Prose memory in patients with idiopathic Parkinson's disease

Parkinsonism and Related Disorders 11 (2005) 453–458 www.elsevier.com/locate/parkreldis

Prose memory in patients with idiopathic Parkinson’s disease Tatia MC Leea,b,*, Chetwyn CH Chanc, SL Hod, Leonard SW Lib,d a

Neuropsychology Laboratory, Department of Psychology, The University of Hong Kong, Pokfulam Road, Hong Kong, Hong Kong, China b Institute of Clinical Neuropsychology, The University of Hong Kong & MacLehose Medical Rehabilitation Centre, Hong Kong, China c Laboratory of Applied Cognitive Neuroscience, The Hong Kong Polytechnic University, Hong Kong, China d Department of Medicine, The University of Hong Kong, Hong Kong, China Received 19 April 2005; revised 29 May 2005; accepted 30 May 2005

Abstract Background: The findings of previous studies have suggested that verbal memory impairments were observed in people suffering from Parkinson’s disease (PD). Very few studies have examined the comprehensive profile of prose memory deficits that challenges people with PD. Methods: Prose memory of 19 patients with PD was examined. Their performance in three constructs, namely recall accuracy, temporal sequence, and distortions, during immediate, delayed and recognition trials was studied. Results: The patients with PD performed significantly worse in recall accuracy and temporal sequencing of information in the immediate recall trial. During the recognition trial, they made more false alarms than their healthy counterparts. Conclusions: Our findings confirm that the performance of people with PD in immediate recall of a prose was impaired. However, the level of performance in subsequent learning and delayed recall trials became comparable to that of the normal controls. The deficit remaining after multiple learning trials was the significantly high false alarms committed in the recognition trial. Our findings highlight the importance of qualitative analysis, in addition to quantitative evaluation, of prose memory in PD. q 2005 Elsevier Ltd. All rights reserved. Keywords: Prose memory; Verbal memory; Parkinson’s disease; Frontal-striatal circuit; Executive dysfunction

1. Introduction Human verbal memory is subserved by a widely distributed neural network involving the frontal [1–3], temporal, and subcortical regions. Within this neural network, it is well recognized that medial temporal-lobe structures play an important role in verbal memory [4,5], and that the interaction of the hippocampus with various subcortical nuclei is essential to memory consolidation [6,7]. Verbal memory impairments have been observed in patients with Parkinson’s disease (PD) [8,9], despite the fact that their verbal skills [9] and overall intellectual functioning [10–12] could be intact. The observed verbal

* Corresponding author. Address: Neuropsychology Laboratory, Department of Psychology, The University of Hong Kong, Pokfulam Road, Hong Kong, Hong Kong, China. Tel.: C852 2857 8394; fax: C852 2858 3518. E-mail address: [email protected] (T.M.C. Lee).

1353-8020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.parkreldis.2005.05.010

memory impairments likely relate to frontal-striatal circuitry damage in these PD patients [9,13,14]. Frontallobe impairments (as evidenced in neuropsychological test performances) have been reported in patients with PD [9, 15–18]. Kulisevsky et al. [19] reported that dopaminergic treatment enhanced frontal-executive functions selectively. Furthermore, since degeneration of the dopaminergic pathways of the substantia nigra first affects the posterior putamen, then the anterior putamen, and then the caudate nucleus [20]. Owen et al. [16] speculated that these subcortical structures may interfere with frontal cognitive loops that are interconnected through the thalamus to the prefrontal cortex. Therefore, patients with PD may produce abnormal basal ganglia outflow through the globus pallidus, which subsequently interrupts normal transmission of information through the frontal-striatal circuitry. Previous studies have found that patients with PD perform significantly worse than their healthy counterparts when recalling prose passages taken from the Wechsler Memory Scale [9]. It was observed that patients with PD

