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Prospective and retrospective memory in Alzheimer's disease and vascular dementia: Similar patterns of impairment
Journal of the Neurological Sciences 283 (2009) 235–239
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Journal of the Neurological Sciences j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j n s
Prospective and retrospective memory in Alzheimer's disease and vascular dementia: Similar patterns of impairment Åsa Livner a,⁎, Erika J. Laukka a, Sari Karlsson a,b, Lars Bäckman a a b
Aging Research Center, Karolinska Institutet, Stockholm, Sweden Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden
a r t i c l e
i n f o
Available online 2 April 2009 Keywords: Alzheimer's disease Vascular dementia Cognition Episodic memory Prospective memory Retrospective memory
a b s t r a c t Prospective memory (ProM) involves remembering to perform actions after a delay, such as buying groceries on the way home from work. Retrospective memory (RetM) involves remembering events from the past. It is known that the memory impairment in Alzheimer's disease (AD) generalizes across (a) these two types of memory, and (b) encoding, storage, and retrieval within RetM. Corresponding knowledge regarding these issues is sparse in vascular dementia (VaD). The aim of this study was, therefore, to compare the two dementia etiologies regarding patterns of impairment in ProM and RetM tasks. From a population-based study, 21 persons with VaD, 79 with AD, and 352 controls were included. Both dementia groups were impaired on all ProM and RetM variables, but did not differ from one another on any measure. The results are discussed relative to a network view of episodic memory, in which alterations at different sites may result in similar functional impairments. © 2009 Elsevier B.V. All rights reserved.
1. Introduction Both Alzheimer's disease (AD) and vascular dementia (VaD) are associated with severe deficits in a variety of cognitive domains, including episodic memory. Many studies demonstrate that the degree of episodic memory impairment is very similar in AD and VaD patients [1–3]. Also for different aspects within an episodic memory task, such as the relative contributions from primary and secondary memory, and the ability to utilize cognitive support for improving performance, the patterns of impairment in AD and VaD are often similar [4]. However, other research suggests differences in episodic memory performance between the two dementia groups, with VaD patients outperforming AD patients [3,5,6]. The majority of studies on episodic memory and dementia have focused on retrospective memory (RetM), which involves remembering events experienced in the past. Prospective memory (ProM) is another form of episodic memory, which involves remembering to perform an action after a delay, such as remembering an appointment or to buy groceries on the way home [7,8]. ProM is important for everyday functioning, and ProM complaints are common in memory clinics as well as among healthy older adults [9,10]. All ProM tasks involve two components: one component that is purely prospective and one component that is essentially a form of RetM. Whereas the prospective component involves remembering ⁎ Corresponding author. Aging Research Center, Karolinska Institutet Gävlegatan 16 S-113 30 Stockholm, Sweden. Tel.: +46 8 6906880; fax: +46 8 6906889. E-mail address: [email protected] (Å. Livner). 0022-510X/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2009.02.377
that something should be done, the retrospective component involves remembering the content of the action that is supposed to be performed [11]. Despite the fact that ProM has a retrospective component, there are important differences between ProM and RetM. Factor-analytic work has shown that ProM and RetM tasks load on different factors [12,13]. Other studies have found that the two types of memory are only weakly correlated, and that the association is further attenuated when the retrospective component of the ProM task is controlled for [14]. Also, ProM and RetM partly draw on different brain regions. Whereas the medial–temporal lobe is critical to RetM [15–17], ProM is more dependent on areas in the prefrontal cortex [18,19]. Whether ProM functioning is impaired to a similar extent in AD and VaD is unknown. There is evidence for a ProM impairment in clinical AD [12,20] as well as in the preclinical phase of this disease [21]. Less is known about the influence of VaD on ProM. There is, however, evidence for impaired performance on ProM tasks among stroke patients [22]. Episodic memory can be divided into the stages of encoding, storage (i.e., consolidation), and retrieval. These stages are all essential for successful episodic remembering. In the current study, data on these aspects of memory were available for the RetM task. Of chief interest was whether AD and VaD would show a similar or differential pattern of impairment with regard to encoding, storage and retrieval operations. Previous research on this topic is limited. There are studies suggesting that persons with AD are more impaired with regard to storage, whereas persons with VaD have more retrieval difficulties, and would thus benefit more from the retrieval support provided in
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cued recall tasks [23]. However, other research reports no differences regarding the relative impairment across the stages of episodic memory in AD and VaD [4]. Thus, the aims of this study were to examine whether (1) the degree of memory impairment is of similar magnitude in AD compared to VaD persons for ProM and RetM; and (2) the patterns of impairment are similar or differential in AD and VaD with regard to the two components of ProM (the prospective versus the retrospective component) as well as the RetM stages of encoding, consolidation, and retrieval. 2. Method The study is based on data from the Kungsholmen project (KP), which is a longitudinal, population-based study targeting the medical, psychological and social aspects of aging. The KP has been approved by the ethics committee of Karolinska Institutet, Sweden, and informed consent was obtained from all participants or next-of-kin. The original sample was taken from all the inhabitants, 75 years and older, living in the Kungsholmen parish of Stockholm, Sweden on October 1, 1987 (n = 2,368). The baseline examination consisted of two phases. First, 1810 persons participated in a screening phase, which consisted of a health examination and an interview including the Mini-Mental State Examination or MMSE [24]. Second, participants who scored 23 or lower on the MMSE (n = 314) and a random sample matched on age and sex (n = 354), were re-examined using a more extensive protocol including a medical, psychiatric and neurological examination, social interviews, and a comprehensive cognitive test battery. At the followup examinations, with approximately three-year intervals, the same protocol was used as in the extensive baseline examination. All participants from the screening phase were then invited. 2.1. Diagnoses of dementia The diagnoses of dementia were based on DSM-III-R criteria [25] and made through a three-step procedure. A preliminary diagnosis was first made by the geriatricians who had examined the participants and reviewed their social and family history. A physician expert in dementia and external to the data collection, independently made a second diagnosis based on computerized data, which was compared to the first diagnosis. In cases of disagreement, a supervising physician made the final diagnosis. Type of dementia was determined using clinical data. The Hachinski Ischemic Scale (HIS) [26] was used to support the clinical judgment. This score takes into account the presence of signs associated with VaD such as an abrupt onset of the dementia disorder, a stepwise deterioration, fluctuating course, and a history of stroke. A HIS score above 6 is an indicator of VaD, a HIS score of 5 or 6 is an indicator of mixed dementia, and a HIS score lower than 5 is an indicator of AD. The sensitivity as well as specificity of the HIS is high in differentiating between AD and VaD [27]. The AD diagnosis corresponds to probable AD according to the NINCDS-ADRDA criteria [28], and the diagnosis of VaD corresponds to possible VaD according to the NINDS-AIREN criteria [29]. In the KP, a majority of the participants diagnosed with VaD had a history of stroke. Thus, the VaD diagnosis in this study is essentially a diagnosis of strategic or multiinfarct dementia. For those participants who died during the follow-up period, the diagnosis was based on the information available through clinical records, discharge diagnoses, and death certificates. A more detailed description of the KP and the diagnostic procedures has been reported elsewhere [30]. 2.2. Study sample Only persons who completed the cognitive test battery were included in the sample. In order to increase the statistical power, data
