The Advanced BRain Imaging on ageing and Memory (ABRIM) data collection: Study design, data processing, and rationale.

To understand the neurocognitive mechanisms that underlie heterogeneity in cognitive ageing, recent scientific efforts have led to a growing public availability of imaging cohort data. The Advanced BRain Imaging on ageing and Memory (ABRIM) project aims to add to these existing datasets by taking an adult lifespan approach to provide a cross-sectional, normative database with a particular focus on connectivity, myelinization and iron content of the brain in concurrence with cognitive functioning, mechanisms of reserve, and sleep-wake rhythms. ABRIM freely shares MRI and behavioural data from 295 participants between 18-80 years, stratified by age decade and sex (median age 52, IQR 36-66, 53.20% females). The ABRIM MRI collection consists of both the raw and pre-processed structural and functional MRI data to facilitate data usage among both expert and non-expert users. The ABRIM behavioural collection includes measures of cognitive functioning (i.e., global cognition, processing speed, executive functions, and memory), proxy measures of cognitive reserve (e.g., educational attainment, verbal intelligence, and occupational complexity), and various self-reported questionnaires (e.g., on depressive symptoms, pain, and the use of memory strategies in daily life and during a memory task). In a sub-sample (n = 120), we recorded sleep-wake rhythms using an actigraphy device (Actiwatch 2, Philips Respironics) for a period of 7 consecutive days. Here, we provide an in-depth description of our study protocol, pre-processing pipelines, and data availability. ABRIM provides a cross-sectional database on healthy participants throughout the adult lifespan, including numerous parameters relevant to improve our understanding of cognitive ageing. Therefore, ABRIM enables researchers to model the advanced imaging parameters and cognitive topologies as a function of age, identify the normal range of values of such parameters, and to further investigate the diverse mechanisms of reserve and resilience.

A multidomain lifestyle intervention to maintain optimal cognitive functioning in Dutch older adults-study design and baseline characteristics of the FINGER-NL randomized controlled trial.

BACKGROUND: Evidence on the effectiveness of multidomain lifestyle interventions to prevent cognitive decline in older people without dementia is mixed. Embedded in the World-Wide FINGERS initiative, FINGER-NL aims to investigate the effectiveness of a 2-year multidomain lifestyle intervention on cognitive functioning in older Dutch at risk individuals. METHODS: Multi-center, randomized, controlled, multidomain lifestyle intervention trial with a duration of 24 months. 1210 adults between 60-79 years old with presence of ≥ 2 modifiable risk factors and ≥ 1 non-modifiable risk factor for cognitive decline were recruited between January 2022 and May 2023 via the Dutch Brain Research Registry and across five study sites in the Netherlands. Participants were randomized to either a high-intensity or a low-intensity intervention group. The multidomain intervention comprises a combination of 7 lifestyle components (physical activity, cognitive training, cardiovascular risk factor management, nutritional counseling, sleep counseling, stress management, and social activities) and 1 nutritional product (Souvenaid®) that could help maintain cognitive functioning. The high-intensity intervention group receives a personalized, supervised and hybrid intervention consisting of group meetings (on-site and online) and individual sessions guided by a trained lifestyle coach, and access to a digital intervention platform that provides custom-made training materials and selected lifestyle apps. The low-intensity intervention group receives bi-monthly online lifestyle-related health advice via the digital intervention platform. Primary outcome is 2-year change on a cognitive composite score covering processing speed, executive function, and memory. RESULTS: Within 17 months, participant recruitment has been successfully completed (N = 1210; mean age: 67.7 years (SD: 4.6); 64% female). Modifiable risk factors commonly present at baseline were physical inactivity (89%), low mental/cognitive activity (50%), low social engagement (39%), hypertension (39%) and high alcohol consumption (39%). The mean body mass index of participants was 28.3 (SD: 4.2) and the total serum cholesterol was 5.4 mmol/L (SD: 1.2). CONCLUSIONS: Baseline lifestyle and clinical measurements showed successful recruitment of participants with sufficient potential for prevention. Results of FINGER-NL will provide further insight into the efficacy of a multidomain lifestyle intervention to prevent cognitive decline in older adults. TRIAL REGISTRATION: ClinicalTrials.gov (ID: NCT05256199)/2022-01-11.

The presence of attentional and interpretation biases in patients with severe MS-related fatigue.