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were unable to benefit from the extra contextual cues provided in the prose, and their level of performance was worse than that of their healthy counterparts. Nonetheless, Levin et al. [9] only studied the level of accuracy in immediate and delayed recalls, but not other components or processes of prose memory. Indeed, developments in cognitive neuroscience have led to a concept of memory that posits multiple interconnected processes served by different cognitive circuits that can be differentially affected by neuropathological conditions [21–23]. Altered patterns of effective connectivity between brain regions may be important indicators of disordered memory [24]. This implies that neuropathologies that affect different parts of the brain and/or their connections, such as PD, would have a characteristic impact on prose memory [25]. Faglioni et al. [26] studied learning and forgetting processes in patients with PD with respect to prose memory performance. The overall findings of their study were that patients with PD were selectively impaired in certain memory processes, namely gist (global) extraction, retaining algorithmical retrieval, and contextualizing. As Faglioni et al. [26] have suggested, the medial frontal cortex is mostly involved in the pathology of patients with PD. However, the organization of content (in terms of the temporal sequencing of the idea units) and the quality of recall (in terms of distortion errors) were not examined in their study. To fill an important gap in the literature on prose memory associated with PD, the present study was conducted to examine the characteristic profile of prose memory of people with PD. A prose passage was constructed [27] to examine the constructs of (1) recall accuracy (idea units), (2) the accuracy of the temporal sequence of the idea units recalled, and (3) distortions (intrusion errors or other errors distorting the meaning of the idea units), during immediate, delayed and recognition memory trials.

2. Method 2.1. Participants Patients with idiopathic PD were recruited from Tung Wah Hospital, Hong Kong. Being screened by the case Neurologist, those patients with a history of other neurological and/or psychiatric illnesses, and those who were suffering from comorbid depression or dementia were excluded from participation. Nineteen PD patients (18 bilateral, 1 right-sided) were invited to participate in this study. Their general cognitive ability was assessed by the Test of Nonverbal Intelligence—third edition (TONI), which is a language-free measure of cognitive ability. According to Hoehn and Yahr (1967) [28] staging of PD, these patients were within stages II–IV. The mean duration of disease for PD patients was 7.86 (SDZ5.07) years. All patients were taking L-dopa for treatment of PD. In addition to L-dopa, some patients were simultaneously taking other

Parkinsonian drugs: bromocriptine or pergolide, selegiline, or benzhexol (nZ5). Twelve healthy volunteers, matched in terms of age, sex, and education, were also recruited for the study. All participants were right-handed (as measured by the Lateral Dominance Questionnaire adopted from Harris’s [29] (1958) Tests of Lateral Dominance). Verbal and written informed consent was obtained from all participants. 2.2. Measurements Prose Learning and Memory Test (PLMT) was used to assess prose memory in all participants [27]. In brief, a prose passage containing 119 Chinese characters, with 35 idea units, was presented to each participant in a one-on-one basis for three consecutive trials. Immediate verbatim recalls for the first and third learning trials were assessed, followed by a 10-min and then a 30-min delayed verbatim recall. Participants’ responses were recorded verbatim on audio-tapes; subsequently, they were transcribed by an independent helper into written Chinese scripts. They were scored by a scorer who was blind to the identify of the participants, and were scored in accordance with the scoring guidelines developed by a panel made up of four native Chinese people who had attained a minimum of university education level. The responses were judged basing on everyday colloquial Cantonese Chinese usage. The prose recalls were scored on three constructs, including recall accuracy, temporal sequence accuracy, and distortions. Scoring of the recall accuracy and temporal sequence accuracy was based on the number of idea units recalled and their positions in the recall sequence. A score of recall accuracy would be given for the correct recall of an idea unit (including the use of synonyms), and a score of temporal sequence accuracy would be given for the correct positioning of that particular idea unit in the recall sequence. A recalled idea was considered as a distortion if it deviated from the original meaning of the ideas in the prose passage. The inter-rater reliability index was 0.975. A recognition word list consisting of 30 items, 10 targets and 20 foils, in a forced-choice format was administered verbally to the participants after the 30-min delayed recall. Accuracy, omission errors (missed targets), and commission errors (identified foils as targets) were scored. The PD participants were requested to report the schedule of drug intake so as to adjust and uniform the time of testing for each of them. 2.3. Statistical analyses One-way analysis of variance (ANOVA) was performed to compare possible group differences in demographic characteristics and their performance in prose memory across time in terms of recall accuracy, temporal sequence recall accuracy, context distortions, delayed recall as well as recognition accuracy and errors. Chi-square analysis was conducted to identify possible between-group gender

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differences. Alpha levels were set at p!0.05 when determining the statistical significance in the present study.