were aggregated from the baseline phase and the first two follow-ups. All participants with Parkinson's disease, psychosis, and major depression were excluded, as well as participants using antidepressive or antipsychotic medication. Diagnoses of psychiatric diseases were based on DSM-III-R criteria at baseline and DSM-IV [31] criteria at the follow-ups. Two AD persons and two VaD persons with MMSE scores below 10 were also excluded from the sample, because of difficulties in complying with the task demands. In the final sample, 21 persons with VaD (including six mixed dementia cases) and 79 persons with AD were included. Of the VaD persons, five (23.8%) were diagnosed at baseline, five (23.8%) at the first follow-up and 11 (52.4%) at the second follow-up. Of the persons with AD, 17 (21.5%) were diagnosed at baseline, 26 (32.9%) at the first follow-up and 36 (45.6%) at the second follow-up. The cognitive data were always taken from the phase where the person was first diagnosed with dementia. Among the controls, persons with other types of dementia were excluded, as well as persons in a preclinical phase of dementia. Thus, only persons who remained free from dementia during baseline and the first three follow-ups were included in the control group. Also, we excluded all control participants with MMSE scores below 25, as this has previously been identified as a cut-off for suspected preclinical dementia [32]. Control participants with data from more than one phase were included only once, and data were randomly taken from one of the three phases. In order to keep age and retest effects similar to the dementia groups, we sought to obtain a control group with approximately the same proportion of persons with cognitive data from each phase. In the final sample, 352 controls were included. Of these, 59 (16.8%) had their data taken from baseline, 105 (29.8%) from the first follow-up, and 188 (53.4%) from the second follow-up. In total, 94 persons were excluded from the analyses due to missing data. This includes persons with missing data on the ProM task (n = 72), RetM task (n = 5) or both tasks (n = 17). Sample characteristics are shown in Table 1. A multivariate analysis of variance (MANOVA) revealed no age differences among the groups. However, there were differences in education, F (2,449) = 10.33, p b .001; MMSE score, F (2,449) = 10.16, p b 001; and length of test session, F (2,449) = 449.76, p b 001. The control group had received more education than the AD group (p b .05). There were no differences between the VaD group and any of the other groups with regard to education (p N .10). The controls also significantly outperformed the AD and VaD groups on the MMSE (p b .05), whereas there were no differences between the two dementia groups (p N .10). The AD and VaD groups had significantly longer test sessions than the controls (p b .05), although there were no differences between the dementia groups with regard to length of test session (p N .10). A χ2-analysis revealed no differences in sex distribution among the groups (p N .10). We also compared the groups on the Clinical Dementia Scale, CDR [33]. The majority of the demented participants had mild or moderate dementia. Only two AD persons (2.5%) were classified as having severe dementia. There were no significant differences in dementia severity between the AD and VaD groups (p N .10). Four participants had missing data on the education variable, and two participants had no data on length of test session. For these participants, the group mean was imputed. Table 1 Subject characteristics. Controls (n = 352) M Age (years) Education (years) MMSE Session length (min) Sex
AD persons (n = 79) SD
85.54 3.96 9.65 3.25 27.53 1.45 60.13 12.26 73.9% women
M
SD
86.49 5.18 7.99 2.54 20.41 3.32 66.96 19.03 83.5% women
VaD persons (n = 21) M
SD
85.14 4.87 8.45 2.04 21.10 3.86 67.67 12.92 66.7% women
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consolidate memories. In order to control for initial free recall performance, we used the forgetting ratio, which was calculated as number of words remembered in free recall but forgotten in cued recall, divided by the free recall score. In calculating forgetting ratio, 7 AD persons were excluded because they did not remember any words in free recall. 3. Results
Fig. 1. Percentage successful persons in the prospective memory task for controls, AD persons, and VaD persons.
2.3. Prospective memory To assess ProM, participants were instructed at the beginning of the test session to remind the test leader to make an important phone call after completion of all tests. If a participant failed to do so, the test leader asked: “What was I supposed to do when we were finished with the testing?” The mean length of test session, which is also the retention interval for the ProM task, was 61.68 min (SD = 13.99). The prospective component of the task involved remembering to remind the test leader without being given the additional prompt. The majority of participants who did so also recalled the content of the instruction correctly (i.e., that the test leader was supposed to make a phone call), whereas a minority (n = 10) failed to remember correctly what was supposed to be done. The retrospective component of the task involved remembering the content of the instruction either with or without a prompt. 2.4. Retrospective memory The RetM task consisted of a word list including 12 nouns presented both visually and auditorily to the participants. The words belonged to four different taxonomic categories (professions, clothes, furniture, and musical instruments), and were presented randomly intermixed. No mention was made of the organizational structure of the word list. All words were typical of their respective categories, according to previously established norms [34]. Performance was measured with free, cued, and total recall. Immediately after the presentation, a free recall task was given during two minutes. Following free recall, the participants were provided with the category names as cues and again instructed to recall as many words as possible during two minutes, including those already remembered in free recall. Total recall denotes the total number of words remembered in either free or cued recall. To provide category cues at retrieval is one way of improving performance, by making previously inaccessible items accessible [35]. The increase in number of recalled words from free to cued recall is thus a measure of the ability to use retrieval support. However, in evaluating cued recall performance, one has to consider that forgetting may occur between free and cued recall, although the time span between the two tasks is relatively short. In a previous study, persons with AD were found to be highly prone to forgetting from free to cued recall [36]. To disentangle the effects of cognitive support and forgetting, it is therefore necessary to compare free recall performance with both cued and total recall performance. Also, three qualitative indicators of RetM were used, which in previous research has been found to tap different stages of the memory process. Number of categories represented in the response protocols for free recall reflects the participant's plan at retrieval, whereas number of items remembered per category denotes the degree of semantic organization at encoding [35,37–40]. A measure of forgetting was also included, as an indicator of difficulties to
