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Neuropsychologia 49 (2011) 2694 2702 Contents lists available at ScienceDirect Neuropsychologia j ourna l ho me pag e: ww w.elsevier.com/locate/neuropsychologia Profiles of recent autobiographical memory retrieval in semantic dementia, behavioural-variant frontotemporal dementia, and Alzheimer s disease M. Irish a,b, M. Hornberger a,b, S. Lah c, L. Miller c,d, G. Pengas e, P.J. Nestor e, J.R. Hodges a,b, O. Piguet a,b, a Neuroscience Research Australia, Barker Street, Randwick, Sydney, Australia b School of Medical Sciences, The University of New South Wales, Sydney, Australia c School of Psychology, The University of Sydney, Sydney, Australia d Department of Neuropsychology, Royal Prince Alfred Hospital, Sydney, Australia e Department of Clinical Neurosciences, University of Cambridge, United Kingdom a r t i c l e i n f o Article history: Received 22 December 2010 Received in revised form 18 May 2011 Accepted 23 May 2011 Available online 30 May 2011 Keywords: Episodic memory Semantic memory Consolidation Emotion Executive function a b s t r a c t Episodic autobiographical memory (ABM) comprises recollection for events that are grounded within a specific spatiotemporal context, and usually accompanied by perceptual and emotional information. The neural substrates mediating ABM retrieval are those harbouring significant pathology in semantic dementia (SD) and behavioural-variant frontotemporal dementia (bvftd), the most common subtypes of FTD. Relatively little is known, however, regarding the differential patterns of contextual details during episodic ABM retrieval across these dementia syndromes. This study investigated episodic ABM retrieval under free and probed recall conditions from 4 time periods with the aim to identify disease-specific profiles of episodic ABM contextual details. Episodic ABM was measured in 25 SD and 15 bvftd patients and their performance contrasted to that of 17 Alzheimer s disease (AD) patients and 19 age-matched controls. Critically, SD patients showed relatively preserved recent ABM in comparison with remote epochs. In contrast, bvftd and AD patients showed a reduced capacity to recall specific and contextually rich ABMs across all life epochs, in both free and probed recall conditions. Analyses of the recent period (last 12 months) provided evidence for different profiles of contextual episodic details recalled in dementia syndromes. Following probing, SD patients recall deficits emanated exclusively from compromised Emotion/Thoughts and Spatiotemporal details. In contrast, bvftd patients were significantly impaired across all categories of contextual details whereas AD patients showed deficits for Event and Emotion/Thoughts details only. As the largest study of ABM in FTD to date, these findings emphasise the differential impairment of recent ABM contextual details contingent on the underlying disease pathology. In addition, these results point towards the importance of investigating the constituent elements of emotion processing and strategic retrieval processes as potential variables mediating recent episodic ABM retrieval. 2011 Elsevier Ltd. All rights reserved. 1. Introduction Frontotemporal dementia (FTD) refers to a progressive neurodegenerative disorder, encompassing a wide range of cognitive, behavioural and/or motor deficits (Neary et al., 1998). Three subgroups of FTD are generally reported; semantic dementia (SD), behavioural-variant FTD (bvftd), and progressive nonfluent aphasia (PNFA). This study focuses on the SD and bvftd subtypes. Patients with SD display a gradual breakdown in semantic memory with relatively preserved episodic memory (Adlam, Patterson, & Hodges, 2009; Hodges & Patterson, 2007). Patients with bvftd present with marked changes in behaviour and personality includ- Corresponding author at: Neuroscience Research Australia, Barker Street, Randwick, NSW 2031, Australia. Tel.: +61 2 9399 1113; fax: +61 2 9399 1047. E-mail address: o.piguet@neura.edu.au (O. Piguet). ing disinhibition, apathy, and lack of insight (Piguet, Hornberger, Mioshi, & Hodges, 2011). The clinical presentations of SD and bvftd patients tend to reflect specific profiles of brain atrophy. In SD, a progressive degeneration of the anterior temporal lobes is observed (Hodges & Patterson, 2007), most severe on the ventral surface, which also includes the rostral hippocampus (Chan et al., 2001; Davies, Graham, Xuereb, Williams, & Hodges, 2004; Galton et al., 2001). In contrast, the bvftd subtype is associated primarily with degeneration of the medial and orbital prefrontal cortices (Kipps, Hodges, Fryer, & Nestor, 2009; Rosen, Gorno-Tempini et al., 2002; Seeley et al., 2008). With disease progression, however, these patients may present with a more mixed profile of neuropsychological impairment, and have evidence of temporal and frontal involvement (Matuszewski et al., 2009; Nestor, Graham, Bozeat, Simons, & Hodges, 2002; Williams, Nestor, & Hodges, 2005). Autobiographical memory (ABM) is a complex construct, generally taken to refer to memory for a personally experienced 0028-3932/$ see front matter 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.neuropsychologia.2011.05.017