OBJECTIVE: Severe fatigue is a prevalent and disabling symptom in multiple sclerosis (MS). This study tested if a fatigue- and physical activity-related attentional bias (AB) and a somatic interpretation bias (IB) are present in severely fatigued patients with MS. Biases were compared to healthy controls and patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). METHOD: Severely fatigued patients with MS or ME/CFS and healthy controls completed a Visual Probe Task (VPT) assessing fatigue- and physical activity-related AB and an IB task that assesses the tendency to interpret ambiguous information in either a somatically threatening way or in a more neutral manner. The VPT was completed by 38 MS patients, 44 ME/CFS patients, and 46 healthy controls; the IB task was completed by 156, 40 and 46 participants respectively. RESULTS: ANOVA showed no statistically significant group differences in a fatigue-related AB or physical activity-related AB (omnibus test of interaction between topic × condition: F2,125 = 1.87; p = .159). Both patient groups showed a tendency to interpret ambiguous information in a somatically threatening way compared to healthy controls (F1,2 = 27.61, p < .001). This IB was significantly stronger in MS patients compared to ME/CFS patients. IB was significantly correlated with cognitive responses to symptoms in MS patients. CONCLUSION: MS patients tend to interpret ambiguous information in a somatically threatening way. This may feed into unhelpful ways of dealing with symptoms, possibly contributing to the perpetuation of severe fatigue in MS.

Disentangling pain and fatigue in chronic fatigue syndrome: a resting state connectivity study before and after cognitive behavioral therapy.

BACKGROUND: Fatigue is a central feature of myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), but many ME/CFS patients also report comorbid pain symptoms. It remains unclear whether these symptoms are related to similar or dissociable brain networks. This study used resting-state fMRI to disentangle networks associated with fatigue and pain symptoms in ME/CFS patients, and to link changes in those networks to clinical improvements following cognitive behavioral therapy (CBT). METHODS: Relationships between pain and fatigue symptoms and cortico-cortical connectivity were assessed within ME/CFS patients at baseline (N = 72) and after CBT (N = 33) and waiting list (WL, N = 18) and compared to healthy controls (HC, N = 29). The analyses focused on four networks previously associated with pain and/or fatigue, i.e. the fronto-parietal network (FPN), premotor network (PMN), somatomotor network (SMN), and default mode network (DMN). RESULTS: At baseline, variation in pain and fatigue symptoms related to partially dissociable brain networks. Fatigue was associated with higher SMN-PMN connectivity and lower SMN-DMN connectivity. Pain was associated with lower PMN-DMN connectivity. CBT improved SMN-DMN connectivity, compared to WL. Larger clinical improvements were associated with larger increases in frontal SMN-DMN connectivity. No CBT effects were observed for PMN-DMN or SMN-PMN connectivity. CONCLUSIONS: These results provide insight into the dissociable neural mechanisms underlying fatigue and pain symptoms in ME/CFS and how they are affected by CBT in successfully treated patients. Further investigation of how and in whom behavioral and biomedical treatments affect these networks is warranted to improve and individualize existing or new treatments for ME/CFS.

Classification Of MeMory InTerventions: Rationale and developmental process of the COMMIT tool.

ABSTRACTOver the last decades, numerous memory interventions have been developed to mitigate memory decline in normal ageing. However, there is a large variability in the success of memory interventions, and it remains poorly understood which memory intervention programs are most effective and for whom. This is partially explained by the heterogeneity of memory intervention protocols across studies as well as often poor reporting of the study design. To facilitate a reporting framework that enables researchers to systemize the content and design of memory intervention paradigms, we developed the Classification Of MeMory InTerventions (COMMIT) tool using a 3-stage developmental process. Briefly, COMMIT was based on qualitative content analysis of already existing memory intervention studies published between April 1983 and July 2020, and iteratively validated by both internal and external expert panels. COMMIT provides an easily-applicable interactive tool that enables systematic description of memory intervention studies, together with instructions on how to use this classification tool. Our main goal is to provide a tool that enables the reporting and classification of memory interventions in a transparent, comprehensible, and complete manner, to ensure a better comparability between memory interventions, and, to ultimately contribute to the question which memory intervention shows the greatest benefits.

"Cinderella was attacked by the big bad wolf, but the police saved her": intrusions and confabulations on story recall in Korsakoff's syndrome and alcohol-related cognitive impairments.

