chapter · chapter 7 | 97 long-term deficits in episodic memory after ischemic stroke: evaluation...

CHAPTER7

Schiemanck_totaal_v4.indd 95 06-03-2007 10:13:44

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Long-term deficits in episodic memory after ischemic stroke:

Evaluation and prediction of verbal and visual memory

performance based on lesion characteristics

Eveline A Schouten1, Sven K Schiemanck2,3,4, Nico Brand1, Marcel WM Post3,4

(1) Department of Clinical and Health Psychology, Faculty of Social Sciences, Utrecht University,

(2) Department of Rehabilitation, Academic Medical Center (AMC) Amsterdam,

(3) Center of Excellence for Rehabilitation Medicine, Rehabilitation Center De Hoogstraat Utrecht,

(4) Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands

Submitted


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Abstract

This study investigated the relationship between ischemic lesion characteristics (hemispheric side, cortical and subcortical level, volume) and episodic memory performance, one year after stroke. Verbal and visual memory performances of 86 ischemic stroke patients were asses-sed with the Rey Auditory-Verbal Learning Test (RAVLT) and the Baddeley Doors Test respectively. Ischemic lesion characteristics and presence of white matter lesions (WML) were assessed on magnetic resonance imaging (MRI). Verbal and visual memory performances were compared between patients with left-hemispheric and right-hemispheric lesions (side), cortical and subcortical lesions (level), and between anterior and posterior cortical lesions using multiple regression analyses. The results demonstrated that poor verbal memory performance of the patient (im-mediate and delayed recall and recognition) could be predicted by lesion characte-ristics obtained on MRI scans: patients with left-hemispheric, subcortical, and large lesions showed poor verbal memory performance. Poor visual recognition per-formance could not be predicted by lesion characteristics but only by the patient characteristic of low educational level. Our results suggest that lesion characteristics such as hemispheric side, cortical and subcortical level and lesion volume, play a more important role in poststroke episodic verbal memory performance poststroke than has been assumed up to now.

Introduction

Cognitive impairment is a common sequel of stroke (Hochstenbach et al., 1998a). It plays an important role in acute functional recovery (Madureira et al., 2001) as well as in long-term outcome such as independency and quality of life (Desmond et al., 1996; Hochstenbach et al., 1996). Memory is one of the cognitive domains frequently found to be affected after stroke (Brown & Eyler Zorrilla, 2001; Schnider & Landis, 1995). Memory function – involving the ability to register, store, save and retrieve information when needed (Lezak et al., 2004) – is particularly important in the process of rehabilitation after stroke, as it is required for learning new skills and relearning old ones (Hochstenbach, 2000). There are many case studies on memory impairment after stroke and its relation-ship with lesion location. However recently, group studies have been performed that investigated acute and chronic cognitive impairment (including memory impairment) after stroke and its relationship with a wide range of determinants, such as vascular risk factors, pre-existent neuropathology and lesion characteris-tics of volume and location (Hochstenbach et al., 1998a; 2003; Rasquin et al., 2004; Sachdev et al., 2004; Van Zandvoort et al., 2005). Yet most of these studies did not consider specific attention to memory impairment and used global indicators of memory function. Few stroke studies investigated memory impairment specifically (Lange et al., 2000; Sorokina et al., 2004) and distinguished between different types of information (i.e., verbal and non-verbal information) and stages of processing (i.e., encoding, storage and retrieval), although it has been frequently assumed that


