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Background and Purpose: Executive dysfunction and slowed processing speed are central cognitive impairments in cerebral small vessel disease (cSVD). It is unclear whether the subcomponents of executive functions become equally affected and whether computerized tests are more sensitive in detecting early cognitive changes over traditional tests. The associations of specific executive abilities (cognitive flexibility, inhibitory control, working memory) and processing speed with white matter hyperintensities (WMHs) and Instrumental Activities of Daily Living (IADL) were examined., Methods: In the Helsinki Small Vessel Disease Study, 152 older individuals without stroke or dementia were assessed with brain magnetic resonance imaging and comprehensive neuropsychological evaluation. WMH volumes were obtained with automated segmentation. Executive functions and processing speed measures included established paper-and-pencil tests and the computer-based Flexible Attention Test (FAT), Simon task and Sustained Attention to Response Task., Results: White matter hyperintensity volume and IADL were associated with multiple cognitive measures across subdomains independently of demographic factors. The highest effect sizes were observed for FAT numbers and number-letter tasks (tablet modifications from the Trail Making Test), FAT visuospatial span, Simon task and semantic verbal fluency. Some of the widely used tests such as Stroop inhibition, phonemic fluency and digit span were not significantly associated with either WMHs or IADL., Conclusion: Processing speed and executive function subcomponents are broadly related to functional abilities and WMH severity in covert cSVD, but the strength of associations within subdomains is heavily dependent on the assessment method. Digital tests providing precise measures of reaction times and response accuracy seem to outperform many of the conventional paper-and-pencil tests., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

A quarter of ischaemic strokes are lacunar subtype, typically neurologically mild, usually resulting from intrinsic cerebral small vessel pathology, with risk factor profiles and outcome rates differing from other stroke subtypes. This European Stroke Organisation (ESO) guideline provides evidence-based recommendations to assist with clinical decisions about management of lacunar ischaemic stroke to prevent adverse clinical outcomes. The guideline was developed according to ESO standard operating procedures and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. We addressed acute treatment (including progressive lacunar stroke) and secondary prevention in lacunar ischaemic stroke, and prioritised the interventions of thrombolysis, antiplatelet drugs, blood pressure lowering, lipid lowering, lifestyle, and other interventions and their potential effects on the clinical outcomes recurrent stroke, dependency, major adverse cardiovascular events, death, cognitive decline, mobility, gait, or mood disorders. We systematically reviewed the literature, assessed the evidence and where feasible formulated evidence-based recommendations, and expert concensus statements. We found little direct evidence, mostly of low quality. We recommend that patients with suspected acute lacunar ischaemic stroke receive intravenous alteplase, antiplatelet drugs and avoid blood pressure lowering according to current acute ischaemic stroke guidelines. For secondary prevention, we recommend single antiplatelet treatment long-term, blood pressure control, and lipid lowering according to current guidelines. We recommend smoking cessation, regular exercise, other healthy lifestyle modifications, and avoid obesity for general health benefits. We cannot make any recommendation concerning progressive stroke or other drugs. Large randomised controlled trials with clinically important endpoints, including cognitive endpoints, are a priority for lacunar ischaemic stroke., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. For details, please see Supplemental Table 1.