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recall (p!0.05). However, the two groups did not perform differently from each other in subsequent recall trials. 3.4. Context distortions

3. Results

No significant difference between the two groups was found for context distortions in all immediate recall and delayed recall conditions between the patients with PD and healthy controls. The patients with PD committed as many context distortions as their healthy counterparts in all immediate and delayed recall trials. (Table 2)

3.1. Demographic characteristics of participants The mean deviation quotient on TONI was 83. The means and standard deviations of the demographic and clinical characteristics of the participants in this study are summarized in Table 1. The patients with PD were matched with their respective healthy volunteers in terms of chronological age, years of education, and gender composition [c2 (dfZ1), pO0.05]. The clinical group consisted of 14 males and 5 females, while there were 5 males and 7 females in the healthy control group.

3.5. Recognition accuracy and errors For recognition, patients with PD did not differ from their healthy counterparts in terms of recognition accuracy or in the number of omission errors made during the recognition trial. However, PD patients committed more commission recognition errors than the healthy control group (p!0.05). (Table 3)

3.2. Immediate and delayed recall accuracy Univariate analyses of variance indicated that, on the whole, the patients with PD performed significantly worse than the healthy volunteers only in their first immediate recall accuracy (p!0.05). No differences in subsequent recall trials between the two groups were observed.

4. Discussion Consistent with previous studies of verbal memory deficits in PD patients [9,30,31], our clinical participants performed significantly worse in immediate recall, in terms of both free recall accuracy and temporal sequence accuracy, evaluated by the PLMT. Nevertheless, during the delayed recall and recognition trials, accuracy of recall in the PD patients was comparable to that of the healthy controls.

3.3. Temporal sequence recall accuracy Similar to recall accuracy, ANOVA revealed a significantly worse performance in PD patients than their healthy counterparts only in the first immediate temporal sequence Table 1 Demographic and clinical characteristics of participants PD (nZ19)

AGE EDU

HV (nZ12)

M

SD

M

SD

64.11 9

11.51 4.96

67.61 5.56

6.39 3.28

F

p

1.524 3.57

0.227 0.07

PD, patients with Parkinson’s disease; HV, healthy volunteers; AGE, chronological age in years; EDU, years of education. Table 2 Performance in Recall Accuracy, Temporal Sequence Recall Accuracy, and Distortion PD vs. HV

Recall Accuracy Group

M

SD

F

p

Group

M

SD

F

p

Group

M

SD

F

p

R1

PD HV PD HV PD HV PD HV

3.42 6.17 8.05 11.17 7.95 9.00 8.21 8.33

2.97 3.19 4.81 3.56 4.25 4.02 4.49 3.20

5.948

0.021*

0.317

0.181

0

0.983

0.295

0.591

0.007

0.935

0.483

0.493

1.65 0.996 2.54 2.08 2.01 1.44 2.42 1.49

1.877

0.498

1.21 0.92 3.37 2.17 2.95 2.58 3.22 2.75

0.584

1.038

PD HV PD HV PD HV PD HV

0.307

0.470

2.29 2.62 4.81 3.75 3.89 4.06 4.32 3.10

0.014*

0.064

2.84 5.17 7.00 8.67 7.05 7.08 7.00 6.00

6.772

3.716

PD HV PD HV PD HV PD HV

0.364

0.551

R2 R3 DR

Temporal Sequence Recall Accuracy

Distortion

R1, recall after the first learning trial; R2, recall after the third learning trial; R3, recall in the 10-min delayed trial; DR, recall in the 30-min delayed trial; PD, patients with Parkinson’s disease; HV, healthy volunteers. *p!0.05.

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Table 3 Recognition Accuracy and Errors PD (nZ19)

Accuracy Omission Errors Commission Errors

HV (nZ12)

M

SD

M

SD

5.79 2.16 6.68

2.44 2.73 2.81

6.42 3.58 3.83

1.51 1.51 1.99

F

p

0.64 2.72 9.33

0.43 0.11 0.005*

PD, patients with Parkinson’s disease and HV, healthy volunteers. *p!0.05.