M. Irish et al. / Neuropsychologia 49 (2011) 2694 2702 2695 event that is imbued with a sense of recollection (Greenberg & Rubin, 2003). Episodic ABMs are typically emotionally laden (Piefke, Weiss, Zilles, Markowitsch, & Fink, 2003), leaving durable and evocative memory traces (Berntsen & Rubin, 2002), often with a rich level of contextual sensory-perceptual details (Conway, Pleydell-Pearce, Whitecross, & Sharpe, 2003; Irish, Lawlor, O Mara, & Coen, 2011). Neuroimaging studies have pointed towards a large neural network subtending ABM retrieval including the hippocampus, parahippocampal gyrus, lateral temporal cortices, posterior parietal cortex, retrosplenial cortex, posterior cingulate cortex, precuneus, thalamus, and the medial prefrontal cortex (Maguire, 2001). Given their pattern of predominant pathology and atrophy, FTD cohorts, in the early stages of the disease, are ideal clinical groups for investigating ABM retrieval (McKinnon et al., 2008). The profile of ABM retrieval appears contingent on clinical FTD subtype, offering potential insights into the underlying mechanism of consolidation (Piolino et al., 2003). Studies of ABM in SD have yielded mixed results, with some documenting a reverse temporal gradient whereby recent memories are relatively preserved in comparison with impoverished remote memories (e.g., Graham & Hodges, 1997; Hou, Miller, & Kramer, 2005; Matuszewski et al., 2009; Nestor et al., 2002), with other studies failing to find ABM temporal gradients in SD (Maguire, Kumaran, Hassabis, & Kopelman, 2010; McKinnon, Black, Miller, Moscovitch, & Levine, 2006). These conflicting reports of ABM performance in SD may be attributable to different experimental paradigms used, or may reflect within-group differences in disease severity (Ivanoiu, Cooper, Shanks, & Venneri, 2006; Matuszewski et al., 2009). Importantly, the sample sizes used in SD studies to date have often been relatively small, limiting their conclusions. ABM performance in bvftd patients is more consistent, most studies reporting deficits irrespective of methodology or the age of the memories, encompassing both recent and remote periods (Hou et al., 2005; Matuszewski et al., 2006; Nestor et al., 2002; Piolino et al., 2007, 2003; Thomas-Antérion, Jacquin, & Laurent, 2000). The absence of temporal gradient in bvftd likely reflects a deficit of strategic processes related to executive dysfunction (Matuszewski et al., 2006; Nestor et al., 2002; Piolino et al., 2007, 2003). Matuszewski et al. (2006) demonstrated that deficits in ABM in bvftd were largely attributable to disruption of executive functioning and semantic memory regardless of the age of the memories. Consideration of the sensory-perceptual details recollected during ABM retrieval represents an important line of enquiry in light of recent studies pointing towards a complex interplay of phenomenological factors such as visual imagery and emotional tone facilitating the retrieval of episodic ABMs (Addis, Moscovitch, Crawley, & McAndrews, 2004; Irish et al., 2011). The importance of emotion during ABM retrieval is well documented (Berntsen & Rubin, 2002). Disrupted emotional re-experiencing during recent ABM retrieval in Alzheimer s disease (AD) has recently been reported (Irish et al., 2011). Recognition of emotions is severely compromised in FTD (Lough et al., 2006; Rankin et al., 2009; Werner et al., 2007), raising the possibility that impaired emotion processing may contribute to the ABM deficits observed in SD and bvftd, although this has not been explored. The objectives of this study were to determine the nature of episodic ABM impairment in SD in comparison with bvftd and AD patients. We hypothesised that SD patients would show preservation of recent ABM in the context of significantly compromised remote memory. In contrast, we predicted that bvftd patients would show a global deficit in ABM retrieval affecting all time periods equally. A second aim of this study was to characterise the breakdown of recent episodic ABM retrieval in SD, focusing on the contextual details retrieved by patients in the recent period. The recent period represents an epoch of considerable interest, as it is the only epoch in which the age of the episodes is identical across participants. We predicted that the patterns of contextual details recalled in the recent period would vary contingent on dementia type, stemming from disruption to different neurocognitive circuits. We further predicted that emotion details would be particularly compromised in the FTD cohorts, given the welldocumented problems in emotion processing in these groups. To our knowledge, no study has systematically studied the profiles of contextual details elicited during ABM retrieval in well characterised cases of SD, in contrast with bvftd and AD patients, to determine how episodic details might be affected contingent on dementia subtype. 2. Methods 2.1. Participants Fifty-seven dementia patients (SD = 25; bvftd = 15; AD = 17) and 19 age- and education-matched healthy controls participated in this study. All bvftd, AD and 11/25 SD patients were recruited through FRONTIER at Neuroscience Research Australia, Sydney. The remainder 14 SD patients were recruited through the Cambridge Memory and Early-Onset Dementia Clinic, UK. All dementia patients met clinical diagnostic criteria for SD, bvftd or AD (McKhann et al., 1984; Neary et al., 1998; Rascovsky et al., 2007). Diagnosis was established by consensus among senior neurologist, neuropsychologist and occupational therapist, based on extensive clinical investigations, cognitive assessment, and evidence of change on structural brain neuroimaging. Briefly, the SD patients exhibited progressive loss of word meaning manifested by impaired