IDEAL monitoring of musical skills during awake craniotomy: From step 1 to step 2.

The aim of awake brain surgery is to perform a maximum resection on the one hand, and to preserve cognitive functions, quality of life and personal autonomy on the other hand. Historically, language and sensorimotor functions were most frequently monitored. Over the years other cognitive functions, including music, have entered the operation theatre. Cases about monitoring musical abilities during awake brain surgery are emerging, and a systematic method how to monitor music would be the next step. According to the IDEAL framework for surgical innovations our study aims to present future recommendation based on a systematic literature search (PRISMA) in combination with lessons learned from three case reports from our own clinical practice with professional musicians (n = 3). We plead for structured procedures including individual tailored tasks. By embracing these recommendations, we can both improve clinical care and unravel music functions in the brain.

Reliability and validity of DTI-based indirect disconnection measures.

White matter connections enable the interaction within and between brain networks. Brain lesions can cause structural disconnections that disrupt networks and thereby cognitive functions supported by them. In recent years, novel methods have been developed to quantify the extent of structural disconnection after focal lesions, using tractography data from healthy controls. These methods, however, are indirect and their reliability and validity have yet to be fully established. In this study, we present our implementation of this approach, in a tool supplemented by uncertainty metrics for the predictions overall and at voxel-level. These metrics give an indication of the reliability and are used to compare predictions with direct measures from patients' diffusion tensor imaging (DTI) data in a sample of 95 first-ever stroke patients. Results show that, except for small lesions, the tool can predict fiber loss with high reliability and compares well to direct patient DTI estimates. Clinical utility of the method was demonstrated using lesion data from a subset of patients suffering from hemianopia. Both tract-based measures outperformed lesion localization in mapping visual field defects and showed a network consistent with the known anatomy of the visual system. This study offers an important contribution to the validation of structural disconnection mapping. We show that indirect measures of structural disconnection can be a reliable and valid substitute for direct estimations of fiber loss after focal lesions. Moreover, based on these results, we argue that indirect structural disconnection measures may even be preferable to lower-quality single subject diffusion MRI when based on high-quality healthy control datasets.

Awake craniotomy does not lead to increased psychological complaints.

BACKGROUND: Patients with brain tumours are increasingly treated by using the awake craniotomy technique. Some patients may experience anxiety when subjected to brain surgery while being fully conscious. However, there has been only limited research into the extent to which such surgeries actually result in anxiety or other psychological complaints. Previous research suggests that undergoing awake craniotomy surgery does not lead to psychological complaints, and that post-traumatic stress disorders (PTSD) are uncommon following this type of surgery. It must be noted, however, that many of these studies used small random samples. METHOD: In the current study, 62 adult patients completed questionnaires to identify the degree to which they experienced anxiety, depressive and post-traumatic stress complaints following awake craniotomy using an awake-awake-awake procedure. All patients were cognitively monitored and received coaching by a clinical neuropsychologist during the surgery. RESULTS: In our sample, 21% of the patients reported pre-operative anxiety. Four weeks after surgery, 19% of the patients reported such complaints, and 24% of the patients reported anxiety complaints after 3 months. Depressive complaints were present in 17% (pre-operative), 15% (4 weeks post-operative) and 24% (3 months post-operative) of the patients. Although there were some intra-individual changes (improvement or deterioration) in the psychological complaints over time, on group-level postoperative levels of psychological complaints were not increased relative to the preoperative level of complaints. The severity of post-operative PTSD-related complaints were rarely suggestive of a PTSD. Moreover, these complaints were seldom attributed to the surgery itself, but appeared to be more related to the discovery of the tumour and the postoperative neuropathological diagnosis. CONCLUSIONS: The results of the present study do not indicate that undergoing awake craniotomy is associated with increased psychological complaints. Nevertheless, psychological complaints may well exist as a result of other factors. Consequently, monitoring the patient's mental wellbeing and offering psychological support where necessary remain important.

A timeline of cognitive functioning in glioma patients who undergo awake brain tumor surgery.