Performance on the ProM task for the three groups is portrayed in Fig. 1. To analyze the ProM data, a χ 2-analysis including all three groups was first performed. This analysis revealed significant differences for both the prospective and retrospective components, χ 2 (2, n = 452) = 21.10, p b 001, and χ 2 (2, n = 452) = 87.93, p b .001, respectively. The proportion of persons who successfully remembered the prospective component was 8.9% in the AD group, 9.5% in the VaD group, and 32.1% in the control group. For the retrospective component, the proportion that succeeded was 26.6% in the AD group, 28.6% in the VaD group, and 77.3% in the control group, respectively. Subsequent analyses demonstrated that the controls outperformed both dementia groups for the prospective and retrospective components alike (p b .001), although there were no differences between the dementia groups for either component (p N .10). Fig. 2 shows free, cued, and total recall performance on the RetM task. Separate analyses of covariance (ANCOVAs), controlling for age, sex, and education, were performed for the memory indicators. There were group differences for free recall, F (2,446) = 103.32, p b .001, η2 = .32, MSE = 3.81; cued recall, F (2,446) = 107.92, p b .001, η2 = .33, MSE = 5.42; and total recall, F (2,446) = 101.76, p b .001, η2 = .31, MSE = 4.19. Bonferroni post-hoc comparisons (p b .05) were made in order to compare all groups separately. Both the AD and the VaD groups were outperformed by the controls on free, cued, and total recall. However, no performance differences were observed between the two dementia groups (p N .10). To examine the effects of retrieval support provided in cued recall, a 3 (group) × 2 (task: free recall, cued recall) mixed ANOVA, with repeated measures on the last factor, was carried out. The results revealed no main effect of task (p N .10). However, a significant interaction between group and task was found, F (2,449) = 7.35, p b .01, η2 = .03, MSE = 1.66. Whereas the controls improved their performance in cued recall compared to free recall (p b .05), the demented groups did not (p N .10). Another mixed ANOVA was carried out where cued recall was substituted with total recall. The results revealed a significant main effect of task F (1,449) = 218.43, p b .001, η2 = .33, MSE = .79. Importantly, there was no longer an interaction between group and task (p N .10), indicating that all three groups improved their performance to a similar extent in total compared to free recall. Contrasting these two analyses, it is obvious that the group × task interaction obtained in the free-cued recall analysis reflects disproportionate forgetting from the time of free to cued recall in the dementia groups.
Fig. 2. Mean retrospective free, cued, and total recall for controls, AD persons, and VaD persons. Error bars represent standard errors around the means.
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Fig. 3. Mean performance on qualitative indicators of retrospective memory for controls, AD persons, and VaD persons. Error bars represent standard errors around the means.
Fig. 3 shows performance on the qualitative indices for the RetM task. Again, separate ANCOVAs controlling for age, sex and education, were carried out. There were differences among the three groups for number of categories, F (2,446) = 78.51, p b .001, η2 = .26, MSE = .61; items per category, F (2,446) = 55.52, p b .001, η2 = .20, MSE = .21; and forgetting ratio, F (2,439) = 79.57, p b .001, η2 = .27, MSE = .06. The analysis of forgetting ratio was based only on those persons who remembered at least one word in free recall (n = 445). Bonferroni post-hoc comparisons (p b .05) showed that both the AD and the VaD groups were outperformed by the controls on all measures, although the two dementia groups were indistinguishable (p N .10). Power analyses were conducted to determine the number of persons required to find significant differences between the AD and VaD groups. The effect sizes ranged from .13 to .31 for the various RetM indicators, which are regarded as small effects [41]. Consequently, depending on the type of RetM measure, between 163 and 982 persons would be required in both the AD and the VaD groups for differences of the same size as in the present study to be significant. Given the prevalence rates of AD and VaD in the population, these are unrealistic numbers. In subsequent analyses, we excluded all participants with mixed dementia (n = 6). We also performed analyses where all participants with a history of stroke were excluded from the AD and control groups. Neither of these exclusions changed the overall pattern of results. 4. Discussion The aim of this study was to examine patterns of ProM and RetM impairment in AD and VaD. The results clearly reveal that both dementia groups had difficulties with the ProM and RetM tasks alike. In addition, the dementia groups performed at similar levels on these tasks. Specifically, both dementia groups were equally impaired on the two components of the ProM task, as well as on the indicators of encoding, consolidation, and retrieval in the RetM task. Thus, the results indicated that AD and VaD persons were indistinguishable on all aspects of memory examined in this study. These results are in line with past research showing similar patterns of cognitive impairment in AD and VaD, including RetM functioning [1,2], and extend previous findings to ProM. The fact that the VaD patients were equally impaired as the AD patients in the RetM task and on the retrospective component of ProM, may appear counterintuitive given the marked medial– temporal lobe affection in AD [42,43] and the fact that the medial temporal lobe is critical to RetM [15,16]. However, RetM functioning draws on a large network involving the hippocampus, thalamus, cerebellum, parietal regions, and the fronto-striatal circuitry [44], and alterations at any site in this network may disrupt performance. Thus, although AD and VaD may affect partly different regions of the brain,