BACKGROUND: The relation between confabulations and intrusions in patients with Korsakoff's syndrome (KS) and patients with alcohol-related cognitive impairments (ARCI) remains under debate. This study examines (1) differences in the production of confabulations and intrusions between patients with KS and ARCI, (2) whether an altered fairy tale induces more intrusions, and (3) whether different types of intrusions were significantly related to confabulations. METHODS: Twenty-three patients with KS and twenty-two patients with ARCI recalled three different types of stories: a novel story, a fairy tale, and a modified fairy tale. Different types of intrusions were correlated with confabulation measures. RESULTS: Patients with KS produced more intrusions in the modified fairy tale condition than patients with ARCI, but these were unrelated to confabulations. Only unrelated intrusions were related to provoked confabulations. CONCLUSIONS: The results of this study indicate that researchers and clinicians must be aware that in general, intrusions on memory tests should not be interpreted as confabulations. Especially spontaneous confabulations appear to be something completely different from intrusions on any type of story recall. When measuring confabulations it is crucial to use validated instruments.

Regression-Based Normative Data for the Montreal Cognitive Assessment (MoCA) and Its Memory Index Score (MoCA-MIS) for Individuals Aged 18-91.

(1) Background: There is a need for a brief assessment of cognitive function, both in patient care and scientific research, for which the Montreal Cognitive Assessment (MoCA) is a psychometrically reliable and valid tool. However, fine-grained normative data allowing for adjustment for age, education, and/or sex are lacking, especially for its Memory Index Score (MIS). (2) Methods: A total of 820 healthy individuals aged 18-91 (366 men) completed the Dutch MoCA (version 7.1), of whom 182 also completed the cued recall and recognition memory subtests enabling calculation of the MIS. Regression-based normative data were computed for the MoCA Total Score and MIS, following the data-handling procedure of the Advanced Neuropsychological Diagnostics Infrastructure (ANDI). (3) Results: Age, education level, and sex were significant predictors of the MoCA Total Score (Conditional R2 = 0.4, Marginal R2 = 0.12, restricted maximum likelihood (REML) criterion at convergence: 3470.1) and MIS (Marginal R2 = 0.14, REML criterion at convergence: 682.8). Percentile distributions are presented that allow for age, education and sex adjustment for the MoCA Total Score and the MIS. (4) Conclusions: We present normative data covering the full adult life span that can be used for the screening for overall cognitive deficits and memory impairment, not only in older people with or people at risk of neurodegenerative disease, but also in younger individuals with acquired brain injury, neurological disease, or non-neurological medical conditions.

Own Pain Distress Mediates the Link Between the Lifestyle Facet of Psychopathy and Estimates of Pain Distress in Others.

Psychopathy is a multifaceted personality construct entailing interpersonal-affective disturbances, antisocial traits, and a tendency to lead an erratic lifestyle. Elevated levels of psychopathic traits have been linked to having an altered experience of pain, reduced responsivity to distress in others, and making poor moral choices that bring harm to others. In the context of moral decision-making, it is possible that the capacity to estimate the distress felt by others is linked to a limitation in the first-hand experience of distress, as the presence of psychopathic traits increases. We employed a model-based approach in a non-offender sample (n = 174) to investigate whether pain-related distress mediated the links between facets of psychopathy and estimates of the pain distress potentially experienced by others. Participants judged the permissibility of moral dilemmas and rated how much pain distress they would experience while making such judgements, as well as how much pain distress they believed the "victims" would feel as a result of the moral choice made by the participant. We found that ratings of own pain distress predicted beliefs about the distress others may experience, and elevated scores on the lifestyle facet of psychopathy uniquely predicted lower estimates of own pain distress. Furthermore, own pain distress mediated the relationship between the lifestyle facet and beliefs about others' distress. Finally, exploratory zero-order correlation analyses revealed that ratings of own pain distress decreased as the scores on multiple psychopathic traits increased. Only the lifestyle facet correlated in the negative direction with beliefs about others' distress. Taken together, our findings suggest that beliefs about how much pain distress others may experience is indeed mediated by own pain distress, and that the tendency to lead an erratic lifestyle is linked to alterations in this mechanism.

Towards a Better Understanding on How Cognitive Impairment Affects Pain.

When judging whether someone is suffering from pain, the simplest and most reliable solution is to ask that person about it [...].

[Pain and neurocognitive disorders: current state of the art and remaining challenges]. / Pijn en neurocognitieve stoornissen: stand van zaken en de weg nog te gaan.

