groups of participants.

There is a linear interaction effect of time and side of stroke for Stroop 3 [(F 1,

21)= 3.876, p=0.038, η2= 0.279]. The means of left and right stroke patients show a

difference on the Stroop 3 with right sided performance improving over time and left

sided worsening over time (see Figure 4). The effect size is large. For all other Stroop

and TMT performances, the interaction effects of time and location as well as time

and side remained non-significant.

20

Effect of time on TMT and Stroop performances

There is a significant linear improvement in time on the Stroop interference T-

score [(F 1,20 )= 4.371, p=0.027, η2= 0.315] and Stroop 3 errors [(F 1,18)= 9.336, p=

0.002, η2= 0.524). Both the effect sizes are large. The significant improvement takes

place between T0 and T2 for Stroop interference [t=3.467, df=23, p= 0.002) and Stroop

3 errors (t=-3.674, df=19, p=0.002). There is no significant improvement in time on

any other of the TMT or Stroop performances.

Discussion

The effect of side and location of stroke on TMT

Previous research, investigating the difference between a left/right,

subcortical and cortical cognitive profile, focussing on executive functioning and

attention measured with the TMT, find different results [4, 9, 28]. Some research

found more impaired performances among subcortical [9, 18], left sided [7] stroke

patients compared to cortical [9, 18], and right sided [7] stroke patients. By looking

at the interaction effect of side and location of stroke, a discrepancy on TMT and

Stroop performances was expected between the four groups. However, the current

study found no significant main or interaction effect of side and location of stroke for

TMT performances. It was hypothesized that by combining side and location of

stroke a significant effect could be found on TMT performances, yet no such effect

was found on any TMT performance. This result is supported by the study of

Hochstenbach et. al. [4] who found no effect for location of stroke on the errors made

and time to complete the TMT. Jokinen et. al. [9] did find a main effect of location for

TMT B/A ratio, an aspect of the TMT which Hochsenbach et. al. [4] did not take into

account. In the current study a non-significant trend was found for location of stroke

21

on TMT B/A ratio. Both the present study and Jokinen et. al. [9] found a more

impaired performance for subcortical stroke patients. Jokinen et. al. [9] used a much

larger sample size (n=323). Perhaps with a larger sample size, a significant result

could be found in the present study as well. All other research that found a

significant difference between subcortical and cortical cognitive profile was done on

a population with other subcortical or cortical diseases than stroke. One can conclude

that this research on other diseases may not be generalized to stroke patients.

The effect of side and location of stroke on Stroop

Exploring the performances on the Stroop, the current study found no

significant main effect for side of stroke except on Stroop 1 errors. A poorer

performance for left sided patients was hypothesized, but left sided stroke patients

showed a better performance and improvement than right sided stroke patients. The

hypothesis was based on the expectation that by combining side and location of

stroke a significant effect could be found on Stroop performances, yet no such effect

was found on Stroop error 1 performances. Previous research found no significant

main effect for side of stroke [10, 14], the results of the present study supports this.

The present study did not find a significant effect for location of stroke. It

was hypothesized, based on Jokine et. al. [9] that subcortical stoke patients would

have a more impaired performance on the Stroop. The present study and Jokine et. al.

[9] show many resemblances: both have a measurement at 3 months post stroke and

measure the same aspects of the Stroop. The fact that these studies do not agree on

the effect of location on Stroop performances concurs with previous research finding

different results on this topic.

Exploring the performances on the Stroop, the current study found no

significant interaction effect for side and location of stroke except on Stroop 2 errors.

22

The performances are as follows in descending order: subcortical left sided stroke

patients have a better performance than cortical right sided, followed by cortical left

sided and finally subcortical right sided stroke patients. No previous research

explored the interaction effect of side and location of stroke on Stroop performances.