they may still produce similar functional impairments in RetM functioning. The RetM free and total recall data showed that all three groups were able to benefit from retrieval support, as evidenced from a performance increase from free to total recall. The total recall score denotes all words that once have been encoded into episodic memory, including additional items retrieved following the provision of category cues. The present data thus confirm previous observations that AD patients can benefit from retrieval support [36], and extend these results to VaD. In contrast to the controls who showed performance gains also from free to cued recall, both dementia groups actually performed slightly worse in cued compared to free recall. Conceivably, this finding reflects dementia-related forgetting over a rather short retention interval, indicating pronounced difficulties in consolidating episodic memories. Also for ProM, the AD and VaD groups performed at similar levels. Frontal regions are strongly implicated in maintaining an intention in mind over longer time intervals [18,19]. Hence, VaD could be expected to be associated with ProM deficits, as frontal–subcortical areas are often affected by the disease process [45]. In light of these lines of reasoning, it is interesting to note that also AD affects several neocortical structures, including the frontal cortex [46,47]. The fact that the VaD diagnoses in this study essentially included multi-infarct or strategic-infarct dementia has implications for the cognitive findings. In subcortical VaD, the frontal–subcortical circuits are often more affected, resulting in frontal-executive dysfunction as a major cognitive sign [45]. Therefore, a study targeting other subtypes of VaD may have rendered performance differences between the AD and VaD persons. More research is needed to verify whether the results from this study generalize to other subtypes of VaD. It is possible that a pure subcortical VaD group would have performed better on the RetM measures [3,45], particularly when retrieval support was provided [23,48]. However, they would probably not have performed worse on the ProM task as both the VaD and the AD groups in this study were strongly impaired on this task, a finding that reinforces the point that AD affects frontal sites to a large degree. Previous research has found that overlap in pathology between AD and VaD is common [49,50], and that the overlap increases with advancing age [51]. The high age of the participants in this study thus implies diagnostic leakage in both directions: AD pathology in VaD and circulatory lesions in AD that may result in difficulties in observing dissociative patterns. However, the overlap in pathology is a reflection of reality in very old age. An interesting avenue for future research is to examine whether the similar patterns of ProM and RetM impairment in AD and VaD observed here generalize to younger dementia patients. The dichotomous measure that was used to assess ProM in this study is a limitation that should be mentioned. ProM is often difficult to measure in a way that combines high external validity and good measurement properties. The ProM task was designed in order to maintain high external validity, focusing on the ability to retrieve the intention after a longer retention interval, rather than on monitoring ongoing activity, which may essentially be a measure of vigilance rather than of ProM functioning. Another caveat is that the VaD group was relatively small. However, this can be expected in population-based studies in general. A power-analysis revealed that the (nonsignificant) differences between the AD and VaD groups were so small that extremely large samples would have been needed in order to find significant effects. Therefore, we are confident in claiming that the two dementia disorders examined here show similar patterns of ProM and RetM deficits. With these caveats in mind, it is important to note that differences between the controls and the demented groups were found for all aspects of the ProM and RetM tasks, whereas no differences whatsoever were obtained when persons diagnosed with AD and VaD were compared. These findings thus provide support for the notion that early clinical VaD and AD have very similar cognitive
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repercussions, and that the two disorders are often difficult to separate on the basis of cognitive performance. It is also interesting to note that the memory impairment seen in VaD generalizes not only to RetM, which has been found in previous research, but also to ProM. Thus, the disease process in VaD can lead to impairments in both components of the ProM task and all stages of the RetM process. These findings provide novel information on the difficulties that persons with VaD are facing. In a previous study, we found that also preclinical AD is associated with a generalized impairment across all aspects of ProM and RetM [21]. Future research should examine whether the same generalized impairment of episodic memory can be seen in preclinical VaD. Another interesting research question is whether the similarities in ProM and RetM functioning are as pronounced in the preclinical phase of the two dementia disorders as in the early clinical stages. Acknowledgments This research was supported by grants from the Swedish Council for Working Life and Social Research and from Swedish Brain Power to Lars Bäckman, by a post-doctoral grant from the Swedish Research Council to Sari Karlsson, and by a grant from Swedish Match (Solstickan Foundation) to Åsa Livner. We are grateful to the participants and staff of the Kungsholmen Project for their efforts. References [1] Loring DW, Meador KJ, Mahurin RK, Largen JW. Neuropsychological performance in dementia of the Alzheimer type and multi-infarct dementia. Arch Clin Neuropsychol 1986;1:335–40. [2] Fahlander K, Wahlin Å, Almkvist O, Bäckman L. Cognitive functioning in Alzheimer's disease and vascular dementia: further evidence for similar patterns of deficits. J Clin Exp Neuropsychol 2002;24(6):734–44. [3] Looi JCL, Sachdev PS. Differentiation of vascular dementia from AD on neuropsychological tests. Neurology 1999;53:670–8. [4] Almkvist O, Fratiglioni L, Aguero-Torres H, Viitanen M, Bäckman L. Cognitive support at episodic encoding and retrieval: similar patterns of utilization in community-based samples of Alzheimer's disease and vascular dementia. J Clin Exp Neuropsychol 1999;21(6):816–30. [5] Libon DJ, Bogdanoff B, Cloud BS, Skalina S, Giovanetti T, Gitlin HL, et al. Declarative and procedural learning, quantitative measures of the hippocampus, and subcortical white alterations in Alzheimer's disease and ischaemic vascular dementia. J Clin Exp Neuropsychol 1998;20(1):30–41. [6] Lafosse JM, Reed BR, Mungas D, Sterling SB, Wahbeh H, Jagust WJ. Fluency and memory differences between ischemic vascular dementia and Alzheimer's disease. Neuropsychology 1997;11(4):514–22. [7] Ellis J. Prospective memory or the realization of delayed intentions: a conceptual framework for research. In: Brandimonte M, Einstein GO, McDaniel MA, editors. Prospective memory: theory and applications. Mahwah, NJ: Lawrence Erlbaum; 1996. p. 1–22. [8] Meacham JA, Singer J. Incentive effects in prospective remembering. J Psychol 1977;97:191–7. [9] Kliegel M, Martin M. Prospective memory research: why is it relevant? Int J Psychol 2003;38:193–4. [10] Smith G, Della Sala S, Logie RH, Maylor EA. Prospective and retrospective memory in normal aging and dementia: a questionnaire study. Memory 2000;8(5):311–21. [11] Maylor EA, Darby RJ, Logie RH, Della Sala S, Smith G. Prospective memory across the lifespan. In: Graf P, Ohta N, editors. Lifespan development of human memory. Cambridge, MA: The MIT Press; 2002. p. 235–56. [12] Maylor EA, Smith G, Della Sala S, Logie RH. Prospective and retrospective memory in normal aging and dementia: an experimental study. Mem Cognit 2002;30(6):871–84. [13] Uttl B, Graf P, Miller J, Tuokko H. Pro- and retrospective memory in late adulthood. Conscious Cogn 2001;10(4):451–72. [14] Graf P, Uttl B, Dixon R. Prospective and retrospective memory in adulthood. In: Graf P, Ohta N, editors. Lifespan development of human memory. Cambridge, MA: The MIT Press; 2002. p. 257–82. [15] Vargha-Khadem F, Gadian DG, Watkins KE, Connelly A, Van Paesschen W, Mishkin M. Differential effects of early hippocampal pathology on episodic and semantic memory. Science 1997;277:376–80. [16] Nyberg L, Tulving E. Classifying human long-term memory: evidence from converging dissociations. Eur J Cogn Psychol 1996;8(2):163–83. [17] Squire LR. Mechanisms of memory. Science 1986;232:1612–9. [18] Okuda J, Fujii T, Yamadori A, Kawashima R, Tsukiura T, Fukatsu R, et al. Participation of the prefrontal cortices in prospective memory: evidence from a PET study in humans. Neurosci Lett 1998;253(2):127–30. [19] Burgess PW, Quayle A, Frith CD. Brain regions involved in prospective memory as determined by positron emission tomography. Neuropsychologia 2001;39(6):545–55.