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different neuroanatomical stroke sites lead to different memory impairments in terms of the type of information and stages of processing (Brown & Eyler Zorrilla, 2001; Ferro, 1995; Schnider & Landis, 1995). The influence of hemispheric lesion side on memory is well known. Verbal me-mory deficits have been consistently demonstrated to occur primarily after left-he-mispheric stroke, and non-verbal (visuo-spatial) memory deficits principally after right-hemispheric stroke (Lezak et al., 2004). However, there is increasing evidence suggesting that this distinction is not absolute: left hemispheric lesions have been reported to produce visual memory impairments, whereas verbal memory deficits are also observed after right hemispheric stroke (Brown & Eyler Zorrilla, 2001; Ferro, 1995; Schnider & Landis, 1995). Functional imaging studies showed either no lateralization of verbal and visual memory function, or only minimal lateralization of verbal memory function to the left hemisphere (Buckner et al., 1996; Gur et al., 1997; Herath et al., 2001). Other studies have shown an increased activity in left prefrontal regions during intentional episodic encoding, whereas episodic retrieval primarily activated right prefrontal brain regions (Buckner et al., 1996; Heun et al., 1999; Nyberg & Cabeza, 2000). Cortical and subcortical lesion levels have been shown to influence memory defi-cits. Previous studies have shown that stroke patients have more severe memory deficits with a cortical lesion than with a subcortical lesion (Madureira et al., 2001; Nys et al., 2005). This is not surprising, since several cortical areas have been demonstrated to play an essential role in episodic memory function. The posterior cortical region of the medial temporal lobe is widely recognized to mediate the associative, contextual and recollective aspects of episodic encoding and retrieval (Daselaar et al., 2004; Kirwan & Stark, 2004; Tsukiura et al., 2002). The multimo-dal association areas of the posterior cortex are generally assumed to be the site for long-term storage of episodic memories (Mayes, 2000; McClelland et al., 1995; Squire & Alvarez, 1995; Squire et al., 2001). Furthermore, results from imaging stu-dies have shown that regions of the anterior (prefrontal) cortex also take part in the networks mediating episodic memory processing (Nyberg & Cabeza, 2000; Tranel et al., 2000), probably facilitating (re)constructive and search processes of episodic en-coding and retrieval by its inherent executive functions (e.g., attentional processes, monitoring, and coordination) (Lezak et al., 2004; Mayes, 2000). Recent studies have shown the important role of subcortical structures in episodic memory (Corbett et al., 1994; Exner et al., 2001; Hochstenbach et al., 1998b; Middleton & Strick, 2000; Van Der Werf et al., 2000; Van Zandvoort et al., 2005). Lesions of the subcortical structure of the thalamus are associated with memory disorders. Results of ima-ging studies have suggested that memory deficits may also result from focal lesions of the anterior and medial cortical portions of the thalamus, particularly if there is involvement of subcortical white matter tracts such as the mammillo-thalamic tract (Exner et al., 2001; Van Der Werf et al., 2001; 2003). Furthermore, studies (Corbett et al., 1994; Hochstenbach et al., 1998b; Middleton & Strick, 2000; Van Zandvoort et al., 2005) have reported an impairment of short-term and long-term memory, particularly of encoding and recall, following stroke in the basal ganglia. Nevertheless, more research is needed to evaluate the influence of cortical and subcortical stroke lesions on memory impairment after stroke.


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Onlyafewstudieshaveexaminedtheinfluenceoflesionvolumeonpoststrokememoryfunction(Hochstenbachetal.,1998b;Nys,2005).However,lesionvolumeisknowntocorrelatemoderatelytostronglywithlong-termfunctionaloutcomeandqualityoflifeafterstroke(Schiemancketal.,2005).Inthisstudy,weinvestigatetherelationshipbetweenischemiclesioncharacteris-tics(side,level,volume)andepisodicmemoryperformance,oneyearafterstroke.Weexpectlong-termmemorydysfunctiontobemorepronouncedinpatientswithlefthemisphericratherthanrighthemisphericlesions,inpatientswithcorticallesionsratherthansubcorticallesions,inpatientswithanteriorratherthanposte-riorcorticallesions,andinpatientswithlargerlesionvolume.

Methods

Procedure

Thestudypopulationconsistedofpatientswithafirst-everischemicstrokeadmit-tedtooneofsixparticipatingstrokeunitsintheNetherlandsbetween1999and2001.Strokewasdefinedasarapidlydevelopingsignoffocalorglobaldisturbanceofcerebralfunctionwithsymptomslasting24hoursorlongerorleadingtodeath,withnoapparentcauseotherthanvascularorigin(1989).Theresearchproto-colwasapprovedbythemedicalethicscommitteeofUniversityMedicalCenterUtrecht.Afterinformedconsent,anMRIscanwasobtainedatameanof11days(SD3.5)afterstroke.ParticipantswerenottreatedwiththrombolysisorneuroprotectiveagentsandshowedavisiblelesionontheMRIscanasdiagnosedbyanindependentneuroradiologist.Measurementofinfarctlocalizationandvolumewasperformedblindedforthepatients’clinicalstatus(Schiemancketal.,2006).Patientsincludedhadasinglefirst-eversupratentorialnon-lacunarischemicinfarctionoftheante-riorcerebralartery(ACA),medialcerebralartery(MCA)orposteriorcerebralartery(PCA),wereagedbetween18and85years,hadapremorbidBarthelIndex≥18,astableneurologicalconditiononeweekafterstroke,anddidnotsufferfromanyphysicalormentalcomorbidity(e.g.,dementia)thatmightinfluenceneuropsycho-logicaloutcome.Patientswithborder-zoneinfarctionswerenotincluded.Afterameanof377daysafterstroke(SD22)patientsweretestedbyanexperiencedneuropsychologist,blindedforMRIfindingsandstrokecharacteristics.