Nys et. al. [7] did show a significant interaction effect of side and location of stroke on

executive functioning (left cortical stroke patients had lower executive functioning

performances than right cortical stroke patients). The present study and the study of

Nys et. al. [7] agreed on left cortical stroke patients having a lower performance on

executive functioning than right sided, however the present study also found that

left sided subcortical stroke patients have a better performance than right sided

subcortical stroke patients. The difference may be explained by the fact that Nys et.

al. [7] did not use the Stroop to measure executive functioning.

The interaction effect of time, side and location

The second aim of this study is to explore if the course of executive

functioning and attention performances over time is dependent on location or side of

stroke. It was hypothesized that there would be a significant interaction effect of side,

location and time. However, no other research studied the improvement of TMT or

Stroop performances in relation to location of stroke. Therefore, hypotheses about

the direction of improvement for location of stroke could not be made. For the TMT

performances, the interaction effect for location, side of stroke and time did not reach

statistical significance. This indicates that there was no differences in TMT

performances over 15 months post stroke between the 4 groups.

The present study did not find a significant interaction effect for location and

time on the Stroop performances or for side and time, except for the 3rd Stroop card.

23

There is a linear interaction effect of time and side of stroke, with right sided stroke

patients performance improving over time and left sided worsening over time (see

Figure 4). This is the same interaction as Hochstenbach et. al. [4] found for TMT B

time and error performance over time. With the TMT B and the 3rd Stroop card both

measuring divided attention, set shifting/mental flexibility, one can assume that the

improvement over time of these aspects of attention and executive functioning may

be affected by side of stroke.

The effect of time

The third aim of this study was to explore the course of executive functioning and

attention performances over time in stroke patients. Although cognitive functioning

in the long-term stays stable for most patients [4, 36] and only a few improve (from

7.8 % to 18%) [5, 36, 37], both attention [4] and executive functioning [5] improved

significantly post-stroke in previous research. It was expected that performances in

the current study would show a small but significant improvement over 15 months.

Results show that there is no significant improvement or decline on TMT

performances or most Stroop performances and therefore no improvement on

attention or executive functioning, over 15 months. There was, however, a significant

improvement on Stroop interference and errors made on the 3rd Stroop card , which

implicates that attention, mental flexibility, interference and response inhibition (see

Table 1) have improved. The unique aspects of executive functioning that the Stroop

interference and the errors on the 3rd Stroop card measure, but the other sections of

the Stroop do not, is ‘interference’ and ‘response inhibition’. One can suggest from

these results that only interference and response inhibition improve over time.

Exploring the improvement over time, it was found that there is only a significant

difference between 3 and 15 months post-stroke. Thus, improvement does occur but

24

only in the longer term. This improvement on the Stroop was also found by Nys et.

al. [5] tested 21 days and 6-10 months post-stroke. Previous research also found a

significant improvement on TMT time and errors [4], though, no such improvement

was found in the present study. However, this improvement occurred over 2 years

[4]. Taking into account that improvement on the Stroop also was in the long-term

(15 months), one can perhaps explain why TMT improvement did not yet occur in

this research. Maybe improvement on the TMT will only occur over a long period of

time and measurement times of a study should be adjusted accordantly.

Conclusion

Taking all previous research and results from the present study into account,

one can conclude that there is only marginal evidence that side or location of a stroke

has an effect on executive functioning and attention over time. Previous studies do

not always find an effect of side and location of stroke on TMT and Stroop

performances, but these studies did not look at the interaction effect of side and

location of stroke. The current study aimed to find an effect of side and location by

combining them. However, this study did not find an interaction effect of side and

location on the course of recovery on TMT score. The same can be said for

performances on the Stroop. Thus, combining location and side of stroke in order to

find a difference on recovery did not find a significant result.

There were some interaction between time and side of stroke. For example the

performance on the 3rd Stroop card with right sided performance improving over

time and left sided worsening over time. This result in combination with the research

from Hochstenbach et. al. [4] may implicate that side of stroke has an effect on the

recovery of divided attention and set shifting/mental flexibility with worsening

25

performances for left sided stroke patients and improving performances for right

sided.