naming and comprehension, semantic paraphasias, prosopagnosia and/or associative agnosia, in the context of relatively preserved everyday memory. Structural neuroradiological reports confirmed the presence of anterior temporal lobe atrophy, more pronounced on the left side. The bvftd patients presented with marked changes in behaviour and personality including decline in social conduct, emotional blunting, loss of insight, disinhibition, diminished motivation, apathy and distractibility. Only bvftd patients with evidence of definite progression impinging on everyday function, and demonstrating bilateral prefrontal cortical atrophy on MRI, were included in the study to exclude cases with the phenocopy syndrome (Kipps, Hodges, & Hornberger, 2010; Piguet et al., 2011). In contrast, the AD patients exhibited significant episodic memory loss in the context of preserved behaviour and personality, with predominant bilateral medial temporal lobe and parietal lobe atrophy. Healthy controls were recruited from the patients family and friends, from the Neuroscience Research Australia brain donor program, and from local community clubs. Controls scored between 27 and 30 on the Mini-Mental State Examination (MMSE; Folstein, Folstein & McHugh, 1975), 0 on the Clinical Dementia Rating scale (CDR; Morris, 1997), and 85 or above on the Addenbrooke s Cognitive Examination-Revised (ACE-R; Mioshi, Dawson, Mitchell, Arnold, & Hodges, 2006). In addition to the ACE-R, the cognitive assessment included the Rey Auditory Verbal Learning Test (RAVLT; Schmidt, 1996), Trail Making Test (Reitan, 1958), Verbal Letter fluency (F, A, S; Strauss, Sherman, & Spreen, 2006), a measure of Naming and Comprehension adapted from the Repeat and Point test (Hodges, Martinos, Woollams, Patterson, & Adlam, 2008), as well as a measure of facial emotion recognition, the Ekman 60 task (Ekman, Friesen, & Press, 1976). The apathy subscale of the Cambridge Behavioural Inventory (CBI; Wedderburn et al., 2008) was completed by the carers of each patient in this study. As SD patients were recruited across two different research sites, the background neuropsychological testing varied for each patient cohort. The SD cases recruited from FRONTIER in Sydney underwent all of the neuropsychological tests listed above. Mann Whitney U-tests revealed no significant differences between the patients for general cognitive function (ACE-R, p =.410) or for disease duration (time of onset of symptoms to time of testing, p =.103). Medical history, current medication use and presence of depression symptomatology were also assessed. Exclusion criteria included prior history of mental illness, significant head injury, movement disorders, cerebrovascular disease, alcohol and other drug abuse, and limited English proficiency. 2.2. Assessment of autobiographical memory Episodic autobiographical memory was examined using a shortened version of the Autobiographical Interview (AI; Levine, Svoboda, Hay, Winocur, & Moscovitch, 2002). This instrument has been employed previously in these cohorts (McKinnon et al., 2006, 2008) and permits the segmentation of episodic from semantic details across life epochs. Briefly, participants were asked to provide a detailed description of a personally experienced event that occurred at a specific time and place from four different life epochs: Teenage Years (11 17 years), Early Adulthood (18 35 years), Middle Adulthood (35 55 years) and Recent Time (within the last year). The Early Childhood epoch (up to age 11) of the original test was omitted to shorten the test session and reduce the burden of testing on patients. The AI was administered according to the standardised protocol. If participants were unable to retrieve an event independently, a list of typical events for each epoch was presented. In keeping with previous studies, we manipulated the level

2696 M. Irish et al. / Neuropsychologia 49 (2011) 2694 2702 of structure available to participants across three conditions: recall, general probe, and specific probe (see Levine et al., 2002 for a full description). The test session thus proceeded with participants speaking extemporaneously about the event in question (free recall), following which general probes were used to encourage greater recall of details. Finally, specific probes targeting five discrete categories were provided (Event, Time, Place, Perceptual, and Emotion/Thoughts). The specific probe condition was administered after all events were retrieved via the free recall and general probe conditions. This procedure ensured that the specific probe process did not contaminate the recall of subsequent memories. All participant interviews were recorded and subsequently transcribed to facilitate the detailed scoring procedure. The AI scoring protocol focuses on the segmentation of each retrieved memory into informational bits or details. A detail was defined as a unique occurrence, observation or thought, typically expressed as a grammatical clause (Levine et al., 2002). Using the AI standardised scoring protocol, each detail was classified as internal or external. Details were labelled as internal if they directly related to the main episode being described and were located within a specific spatiotemporal context, conveying a sense of episodic re-experiencing. These details were then assigned to one of five separate categories (Event, Time, Place, Perceptual and Emotion/Thoughts). Otherwise, details were labelled as external if they consisted