Background: The competencies of educators in social and health care, and health sciences fields have been studied; however, studies related specifically to hybrid (synchronous face-to-face and online) teaching competence are scarce., Aim: To develop and psychometrically test the hybrid education competence instrument for the purpose of self-assessment of hybrid education competence., Design: A cross-sectional study was conducted to develop and psychometrically test the instrument., Methods: The instrument was developed in four phases: (I) establishing the conceptual framework, (II) testing the face and content validity, (III) testing the construct validity, and (IV) testing the internal consistency of the instrument. The conceptual framework was based on studies related to digital pedagogy and hybrid teaching. The face and content validity were tested using an expert panel (n = 12). Pre-testing (n = 10) was performed prior to the cross-sectional data collection (N = 1689, n = 206) which was performed during the autumn of 2022. The data was collected from educators in social and health care, and health sciences fields at six universities and twelve universities of applied sciences in Finland. Construct validity was tested using exploratory factor analysis and internal consistency was tested using Cronbach's alpha., Results: The newly developed and psychometrically tested instrument contains 46 items across 5 factors: (1) Competence in planning and resourcing hybrid teaching; (2) technological competence in hybrid teaching; (3) interaction competence in hybrid teaching; (4) digital pedagogy competence in hybrid teaching; and (5) ethical competence in hybrid teaching. These five factors explain 70.83 % of the total variance. Cronbach's alpha values ranged from 0.901 to 0.951., Conclusion: The instrument developed in this study can be used to measure the hybrid education competence of educators in social and health care, and health sciences fields. The instrument can also be utilised in an interdisciplinary manner to assess hybrid teaching competence in other educational fields, but also it can be used in the design of continuous learning and training for educators., Competing Interests: Declaration of competing interest Given her role as Editor of the target journal, Professor Kristina Mikkonen was not involved in the peer-review of this article and has no access to information regarding its peer-review. An independent editor was given full responsibility for the editorial process of this article., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Subjective cognitive complaints are common in patients with cerebral small vessel disease (cSVD), yet their relationship with informant evaluations, objective cognitive functions and severity of brain changes are poorly understood. We studied the associations of subjective and informant reports with findings from comprehensive neuropsychological assessment and brain MRI., Method: In the Helsinki SVD Study, 152 older adults with varying degrees of white matter hyperintensities (WMH) but without stroke or dementia were classified as having normal cognition or mild cognitive impairment (MCI) based on neuropsychological criteria. The measures also included continuous domain scores for memory and executive functions. Cognitive complaints were evaluated with the subjective and informant versions of the Prospective and Retrospective Memory Questionnaire (PRMQ) and Dysexecutive Questionnaire (DEX); functional abilities with the Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL); and depressive symptoms with the Geriatric Depression Scale (GDS-15)., Results: Subjective cognitive complaints correlated significantly with informant reports ( r =0.40-0.50, p<0.001). After controlling for demographics, subjective and informant DEX and PRMQ were not related to MCI, memory or executive functions. Instead, subjective DEX and PRMQ significantly associated with GDS-15 and informant DEX and PRMQ with WMH volume and A-IADL., Conclusions: Neither subjective nor informant-reported cognitive complaints associated with objective cognitive performance. Informant-evaluations were related to functional impairment and more severe WMH, whereas subjective complaints only associated with mild depressive symptoms. These findings suggest that awareness of cognitive impairment may be limited in early-stage cSVD and highlight the value of informant assessments in the identification of patients with functional impairment., Competing Interests: MA has received a personal fee for educational event from Merck KGaA. AK has received payment for expert testimony from the Finnish National Insurance Centre, for a neuroradiologist expert testimony on a court of justice, support for travel from Helsinki University Hospital and is the board member of the Finnish Radiological Society. JK and JL are shareholders at Combinostics Ltd. TP is a board member at the Finnish Brain Council, the Finnish Neuropsychological Society, and the Finnish Alzheimer's Disease Research Society. The other authors report no competing of interests., (© 2023 The Authors.)

Cerebral small vessel disease (SVD) is common during ageing and can present as stroke, cognitive decline, neurobehavioural symptoms, or functional impairment. SVD frequently coexists with neurodegenerative disease, and can exacerbate cognitive and other symptoms and affect activities of daily living. Standards for Reporting Vascular Changes on Neuroimaging 1 (STRIVE-1) categorised and standardised the diverse features of SVD that are visible on structural MRI. Since then, new information on these established SVD markers and novel MRI sequences and imaging features have emerged. As the effect of combined SVD imaging features becomes clearer, a key role for quantitative imaging biomarkers to determine sub-visible tissue damage, subtle abnormalities visible at high-field strength MRI, and lesion-symptom patterns, is also apparent. Together with rapidly emerging machine learning methods, these metrics can more comprehensively capture the effect of SVD on the brain than the structural MRI features alone and serve as intermediary outcomes in clinical trials and future routine practice. Using a similar approach to that adopted in STRIVE-1, we updated the guidance on neuroimaging of vascular changes in studies of ageing and neurodegeneration to create STRIVE-2., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: Neuropsychiatric symptoms are related to disease progression and cognitive decline over time in cerebral small vessel disease (SVD) but their significance is poorly understood in covert SVD. We investigated neuropsychiatric symptoms and their relationships between cognitive and functional abilities in subjects with varying degrees of white matter hyperintensities (WMH), but without clinical diagnosis of stroke, dementia or significant disability., Methods: The Helsinki Small Vessel Disease Study consisted of 152 subjects, who underwent brain magnetic resonance imaging (MRI) and comprehensive neuropsychological evaluation of global cognition, processing speed, executive functions, and memory. Neuropsychiatric symptoms were evaluated with the Neuropsychiatric Inventory Questionnaire (NPI-Q, n = 134) and functional abilities with the Amsterdam Instrumental Activities of Daily Living questionnaire (A-IADL, n = 132), both filled in by a close informant., Results: NPI-Q total score correlated significantly with WMH volume ( r s = 0.20, p = 0.019) and inversely with A-IADL score ( r s  = -0.41, p < 0.001). In total, 38% of the subjects had one or more informant-evaluated neuropsychiatric symptom. Linear regressions adjusted for age, sex, and education revealed no direct associations between neuropsychiatric symptoms and cognitive performance. However, there were significant synergistic interactions between neuropsychiatric symptoms and WMH volume on cognitive outcomes. Neuropsychiatric symptoms were also associated with A-IADL score irrespective of WMH volume., Conclusions: Neuropsychiatric symptoms are associated with an accelerated relationship between WMH and cognitive impairment. Furthermore, the presence of neuropsychiatric symptoms is related to worse functional abilities. Neuropsychiatric symptoms should be routinely assessed in covert SVD as they are related to worse cognitive and functional outcomes.