Materials

Demographicvariables(age,gender,educationallevel)wereobtainedfromthepatient.EducationlevelwasscoredusingtherevisedDutchclassificationsystemofVerhage(1964):Levels1and2indicatealoweducationallevel;levels3through5anintermediatelevel;andlevels6and7ahighlevelofeducation.Sincethepre-senceofdepressionmightinfluencelong-termmemoryfunction,thepresenceofdepressionwasassessedwiththeCenterforEpidemiologicStudies-DepressionScale


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(CES-D) (Radloff, 1977). This scale measures the presence and severity of depressive symptoms, with scores ≥16 (range 0–60) indicating a clinically significant level of psychological distress.

The memory tests used in this study assessed episodic anterograde memory. Verbal learning and memory were assessed with the Dutch version of the Rey Auditory-Verbal Learning Test (RAVLT) (Rey, 1964). This test comprises a list of 15 words, read to the subjects at 5 trials. Recall was tested immediately after each trial and the total number of correctly remembered words in all 5 trials was taken as the score for “immediate recall”. After a delay of 20 minutes the patient was asked to recall as many words as possible (“delayed recall”), followed by a recognition test in which the 15 words had to be recognized from a mix with 15 distracter words (“recogni-tion”) (Lezak et al., 2004). Raw scores on immediate and delayed recall were conver-ted into decile scores, corrected for age, gender and educational level (Kalverboer & Deelman, 1986). Scores equal to or below the 10th percentile of the norm group were considered to indicate clinically relevant memory deficits (Rasquin et al., 2004). Norm scores were not available for verbal recognition, but raw scores of correctly recognized items ≤27 are generally considered as an impaired performance. Visual memory was assessed with the Doors Test, a subtest of the “Doors and People Test” (Baddeley et al., 1994). The Doors Test evaluates visual recognition memory by presenting 2 sets (easy and difficult) of 12 pictures of doors (e.g. front doors, church doors) that have to be memorized and recognized from arrays of 4 pictures (1 target and 3 distracters) of similar doors. Patients in this study were tested with the easy set only. Raw scores were converted into age-scaled scores in accordance to norma-tive data (Mean 10; SD 3). Scaled scores ≤5 were considered ‘impaired’ scores (Davis et al., 1999).

Lesion analysis

All scans were performed with a standard scanning protocol. Scans were stored and further analyzed using a Philips Easy Vision Workstation. Surfaces of areas of abnormal hyper-intensity were summed and multiplied with slice thickness (6 mm) and interslice gap (1.2 mm) to calculate lesion volumes (Schiemanck et al., 2006). Lesions were defined as “cortical” if they were located for 50% or more in the cortex and as “subcortical” if they were located for 50% or more in subcortical areas. Corti-cal lesion localization was further divided into “frontal”, “parietal”, “temporal” or “occipital” dependent on the location of the largest part of the lesion, using Dama-sio and Damasio’s atlas (Damasio & Damasio, 1989). Based on this classification two groups of patients were obtained: the “anterior group” consisting of patients with frontal lesions and a “posterior group” consisting of patients with parietal, tempo-ral and occipital lesions. As pre-existent white matter lesions (WML) could influence memory function, they were also determined on the MRI scans.