The detection and treatment of pain is hampered by cognitive disorders. In this review we discuss the epidemiology of pain in cognitive disorders, and elaborate further on the current state of the art on pain in these populations. We will specifically highlight current gaps and recommendations for the future for the following knowledge domains: 1) Biology and neuropathology,  2) Assessment and evaluation, 3) Treatment and management , and 4) Contextual factors such as the organization and education.  We identify the following knowledge gaps: 1) (Biology): Do pain experience and pain expressions change in different types of cognitive disorders, and how? 2) (Assessment): How to recognize, evaluate and assess pain, in case the self-report of pain is no longer reliable? 3) (Treatment): Which treatment possibilities are effective? How can we organize this in an interdisciplinary way? And how to monitor this? How can we ensure proper implementation of pain assessment and treatment in clinical practice? Specifically with regard to non-pharmacological treatment, how can we communicate observations from different disciplines, family members and clinicians to improve the detection of pain as well as treatment monitoring/evaluation? 4) (Contextual): How can we increase knowledge and skills on pain in cognitive impairment within educational training?

The interaction between pain and cognition: on the roles of task complexity and pain intensity.

OBJECTIVES: The interaction between pain and cognition includes a concurrent negative effect of pain on cognitive performance and an analgesic effect of cognitive distraction on pain experience. The purpose of this exploratory study was to investigate the role of pain intensity and task complexity on this interaction. METHODS: Two experiments were conducted in healthy volunteers. In both experiments, participants completed 3 conditions: a pain only condition (consisting of the cold pressor test), a cognition only condition (consisting of the cognitive task) and a combined condition (concurrent administration of the cold pressor and cognitive task). In experiment I, participants performed one out of three possible tasks that differed in cognitive load (low, medium, high). In experiment II the parameters of the pain stimulus, induced by a cold pressor test, were adapted and only the high load cognitive task was employed. Pain scores, reaction times, and accuracy rates were recorded. RESULTS: In experiment I, cognitive distraction significantly decreased pain scores, irrespective of the cognitive load of the task. Pain did not affect cognitive performance. In experiment II, pain diminished accuracy rates. No effect of cognitive distraction on pain was observed. Individual characteristics did not noticeably influence the interaction between pain and cognition. CONCLUSIONS: The results of this study suggest a two-way interaction, however no evidence for a simultaneous bidirectional relationship was found. Cognitive distraction successfully reduces pain, up until a certain point where this relationship is reversed, and pain starts to interfere with cognitive performance. This may imply that priorities shift at a certain pain-threshold, however further research should confirm this hypothesis. This study could contribute to further understanding of cognitive mechanisms related to pain perception.

Determining the effectiveness of cognitive behavioural therapy in improving quality of life in patients undergoing endometriosis surgery: a study protocol for a randomised controlled trial.

INTRODUCTION: Endometriosis can cause chronic pain and subfertility thereby negatively affecting quality of life (QoL). Surgical removal of endometriosis lesions leads to improved health-related QoL, although not to the level of QoL of healthy controls. Pain intensity and cognitions regarding pain can play a crucial role in this health-related QoL following surgical treatment. Cognitive behavioural therapy (CBT) is a psychological treatment. In patients with chronic pain caused by a variety of medical conditions, CBT is effective in improving QoL. We designed a research protocol to investigate the effect of CBT on QoL in patients with endometriosis-associated chronic pain who are undergoing surgery. METHODS AND ANALYSIS: This is a study protocol for a randomised controlled trial in which 100 patients, undergoing endometriosis removal surgery due to endometriosis-associated chronic pain, will be randomised between post-surgery usual care with CBT and post-surgery usual care only. Participants in the CBT group will additionally receive seven sessions of CBT, focused on expectancy management, cognitions regarding pain and emotional and behavioural impact of pain. To determine the primary outcome Quality of life, both groups will complete questionnaires assessing QoL. The secondary outcomes pain intensity, pain cognitions, fatigue and perceived stress are also measured using questionnaires. Additionally, a marker for stress (cortisol extracted from a hair sample) will be assessed at T0 (baseline assessment), T1 (post-intervention; 2 weeks after completion of all CBT sessions) and T2 (follow-up; 14 weeks after T1). Statistical analysis will be performed using SPSS software. ETHICS AND DISSEMINATION: The study protocol has been approved by the Medical Ethical Committee of the region Arnhem-Nijmegen from the Radboud University Medical Centre on 2 September 2020. The findings of this study will be published in scientific journals and will be presented at scientific conferences. TRIAL REGISTRATION NUMBER: NCT04448366.