of autobiographical details tangential or unrelated to the main event, repetitions, semantic facts, or metacognitive statements. Details from each category were summed to form internal and external composite scores, separately for each condition (free recall, general probe, specific probe). Because the effect of general probing on general performance is minimal in comparison to that of specific probing (Levine et al., 2002), free recall and general probing scores were combined. This resulted in two composite scores for each epoch namely (i) low retrieval support comprising recall plus general probing and referred to here as free recall, and (ii) high retrieval support condition which consisted of the total score following probing, referred to here as probed recall. Examples of scoring of internal and external details are provided in Appendix A. A panel of research staff were trained to administer and score the AI according to the standardised protocol (Levine et al., 2002). Regular scoring review meetings were held to compare scores across four raters, which were scored blinded to group membership. Each rater scored 20 randomly selected stories from the AI and achieved the following intraclass correlation coefficients: Internal free recall:.98, Internal probed recall:.98, External free recall:.96, External probed recall:.98. 2.3. Statistical analyses Prior to analyses, the suitability of variables for parametric analyses was determined using Kolmogorov Smirnov tests. Between-group differences were investigated using univariate and multivariate analyses of variance (ANOVA) with Sidak post hoc tests. The rationale for using Sidak modification of the traditional Bonferroni post hoc test is that the statistical power of the analyses is not affected, whilst the flexibility of the original Bonferroni method is maintained (discussed by Keppel & Wickens, 2004). Paired-samples t-tests were used to explore group and epoch effects further. Mann Whitney U and Kruskal Wallis nonparametric tests were used for variables that were not normally distributed. Chi-squared tests ( 2 ), based on the frequency patterns of dichotomous variables, were also used. 3. Results 3.1. Clinical characteristics Groups were well matched for age (F(3, 72) = 2.12, p =.105), and years in education (F(3, 72) =.12, p =.948). Sex was not evenly distributed ( 2 (3) = 12.76, p =.005), due to a greater number of females in the control group compared to the other groups (Table 1). Disease duration significantly varied across groups (F(2, 48) = 4.28, p =.019), with the AD group showing a shorter disease duration compared with the SD group. 3.2. Cognitive screening Controls scored significantly higher than all patient groups on the MMSE (F(3, 72) = 8.90, p <.0001) and ACE-R screening tests (F(3, 72) = 32.07, p <.0001). Post hoc tests failed to reveal significant differences between the patient groups on the MMSE (all ps >.2). SD patients scored significantly lower than bvftd (p <.0001) and AD groups (p =.005) on the ACE-R. Significant group differences were evident on the Trail Making Test (F(3, 54) = 5.91, p =.001), with AD patients performing significantly worse than controls (p =.005) and SD patients (p =.011). Significant group differences were also evident for total letter fluency (F(3, 53) = 8.07, p <.0001), Fig. 1. Total scores for internal and external details summed across all time periods in the free and probed retrieval conditions on the AI (error bars represent SEM). Ekman 60 emotion processing (F(3, 53) = 10.38, p <.0001), Naming (F(3, 53) = 108.07, p <.0001) and Comprehension (F(3, 53) = 15.92, p <.0001). Controls scored significantly higher than all patient groups for letter fluency, emotion processing and Naming. For Comprehension, controls scored significantly higher than the SD group (p <.0001), with the suggestion of impaired comprehension in AD (p =.059), but no impairments in bvftd (p =.278). Sidak post hoc tests failed to reveal any significant differences between patient groups for letter fluency and emotion processing (all ps >.9). For Naming and Comprehension, the SD group was significantly impaired compared to both the bvftd (p <.0001) and AD (p <.0001) groups. A significant group effect was found on the RAVLT (F(2, 40) = 49.89, p <.0001) with controls scoring higher than bvftd and AD patients, and no significant differences between the patient groups (p =.851). On the CBI apathy subscale, no significant group effect was found (F(2, 37) = 2.60, p =.087). 3.3. Overall performance on the AI Fig. 1 shows the total scores for internal and external details summed across all time periods in the free and probed retrieval conditions of the AI. Significant group differences were found for free (F(3, 72) = 14.80, p <.0001) and probed (F(3, 72) = 13.64, p <.0001) recall. Controls recalled significantly more internal details across both retrieval conditions in comparison to all patient groups (p <.0001). No differences were present among the patient groups for free or probed recall (all ps >.3). For external details, no significant group differences were found for free (p =.64) or probed (p =.58) recall. Further analyses, therefore, were confined to internal details. A multivariate ANOVA was run including sex as a covariate to control for possible sex differences in ABM retrieval. This analysis revealed that sex did not have a significant effect on the model for free (p =.85) or probed recall (p =.71), nor did it alter the group differences for