BACKGROUND: The purpose of awake brain tumor surgery is to maximize the resection of the tumor and to minimize the risk of neurological and cognitive impairments. The aim of this study is to gain understanding of the development of possible postoperative cognitive deficits after awake brain tumor surgery in patients with suspected gliomas, by comparing preoperative, early postoperative, and late postoperative functioning. A more detailed timeline will be helpful in informing candidates for surgery about what to expect regarding their cognitive functioning. METHODS: Thirty-seven patients were included in this study. Cognitive functioning was measured by means of a broad cognitive screener preoperatively, days after surgery and months after surgery in patients who underwent awake brain tumor surgery with cognitive monitoring. The cognitive screener included tests for object naming, reading, attention span, working memory, inhibition, inhibition/switching, and visuoperception. We performed a Friedman ANOVA to analyze on group level. RESULTS: Overall, no significant differences were found between preoperative cognitive functioning, early postoperative cognitive functioning, and late postoperative cognitive functioning, except for performances on the inhibition task. Directly after surgery, patients were significantly slower on this task. However, in the following months after surgery, they returned to their preoperative level. CONCLUSION: The timeline of cognitive functioning after awake tumor surgery appeared overall stable in the early and late postoperative phase, except for inhibition, which is more difficult in the first days after awake brain tumor surgery. This more detailed timeline of cognitive functioning, in combination with future research, can possibly be contributing in informing patients and caregivers what to expect after awake brain tumor surgery.

The impact of etiology in lesion-symptom mapping - A direct comparison between tumor and stroke.

INTRODUCTION: Lesion-symptom mapping is a key tool in understanding the relationship between brain structures and behavior. However, the behavioral consequences of lesions from different etiologies may vary because of how they affect brain tissue and how they are distributed. The inclusion of different etiologies would increase the statistical power but has been critically debated. Meanwhile, findings from lesion studies are a valuable resource for clinicians and used across different etiologies. Therefore, the main objective of the present study was to directly compare lesion-symptom maps for memory and language functions from two populations, a tumor versus a stroke population. METHODS: Data from two different studies were combined. Both the brain tumor (N = 196) and stroke (N = 147) patient populations underwent neuropsychological testing and an MRI, pre-operatively for the tumor population and within three months after stroke. For this study, we selected two internationally widely used standardized cognitive tasks, the Rey Auditory Verbal Learning Test and the Verbal Fluency Test. We used a state-of-the-art machine learning-based, multivariate voxel-wise approach to produce lesion-symptom maps for these cognitive tasks for both populations separately and combined. RESULTS: Our lesion-symptom mapping results for the separate patient populations largely followed the expected neuroanatomical pattern based on previous literature. Substantial differences in lesion distribution hindered direct comparison. Still, in brain areas with adequate coverage in both groups, considerable LSM differences between the two populations were present for both memory and fluency tasks. Post-hoc analyses of these locations confirmed that the cognitive consequences of focal brain damage varied between etiologies. CONCLUSION: The differences in the lesion-symptom maps between the stroke and tumor population could partly be explained by differences in lesion volume and topography. Despite these methodological limitations, both the lesion-symptom mapping results and the post-hoc analyses confirmed that etiology matters when investigating the cognitive consequences of lesions with lesion-symptom mapping. Therefore, caution is advised with generalizing lesion-symptom results across etiologies.

Morphological changes after cranial fractionated photon radiotherapy: Localized loss of white matter and grey matter volume with increasing dose.

PURPOSE: Numerous brain MR imaging studies have been performed to understand radiation-induced cognitive decline. However, many of them focus on a single region of interest, e.g. cerebral cortex or hippocampus. In this study, we use deformation-based morphometry (DBM) and voxel-based morphometry (VBM) to measure the morphological changes in patients receiving fractionated photon RT, and relate these to the dose. Additionally, we study tissue specific volume changes in white matter (WM), grey matter (GM), cerebrospinal fluid and total intracranial volume (TIV). METHODS AND MATERIALS: From our database, we selected 28 patients with MRI of high quality available at baseline and 1 year after RT. Scans were rigidly registered to each other, and to the planning CT and dose file. We used DBM to study non-tissue-specific volumetric changes, and VBM to study volume loss in grey matter. Observed changes were then related to the applied radiation dose (in EQD2). Additionally, brain tissue was segmented into WM, GM and cerebrospinal fluid, and changes in these volumes and TIV were tested. RESULTS: Performing DBM resulted in clusters of dose-dependent volume loss 1 year after RT seen throughout the brain. Both WM and GM were affected; within the latter both cerebral cortex and subcortical nuclei show volume loss. Volume loss rates ranging from 5.3 to 15.3%/30 Gy were seen in the cerebral cortical regions in which more than 40% of voxels were affected. In VBM, similar loss rates were seen in the cortex and nuclei. The total volume of WM and GM significantly decreased with rates of 5.8% and 2.1%, while TIV remained unchanged as expected. CONCLUSIONS: Radiotherapy is associated with dose-dependent intracranial morphological changes throughout the entire brain. Therefore, we will consider to revise sparing of organs at risk based on future cognitive and neurofunctional data.