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Contents lists available at ScienceDirect
Journal of the Neurological Sciences j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j n s
Prospective and retrospective memory in Alzheimer's disease and vascular dementia: Similar patterns of impairment Åsa Livner a,⁎, Erika J. Laukka a, Sari Karlsson a,b, Lars Bäckman a a b
Aging Research Center, Karolinska Institutet, Stockholm, Sweden Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden
a r t i c l e
i n f o
Available online 2 April 2009 Keywords: Alzheimer's disease Vascular dementia Cognition Episodic memory Prospective memory Retrospective memory
a b s t r a c t Prospective memory (ProM) involves remembering to perform actions after a delay, such as buying groceries on the way home from work. Retrospective memory (RetM) involves remembering events from the past. It is known that the memory impairment in Alzheimer's disease (AD) generalizes across (a) these two types of memory, and (b) encoding, storage, and retrieval within RetM. Corresponding knowledge regarding these issues is sparse in vascular dementia (VaD). The aim of this study was, therefore, to compare the two dementia etiologies regarding patterns of impairment in ProM and RetM tasks. From a population-based study, 21 persons with VaD, 79 with AD, and 352 controls were included. Both dementia groups were impaired on all ProM and RetM variables, but did not differ from one another on any measure. The results are discussed relative to a network view of episodic memory, in which alterations at different sites may result in similar functional impairments. © 2009 Elsevier B.V. All rights reserved.
1. Introduction Both Alzheimer's disease (AD) and vascular dementia (VaD) are associated with severe deficits in a variety of cognitive domains, including episodic memory. Many studies demonstrate that the degree of episodic memory impairment is very similar in AD and VaD patients [1–3]. Also for different aspects within an episodic memory task, such as the relative contributions from primary and secondary memory, and the ability to utilize cognitive support for improving performance, the patterns of impairment in AD and VaD are often similar [4]. However, other research suggests differences in episodic memory performance between the two dementia groups, with VaD patients outperforming AD patients [3,5,6]. The majority of studies on episodic memory and dementia have focused on retrospective memory (RetM), which involves remembering events experienced in the past. Prospective memory (ProM) is another form of episodic memory, which involves remembering to perform an action after a delay, such as remembering an appointment or to buy groceries on the way home [7,8]. ProM is important for everyday functioning, and ProM complaints are common in memory clinics as well as among healthy older adults [9,10]. All ProM tasks involve two components: one component that is purely prospective and one component that is essentially a form of RetM. Whereas the prospective component involves remembering ⁎ Corresponding author. Aging Research Center, Karolinska Institutet Gävlegatan 16 S-113 30 Stockholm, Sweden. Tel.: +46 8 6906880; fax: +46 8 6906889. E-mail address: [email protected] (Å. Livner). 0022-510X/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.jns.2009.02.377
that something should be done, the retrospective component involves remembering the content of the action that is supposed to be performed [11]. Despite the fact that ProM has a retrospective component, there are important differences between ProM and RetM. Factor-analytic work has shown that ProM and RetM tasks load on different factors [12,13]. Other studies have found that the two types of memory are only weakly correlated, and that the association is further attenuated when the retrospective component of the ProM task is controlled for [14]. Also, ProM and RetM partly draw on different brain regions. Whereas the medial–temporal lobe is critical to RetM [15–17], ProM is more dependent on areas in the prefrontal cortex [18,19]. Whether ProM functioning is impaired to a similar extent in AD and VaD is unknown. There is evidence for a ProM impairment in clinical AD [12,20] as well as in the preclinical phase of this disease [21]. Less is known about the influence of VaD on ProM. There is, however, evidence for impaired performance on ProM tasks among stroke patients [22]. Episodic memory can be divided into the stages of encoding, storage (i.e., consolidation), and retrieval. These stages are all essential for successful episodic remembering. In the current study, data on these aspects of memory were available for the RetM task. Of chief interest was whether AD and VaD would show a similar or differential pattern of impairment with regard to encoding, storage and retrieval operations. Previous research on this topic is limited. There are studies suggesting that persons with AD are more impaired with regard to storage, whereas persons with VaD have more retrieval difficulties, and would thus benefit more from the retrieval support provided in
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cued recall tasks [23]. However, other research reports no differences regarding the relative impairment across the stages of episodic memory in AD and VaD [4]. Thus, the aims of this study were to examine whether (1) the degree of memory impairment is of similar magnitude in AD compared to VaD persons for ProM and RetM; and (2) the patterns of impairment are similar or differential in AD and VaD with regard to the two components of ProM (the prospective versus the retrospective component) as well as the RetM stages of encoding, consolidation, and retrieval. 2. Method The study is based on data from the Kungsholmen project (KP), which is a longitudinal, population-based study targeting the medical, psychological and social aspects of aging. The KP has been approved by the ethics committee of Karolinska Institutet, Sweden, and informed consent was obtained from all participants or next-of-kin. The original sample was taken from all the inhabitants, 75 years and older, living in the Kungsholmen parish of Stockholm, Sweden on October 1, 1987 (n = 2,368). The baseline examination consisted of two phases. First, 1810 persons participated in a screening phase, which consisted of a health examination and an interview including the Mini-Mental State Examination or MMSE [24]. Second, participants who scored 23 or lower on the MMSE (n = 314) and a random sample matched on age and sex (n = 354), were re-examined using a more extensive protocol including a medical, psychiatric and neurological examination, social interviews, and a comprehensive cognitive test battery. At the followup examinations, with approximately three-year intervals, the same protocol was used as in the extensive baseline examination. All participants from the screening phase were then invited. 2.1. Diagnoses of dementia The diagnoses of dementia were based on DSM-III-R criteria [25] and made through a three-step procedure. A preliminary diagnosis was first made by the geriatricians who had examined the participants and reviewed their social and family history. A physician expert in dementia and external to the data collection, independently made a second diagnosis based on computerized data, which was compared to the first diagnosis. In cases of disagreement, a supervising physician made the final diagnosis. Type of dementia was determined using clinical data. The Hachinski Ischemic Scale (HIS) [26] was used to support the clinical judgment. This score takes into account the presence of signs associated with VaD such as an abrupt onset of the dementia disorder, a stepwise deterioration, fluctuating course, and a history of stroke. A HIS score above 6 is an indicator of VaD, a HIS score of 5 or 6 is an indicator of mixed dementia, and a HIS score lower than 5 is an indicator of AD. The sensitivity as well as specificity of the HIS is high in differentiating between AD and VaD [27]. The AD diagnosis corresponds to probable AD according to the NINCDS-ADRDA criteria [28], and the diagnosis of VaD corresponds to possible VaD according to the NINDS-AIREN criteria [29]. In the KP, a majority of the participants diagnosed with VaD had a history of stroke. Thus, the VaD diagnosis in this study is essentially a diagnosis of strategic or multiinfarct dementia. For those participants who died during the follow-up period, the diagnosis was based on the information available through clinical records, discharge diagnoses, and death certificates. A more detailed description of the KP and the diagnostic procedures has been reported elsewhere [30]. 2.2. Study sample Only persons who completed the cognitive test battery were included in the sample. In order to increase the statistical power, data