The present study did not find a significant interaction effect for location and

time on the Stroop performances. However, there was a trend found for location of

stroke on TMT B/A ratio measuring set shifting. This result is supported by other

research [9]. Set shifting may be affected by location of stroke, with subcoritcal stroke

patients showing a more impaired performance. All other research that found a

significant difference between subcortical and cortical cognitive profiles was done on

a population with other subcortical or cortical diseases than stroke. One can conclude

that the cognitive profile of stroke patients can not be compared with the cognitive

profile of patients with other subcortical or cortical diseases.

The current study found no significant interaction effect for side and location

of stroke except on Stroop 2 errors, with subcortical left sided stroke patients having

a better performance than cortical right sided, followed by cortical left sided and

finally subcortical right sided stroke patients . Because all other Stroop performances

did not show a trend in interaction between side and location, the value of the effect

found on one aspect of the Stroop, is diminished.

Previous research found no significant main effect for side of stroke on Stroop

performances [10, 14], the results of the present study supports this. Neither did the

present study find a significant effect for location of stroke. It was hypothesized,

based on Jokine et. al. [9], that subcortical stoke patient would have a more impaired

performance on the Stroop. The fact that present study and the study of Jokine et. al.

[9] show many resemblances, but do not agree on the effect of location on Stroop

performances concurs with previous research finding different results on this topic.

Neither the Stroop or the TMT performances improved over 15 months for

any of the 4 groups (left cortical, right cortical, left subcortical and right subcortical

26

stroke patients) except for Stroop interference and errors on the 3rd Stroop card. This

result seems logical: if a patient has lower interference, a lower number of errors is

made. The unique aspects of executive functioning that the Stroop interference and

the errors on the 3rd Stroop card measure but the other sections of the Stroop do not,

is ‘interference’ and ‘response inhibition’. So one can conclude that over 15 months

interference and response inhibition improved and this improvement only occurred

on the longer term (over 12 months). Maybe improvement on other aspects of the

Stroop and on the TMT will only occur in the long term, and the current study does

not have a long enough measurement time to find a significant improvement on

them yet.

Overall, one can conclude that there is no statistical beneficial effect of

combining location and side of stroke in predicting the recovery course of stroke

patients. If improvement occurs, it is on the long term. Improvement is not

dependent on side or location of stroke. There are some differences between side and

location of stroke, but the effects found are not found in other aspects of the same

test, this diminishes the effect found on only one aspect of the test. The most

significant effects were found in Stroop performances, a task not yet explored by

much previous research. It is still not clear if location and side have any effect on

executive functioning and attention at all.

Limitations

One of the limitation of the present study is the size of the population: it may

be relatively small. There was only a limited time to collect data (24 months in total)

and therefore around 26 follow-up assessments at 15 months post-stroke could be

included in the analysis.

For several reasons the degree to which results can be generalized is limited.

27

The duration of the assessments is a reason why some stroke patients who were

selected, refused to participate. The assessment takes 1.5 hours and the

questionnaires that had to be filled out at home take approximately an hour on top of

that. This may discourage many patients with a busy life. It is also a fatiguing

assessment, therefore older patients may not be willing to participate. Older patients

were not more likely to drop out this study (mean age on 3 months was 66.42 (12.95),

at 6 months 65.47 (11.13) and at 15 months 65.46 (10.41). People with severe physical

or psychological problems usually are not willing to participate in a study. Also,

patients with little complaints after stroke do not see the need for them to participate

in a study examining the effects of stroke. Including only patients that were

discharged home (about 50% of the total stroke patients), limits the sample size as

well. This study has three assessment points in time and therefore is very susceptible

to drop-outs. A consequence of a small sample size is the reduction in statistical

power.