The relationship between ischaemic brain lesions and cognitive outcome after aneurysmal subarachnoid haemorrhage.

BACKGROUND: Cerebral ischaemia is thought to be an important determinant of cognitive outcome after aneurysmal subarachnoid haemorrhage (aSAH), but the exact relationship is unclear. We studied the effect of ischaemic brain lesions during clinical course on cognitive outcome 2 months after aSAH. METHODS: We studied 74 consecutive patients admitted to the University Medical Center Utrecht who had MRI post-coiling (3-21 days post-aSAH) and neuropsychological examination at 2 months. An ischaemic lesion was defined as hyperintensity on T2-FLAIR and DWI images. We measured both cognitive complaints (subjective) and cognitive functioning (objective). The relationship between ischaemic brain lesions and cognitive outcome was analysed by logistic regression analyses. RESULTS: In 40 of 74 patients (54%), 152 ischaemic lesions were found. The median number of lesions per patient was 2 (1-37) and the median total lesion volume was 0.2 (0-17.4) mL. No difference was found between the group with and the group without ischaemic lesions with respect to the frequency of cognitive complaints. In the group with ischaemic lesions, significantly more patients (55%) showed poor cognitive functioning compared to the group without ischaemic lesions (26%) (OR 3.4, 95% CI 1.3-9.1). We found no relationship between the number and volume of the ischaemic lesions and cognitive functioning. CONCLUSIONS: Ischaemic brain lesions detected on MRI during clinical course after aSAH is a marker for poor cognitive functioning 2 months after aSAH, irrespective of the number or volume of the ischaemic lesions. Network or connectivity studies are needed to better understand the relationship between location of the ischaemic brain lesions and cognitive functioning.

Effect of magnesium on cognition after aneurysmal subarachnoid haemorrhage in a randomized trial.

BACKGROUND AND PURPOSE: In randomized trials magnesium supplementation did not improve clinical outcome after aneurysmal subarachnoid haemorrhage (aSAH) on handicap scales. After aSAH, many patients have cognitive problems that may not translate into handicap. The effect of magnesium on cognitive outcome after aSAH was studied. METHODS: In total, 209 patients who had been included in the Magnesium for Aneurysmal Subarachnoid Haemorrhage (MASH-2) trial in the University Medical Centre of Utrecht were studied. Patients had been randomized to 64 mmol magnesium sulfate daily or placebo during hospitalization. Three months after aSAH patients underwent a neuropsychological examination (NPE) consisting of six neuropsychological tests or a brief cognitive assessment. Poisson and linear regression analyses were used to analyse the effect of magnesium on cognition. RESULTS: In the magnesium group 53 (49.5%) of the 107 patients and in the placebo group 51 (50.0%) of the 102 patients scored lower than the median cognitive score [relative risk 0.99, 95% confidence interval (CI) 0.76-1.30]. Linear regression analyses showed no significant relationship between intervention and cognition (B = 0.05, 95% CI -0.15 to 0.33). CONCLUSIONS: Treatment with magnesium has no effect on cognitive outcome after aSAH.

The Montreal Cognitive Assessment-Basic (MoCA-B) is not a reliable screening tool for cognitive decline in HIV patients receiving combination antiretroviral therapy in rural South Africa.

BACKGROUND: HIV-associated neurocognitive disorders (HAND) are frequently occurring comorbidities in HIV-positive patients, diagnosed by means of a neuropsychological assessment (NPA). Due to the magnitude of the HIV-positive population in Sub-Saharan Africa, easy-to-use cognitive screening tools are essential. METHODS: This was a cross-sectional clinical trial involving 44 HIV-positive patients (on stable cART) and 73 HIV-negative controls completing an NPA, the International HIV Dementia Scale (IHDS), and a culturally appropriate cognitive screening tool, the Montreal Cognitive Assessment-Basic (MoCA-B). HAND were diagnosed by calculating Z-scores using internationally published normative data on NPA, as well as by using data from the HIV-negative group to validate the MoCA-B. RESULTS: One hundred and seventeen patients were included (25% male, median age 35 years, median 11 years of education). A moderate correlation was found between the MoCA-B and NPA total Z-score (Pearson's r=0.36, p=0.02). Area under the curve (AUC) values for MoCA-B and IHDS were 0.59 and 0.70, respectively. The prevalence of HAND in HIV-positive patients was 66% when calculating Z-scores using published normative data versus 48% when using the data from the present HIV-negative cohort. CONCLUSION: The MoCA-B appeared not to be a valid screening tool for HAND in this setting. The prevalence of HAND in this setting is high, but appeared overestimated when using published norms.