free (F(3, 71) = 13.29, p <.0001) or probed (F(3, 71) = 13.41, p <.0001) recall of internal details. To control for language deficits exhibited by the SD group, differences in ABM performance across groups were investigated with letter fluency and Naming performance as a covariate. The significant group differences persisted for both free (Letter fluency: F(3,58) = 3.93, p =.013; Naming: F(3, 54) = 8.49, p <.0001) and probed (Letter fluency: F(3, 58) = 7.01, p <.0001; Naming: F(3, 54) = 6.47, p =.001) conditions. Considering each group, controls recalled significantly more internal details in comparison with external details for both free (t = 3.09) and probed (t = 8.58) conditions (both ps <.01). SD patients produced significantly more internal than external details following probing (t = 2.73, p <.05). For bvftd patients, no differences were present between production of internal and external details in either free or probed conditions, whereas AD patients tended

M. Irish et al. / Neuropsychologia 49 (2011) 2694 2702 2697 Table 1 Demographic and clinical characteristics of study cohort (standard deviations in brackets). a,b bvftd SD AD Controls Group effect F-test N 15 25 17 19 Sex (M/F) 13/2 18/7 14/3 7/12 Age (years) 61.6 (7.4) 62.6 (8.1) 66.1 (8.6) 66.7 (4.9) 2.12 Education (years) 12.3 (3.5) 12.5 (2.8) 12.3 (3.1) 12.8 (3.4) 0.12 Disease duration (months) 38.4 (26.0) 53.0 (25.4) 30.8 (15.1) n/a 4.28 MMSE (30) 26.0 (2.8) 25.0 (3.6) 24.5 (3.9) 29.2 (1.0) 8.90 ACE-R (100) 78.1 (8.8) 62.2 (13.1) 73.1 (13.0) 93.7 (3.6) 32.07 Trail Making Test Part B-A (s) 101.9 (65.7) 56.7 (31.9) 125.5 (75.9) 56.6 (30.7) 5.91 Letter Fluency 26.6 (11.9) 27.1 (11.5) 26.9 (10.6) 43.8 (13.3) 8.07 Naming (30) 22.5 (3.9) 5.4 (2.6) 19.5 (4.8) 26.4 (2.1) 108.07 Comprehension (30) 26.5 (1.7) 20.4 (5.6) 25.1 (4.0) 28.7 (1.5) 15.92 RAVLT delayed recall (15) 3.1 (2.8) n/a 2.3 (2.3) 10.4 (2.5) 49.89 Ekman 60 (60) 38.1 (5.4) 37.9 (8.8) 37.4 (8.8) 49.4 (2.6) 10.38 CBI Apathy subscale (20) 10.4 (6.6) 7.0 (5.2) 5.9 (4.7) n/a 2.60 a Maximum score for each test in brackets where applicable. b Data reported for subset of SD cases on all tasks (n = 11). On Rey Auditory-Verbal Learning Test (RAVLT), data reported for 12 bvftd. Data reported for 12 AD patients on RAVLT and Trail Making Test. to produce more external than internal details in the free recall condition (t = 3.08, p <.01). 3.4. Free recall of internal details across life epochs Fig. 2 shows the profile of free recall of internal details across life epochs. A repeated-measures ANOVA revealed a significant main effect for group (F(3, 72) = 15.19, p <.0001), with controls recalling significantly more details than patient groups. This effect was present across all epochs with the exception of the Recent period, in which no significant differences between SD patients and controls were found (p =.13). Within-group differences across epochs were examined for each group separately using paired-samples t-tests. The SD group demonstrated significantly better performance in the Recent period in comparison with Teenage (t = 4.09), Early Adulthood (t = 2.95), and Middle Adulthood (t = 2.79) epochs (all ps <.01). No differences across epochs were found for controls, bvftd or AD groups. SD patients recalled significantly more internal details in the Recent period in comparison with bvftd patients (p <.05), but no other significant intergroup differences were found. 3.5. Recall of internal details following probing Fig. 3 shows the profile of probed recall of internal details across all life epochs. A significant main effect of group (F(3, 72) = 13.55, p <.0001) was found, with controls recalling significantly more internal details following probing in comparison with all patient groups. No significant differences were found between the patient groups (all ps >.7). A main effect of epoch (F(3, 216) = 5.96, p =.001), and a significant epoch by group interaction (F(9, 216) = 1.88, p =.05), was found. Paired-samples t-tests showed that recall in the Recent period was significantly higher than in the Teenage period (p <.0001) and the Middle Adulthood period (p <.0001). These differences remained significant following correction for multiple comparisons. SD patients continued to recall significantly more internal details following probing in the Recent period compared with their retrieval in the Teenage (t = 5.57), Early Adulthood (t = 2.57) and Middle Adulthood epochs (t = 4.86) (all ps <.01). Other paired-samples t-tests failed to reveal significant differences across epochs for controls, bvftd or AD patients. 3.6. Detailed retrieval of recent versus remote memories Place and Time categories were aggregated into a Spatiotemporal details category because of the limited range of possible details compared to the other detail categories. The internal detail scores for the Teenage, Early Adulthood, and Middle Adulthood time periods were averaged to give free and probed remote memory scores for each detail type. 3.6.1. Detailed free recall: recent period As shown in Fig. 4, overall group differences were present in the Recent period for Event (p =.003), Perceptual (p =.003), and Emotion/Thoughts (p <.0001) internal details, with a difference on the Fig. 2. Profile of free recall of internal details across life epochs on the AI for all participants (error bars represent SEM). Fig. 3. Profile of probed recall of internal details across all life epochs on the AI for all participant groups (error bars represent SEM).