Another small limitation is the lack of a healthy control group. The

performances on the TMT and Stroop had to be compared within subjects and

between subjects. Due to time restrain it was not possible to create a control group.

Without a healthy control group one can not explore if recovery in stroke patients is

significant.

The location and side of stroke are not clear cut variables. Stroke diagnosis

and location were based on CT scans and evaluated according to standard but

limited criteria, which may have missed some important clinical characteristics. For

example, the distinction between anterior and posterior regions of the brain was not

taken into account. It is also hard to decide if a stroke only occurred in the subcortical

region of the brain or if other parts of the brain were involved. Also, the relationship

between location of stroke and functional outcome is difficult because the

28

(sub)cortical regions interact with other parts of the brain, as does the left and right

side of the brain. There is no linear correlation between damage in one area of the

brain and its effects on (cognitive)functioning. Thus, cognitive functioning results

found in the present study in patients with the majority of the damage subcortically,

does not indicate that this deficit can be entirely attributed to the subcortical location

of stroke, there are interactions in the brain that may have been affected by the

stroke.

Implications for clinical treatment and future research

Overall there is little known about the effect of side, location and time on the

Stroop. Yet, in this study the most significant effects were present in Stroop

performances. The Stroop task is an area left to be explored in future research on the

effect of side and location on executive functioning and attention. It is advised that

future research should focus on the Stroop task. If recovery on executive and attention

performances took place, it was on the long-term. In this study almost all

performances (except 2 aspects of the Stroop) did not show improvement over time,

while previous research showed that it does occur over a 2 year period. Future

research should be long-term, preferably 2 years.

Side and location of stroke are diagnosed in the acute phase after stroke. This

study aimed to find an influence of side and location on the recovery of cognitive

functioning after stroke. Longitudinal research found that cognitive impairment

identified in a early phase post-stroke (3 months), predicts functional impairment in

the long term (4 years [4]). Executive functioning measured within 3 weeks post-

stroke is a good predictor of cognitive impairment and attention is a good predictor

of functional impairment 6 to 10 months post-stroke [5]. Knowing what to expect

29

with respect to the cognitive functioning of a patient could help to improve

treatment. Unfortunately, no such clear-cut relation between side and location of

stroke was found. Therefore it is hard to incorporate the result from this study into

an advise for clinical treatment. This study only found a poorer result for right sided

subcortical stroke patients, followed by left sided cortical, right sided cortical and

finally best results for left sided subcortical stroke patients on executive functioning

(measured with errors made on the 2nd Stroop card). There was an improvement in

right sided stroke patients and a descending performances for left sided stroke

patients on divided attention and set shifting/mental flexibility (measured with the

3rd Stroop card). Taking these results into account, one could say that right sided

stroke patients may have problems with attention and executive functioning,

especially divided attention and set shifting/mental flexibility, but they will improve

over time. However, left sided stroke patients, cortical al well as subcortical, need to

be warned about the difficulty they will encounter on these cognitive domains. In the

treatment extra attention should be paid to planning activities where they will have

to divide their attention, like cooking. Extra practical advise could be given to this

left sided stroke patients, knowing they will encounter more difficulties then the

right sided stroke patients. Adapting treatment to research finding like this paper

suggests, will better prepare a patient on what is to come. Future research should

aim to find more clinical, demographic or medical variables that effect the course of

recovery, like this study, to adapt treatment of stroke patient accordantly.