Primary antibody deficiencies, such as common variable immunodeficiency (CVID), are heterogenous disease entities consisting of primary hypogammaglobulinemia and impaired antibody responses to vaccination and natural infection. CVID is the most common primary immunodeficiency in adults, presenting with recurrent bacterial infections, enteropathy, autoimmune disorders, interstitial lung diseases and increased risk of malignancies. Patients with CVID are recommended to be vaccinated against SARS-CoV-2, but there are relatively few studies investigating humoral and cellular responses to immunization. We studied the dynamics of humoral and cell-mediated immunity responses up to 22 months in 28 patients with primary immunodeficiency and three patients with secondary immunodeficiency receiving ChAdOx1, BNT162b2 and mRNA-1273 COVID-19 vaccines. Despite inadequate humoral response to immunization, we demonstrate a robust T cell activation likely protecting from severe COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hurme, Jalkanen, Marttila-Vaara, Heroum, Jokinen, Vara, Liedes, Lempainen, Melin, Julkunen and Kainulainen.)

Background: The usefulness of neurofilament light (NfL) as a biomarker for small vessel disease has not been established. We examined the relationship between NfL, neuroimaging changes, and clinical findings in subjects with varying degrees of white matter hyperintensity (WMH)., Methods: A subgroup of participants (n = 35) in the Helsinki Small Vessel Disease Study underwent an analysis of NfL in cerebrospinal fluid (CSF) as well as brain magnetic resonance imaging (MRI) and neuropsychological and motor performance assessments. WMH and structural brain volumes were obtained with automatic segmentation., Results: CSF NfL did not correlate significantly with total WMH volume (r = 0.278, p = 0.105). However, strong correlations were observed between CSF NfL and volumes of cerebral grey matter (r = -0.569, p < 0.001), cerebral cortex (r = -0.563, p < 0.001), and hippocampi (r = -0.492, p = 0.003). CSF NfL also correlated with composite measures of global cognition (r = -0.403, p = 0.016), executive functions (r = -0.402, p = 0.017), memory (r = -0.463, p = 0.005), and processing speed (r = -0.386, p = 0.022). Regarding motor performance, CSF NfL was correlated with Timed Up and Go (TUG) test (r = 0.531, p = 0.001), and gait speed (r = -0.450, p = 0.007), but not with single-leg stance. After adjusting for age, associations with volumes in MRI, functional mobility (TUG), and gait speed remained significant, whereas associations with cognitive performance attenuated below the significance level despite medium to large effect sizes., Conclusion: NfL was strongly related to global gray matter and hippocampal atrophy, but not to WMH severity. NfL was also associated with motor performance. Our results suggest that NfL is independently associated with brain atrophy and functional mobility, but is not a reliable marker for cerebral small vessel disease., Competing Interests: JKo and JLö are employed by Combinostics Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kartau, Melkas, Kartau, Arola, Laakso, Pitkänen, Lempiäinen, Koikkalainen, Lötjönen, Korvenoja, Ahlström, Herukka, Erkinjuntti and Jokinen.)

This paper provides information on different training models within clinical neuropsychology in Finland. Systematic specialization training program began in Finland in 1983. It was first organized mainly by the Finnish Neuropsychological Society and since 1997 by the Finnish universities. At present, close to 400 clinical neuropsychologists have completed the training. The number of professionals still does not cover the needs of the country (population 5.5 million, area 338,440 km 2 ), and geographical disparities are a constant concern. The training models in Finland have changed over the years and will continue to evolve. Specialization training can be organized by national societies or by universities. It can lead to an academic degree or a diploma. It can be linked to doctoral studies or form a parallel track. Financial model can involve student fees or be governed by ministries (such as the Ministry of Education or Ministry of Health). This paper describes and compares different strategies in education that have impact on the output of professionals. One model does not fit all, or even one country at all times. The strategies of the stakeholder ministries can change over time. The experiences from Finland can be useful for other countries that are developing their models. The estimated need of practitioners and the educational resources including the available financial models for training differ between countries. The guiding principles in specialist training should focus on the advanced competencies expected from the neuropsychologist when entering the profession., Competing Interests: LH was the Professor responsible for the clinical neuropsychology specialist program at the University of Helsinki, Finland. HJ and KR had 50% positions as Senior Lecturers in the same program. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hokkanen, Jokinen, Rantanen, Nybo and Poutiainen.)