were aggregated from the baseline phase and the first two follow-ups. All participants with Parkinson's disease, psychosis, and major depression were excluded, as well as participants using antidepressive or antipsychotic medication. Diagnoses of psychiatric diseases were based on DSM-III-R criteria at baseline and DSM-IV [31] criteria at the follow-ups. Two AD persons and two VaD persons with MMSE scores below 10 were also excluded from the sample, because of difficulties in complying with the task demands. In the final sample, 21 persons with VaD (including six mixed dementia cases) and 79 persons with AD were included. Of the VaD persons, five (23.8%) were diagnosed at baseline, five (23.8%) at the first follow-up and 11 (52.4%) at the second follow-up. Of the persons with AD, 17 (21.5%) were diagnosed at baseline, 26 (32.9%) at the first follow-up and 36 (45.6%) at the second follow-up. The cognitive data were always taken from the phase where the person was first diagnosed with dementia. Among the controls, persons with other types of dementia were excluded, as well as persons in a preclinical phase of dementia. Thus, only persons who remained free from dementia during baseline and the first three follow-ups were included in the control group. Also, we excluded all control participants with MMSE scores below 25, as this has previously been identified as a cut-off for suspected preclinical dementia [32]. Control participants with data from more than one phase were included only once, and data were randomly taken from one of the three phases. In order to keep age and retest effects similar to the dementia groups, we sought to obtain a control group with approximately the same proportion of persons with cognitive data from each phase. In the final sample, 352 controls were included. Of these, 59 (16.8%) had their data taken from baseline, 105 (29.8%) from the first follow-up, and 188 (53.4%) from the second follow-up. In total, 94 persons were excluded from the analyses due to missing data. This includes persons with missing data on the ProM task (n = 72), RetM task (n = 5) or both tasks (n = 17). Sample characteristics are shown in Table 1. A multivariate analysis of variance (MANOVA) revealed no age differences among the groups. However, there were differences in education, F (2,449) = 10.33, p b .001; MMSE score, F (2,449) = 10.16, p b 001; and length of test session, F (2,449) = 449.76, p b 001. The control group had received more education than the AD group (p b .05). There were no differences between the VaD group and any of the other groups with regard to education (p N .10). The controls also significantly outperformed the AD and VaD groups on the MMSE (p b .05), whereas there were no differences between the two dementia groups (p N .10). The AD and VaD groups had significantly longer test sessions than the controls (p b .05), although there were no differences between the dementia groups with regard to length of test session (p N .10). A χ2-analysis revealed no differences in sex distribution among the groups (p N .10). We also compared the groups on the Clinical Dementia Scale, CDR [33]. The majority of the demented participants had mild or moderate dementia. Only two AD persons (2.5%) were classified as having severe dementia. There were no significant differences in dementia severity between the AD and VaD groups (p N .10). Four participants had missing data on the education variable, and two participants had no data on length of test session. For these participants, the group mean was imputed. Table 1 Subject characteristics. Controls (n = 352) M Age (years) Education (years) MMSE Session length (min) Sex
AD persons (n = 79) SD
85.54 3.96 9.65 3.25 27.53 1.45 60.13 12.26 73.9% women
M
SD
86.49 5.18 7.99 2.54 20.41 3.32 66.96 19.03 83.5% women
VaD persons (n = 21) M
SD
85.14 4.87 8.45 2.04 21.10 3.86 67.67 12.92 66.7% women
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consolidate memories. In order to control for initial free recall performance, we used the forgetting ratio, which was calculated as number of words remembered in free recall but forgotten in cued recall, divided by the free recall score. In calculating forgetting ratio, 7 AD persons were excluded because they did not remember any words in free recall. 3. Results
Fig. 1. Percentage successful persons in the prospective memory task for controls, AD persons, and VaD persons.
2.3. Prospective memory To assess ProM, participants were instructed at the beginning of the test session to remind the test leader to make an important phone call after completion of all tests. If a participant failed to do so, the test leader asked: “What was I supposed to do when we were finished with the testing?” The mean length of test session, which is also the retention interval for the ProM task, was 61.68 min (SD = 13.99). The prospective component of the task involved remembering to remind the test leader without being given the additional prompt. The majority of participants who did so also recalled the content of the instruction correctly (i.e., that the test leader was supposed to make a phone call), whereas a minority (n = 10) failed to remember correctly what was supposed to be done. The retrospective component of the task involved remembering the content of the instruction either with or without a prompt. 2.4. Retrospective memory The RetM task consisted of a word list including 12 nouns presented both visually and auditorily to the participants. The words belonged to four different taxonomic categories (professions, clothes, furniture, and musical instruments), and were presented randomly intermixed. No mention was made of the organizational structure of the word list. All words were typical of their respective categories, according to previously established norms [34]. Performance was measured with free, cued, and total recall. Immediately after the presentation, a free recall task was given during two minutes. Following free recall, the participants were provided with the category names as cues and again instructed to recall as many words as possible during two minutes, including those already remembered in free recall. Total recall denotes the total number of words remembered in either free or cued recall. To provide category cues at retrieval is one way of improving performance, by making previously inaccessible items accessible [35]. The increase in number of recalled words from free to cued recall is thus a measure of the ability to use retrieval support. However, in evaluating cued recall performance, one has to consider that forgetting may occur between free and cued recall, although the time span between the two tasks is relatively short. In a previous study, persons with AD were found to be highly prone to forgetting from free to cued recall [36]. To disentangle the effects of cognitive support and forgetting, it is therefore necessary to compare free recall performance with both cued and total recall performance. Also, three qualitative indicators of RetM were used, which in previous research has been found to tap different stages of the memory process. Number of categories represented in the response protocols for free recall reflects the participant's plan at retrieval, whereas number of items remembered per category denotes the degree of semantic organization at encoding [35,37–40]. A measure of forgetting was also included, as an indicator of difficulties to