Post-traumatic stress disorder in patients 3 years after aneurysmal subarachnoid haemorrhage.

BACKGROUND: Subarachnoid haemorrhage (SAH) from a ruptured intracranial aneurysm accounts for approximately 5% of all strokes. Post-traumatic stress disorder (PTSD) is common in the early phase after recovery from aneurysmal SAH. The aim of our study was to examine the prevalence of PTSD 3 years after SAH, its predictors, and relationship with health-related quality of life (HRQoL) in patients living independently in the community. METHODS: From a prospectively collected cohort of 143 patients with aneurysmal SAH who visited our outpatient clinic 3 months after SAH, 94 patients (65.7%) completed a mailed questionnaire 3 years after SAH. We assessed PTSD with the Impact of Event Scale and HRQoL with the Stroke-Specific Quality of Life Scale (SS-QoL). The χ(2) and t tests were used to investigate if patients who returned the questionnaires were different from those who did not reply. Non-parametric tests (χ(2) and Mann-Whitney tests) were used to test for differences between patients with and without PTSD. Relative risks and 95% confidence intervals were calculated. RESULTS: No relevant differences in demographic (age, sex, education) or SAH characteristics (clinical condition on admission, complication, location of aneurysm, Glasgow Outcome Scale score at 3 months) were seen between participants and drop-outs. In 24 patients (26%), Impact of Event Scale scores indicated PTSD. Passive coping style (relative risk, 5.7; 95% confidence interval, 2.1-15.3), but none of the demographic or SAH-related factors, predicted PTSD. The mean SS-QoL total score was 4.2 (SD 1.1), indicative of a relatively satisfactory HRQoL. PTSD was associated with lower HRQoL (p < 0.001), a mean SS-QoL score of 4.4 (SD 1.0) without PTSD, and a mean SS-QoL score of 3.5 (SD 1.1) with PTSD. CONCLUSIONS: Even 3 years after SAH, 1 out of 4 patients had PTSD, which was associated with reduced HRQoL. Passive coping style was the most important predictor. There is a need to organize SAH care with more attention to and treatment of PTSD. Strategies shown to reduce PTSD in other conditions should be tested for effectiveness in SAH patients.

Frequency specific spatial interactions in human electrocorticography: V1 alpha oscillations reflect surround suppression.

Electrical brain signals are often decomposed into frequency ranges that are implicated in different functions. Using subdural electrocorticography (ECoG, intracranial EEG) and functional magnetic resonance imaging (fMRI), we measured frequency spectra and BOLD responses in primary visual cortex (V1) and intraparietal sulcus (IPS). In V1 and IPS, 30-120 Hz (gamma, broadband) oscillations allowed population receptive field (pRF) reconstruction comparable to fMRI estimates. Lower frequencies, however, responded very differently in V1 and IPS. In V1, broadband activity extends down to 3 Hz. In the 4-7 Hz (theta) and 18-30 Hz (beta) ranges broadband activity increases power during stimulation within the pRF. However, V1 9-12 Hz (alpha) frequency oscillations showed a different time course. The broadband power here is exceeded by a frequency-specific power increase during stimulation of the area outside the pRF. As such, V1 alpha oscillations reflected surround suppression of the pRF, much like negative fMRI responses. They were consequently highly localized, depending on stimulus and pRF position, and independent between nearby electrodes. In IPS, all 3-25 Hz oscillations were strongest during baseline recording and correlated between nearby electrodes, consistent with large-scale disengagement. These findings demonstrate V1 alpha oscillations result from locally active functional processes and relate these alpha oscillations to negative fMRI signals. They highlight that similar oscillations in different areas reflect processes with different functional roles. However, both of these roles of alpha seem to reflect suppression of spiking activity.