2698 M. Irish et al. / Neuropsychologia 49 (2011) 2694 2702 Fig. 4. Breakdown of remote and recent period free recall of internal details for all participant groups (error bars represent SEM). Spatiotemp = Spatiotemporal, Percept = Perceptual, Emotion = Emotion/Thoughts. threshold of significance for Spatiotemporal details (p =.055). Post hoc tests between control and patient groups revealed the following results: SD patients recalled fewer Emotion/Thoughts details in comparison with controls (p <.001), with no significant differences for any other category of details (all ps >.1). BvFTD patients were significantly impaired for all categories (Event, p =.005; Spatiotemporal, p =.028, Emotion/Thoughts, p <.0001), except Perceptual (p =.097). AD patients showed deficits for free recall of Event (p =.001), Emotion/Thoughts (p =.006) and Perceptual (p =.005) details. Comparisons across patient groups showed that SD patients recalled significantly more details in the Recent period across all categories relative to bvftd (all ps <.05), and more Event and Perceptual details compared to AD patients (all ps <.01). BvFTD and AD patients were similar in recall of details across all categories, except that of Emotion/Thoughts, where AD patients recalled significantly more details (p <.001). 3.6.2. Detailed free recall: remote period For the remote period, a multivariate ANOVA revealed significant group differences across all internal free recall details (all ps <.0001). Sidak post hoc tests showed that controls scored significantly higher than all patient groups for all detail types. No significant differences were evident between the patient groups for the remote period details (all ps > 2). 3.6.3. Detailed free recall: recent versus remote periods Paired-samples t-tests with Bonferroni corrections (corrected alpha =.012) for each group revealed the following differences between periods; Controls recalled more Emotion/Thoughts details in the Recent period (p =.009). SD patients recalled more Perceptual (p =.002) and Emotion/Thoughts details (p =.002) in the Recent period compared with the remote period. BvFTD patients showed no differences in their details profile between remote and recent periods (all ps >.4). AD patients showed no differences between periods (all ps >.06). 3.6.4. Detailed probed recall: recent period For Recent period probed recall (see Fig. 5), significant group differences were again present across all categories of details (Event, p <.0001; Spatiotemporal, p <.0001; Perceptual, p =.02; Emotion/Thoughts, p <.0001). Specifically, in comparison with controls (i) SD patients recalled significantly fewer Spatiotemporal (p <.0001) and Emotion/Thoughts (p <.0001) details, (ii) bvftd patients were impaired across all categories (Event, p =.006; Spatiotemporal, p =.03; Perceptual, p =.04; Emotion/Thoughts, p <.0001), and (iii) AD patients showed significant deficits for recall of Event (p =.001) and Emotion/Thoughts (p =.01) details. Post hoc tests across patient groups revealed that bvftd patients were significantly impaired relative to both SD (p =.007) and AD (p <.0001) patients in recall of Emotion/Thoughts details. AD patients scored significantly lower than SD patients for Event details (p =.05). 3.6.5. Detailed probed recall: remote period For remote epochs, a multivariate ANOVA revealed significant group differences across all probed details categories (Event, p =.002; Spatiotemporal, p <.0001; Perceptual, p <.0001; Emotion/Thoughts, p <.0001). Sidak post hoc tests revealed that controls scored significantly higher than all patient groups across all details categories. SD patients recalled significantly less Spatiotemporal details following probing in comparison with bvftd (p =.005) and Fig. 5. Breakdown of remote and recent period internal details following probing for all participant groups (error bars represent SEM). Spatiotemp = Spatiotemporal, Percept = Perceptual, Emotion = Emotion/Thoughts.

M. Irish et al. / Neuropsychologia 49 (2011) 2694 2702 2699 AD patients (p =.003), with no other significant differences between the patient groups. 3.6.6. Detailed probed recall: recent versus remote periods Paired-samples t-tests with Bonferroni corrections (corrected alpha =.012) for each group revealed the following differences between periods; SD patients recalled more Event (p =.003), Spatiotemporal (p =.002), Perceptual (p =.008) and Emotion/Thoughts details (p =.001) in the Recent compared with the remote period. BvFTD patients recalled more Perceptual details in the remote epoch (p =.012). AD patients recalled more Emotion/Thoughts details in the Recent period (p =.001). 4. Discussion The objectives of this study were to characterise the nature of episodic ABM impairment in SD using a detailed assessment procedure, and to determine whether their episodic ABM performance could be dissociated from that found in bvftd and AD. This study reveals differential ABM impairments in FTD subtypes and AD based on the profile of episodic contextual details elicited during recent ABM retrieval. The findings in SD are novel and intriguing, particularly when contrasted with the patterns seen in bvftd and AD. 4.1. Patterns of deficits in recent episodic ABM across dementia groups The most important findings to emerge from this study are that the fine-grained analysis of the contextual and phenomenological elements of ABMs drawn from the Recent period (the last 12 months) identified significant qualitative differences among dementia syndromes. Whilst SD patients demonstrated better performance in the Recent time period compared to remote epochs, deficits in contextual details were nevertheless evident across both free and probed conditions. This deficit appeared to be mediated by reduced retrieval of Emotion/Thoughts details in both free and probed recall conditions. The disrupted recall of Emotion/Thoughts ABM details in SD is not unexpected but has not been reported before. The prior finding of impaired comprehension of emotion in the context of bilateral amygdala damage is of particular relevance (Rosen, Perry et al., 2002). BvFTD and AD patients displayed a comparable pattern of retrieval in the free recall condition, with Event and