Positive Effects of Education on Cognitive Functioning Depend on Clinical Status and Neuropathological Severity.

Background: Variability in cognitive functions in healthy and pathological aging is often explained by educational attainment. However, it remains unclear to which extent different disease states alter protective effects of education. We aimed to investigate whether protective effects of education on cognition depend on (1) clinical diagnosis severity, and (2) the neuropathological burden within a diagnosis in a memory clinic setting. Methods: In this cross-sectional study, we included 108 patients with subjective cognitive decline [SCD, median age 71, IQR (66-78), 43% men], 190 with mild cognitive impairment [MCI, median age 78, IQR (73-82), 44% men], and 245 with Alzheimer's disease dementia (AD) [median age 80, IQR (76-84), 35% men]. We combined visual ratings of hippocampal atrophy, global atrophy, and white matter hyperintensities on MRI into a single neuropathology score. To investigate whether the contribution of education to cognitive performance differed across SCD, MCI, and AD, we employed several multiple linear regression models, stratified by diagnosis and adjusted for age, sex, and neurodegeneration. We re-ran each model with an additional interaction term to investigate whether these effects were influenced by neuropathological burden for each diagnostic group separately. False discovery rate (FDR) corrections for multiple comparisons were applied. Results: We observed significant positive associations between education and performance for global cognition and executive functions (all adjusted p-values < 0.05). As diagnosis became more severe, however, the strength of these associations decreased (all adjusted p-values < 0.05). Education related to episodic memory only at relatively lower levels of neuropathology in SCD (ß = -0.23, uncorrected p = 0.02), whereas education related to episodic memory in those with higher levels of neuropathology in MCI (ß = 0.15, uncorrected p = 0.04). However, these interaction effects did not survive FDR-corrections. Conclusions: Altogether, our results demonstrated that positive effects of education on cognitive functioning reduce with diagnosis severity, but the role of neuropathological burden within a particular diagnosis was small and warrants further investigation. Future studies may further unravel the extent to which different dimensions of an individual's disease severity contribute to the waxing and waning of protective effects in cognitive aging.

Association between Self-Reported Pain, Cognition, and Neuropathology in Older Adults Admitted to an Outpatient Memory Clinic-A Cross-Sectional Study.

Cognitive impairment has been linked to reduced self-reporting of pain. However, it is unclear whether the various cognitive functions are similarly and/or independently associated with such pain report measures. In the present study, we explored how executive functioning (EF), memory, and global cognition relate to self-reported pain and investigated whether underlying neuropathology partially accounts for these results. We used Lasso categorical regression to analyze data from 179 individuals visiting a memory clinic. The data included the self-reported pain occurrence, intensity, severity and frequency, clinical diagnoses, neuropsychological scores, white matter hyperintensities, medial temporal lobe atrophy, depressive symptoms, and demographics. Our results showed that worse memory and EF performance predicted a lower pain occurrence. In those individuals who did report pain, worse memory predicted lower pain intensity, severity, and frequency levels, but for EF reversed effects were found, with worse EF predicting higher pain scores. These relationships were only partially explained by reductions in white matter and medial temporal lobe integrity. Similar effects were found for depressive symptoms. Our findings highlight the distinct associations of EF and memory with self-reported pain. A similar pattern of relationships found for both self-reported pain and depressive symptoms may reflect shared latent affective components.

Patients' perspective on cognitive behavioural therapy after surgical treatment of endometriosis: a qualitative study.

RESEARCH QUESTION: Would adding cognitive behavioural therapy (CBT) to the treatment of endometriosis improve the quality of life of patients suffering from endometriosis-associated pain? The aim of this study was to identify if patients believed CBT should be added to endometriosis treatment and which form of CBT they would prefer: face-to-face individual or group, or web-based individual, sessions. DESIGN: Between November 2019 and January 2020, semi-structured focus groups were conducted using an interview guide to ensure all topics were discussed. Data collection was continued until saturation was obtained. The focus groups were transcribed word for word and openly encoded. Finally, themes were formulated. RESULTS: All participating women believed CBT should be offered to patients undergoing endometriosis surgery. They believed it could be an asset to improve quality of life. Participants preferred either in-person individual or group therapy. They stressed the importance of being offered a custom-made treatment plan, individually tailored to the different needs of different patients. CONCLUSION: This study has shown that patients with endometriosis believe that CBT should be added to the standard treatment regimen of endometriosis in either group or individual face-to-face sessions, because they expect that CBT will improve their quality of life after surgery.