30

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Table 1. Flow-chart of study sample

35

Table 2. Instruments and questionnaires used

Name of the test Rating scales

Clinical Dementia Rating Scale Total score (0 – 3; cut-off > 0.5)

Cognitive Impairment / Dementia

Trail Making Test total seconds trail A Attention Executive functioning: Speed of mental processing

Trail Making Test total seconds trail B Divided attention Executive functioning: Speed of mental processing Set shifting

Trial Making Test B/A ratio Divided attention Executive functioning: Set shifting

Trail Making Test errors A

Attention Executive functioning

Trail Making Test errors B Divided attention Executive functioning: Set shifting

Stroop colour word test Total seconds chart 1 Total seconds chart 2 Total seconds chart 3

Working memory Language Attention Executive functioning: Mental flexibility Interference

Stroop colour word test errors chart 1 (max. 100) errors chart 2 (max. 100) errors chart 3 (max. 100)

Working memory Language Attention Executive functioning: Mental flexibility Interference Responds inhibition

Neuropsychological Exam

ination

Stroop color word test interference raw score Working memory Language Attention Executive functioning: Mental flexibility Interference Responds inhibition

36

Table 3. Statistical tests used on demographical and clinical variables, as well as instruments used during neuropsychological examination.

Variable Data Statistical Test

Age Interval ANOVA

Gender Categorical Chi-square test

Marital status Categorical Chi-square test

Demographic

Level of education Ordinal Kruskal-Wallis test

Stroke characteristics Categorical Chi-square test

Vascular risk factors Categorical Chi-square test

Clinical

Medication Categorical Chi-square test

Trail Making Test total seconds trail A

Interval ANOVA

Trail Making Test total seconds trail B

Interval ANOVA

Trial Making Test B/A ratio Interval ANOVA

Trail Making Test errors A Interval ANOVA

Trail Making Test errors B Interval ANOVA

Stroop color word test Total seconds chart 1 Total seconds chart 2 Total seconds chart 3

Interval ANOVA

Stroop color word test interference raw score

Interval ANOVA

Neuro-psychological examination

Stroop color word test Total errors chart 1 Total errors chart 2 Total errors chart 3

Interval ANOVA

37

38

39

Table 6. Between subject interaction effect of location * side on test performances Measurement F p-value η2-value TMT A 0.615 0.441 0.027 TMT B 1.208 0.284 0.052 TMT B/A 0.787 0.385 0.036 TMT A error 0.475 0.498 0.020 TMT B error 0.217 0.646 0.010 Stroop 1 0.256 0.618 0.012 Stroop 2 0.669 0.423 0.031 Stroop 3 0.640 0.433 0.030 Stroop Interf. 0.988 0.332 0.047 Stroop 1 error 0.022 0.885 0.001 Stroop 2 error 10.175 0.005** 0.361 Stroop 3 error 0.000 1.000 0.000 Note. * Significant at an alpha level of .05. ** Significant at an alpha level of .01 Table 7. Within subject effect of location and side of stroke on test performances . Measurement F p-value η2-value Wilks lambda

TMT A Time 1.469 0.253 0.123 0.877 Time * location 0.677 0.519 0.061 0.939 Time * side 0.113 0.893 0.011 0.989 Time * loc. * side 1.664 0.213 0.137 0.863 TMT B Time 0.500 0.951 0.005 0.995 Time * location 0.991 0.388 0.086 0.914 Time * side 0.596 0.560 0.054 0.946 Time * loc. * side 0.704 0.506 0.063 0.937 TMT B/A Time 1.158 0.334 0.104 0.896 Time * location 1.139 0.340 0.102 0.898 Time * side 0.260 0.774 0.025 0.975 Time * loc. * side 0.111 0.895 0.011 0.989 TMT A error Time 0.027 0.871 0.001 0.999 Time * location 0.027 0.871 0.001 0.999 Time * side 0.027 0.871 0.001 0.999 Time * loc. * side 0.027 0.871 0.001 0.999 TMT B error Time 1.095 0.354 0.099 0.901 Time * location 0.451 0.643 0.043 0.957 Time * side 1.571 0.232 0.136 0.864 Time * loc. * side 0.986 0.390 0.090 0.910 Stroop 1 Time 1.083 0.358 0.098 0.902 Time * location 0.830 0.451 0.077 0.923 Time * side 0.389 0.682 0.037 0.963 Time * loc. * side 1.422 0.265 0.125 0.875