Emotion/Thoughts details significantly disrupted. Following structured probing, distinct profiles were evident in the three patient groups. SD patients displayed compromised Spatiotemporal and Emotion/Thoughts details, and AD patients demonstrated impaired Event and Emotion/Thoughts details with preserved Spatiotemporal and Perceptual details. In contrast, bvftd patients exhibited deficits across all internal details categories. Importantly, of all the dementia groups, bvftd patients had the highest MMSE and ACE-R scores and deficits in this group cannot be explained by greater disease severity compared to the other groups. A plausible explanation for the discrete profiles across dementia syndromes is the breakdown of differing neurocognitive mechanisms, contingent on the underlying disease pathology. In SD, the amodal disruption of semantic knowledge (Mion et al., 2010) is a likely candidate to explain ABM impairments, given the strong overlap between episodic and semantic memory (Hodges & Graham, 2001). The retrieval deficit for Spatiotemporal details in this group may reflect the nature of time and location details, which draw on semantic representations supported by extrahippocampal structures in the anterior temporal lobes, and are particularly vulnerable to disruption in SD. This impairment also aligns well with the global naming disturbance characteristic of SD. When language and naming proficiency was taken into account, however, overall group differences persisted, suggesting that such language deficits do not fully explain compromised ABM retrieval in SD. Critically, the disruption of emotion processing can account for the Recent memory decrements in Emotion/Thoughts details in SD, and fits well with research pointing to reduced empathy in SD (Rankin et al., 2006), highlighting the role of the anterior temporal lobes in social cognition (Ross & Olson, 2010). In contrast, compromised strategic retrieval appears the likely candidate mechanism in bvftd, producing ABM deficits irrespective of epoch or detail type (Piolino et al., 2003). Importantly, the extent to which MTL atrophy contributes to episodic memory impairment in bvftd remains unknown and is an avenue worthy of further exploration. The ABM profile in AD may reflect the severe MTL pathology with possible additional frontal pathology contributing to an access deficit to the source of the memories (Greene, Hodges, & Baddeley, 1995; Piolino et al., 2003). 4.2. Profiles of episodic ABM retrieval across the lifespan in SD Importantly, as the largest study of ABM in SD to date, we have confirmed the relative preservation of recent ABM retrieval in SD under free and probed recall conditions. Not all investigators have found this preservation of recent ABM in SD (Maguire et al., 2010; McKinnon et al., 2006), possibly due to small sample sizes used in those studies (n of 1 and 2, respectively). Matuszewski et al. (2009) have interpreted the relative sparing of recent ABM as reflecting preserved anterograde memory processes and a preservation of the ability to encode and retrieve new ABMs. Similarly, using a naturalistic anterograde memory assessment method, Adlam et al. (2009) demonstrated that the retrieval of recently experienced events, occurring 1 day prior, was relatively intact in SD, supporting the view that in mild SD, impaired personal semantic information does not preclude the retrieval of recent episodic events (Matuszewski et al., 2009). Remote memory impairment in SD likely reflects a loss of semantic information that is integral to the memory trace or is required to access the memory (Westmacott, Leach, Freedman, & Moscovitch, 2001). Accordingly, recent memories will rely more heavily on perceptual elements rather than on semanticised, overgeneral information, and will be better preserved than older memories (Hodges & Graham, 2001; Nestor et al., 2002). Our findings resonate well with this position, given that the SD cohort demonstrated free recall of recent Perceptual details at control levels. Furthermore, in comparison with the remote period, higher levels of Event, Spatiotemporal, Perceptual and Emotion/Thoughts contextual details were evident in the SD patients free recall recent memories. The anatomical bases of the relatively preserved ABM for recent life events shown here remain somewhat mysterious. The early assumption that the hippocampus is spared in SD (Graham & Hodges, 1997) has been shown to be fallacious. Volumetric MRI studies have demonstrated that the degree of hippocampal atrophy in SD is equivalent, or greater, to that seen in AD, albeit in the context of much more severe atrophy of other temporal lobe structures (Chan et al., 2001; Galton et al., 2001) with a typically asymmetric pattern. One critical difference between SD and AD, however, is the degree of involvement of the posterior cingulate region, which is affected early in the course of AD but spared in SD (Nestor, Fryer, & Hodges, 2006). Changes in the posterior cingulate region, therefore, may be critical in the genesis of the differential patterns of episodic memory loss across the dementia syndromes of SD and AD. 4.3. The role of frontally mediated processes in episodic ABM recall The flat performance across epochs in bvftd has been documented previously (Hou et al., 2005; Matuszewski et al., 2006;