Predictors of long-term health-related quality of life in patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVE: To determine the predictive value of physical and psychological factors assessed three months after aneurysmal subarachnoid hemorrhage (SAH) for health-related quality of life (HRQoL) one year after the SAH. DESIGN: Prospective cohort study. SUBJECTS: Patients with SAH (n=113) who visited our SAH-outpatient clinic three months after SAH and who were living independently in the community one year after SAH. METHODS: HRQoL was evaluated using the Stroke Specific Quality of Life scale (SS-QoL). We used Spearman correlations, Somers'd, and linear regression analyses. Independent variables were demographic and SAH characteristics, cognitive and emotional complaints, depressive symptoms, anxiety, cognitive functioning, and passive coping style. RESULTS: In the regression analysis, female gender (beta value -0.17), cognitive complaints (-0.31 ), cognitive functioning (0.40) and passive coping style (-0.23) were independent predictors, and together explained 45.9% of the variance of the SS-QoL total score. CONCLUSION: Female gender, cognitive complaints, cognitive functioning and passive coping style assessed at 3 months after SAH are important predictors of HRQoL 1 year after SAH. Early interventions to improve cognitive and emotional functioning should be evaluated for their ability to improve long-term HRQoL after SAH.

The role of self-touch in somatosensory and body representation disorders after stroke.

Somatosensory impairments occur in about half of the cases of stroke. These impairments range from primary deficits in tactile detection and the perception of features, to higher order impairments in haptic object recognition and bodily experience. In this paper, we review the influence of active- and self-touch on somatosensory impairments after stroke. Studies have shown that self-touch improves tactile detection in patients with primary tactile deficits. A small number of studies concerned with the effect of self-touch on bodily experience in healthy individuals have demonstrated that self-touch influences the structural representation of one's own body. In order to better understand the effect of self-touch on body representations, we present an informal study of a stroke patient with somatoparaphrenia and misoplegia. The role of self-touch on body ownership was investigated by asking the patient to stroke the impaired left hand and foreign hands. The patient reported ownership and a change in affect over all presented hands through self-touch. The time it took to accomplish ownership varied, based on the resemblance of the foreign hand to the patient's own hand. Our findings suggest that self-touch can modulate impairments in body ownership and affect, perhaps by helping to reinstate the representation of the body.

Cognition after carotid endarterectomy or stenting: a randomized comparison.

OBJECTIVE: To compare the effect on cognition of carotid artery stenting (CAS) and carotid endarterectomy (CEA) for symptomatic carotid artery stenosis. METHODS: Patients randomized to CAS or CEA in the International Carotid Stenting Study (ICSS; ISRCTN25337470) at 2 participating centers underwent detailed neuropsychological examinations (NPE) before and 6 months after revascularization. Ischemic brain lesions were assessed with diffusion-weighted imaging before and within 3 days after revascularization. Cognitive test results were standardized into z scores, from which a cognitive sumscore was calculated. The primary outcome was the change in cognitive sumscore between baseline and follow-up. RESULTS: Of the 1,713 patients included in ICSS, 177 were enrolled in the 2 centers during the substudy period, of whom 140 had an NPE at baseline and 120 at follow-up. One patient with an unreliable baseline NPE was excluded. CAS was associated with a larger decrease in cognition than CEA, but the between-group difference was not statistically significant: -0.17 (95% CI -0.38 to 0.03; p = 0.092). Eighty-nine patients had a pretreatment MRI and 64 within 3 days after revascularization. New ischemic lesions were found twice as often after CAS than after CEA (relative risk 2.1; 95% CI 1.0 to 4.4; p = 0.041). CONCLUSIONS: Differences between CAS and CEA in effect on cognition were not statistically significant, despite a substantially higher rate of new ischemic lesions after CAS than after CEA. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that any difference between the effects of CAS and CEA on cognition at 6 months after revascularization is small.

The posterior parietal paradox: Why do functional magnetic resonance imaging and lesion studies on episodic memory produce conflicting results?

Recent functional magnetic resonance imaging (fMRI) studies addressing healthy subjects point towards posterior parietal cortex (PPC) involvement in episodic memory tasks. This is noteworthy, since neuropsychological studies usually do not connect parietal lesions to episodic memory impairments. Therefore an inventory of the possible factors behind this apparent paradox is warranted. This review compared fMRI studies which demonstrated PPC activity in episodic memory tasks, with findings with studies of patients with PPC lesions. A systematic evaluation of possible explanations for the posterior parietal paradox indicates that PPC activation in fMRI studies does not appear to be attributable to confounding cognitive/psychomotor processes, such as button pressing or stimulus processing. What may be of more importance is the extent to which an episodic memory task loads on three closely related cognitive processes: effort and attention, self-related activity, and scene and image construction. We discuss to what extent these cognitive processes can account for the paradox between lesion and fMRI results. They are strongly intertwined with the episodic memory and may critically determine in how far the PPC plays a role in a given memory task. Future patient studies might profit from specifically taking these cognitive factors into consideration in the task design.