Performance on the ProM task for the three groups is portrayed in Fig. 1. To analyze the ProM data, a χ 2-analysis including all three groups was first performed. This analysis revealed significant differences for both the prospective and retrospective components, χ 2 (2, n = 452) = 21.10, p b 001, and χ 2 (2, n = 452) = 87.93, p b .001, respectively. The proportion of persons who successfully remembered the prospective component was 8.9% in the AD group, 9.5% in the VaD group, and 32.1% in the control group. For the retrospective component, the proportion that succeeded was 26.6% in the AD group, 28.6% in the VaD group, and 77.3% in the control group, respectively. Subsequent analyses demonstrated that the controls outperformed both dementia groups for the prospective and retrospective components alike (p b .001), although there were no differences between the dementia groups for either component (p N .10). Fig. 2 shows free, cued, and total recall performance on the RetM task. Separate analyses of covariance (ANCOVAs), controlling for age, sex, and education, were performed for the memory indicators. There were group differences for free recall, F (2,446) = 103.32, p b .001, η2 = .32, MSE = 3.81; cued recall, F (2,446) = 107.92, p b .001, η2 = .33, MSE = 5.42; and total recall, F (2,446) = 101.76, p b .001, η2 = .31, MSE = 4.19. Bonferroni post-hoc comparisons (p b .05) were made in order to compare all groups separately. Both the AD and the VaD groups were outperformed by the controls on free, cued, and total recall. However, no performance differences were observed between the two dementia groups (p N .10). To examine the effects of retrieval support provided in cued recall, a 3 (group) × 2 (task: free recall, cued recall) mixed ANOVA, with repeated measures on the last factor, was carried out. The results revealed no main effect of task (p N .10). However, a significant interaction between group and task was found, F (2,449) = 7.35, p b .01, η2 = .03, MSE = 1.66. Whereas the controls improved their performance in cued recall compared to free recall (p b .05), the demented groups did not (p N .10). Another mixed ANOVA was carried out where cued recall was substituted with total recall. The results revealed a significant main effect of task F (1,449) = 218.43, p b .001, η2 = .33, MSE = .79. Importantly, there was no longer an interaction between group and task (p N .10), indicating that all three groups improved their performance to a similar extent in total compared to free recall. Contrasting these two analyses, it is obvious that the group × task interaction obtained in the free-cued recall analysis reflects disproportionate forgetting from the time of free to cued recall in the dementia groups.
Fig. 2. Mean retrospective free, cued, and total recall for controls, AD persons, and VaD persons. Error bars represent standard errors around the means.
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Fig. 3. Mean performance on qualitative indicators of retrospective memory for controls, AD persons, and VaD persons. Error bars represent standard errors around the means.
Fig. 3 shows performance on the qualitative indices for the RetM task. Again, separate ANCOVAs controlling for age, sex and education, were carried out. There were differences among the three groups for number of categories, F (2,446) = 78.51, p b .001, η2 = .26, MSE = .61; items per category, F (2,446) = 55.52, p b .001, η2 = .20, MSE = .21; and forgetting ratio, F (2,439) = 79.57, p b .001, η2 = .27, MSE = .06. The analysis of forgetting ratio was based only on those persons who remembered at least one word in free recall (n = 445). Bonferroni post-hoc comparisons (p b .05) showed that both the AD and the VaD groups were outperformed by the controls on all measures, although the two dementia groups were indistinguishable (p N .10). Power analyses were conducted to determine the number of persons required to find significant differences between the AD and VaD groups. The effect sizes ranged from .13 to .31 for the various RetM indicators, which are regarded as small effects [41]. Consequently, depending on the type of RetM measure, between 163 and 982 persons would be required in both the AD and the VaD groups for differences of the same size as in the present study to be significant. Given the prevalence rates of AD and VaD in the population, these are unrealistic numbers. In subsequent analyses, we excluded all participants with mixed dementia (n = 6). We also performed analyses where all participants with a history of stroke were excluded from the AD and control groups. Neither of these exclusions changed the overall pattern of results. 4. Discussion The aim of this study was to examine patterns of ProM and RetM impairment in AD and VaD. The results clearly reveal that both dementia groups had difficulties with the ProM and RetM tasks alike. In addition, the dementia groups performed at similar levels on these tasks. Specifically, both dementia groups were equally impaired on the two components of the ProM task, as well as on the indicators of encoding, consolidation, and retrieval in the RetM task. Thus, the results indicated that AD and VaD persons were indistinguishable on all aspects of memory examined in this study. These results are in line with past research showing similar patterns of cognitive impairment in AD and VaD, including RetM functioning [1,2], and extend previous findings to ProM. The fact that the VaD patients were equally impaired as the AD patients in the RetM task and on the retrospective component of ProM, may appear counterintuitive given the marked medial– temporal lobe affection in AD [42,43] and the fact that the medial temporal lobe is critical to RetM [15,16]. However, RetM functioning draws on a large network involving the hippocampus, thalamus, cerebellum, parietal regions, and the fronto-striatal circuitry [44], and alterations at any site in this network may disrupt performance. Thus, although AD and VaD may affect partly different regions of the brain,
they may still produce similar functional impairments in RetM functioning. The RetM free and total recall data showed that all three groups were able to benefit from retrieval support, as evidenced from a performance increase from free to total recall. The total recall score denotes all words that once have been encoded into episodic memory, including additional items retrieved following the provision of category cues. The present data thus confirm previous observations that AD patients can benefit from retrieval support [36], and extend these results to VaD. In contrast to the controls who showed performance gains also from free to cued recall, both dementia groups actually performed slightly worse in cued compared to free recall. Conceivably, this finding reflects dementia-related forgetting over a rather short retention interval, indicating pronounced difficulties in consolidating episodic memories. Also for ProM, the AD and VaD groups performed at similar levels. Frontal regions are strongly implicated in maintaining an intention in mind over longer time intervals [18,19]. Hence, VaD could be expected to be associated with ProM deficits, as frontal–subcortical areas are often affected by the disease process [45]. In light of these