2700 M. Irish et al. / Neuropsychologia 49 (2011) 2694 2702 McKinnon et al., 2008; Nestor et al., 2002; Piolino et al., 2007, 2003). Impairments in generative processes are commonly observed in bvftd, and represent a potential underlying mechanism for ABM disruption (Piolino, Desgranges, & Eustache, 2009), which is related to left frontal lobe and temporal pole atrophy (Conway & Fthenaki, 2000; Conway, Pleydell-Pearce, Whitecross, & Sharpe, 2002). Disruption to this strategic retrieval system, therefore, manifests in memories that are characteristically overgeneral, divested of specific episodic details, with a tendency to recall repeated or extended events (Piolino et al., 2007). The provision of structured probing failed to ameliorate the deficits exhibited by the bvftd patient group suggesting that medial temporal pathology may be contributing to these impairments (see also McKinnon et al., 2008). Atrophy of the medial temporal lobe region is present in bvftd particularly with disease progression (Rabinovici et al., 2007). Disrupted ABM performance in bvftd is likely to be multifactorial with contributions from impaired retrieval, pathological involvement of MTL structures, and deficits in self-reflective processes. Furthermore, the possible role of apathy in the compromised performance of these patients, which cannot be ameliorated through structured cueing, must be considered. The capacity to reflect on past events requires the evaluation of internally generated information (Christoff & Gabrieli, 2000), and self-referential processes (Craik et al., 1999; Northoff & Bermpohl, 2004), which are both subserved by the medial prefrontal cortex (Wheeler, Stuss, & Tulving, 1997). Medial prefrontal cortex atrophy (Schroeter, Raczka, Neumann, & Yves von Cramon, 2007) may produce additional deficits over and above those in generative processes, specifically a compromised capacity to direct one s attention inwards and reflect upon past events (Gallagher & Frith, 2003), irrespective of epoch. This proposition dovetails with mounting evidence documenting impairments in autonoetic consciousness (Piolino et al., 2007, 2003) and prominent deficits in theory of mind (Gregory et al., 2002) in bvftd, and supports the existence of meta-memory difficulties that are closely aligned with executive dysfunction in bvftd (Souchay, Isingrini, Pillon & Gil, 2003). 4.4. The role of emotion in ABM retrieval Perhaps the most striking finding of the current study is that impairment in the retrieval of Emotion/Thoughts ABM details was common to all dementia syndromes. The ability to retrieve personally salient emotive details is an essential feature for a rich recollective ABM experience (Irish, Lawlor, O Mara, & Coen, 2010; Piefke et al., 2003), resulting in durable and evocative memory traces (Berntsen & Rubin, 2002; Conway et al., 2003). The present findings of severely disrupted emotional ABM recall indicate impaired emotion processing as a contributing factor to the recent ABM deficits exhibited by all patient groups. Importantly, however, this impaired emotion processing was the exclusive driver of the recent free recall deficit in the SD group. This finding of a selective disruption of emotional recall in SD aligns with reports of significant atrophy in the amygdala in SD (Williams et al., 2005) and has been implicated in ABM disturbance (McKinnon et al., 2006). In contrast, the deficit in Emotion/Thoughts details was not as marked in AD when compared with the bvftd cohort, in keeping with the relative sparing of emotional processing in AD (Fernandez-Duque & Black, 2005). Our observation of differential impairment of emotional episodic details across dementia syndromes suggests that pathology involving the amygdala may not be as pronounced in AD as in the FTD subgroups. Further research incorporating structural imaging analyses will be required to tease this issue apart. Nevertheless, our results reinforce the importance of emotion in the retrieval of personally salient ABMs from across the lifespan. This finding corroborates the idea that ABM is a multifaceted and complex construct, which benefits from a series of activation. Damage to any of the critical components of this network, for example emotional details, can disrupt the reactivation process, resulting in compromised ABM retrieval (Greenberg & Rubin, 2003; Piolino et al., 2003; Nestor et al., 2002). In summary, our findings highlight an impoverished capacity to retrieve episodic details across the lifespan during ABM recall in FTD, with contrasting profiles depending on the FTD subgroup: a relative preservation of recent memory in comparison with remote epochs in SD, and a flat ungraded profile in bvftd. When strategic retrieval deficits and retention interval are controlled for, dissecting the profile of internal details recalled following probing in the Recent period revealed distinct patterns among the participant groups: impaired Spatiotemporal and Emotion/Thoughts details in SD, impaired Event and Emotion/Thoughts details in AD, and global impairments across all detail categories in bvftd. Critically, this study is the first to uncover a common mechanism underlying recent episodic ABM impairments in SD, bvftd, and AD, namely impaired emotion processing, and provides greater understanding of these patients whose phenomenological experience of remembering and sense of identity has become compromised. Acknowledgements We are grateful to the patients and their families for generously giving their time. We thank David Foxe, Sharpley Hsieh, Felicity Leslie, and Sharon Savage for help in test administration and with scoring of the memories. This project was supported by a National Health and Medical Research Council (NHMRC) of Australia Project Grant (#510106). JRH is supported by an Australian Research Council Federation Fellowship (#FF0776229). OP is supported by an NHMRC Clinical Career Development Award fellowship (#510184). Appendix A. Example of a control participant s memory with internal (int) and external (ext) details separated according to the Levine et al. (2002) scoring protocol. Oh well it was at the Trocadero [place int] which was at the place all the balls were held in those days [semantic ext]. Going to a ball was quite common [semantic ext] and quite a big event [semantic ext] and everybody got dressed up [semantic ext] and things like that [other ext]. I was invited by the young man [event int] I had been out with a few times [event ext] and I actually had a dress made to go to that ball [event ext] which was quite pretty, a white dress [perceptual int], I can remember that [other ext] and um, yeah it was just a great night [emotion/thoughts int]. It was good [emotion/thoughts int] because I loved dancing [semantic ext] so it was a great night [repetition ext] um, and none of us drank very much in those days [semantic ext] and the food was pretty awful at those kinds of do s [semantic ext] you know you just dance the whole time [event int] and everybody laughing [perceptual int] and having a good time [perceptual int]. 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