Confabulations in Alcoholic Korsakoff's Syndrome: A Factor Analysis of the Nijmegen-Venray Confabulation List.

Confabulations generally refer to the emergence of memories of experiences and events that, in reality, never took place, and which are unintentionally produced. They are frequently observed in alcoholic Korsakoff's syndrome. The aim of the current study was to validate the Nijmegen-Venray Confabulation List (NVCL), an observation scale for quantifying both spontaneous and provoked confabulations. The NVCL was completed for 252 patients with alcoholic Korsakoff's syndrome. Exploratory and confirmatory factor analyses were conducted to test three- and four-factor models of the NVCL structure. A four-factor model (provoked confabulations, spontaneous confabulations, severity of spontaneous confabulations, and distorted sense of reality) fitted the data better than the initially proposed three-factor model (provoked confabulations, spontaneous confabulations, memory, and orientation). The new instrument is therefore referred to as the NVCL-R. We encourage clinicians to include the assessment of confabulations in the neuropsychological examination, and to do so with validated instruments such as the NVCL-R.

Cognitive reserve relates to executive functioning in the old-old.

Cognitive reserve (CR) is known to reduce or even protect against the negative effects of aging on cognitive functioning. Nonetheless, little is known about how CR influences the relationship between different cognitive abilities and age in the old-old. The goal of the present study was, therefore, to test the hypothesis whether, in the old-old, CR still modifies the relationship between age and cognitive functioning. Eighty-three adults (aged 71-94) without mild cognitive impairment or dementia residing in residential care facilities completed a detailed neuropsychological test battery. CR was estimated using a combination of educational attainment and an estimation of verbal intelligence. Moderation analyses revealed a significant effect for fluency and a trend for flexibility, showing that the negative relationship between age and cognitive performance is reduced as the level of CR increases. These results demonstrate that CR still influences the relationship between age and executive functions in adults of advanced age.

Validity of the Mini-Mental State Examination-2 in Diagnosing Mild Cognitive Impairment and Dementia in Patients Visiting an Outpatient Clinic in the Netherlands.

This study examined the utility of the recently published MMSE-2:SV in detecting cognitive impairment. We used receiver operating characteristics to test the discriminative power of the MMSE-2:SV for distinguishing between older adults without mild cognitive impairment (MCI) or dementia (n=67) and patients with MCI (n=76) or dementia (n=79). The results show that the MMSE-2:SV had excellent discriminative ability in distinguishing older controls from patients with dementia, with cut-off scores of 26 and 27 (max=30) yielding appropriate sensitivity (0.810 and 0.924, respectively) and specificity (0.940 and 0.806). Discriminative power was close to good in distinguishing between older controls and patients with MCI. Here, however, no optimal cut-off point could be determined. Even though this study shows good sensitivity and adequate specificity for the MMSE-2:SV in discriminating individuals without MCI or dementia from those with dementia, its validity is limited for identifying patients with MCI.

Egocentric and Allocentric Spatial Memory in Korsakoff's Amnesia.

The goal of the present study was to investigate spatial memory in a group of patients with amnesia due to Korsakoff's syndrome (KS). We used a virtual spatial memory task that allowed us to separate the use of egocentric and allocentric spatial reference frames to determine object locations. Research investigating the ability of patients with Korsakoff's amnesia to use different reference frames is scarce and it remains unclear whether these patients are impaired in using ego- and allocentric reference frames to the same extent. Twenty Korsakoff patients and 24 matched controls watched an animation of a bird flying in one of three trees standing in a virtual environment. After the bird disappeared, the camera turned around, by which the trees were briefly out of sight and then turned back to the center of the environment. Participants were asked in which tree the bird was hiding. In half of the trials, a landmark was shown. Half of the trials required an immediate response whereas in the other half a delay of 10 s was present. Patients performed significantly worse than controls. For all participants trials with a landmark were easier than without a landmark and trials without a delay were easier than with a delay. While controls were above chance on all trials patients were at chance in allocentric trials without a landmark present and with a memory delay. Patients showed no difference in the ego- and the allocentric condition. Together the findings suggest that despite the amnesia, spatial memory and especially the use of ego- and allocentric reference frames in Korsakoff patients are spared.