Predicting fatigue 1 year after aneurysmal subarachnoid hemorrhage.

Fatigue is an important contributor to quality of life in patients who survive aneurysmal subarachnoid hemorrhage (SAH), but the determinants of this fatigue are unclear. We assessed the occurrence of fatigue 1 year after SAH and its relation to physical or cognitive impairment, passive coping, and emotional problems, measured 3 months after SAH. This was a prospective cohort study of 108 patients who visited our SAH outpatient clinic 3 months after SAH and who were living independently in the community 1 year after SAH. Fatigue was evaluated using the Fatigue Severity Scale (FSS). Analysis of variance was used to analyze the data. Fatigue (FSS ≥ 4) was present in 77 patients (71%). Mean FSS scores were 4.1 (SD 1.6) in the group of patients having 'neither physical nor cognitive impairment,' 5.2 (1.4) having 'either physical or cognitive impairment,' and 5.9 (0.9) having 'both physical and cognitive impairments.' Mean FSS scores were higher in patients scoring high on passive coping (85 vs. 58%; RR 1.46, 95% CI 1.13-1.87), anxiety (84 vs. 55%; RR 1.53, 95% CI 1.17-2.02), or depression (85 vs. 62%; RR 1.36, 95% CI 1.08-1.72) than in patients without these complaints. Relationships between these complaints and FSS scores were higher in patients having neither physical nor cognitive impairments than in patients having physical or cognitive impairments. Fatigue is common after SAH and is related to physical and cognitive impairments. In patients with neither physical nor cognitive impairments, passive coping style and emotional problems are important predictors of fatigue.

Prevalence and determinants of cognitive complaints after aneurysmal subarachnoid hemorrhage.

BACKGROUND: To investigate the prevalence of cognitive complaints after subarachnoid hemorrhage (SAH) and the relationships between cognitive complaints and cognitive impairments, disability and emotional problems. METHODS: Cognitive complaints were assessed with the Checklist for Cognitive and Emotional Consequences following stroke (CLCE-24) in 111 persons who visited our outpatient clinic 3 months after SAH. Associations between cognitive complaints and cognitive functioning, demographic characteristics, disability and emotional problems were examined using Spearman correlations and linear regression analysis. RESULTS: In this study group, 105 patients (94.6%) reported at least one cognitive or emotional complaint that hampered everyday functioning. The most frequently reported cognitive complaints were mental slowness, short-term memory problems and attention deficits. All cognitive domains, disability, depressive symptoms and feelings of anxiety were significantly associated with the CLCE-24 cognition score. In the final regression model, memory functioning (beta value -0.21), disability (-0.28) and depressive symptoms (0.40) were significant determinants of cognitive complaints, together explaining 35.4% of the variance. CONCLUSION: Cognitive complaints are common after SAH and associated with memory deficits, disability and depressive symptoms. Rehabilitation programs should focus on these symptoms and deficits.

Cognitive dysfunction and its clinical and radiological determinants in patients with symptomatic arterial disease and diabetes.

BACKGROUND AND AIMS: Both vascular disease and diabetes type 2 (DM2) decrease cognitive functioning in elderly people. It is uncertain if DM2 affects cognition independent of vascular disease. In patients with symptomatic arterial disease, we studied the effect of DM2 on cognition and identified clinical and radiological determinants for impaired cognition in patients with DM2. METHODS: 766 patients (mean age 58.8+/-9.5 years; 108 DM2) with symptomatic arterial disease underwent neuropsychological testing. In 542 patients (77 DM2), volumes of brain tissue, ventricles and white matter lesions were obtained by segmentation of brain MR images. Infarcts were distinguished into small (lacunar) or large (cortical or subcortical). RESULTS: Patients with arterial disease and DM2 performed worse on neuropsychological tests compared to similar patients without DM2 (adjusted composite z-score: beta -0.14 [-0.25 to -0.02]). Insulin treatment, systolic and diastolic blood pressures were significantly associated with cognition in patients with DM2. Large infarcts, global and cortical atrophy on MRI were independently associated with cognition in patients with DM2. CONCLUSION: The presence of DM2 in patients with symptomatic arterial disease is associated with decreased cognitive functioning. Insulin treatment, high blood pressure, brain atrophy and large infarcts were determinants for cognitive dysfunction in patients with DM2 and arterial disease.