lines of reasoning, it is interesting to note that also AD affects several neocortical structures, including the frontal cortex [46,47]. The fact that the VaD diagnoses in this study essentially included multi-infarct or strategic-infarct dementia has implications for the cognitive findings. In subcortical VaD, the frontal–subcortical circuits are often more affected, resulting in frontal-executive dysfunction as a major cognitive sign [45]. Therefore, a study targeting other subtypes of VaD may have rendered performance differences between the AD and VaD persons. More research is needed to verify whether the results from this study generalize to other subtypes of VaD. It is possible that a pure subcortical VaD group would have performed better on the RetM measures [3,45], particularly when retrieval support was provided [23,48]. However, they would probably not have performed worse on the ProM task as both the VaD and the AD groups in this study were strongly impaired on this task, a finding that reinforces the point that AD affects frontal sites to a large degree. Previous research has found that overlap in pathology between AD and VaD is common [49,50], and that the overlap increases with advancing age [51]. The high age of the participants in this study thus implies diagnostic leakage in both directions: AD pathology in VaD and circulatory lesions in AD that may result in difficulties in observing dissociative patterns. However, the overlap in pathology is a reflection of reality in very old age. An interesting avenue for future research is to examine whether the similar patterns of ProM and RetM impairment in AD and VaD observed here generalize to younger dementia patients. The dichotomous measure that was used to assess ProM in this study is a limitation that should be mentioned. ProM is often difficult to measure in a way that combines high external validity and good measurement properties. The ProM task was designed in order to maintain high external validity, focusing on the ability to retrieve the intention after a longer retention interval, rather than on monitoring ongoing activity, which may essentially be a measure of vigilance rather than of ProM functioning. Another caveat is that the VaD group was relatively small. However, this can be expected in population-based studies in general. A power-analysis revealed that the (nonsignificant) differences between the AD and VaD groups were so small that extremely large samples would have been needed in order to find significant effects. Therefore, we are confident in claiming that the two dementia disorders examined here show similar patterns of ProM and RetM deficits. With these caveats in mind, it is important to note that differences between the controls and the demented groups were found for all aspects of the ProM and RetM tasks, whereas no differences whatsoever were obtained when persons diagnosed with AD and VaD were compared. These findings thus provide support for the notion that early clinical VaD and AD have very similar cognitive
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repercussions, and that the two disorders are often difficult to separate on the basis of cognitive performance. It is also interesting to note that the memory impairment seen in VaD generalizes not only to RetM, which has been found in previous research, but also to ProM. Thus, the disease process in VaD can lead to impairments in both components of the ProM task and all stages of the RetM process. These findings provide novel information on the difficulties that persons with VaD are facing. In a previous study, we found that also preclinical AD is associated with a generalized impairment across all aspects of ProM and RetM [21]. Future research should examine whether the same generalized impairment of episodic memory can be seen in preclinical VaD. Another interesting research question is whether the similarities in ProM and RetM functioning are as pronounced in the preclinical phase of the two dementia disorders as in the early clinical stages. Acknowledgments This research was supported by grants from the Swedish Council for Working Life and Social Research and from Swedish Brain Power to Lars Bäckman, by a post-doctoral grant from the Swedish Research Council to Sari Karlsson, and by a grant from Swedish Match (Solstickan Foundation) to Åsa Livner. We are grateful to the participants and staff of the Kungsholmen Project for their efforts. References [1] Loring DW, Meador KJ, Mahurin RK, Largen JW. Neuropsychological performance in dementia of the Alzheimer type and multi-infarct dementia. Arch Clin Neuropsychol 1986;1:335–40. [2] Fahlander K, Wahlin Å, Almkvist O, Bäckman L. Cognitive functioning in Alzheimer's disease and vascular dementia: further evidence for similar patterns of deficits. J Clin Exp Neuropsychol 2002;24(6):734–44. [3] Looi JCL, Sachdev PS. Differentiation of vascular dementia from AD on neuropsychological tests. Neurology 1999;53:670–8. [4] Almkvist O, Fratiglioni L, Aguero-Torres H, Viitanen M, Bäckman L. Cognitive support at episodic encoding and retrieval: similar patterns of utilization in community-based samples of Alzheimer's disease and vascular dementia. J Clin Exp Neuropsychol 1999;21(6):816–30. [5] Libon DJ, Bogdanoff B, Cloud BS, Skalina S, Giovanetti T, Gitlin HL, et al. Declarative and procedural learning, quantitative measures of the hippocampus, and subcortical white alterations in Alzheimer's disease and ischaemic vascular dementia. J Clin Exp Neuropsychol 1998;20(1):30–41. [6] Lafosse JM, Reed BR, Mungas D, Sterling SB, Wahbeh H, Jagust WJ. Fluency and memory differences between ischemic vascular dementia and Alzheimer's disease. Neuropsychology 1997;11(4):514–22. [7] Ellis J. Prospective memory or the realization of delayed intentions: a conceptual framework for research. In: Brandimonte M, Einstein GO, McDaniel MA, editors. Prospective memory: theory and applications. Mahwah, NJ: Lawrence Erlbaum; 1996. p. 1–22. [8] Meacham JA, Singer J. Incentive effects in prospective remembering. J Psychol 1977;97:191–7. [9] Kliegel M, Martin M. Prospective memory research: why is it relevant? Int J Psychol 2003;38:193–4. [10] Smith G, Della Sala S, Logie RH, Maylor EA. Prospective and retrospective memory in normal aging and dementia: a questionnaire study. Memory 2000;8(5):311–21. [11] Maylor EA, Darby RJ, Logie RH, Della Sala S, Smith G. Prospective memory across the lifespan. In: Graf P, Ohta N, editors. Lifespan development of human memory. Cambridge, MA: The MIT Press; 2002. p. 235–56. [12] Maylor EA, Smith G, Della Sala S, Logie RH. Prospective and retrospective memory in normal aging and dementia: an experimental study. Mem Cognit 2002;30(6):871–84. [13] Uttl B, Graf P, Miller J, Tuokko H. Pro- and retrospective memory in late adulthood. Conscious Cogn 2001;10(4):451–72. [14] Graf P, Uttl B, Dixon R. Prospective and retrospective memory in adulthood. In: Graf P, Ohta N, editors. Lifespan development of human memory. Cambridge, MA: The MIT Press; 2002. p. 257–82. [15] Vargha-Khadem F, Gadian DG, Watkins KE, Connelly A, Van Paesschen W, Mishkin M. Differential effects of early hippocampal pathology on episodic and semantic memory. Science 1997;277:376–80. [16] Nyberg L, Tulving E. Classifying human long-term memory: evidence from converging dissociations. Eur J Cogn Psychol 1996;8(2):163–83. [17] Squire LR. Mechanisms of memory. Science 1986;232:1612–9. [18] Okuda J, Fujii T, Yamadori A, Kawashima R, Tsukiura T, Fukatsu R, et al. Participation of the prefrontal cortices in prospective memory: evidence from a PET study in humans. Neurosci Lett 1998;253(2):127–30. [19] Burgess PW, Quayle A, Frith CD. Brain regions involved in prospective memory as determined by positron emission tomography. Neuropsychologia 2001;39(6):545–55.
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