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Data analyses

Bivariate relationships between variables were analyzed using different non-pa-rametric techniques: Cramér’s V for associations between dichotomous variables, Spearman’s rank correlation coefficient for the associations between continuous variables and Mann-Whitney U test for differences between subgroups based on lesion characteristics. Correlation coefficients <0.3 were considered weak, between 0.3 and 0.6 as moderate, and >0.6 as strong. Hierarchic multiple regression analyses were performed to evaluate the indepen-dent predictive value of lesion side (left and right hemisphere), lesion level (cortical and subcortical), cortical location (anterior and posterior) and lesion volume on ischemic stroke patients’ verbal (RAVLT) and visual (Doors Test) memory perfor-mance. To control for the presence of WML and depression, age, gender and edu-cational level, these variables were first entered as predictors into the regression model, and then lesion characteristics were entered in the second step. All analyses were performed using SPSS.

Results

Group characteristics

Of 105 included patients, 19 patients could not be evaluated one year after stroke: 9 patients had died; 4 patients had recurrent stroke; 2 patients developed comorbi-dity seriously affecting functional outcome; and 4 patients refused further exami-nation. Demographic, clinical and lesion characteristics of the resulting 86 patients (42 men; 44 women) are presented in Table 1. Forty-six patients had a left and 40 patients had a right hemispheric lesion. Forty-eight patients had subcortical lesions (32 “purely subcortical” and 16 “mixed”). Thirty-eight patients had cortical lesions that were all “mixed” lesions. Thirty-three (61.1%) of all “mixed” lesions (N=54) were located in anterior regions. Mean lesion volume was 58.6 ml (SD 77). Lesion volume was not normally distributed (Median 29.3; 25%–75% IQR (IQR) 6.4–81.2). WML were present in 31 patients. CES-D scores were normally distributed (Median 17; IQR 11–24). Fifty-five percent of the patients obtained a score of 16 or higher, indicating at least psychological distress.


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Table 1. Demographic, clinical and lesion characteristics of first-ever ischemic stroke patients at one year poststroke (N=86).

N % M SD Range

DemographicsAge, years 86 100.0 63.3 14.3 22–84

Gender

MaleFemale

4244

48.851.2

Educational level

Low (2)¹Intermediate (3–5)High (6)

264317

30.250.019.8

Lesion characteristicsSide

Left hemisphere Right hemisphere

4640

53.546.5

Level

Cortical pure mixed, >50% in cortex Subcortical pure mixed, >50% in subcortex

380

38483216

44.2

55.8

Cortical location 54

Anterior Posterior

3321

61.138.9

Volume, in ml 86 100.0 58.6 76.5 0.95–373.6

Additional clinical characteristicsDepressive mood, CES-D total score (0–60)² 85 17.6 9.2 2–45

White matter lesions

PresentAbsent

3155

36.064.0

Abbreviations:

CES-D=Center for Epidemiological Studies-Depression Scale1 Numbers in parentheses indicate the corresponding educational levels according to the revised classification

system of Verhage (1964)2 Numbers in parentheses indicate the range of possible scores

Correlational patterns

Results on the RAVLT were available for 76 patients. The RAVLT could not be obtained from 8 patients due to severe aphasia. Test results of 2 other patients were incomplete. Results on the Doors Test were available for 83 patients, since 3 patients had incomplete test results. Bivariate analyses showed weak to moderate associations of patient characteristics (age, gender, educational level), lesion characteristics and memory tests


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(r 0.22–0.46). Even though we used the norm scores of the RAVLT and the Doors Test corrected for age, gender and educational level, age correlated weakly with delayed recall and all patient characteristics correlated weakly with recognition.A moderate association between the presence of WML and lesion volume (V=0.36), age (V=0.46) and lesion level (V=0.23) was found. Patients with pre-existent WML were older, had larger lesions and had more often cortical lesions. Lesion level was moderately associated with lesion volume (V=0.33), indicating that subcortical lesions were smaller than cortical lesions. Patients with a lesion located predominantly in the posterior cortex (parietal, temporal or occipital lobes) obtained higher scores on the CES-D, indicating more symptoms of a depressive mood, than patients with frontal lobe lesions (V=0.38). Furthermore, women sho-wed slightly more depressive symptoms than men (V=0.25). Patients’ performance on the immediate recall, delayed recall and recognition subtests of the RAVLT were strongly intercorrelated (r 0.62–0.72). However, no significant correlation was found between verbal memory performance and visual recognition memory performance (Doors Test).