40

Stroop 2 Time 0.295 0.747 0.029 0.971 Time * location 0.891 0.426 0.082 0.981 Time * side 0.268 0.767 0.026 0.974 Time * loc. * side 0.013 0.987 0.001 0.999 Stroop 3 Time 0.750 0.485 0.070 0.930 Time * location 0.002 0.997 0.000 1.000 Time * side 3.876 0.038* 0.279 0.721 Time * loc. * side 1.636 0.220 0.141 0.859 Stroop Interf. Time 4.371 0.027* 0.315 0.685 Time * location 0.583 0.568 0.058 0.942 Time * side 2.313 0.126 0.196 0.804 Time * loc. * side 1.677 0.213 0.150 0.850 Stroop 1 error Time 0.165 0.850 0.019 0.981 Time * location 0.165 0.850 0.019 0.981 Time * side 0.152 0.340 0.119 0.881 Time * loc. * side 1.152 0.340 0.119 0.881 Stroop 2 error Time 1.030 0.378 0.108 0.892 Time * location 0.190 0.829 0.022 0.978 Time * side 0.129 0.880 0.015 0.985 Time * loc. * side 2.178 0.144 0.204 0.796 Stroop 3 error Time 9.336 0.002** 0.524 0.476 Time * location 1.365 0.282 0.138 0.862 Time * side 1.608 0.229 0.159 0.841 Time * loc. * side 3.238 0.064 0.276 0.724 Note. * Significant at an alpha level of .05. ** Significant at an alpha level of .01

41

Figure 1. Mean errors made on Stroop card 2 for left/right sided, cortical/subcortical stroke patients.

Figure 2. Mean errors made on Stroop card 1 for left/right sided stroke patients over time.

42

Figure 3. Mean TMT B/A ratio for cortical/subcortical location of stroke patients over time.

Figure 4. Means seconds to complete Stroop card 3 for left and right sided stroke patients and their change over time.

43

Appendix I: Review of demographical and clinical variables used in the present study.

Variables Categories

Age Years

Gender Male / female

Partnership status Single / married / widowed / divorced / Partner living together / Partner not living together

Living situation Living together with partner / sibling / children / living alone

Level of education (1) primary school not finished / (2) primary school / (3) more than primary school without a diploma / (4) completed secondary school less than MULO / (5) MULO / (6) VHMO / (7) university degree obtained

Job before stroke Full-time / part-time / unemployed / unemployment due to illness or on sickness benefit / stay at home mother or father / retired

Rehabilitation after stroke and momentarily

No / Yes – day care / in the neighbourhood / admitted at a rehabilitation centre

Psychological /Psychiatric guidance before or after stroke

No / Yes - why

Smoking before or after stroke Never / No, stopped .. years ago / Yes smoke before and after stoke – cigarettes / shag / cigars / pipe

Alcohol intake before or after stroke

Never / Yes – beer / wine / heavy drinks - … glasses per week

Location intake alcohol At home / social gatherings / otherwise

Neurological problems before No / Yes – whiplash / traumatic brain injury / epilepsy / migraine / balance disorder

Dem

ographic variables

Cardiac problems before No / Yes – atrium fibrillation / myocard infarct

Stroke characteristics:

Ischemic / haemorrhagic

Lacunar Stroke (LAC) / Total Anterior Circulation (TAC) / Partial Anterior Circulation Stroke (PAC) / Posterior Circulation Stroke (POC)

Stroke type Large-artery atherosclerosis Cardioembolism Small-vessel occlusion, i.e. lacunar Stroke of other determined aetiology stroke of undetermined aetiology

Lesion location Supratentorial / infratentorial*

Clinical variables

Supratentorial Cortial / Subcortical

44

Location side Left / right

Vascular risk factors:

Diabetes mellitus Yes / no

Hypertension Yes / no

Hypercholesterolaemia Yes / no

Atrium Fibrillation Yes / No

Ischemic hart disease Yes / no

Decompensatio cordis Yes / no

Peripheral vain disease Yes / no

Stroke / TIA number

Medication:

Trombocyteaggr. Inhibitor Yes / no

Antiplatelets Yes / no

Anticoagulants Yes / no

Diuretics Yes / no

Beta-blockers Yes / no

ACE inhibitors Yes / no

Calcium channel blockers Yes / no

Angiotensin receptor Blockers

Yes / no

Statins Yes / no

Antidepressants Yes / no

Anxiolytica Yes / no

Analgetica Yes / no

* Supratentorial = cortical (frontal, parietal, temporal, occipital lobe) or subcortical (caudate nucleus, striatum, thalamus). Infratentorial = brain stem, cerebellum

45

Appendix II. Test descriptions

Clinical Dementia Rating Scale

The Clinical Dementia Rating (CDR) [39] scale rates severity of cognitive decline /

dementia on a 5-point scale:

- 0 no evidence of dementia

- 0.5 questionable dementia

- 1 mild dementia

- 2 moderate dementia

- 3 severe dementia

Ratings are based on information collected in a structured interview. The scale

contains six cognitive abilities, which each are scored 0 to 3:

1) memory

2) orientation

3) judgment and problem solving

4) community activities

5) home activities and hobbies

6) personal care

Ratings are based on cognitive abilities to function in these areas.

The global CDR is derived from the scores in each of the six categories as follows:

memory is considered the primary category and all others are secondary. Global

CDR is the score on memory if at least three secondary categories are given the same

score as memory. Whenever three or more secondary categories have a score greater

or less than the memory score, global CDR is the score of the majority of secondary

categories. The scale is reported to be a valid and reliable instrument [40].

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Trial Making Test

The Trial Making Test (TMT) [23] is a test of scanning and visuomotor tracking,

divided attention, and cognitive flexibility. The test is given in two parts, A and B.

- Part A: the subject must draw lines to connect consecutively numbered circles

one to 25.

- Part B: the subject must connect consecutively numbered (1-13) and lettered

circles (A-L) by alternating between these two.

Both tasks have to be completed as quickly as possible. Reaction time in seconds is

recorded on each trial. Usually, trial B is more difficult and takes longer to complete

than trial A. Difference in time between both parts is an indication for problems in

divided attention. Raw scores, adjusted for age and education, could be converted

into percentiles using normative data. Patients are considered to have problems in

divided attention and concentration on a percentile ≤ 16.

Psychometric qualities, both reliability and validity, of the Dutch version have been

reported to be unsatisfactory [41].

Stroop Color Word Test

The Stroop Color Word test [22, 30] is a measure of selective attention and

interference susceptibility. It contains three trials of 100 items with the colors yellow,

green, blue and red:

1) Read the words ‘yellow’, ‘green’, ‘blue’, and ‘red’ printed in black ink.

2) Call out the color names of colored patches.

3) Name the color of the ink in which a color name is printed. The print ink is a

color different than the color name (color-word interference trial).

The test is based on the finding that it takes longer to complete trial two compared to

one. Trial three is usually the hardest and takes even longer. The variable of interest

47

is the time needed to complete each of the tree subtests. Raw scores, adjusted for age,

education and sex, can be converted into percentiles. Patients are considered to have

problems in selective attention and sensitivity in interference on a percentile ≤ 16.

Reliability is reported to be good and content validity is satisfactory [41]. No research

has been done on criterion validity.

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Appendix III. Sequences of tests

1 2 3

MMSE Clock drawing Category fluency

FAB RBMT Stroop

RBMT Letter fluency RBMT

TMT Stroop MMSE

Category fluency FAB Letter fluency

Clock drawing Category fluency

TMT

Letter fluency TMT Clock drawing

Stroop MMSE FAB