Prose memory profile in our PD participants suggested poor immediate free recall accuracy, while such recall accuracy could be augmented to a normal level through repeated exposure of the verbal materials. Our findings are consistent with, and explain why memory complaints are common among clinical patients with PD [32], and yet their overall performance in instruments assessing memory functioning were often comparable to normal controls [33]. This further implies that the subtle memory deficit in PD patients could affect daily functioning because everyday information conveyed in social contexts is usually not being repeated. Basal ganglia dysfunction, being a hallmark of PD, has been widely studied. Evidence supporting that dopamine (DA) activity in the basal ganglia-thalamocortical pathways is related to temporal sequencing [34–36] has been accumulating. However, previous findings have mainly focused on sequential behaviors, motor activities, or time perception [34,37,38]. Reports on the explicit perception of temporal order of information were scarce [39]. The findings of this study have illustrated that impairment of temporal sequencing of information embedded in a prose is associated with PD. Difficulty with spatial-temporal organization of incoming information in PD has been reported, which is related to dysfunctional frontal-striatal connections [40,41]. Furthermore, emerging evidence from imaging studies [42,43], such as positron emission tomography [44] and other animal studies [45–47], has confirmed the specific role of frontal-striatal circuits in the encoding of sequential information. Therefore, the observation of impaired organization of the temporal sequence of information observed in our clinical participants appears to be consistent with the expectation of the pathology of PD, which is related to the depletion of dopamine within the striatal circuits. Our findings are also in line with the speculation of possible neuropathology involving the striatum and its nigral afferents, considering their role in encoding of initial learning and retrieval of sequences [48]. Despite the fact that recall accuracy and temporal sequencing of information were impaired in immediate recall, people with PD appeared to be able to catch up with repeated learning. Their performance in the delayed recall trial became comparable to that of their healthy counterparts. Therefore, rehearsal appears to be helpful for rectifying the impaired performance observed in the immediate recall. Could L-dopa treatment help ameliorate

the temporal sequence deficit observed in people with PD [49–52], when a multiple learning trial format were adopted? To verify this speculation, future investigation adopting between group comparisons of PD patients on— and off L-dopa medication would be required. Furthermore, Shohamy et al. [51] proposed that learning of sequential information in people with PD relies on both individual learning strategies and degree of dopaminergic cell loss. The effect of the two factors over learning of temporal sequence materials in successive and repeated trials would allure further investigation. In the recognition trial, the PD patients made more commission errors than their healthy counterparts. In other words, the PD patients had a significantly higher false alarm rate during the recall in a recognition format, relative to the healthy controls. According to Kopelman [53], recognition memory judgment can be made either on the basis of feelings of familiarity or recollection of contextual memories. Yonelinas [54] argued that judgment based on feelings of familiarity and that based on recollection of contextual memories are independent processes involving very different response characteristics. Recognition memory, which is based on the recollection of contextual memories, yields all-or-none responses. On the other hand, recognition judgment relies on familiarity and therefore produces a much more variable response pattern [53,54]. With limited contextual memory [40,41] to utilize during a recognition task, judgment based on familiarity would probably be the method adopted by PD patients. The overdependence on familiarity may therefore produce a high false alarm rate, which could again relate to frontal executive dysfunction [55] whereby the ability to differentiate targets from distracters is impaired. This speculation awaits confirmation in further research. Our findings suggest that prose memory deficits are associated with PD. One possible source of confound of the data is from the medications that our PD participants were taking. A few of them were prescribed Benzhexol. Since cholinergic function and memory are strongly connected [56], benzhexol, being an anticholinergic drug, may produce an amnesic effect due to its reversible binding to muscarinic receptor and thus impairing normal cholinergic function [57]. The profile of prose memory in PD suggests that prose memory may be a multifaceted construct that each of its

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processes may be subserved by dissociable neural circuits. Following this line of thinking, in order to truly appreciate the range and nature of prose memory deficits associated with PD, a comprehensive approach to the evaluation of the different processes of prose memory and error patterns, focusing not only on the quantity but also on the quality of recall, should be an integral part of neuropsychological evaluation for PD. Due to the time constraint expressed by our participants, we have no choice but to exclude the administration of a word list recall task. In future research, we recommend studies comparing between contextual and non-contextual memory for people with PD. The data would provide important insight into human memory. Furthermore, longitudinal studies to understand how the rate of impairment of each process unfolds would generate data essential to the development of effective therapeutic interventions for prose memory deficits that challenge PD patients at various stages of pathology.

Acknowledgements This study was supported by the University Development Fund of The University of Hong Kong.

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