Memory performance and lesion characteristics

Table 2 presents RAVLT and Doors Test scores for the total patient group and for subgroups with different lesion characteristics. On the subtests of verbal immediate and delayed recall the mean score of all patients was equal to the 32nd percentile of the norm group. Respectively 43% and 29% of all patients scored beneath the 10th percentile, indicating a disordered memory performance. On the verbal recogni-tion subtest, 59% of the patients recognized 27 or less items correctly, indicating disturbed verbal recognition memory. On the visual recognition task, patients obtained a mean scaled score of 8.0 (SD 3.5) with a median of 7 (IQR 5–10). Twenty-five percent of the patients obtained a scaled score of 5 or less, indicating impaired visual recognition.Results showed that patients with a left hemispheric lesion scored significantly lo-wer on the subtests of verbal immediate recall (p=0.026) and delayed recall (p=0.016) than patients with a right hemispheric lesion. Scores on verbal recognition (RAVLT) and visual recognition (Doors Test) did not differ significantly between left hemisp-heric and right hemispheric patient groups. No significant differences in scores on the RAVLT and the Doors Test were found between patients with cortical and subcortical lesions, or between patients with anterior and posterior lesions.


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Table 2. Mean performance (SD) of ischemic stroke patients on the RAVLT and the Doors Test, and differences in performance between patients with left and right hemispheric lesions, cortical and subcortical lesions, frontal and non-frontal lesions.Mann-Whitney U Test

AllPatients

LH RH p Cortical Sub-cortical

p Anterior Posterior p

Verbal Memory N=76 N=37 N=39 N=31 N=45 N=26 N=18

RAVLTImmediate recall,(1–10)1

3.2(2.7)

2.6(2.4)

3.7(2.8)

0.03* 3.7 (2.9)

2.8(2.5)

0.18 3.3 (2.8)

3.1 (2.5)

0.87

RAVLTDelayed recall, (1–10)1

3.2(2.4)

2.7(2.3)

3.6(2.3)

0.02* 3.9 (2.8)

2.7(1.9)

0.10 3.7 (2.6)

3.3 (2.5)

0.49

RAVLTRecognition,(0–30)2

25.9(3.8)

25.3(4.0)

26.4(3.5)

0.21 26.6 (3.0)

25.4(4.2)

0.37 25.5(4.3)

26.6 (3.1)

0.61

Visual memory N=83 N=44 N=39 N=37 N=46 N=31 N=20

Doors Test, Set A(1–19)3

8.0 (3.5)

7.9(3.1)

8.2(3.9)

0.85 8.1 (3.3)

8.3(3.7)

0.54 7.0(2.5)

8.8 (3.9)

0.12

Abbreviations:

RAVLT=Rey Auditory-Verbal Learning Test

LH=Left hemisphere

RH=Right hemisphere

N indicates sample size for each memory domain1 Range of possible scores in deciles, corrected for age, gender and educational level2 Range of possible scores, total words correctly recognized3 Range of possible scores, age-scaled scores (Baddeley et al., 1994)

Predictive models for memory performance

Table 3 shows the results from hierarchic multiple regression analyses of patient performance on the RAVLT and the Doors Test. Lesion side, level, and volume were independent predictors of verbal immediate recall performance. Patients with a left hemispheric lesion, subcortical lesion and larger lesion were associated with lower scores on the subtest of verbal immediate recall. These variables explained 17% of the variance of verbal immediate recall scores (p<0.001) in addition to the 7% explained by patient characteristics, CES-D score and presence of WML. Patients with a left hemispheric lesion, subcortical lesion, and larger lesion volume pre-dicted lower scores on verbal delayed recall and together explained an additional 23% of the variance (p <0.001). Verbal recognition performance was independently predicted by left lesion side and larger lesion volume, with an additional explained variance of 11% (p=0.02). Performance on visual recognition (Doors Test) was only predicted by educational level, with a total explained variance of 28%.


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Table 3. Hierarchic regression analyses for the prediction of ischemic stroke patients’ performance on the RAVLT (N=76) and the Doors Test (N=83).

RAVLTImmediate Recall1

RAVLTDelayed recall1

RAVLTRecognition2

Doors TestSet A3

Predictor variable Beta p Beta P Beta p Beta p

Age –0.19 0.15 –0.32 0.01** –0.39 0.01** 0.18 0.14

Gender 0.12 0.30 –0.06 0.56 0.24 0.02* 0.04 0.71

Educational level 0.02 0.84 0.01 0.90 0.23 0.04* 0.33 0.01**

CES-D (N=75) 0.03 0.77 0.13 0.25 –0.11 0.31 –2.00 0.07

WML –0.18 0.17 –0.10 0.41 0.04 0.75 0.19 0.11

Lesion side 0.36 0.01** 0.39 0.01** 0.27 0.01** 0.01 0.90

Lesion level 0.29 0.02* 0.38 0.01** 0.20 0.07 –0.02 0.83

Lesion volume –0.24 0.05* –0.30 0.01** –0.26 0.03* –0.22 0.06

R2 p R2 p R2 p R2 p

0.24 0.02* 0.32 0.01** 0.35 0.01** 0.28 0.01**

Abbreviations:

RAVLT=Rey Auditory-Verbal Learning Test

WML= White Matter Lesions

CES-D=Center for Epidemiological Studies-Depression Scale1 Scores in deciles, corrected for age, gender and educational level2 Raw scores (total words correctly recognized), uncorrected for age, gender and educational level3 Age-scaled scores (Baddeley et al., 1994), uncorrected for gender and educational level

*) p <0.05

**) p <0.001

Discussion

Ourstudyinvestigatedtherelationshipbetweenlesioncharacteristics(lesionside,levelandvolume)andepisodicmemoryperformanceofischemicstrokepatientsinthechronicphaseafterstroke.Ourresultsshowthatafteroneyearafterstroke,mostpatientswereimpairedonverbalrecognitionandamajorityshoweddeficitsofverbalimmediateanddelayedrecall.Further,one-quarterofthepatientshadimpairmentsofrecognizinglearnedvisualinformation.StudiesofHochstenbachetal.,(1998a;2003),administeringtheRAVLTat3monthsand2yearsafterstroke,showedconsistentfiguresofimpairedverbalmemoryperformance.

Lesion side

Ourresultswereonlypartlyconsistentwiththeclassicassociationofverbalmemorydysfunctionwithlesionsofthelefthemisphereandnon-verbalmemorydysfunctionwithlesionsoftherighthemisphere(Lezaketal.,2004;Schnider&


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Landis, 1995). Patients with left hemispheric lesions showed a poorer performance on the verbal memory subtests than patients with right hemispheric lesions, but the difference was not as large as expected. However, these findings are consistent with results of Hochstenbach et al. (1998a) showing that left hemispheric lesion side predicts poorer performance on the RAVLT subtests of immediate recall, de-layed recall and recognition at 3 months after stroke than right hemispheric lesion side. In our study, lesion side was found to be a moderate predictor of verbal imme-diate and delayed recall, but only a weak predictor of verbal recognition. A possible explanation might be that the active process of verbal recall is more dependent on verbal processes mediated by the left hemisphere than the more passive process of verbal recognition. Although our finding that lesion side was not a predictor of visual recognition performance contradicts the classic association, it is consistent with recent results of Van Zandvoort et al. (2005) who found no significant effect of lesion side on visual recognition performance on the Doors test in the first 3 weeks and at one to two years after stroke. In the thesis by Nys (2005), it was also found that lesion side was not a predictor of visual memory performance in the acute phase of stroke. From these results and ours it can be assumed that visual memory function is sensitive for both left and right hemispheric damage, whereas verbal memory function is mainly sensitive for left hemispheric lesions (Brown & Eyler Zorrilla, 2001; Ferro, 1995; Schnider & Landis, 1995). It has been proposed that in addition to verbal function, the “dominant” left hemisphere mediates generalized cognitive activities other than language, thereby playing a role in visual memory as well (Desmond et al., 1996; Madureira et al., 2001; Van Zandvoort et al., 2005). Further, Lange et al. (2000) have suggested that problems with the initial organiza-tion of visual information arising from right hemispheric lesions, lead to a dimini-shed encoding of information and hence to visual memory deficits. However, our results might also be explained by the fact that the relatively passive process of vi-sual recognition was assessed. This process of visual recognition might depend less on visual constructive capacities and hence on right hemispheric structures than the active process of visual recall, often assessed by the reconstruction of figures. A last explanation might be that the Doors Test supposes an unintended assessment of verbal (memory) function as well, by means of unaware verbal encoding or verbal mediation of the pictures.

Lesion level

Lesion level was found to be a predictor of verbal memory function. It was a mo-derate predictor of verbal delayed recall and a weak predictor of verbal immediate recall. We found that patients with subcortical lesions performed less well on ver-bal memory subtests than patients with cortical lesions. This is in contrast with the results of Nys (2005), who found more cognitive dysfunctions after cortical stroke. Nevertheless, it is in line with the study by Wagner & Cushman (1992) who found that patients with subcortical vascular lesions have more verbal memory impair-ments than patients with cortical lesions. Previous studies (Corbett et al., 1994; Ferro, 1995; Madureira et al., 2001) have proposed that cognitive impairments after


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subcortical infarction could be explained on the basis of frontal lobe dysfunction. They assumed that small subcortical infarctions disrupt cortico-cortical associa-tion pathways, thalamocortical pathways, and corticostriatal pathways, producing frontal cortical disconnection. Memory functions are mediated by various neural networks of widely distributed cortical and subcortical areas and their multiple, reciprocal interconnections. A strategically positioned subcortical lesion may disrupt an entire neuronal circuit and its memory processing, provided that other structures cannot take over the function of the damaged area. As it is assumed that more widespread functional zones of the cortex have more options to restore cog-nitive processing through neural plasticity, a subcortical lesion might have a larger impact on memory function than a cortical lesion. No significant effect of lesion level was found in our study with regard to visual memory performance. This result is consistent with findings of Lange et al. (2000), showing no differences in visual memory performance between patients with cortical and subcortical lesions. Unfortunately, the more precise location of lesions within subcortical areas could not be incorporated as a variable in our study, due to the small sample size. Likewise lesion location within the cortex was not entered into the regression model. However, Nys (2005) demonstrated that cortical lesions located in the temporal lobes hampered recovery of verbal memory in the first year of stroke, whereas lesions of the temporal and temporo-occipital lobes hampered recovery of visual memory. Further research is needed to clarify the influence of specific cortical and subcortical sites on verbal and visual memory functioning in stroke patients.

Lesion volume

Lesion volume was a significant but weak predictor of all memory functions examined in our study, except visual memory function. Larger lesions produced poorer verbal memory performance. Previous studies examining the effect of lesion volume on cognitive functioning show different results. Corbett et al. (1994), found a weak correlation between lesion volume and verbal recognition performance. Nys (2005) found lesion volume to be an independent predictor of visual memory reco-very. Patients with smaller lesions showed better recovery. However, both Hochsten-bach et al. (1998b) in their study on stroke in the basal ganglia and Nys et al. (2005) in their study on acute cognitive impairment after stroke, failed to demonstrate a significant effect of lesion volume on memory. Further research is needed into the influence of lesion volume on poststroke memory impairment.

One of the strengths of our study was the large sample size, compared to other (follow-up) studies investigating the long-term outcomes of cognitive function in stroke patients (Nys et al., 2005; Van Zandvoort et al., 2005). A limitation of our study was that the influence of other possible determinants of poststroke memory performance, such as lesion location within cortical and subcortical areas, could not be investigated. The influence of other poststroke cognitive impairments on memory performance were not studied either, such as deficits of attention, langu-


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age and visual perception. Furthermore, our results might be limited by the fact that the Doors Test used to assess visual memory performance, assesses the visual recognition process only. Learning, active, immediate and delayed recall of visual material were not assessed in our study. Since different structures are involved in encoding rather than in retrieval, results of this study with regard to visual recog-nition cannot be generalized to processes of visual encoding and recall. Further research should include tests that measure more active visuoconstructive abilities in addition to passive recognition of learned visual material.In conclusion, our study demonstrated that the lesion characteristics of hemisphe-ric lesion side, cortical and subcortical level and lesion volume are weak to mode-rate predictors of verbal memory performance one year after stroke. Visual memory performance could not be predicted from these lesion characteristics. A lot still needs to be clarified with respect to the relationships between lesion characteristics and poststroke memory performance. Further research with larger samples, more clinical variables and newer imaging techniques to visualize real-time neurological activity during memory testing, is recommended so that a clear picture of the neural mechanisms underlying poststroke memory dysfunction can be obtained.


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