Objective: Traditionally, asymmetric spatial processing (i.e., hemispatial neglect) has been assessed with paper-and-pencil tasks, but growing evidence indicates that computer-based methods are a more sensitive assessment modality. It is not known, however, whether simply converting well-established paper-and-pencil methods into a digital format is the best option. The aim of the present study was to compare sensitivity in detecting contralesional omissions of two different computer-based methods: a "digitally converted" cancellation task was compared with a computer-based Visual and Auditory dual-tasking approach, which has already proved to be very sensitive. Methods: Participants included 40 patients with chronic unilateral stroke in either the right hemisphere (RH patients, N = 20) or the left hemisphere (LH patients, N = 20) and 20 age-matched healthy controls. The cancellation task was implemented on a very large format (173 cm × 277 cm) or in a smaller (A4) paper-and-pencil version. The computer-based dual-tasks were implemented on a 15'' monitor and required the detection of unilateral and bilateral briefly presented lateralized targets. Results: Neither version of the cancellation task was able to show spatial bias in RH patients. In contrast, in the Visual dual-task RH patients missed significantly more left-sided targets than controls in both unilateral and bilateral trials. They also missed significantly more left-sided than right-sided targets only in the bilateral trials of the Auditory dual-task. Conclusion: The dual-task setting outperforms the cancellation task approach even when the latter is implemented on a (large) screen. Attentionally demanding methods are useful for revealing mild forms of contralesional visuospatial deficits., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Villarreal, Linnavuo, Sepponen, Vuori, Bonato, Jokinen and Hietanen.)

Background: Cognitive and motor impairments are the key clinical manifestations of cerebral small vessel disease (SVD), but their combined effects on functional outcome have not been elucidated. This study investigated the interactions and mediating effects of cognitive and motor functions on instrumental activities of daily living (IADL) and quality of life in older individuals with various degrees of white matter hyperintensities (WMH)., Methods: Participants of the Helsinki Small Vessel Disease Study (n = 152) were assessed according to an extensive clinical, physical, neuropsychological and MRI protocol. Volumes of WMH and gray matter (GM) were obtained with automated segmentation., Results: Cognitive (global cognition, executive functions, processing speed, memory) and motor functions (gait speed, single-leg stance, timed up-and-go) had strong interrelations with each other, and they were significantly associated with IADL, quality of life as well as WMH and GM volumes. A consistent pattern on significant interactions between cognitive and motor functions was found on informant-evaluated IADL, but not on self-evaluated quality of life. The association of WMH volume with IADL was mediated by global cognition, whereas the association of GM volume with IADL was mediated by global cognition and timed up-and-go performance., Conclusion: The results highlight the complex interplay and synergism between motor and cognitive abilities on functional outcome in SVD. The combined effect of motor and cognitive disturbances on IADL is likely to be greater than their individual effects. Patients with both impairments are at disproportionate risk for poor outcome. WMH and brain atrophy contribute to disability through cognitive and motor impairment., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Purpose: Post-stroke cognitive impairment is a common and well-known consequence of supra-tentorial infarct, but its prevalence and severity after infra-tentorial infarct is unclear. We compared the frequencies and prognostic value of domain-specific cognitive deficits after supra-tentorial and infra-tentorial infarct., Methods: In a consecutive cohort of patients with first-ever stroke (N = 244) admitted to Helsinki University Hospital, 37 patients had an infra-tentorial infarct. Patients were assessed with a comprehensive neuropsychological examination 3 months post-stroke covering 9 cognitive domains and functional disability was assessed at 15 months with the modified Rankin Scale., Results: There were no statistically significant differences between the frequencies of cognitive deficits in patients with infra-tentorial vs supra-tentorial infarct. Altogether 73% of patients with infra-tentorial infarct and 82% of patients with supra-tentorial infarct had impairment in at least one cognitive domain. Further 42% of patients with infra-tentorial infarct and 47% of those with supra-tentorial infarct had deficits in 3 or more cognitive domains. In patients with infra-tentorial infarct, visuo-constructional deficits were significantly associated with functional disability at 15 months (OR 9.0, 95%CI 1.3-62.5, p = 0.027). In patients with supratentorial infarct, executive deficits (OR 2.9, 95%CI 1.5-5.8, p = 0.002) and visuo-constructional deficits (OR 2.9, 95%CI 1.5-5.7, p = 0.001) showed associations with functional disability at 15 months., Conclusion: Cognitive deficits are as common in patients with infra-tentorial infarct as in those with supra-tentorial infarct, and it is important to recognize them to meet the needs of rehabilitation., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Automated analysis of neuroimaging data is commonly based on magnetic resonance imaging (MRI), but sometimes the availability is limited or a patient might have contradictions to MRI. Therefore, automated analyses of computed tomography (CT) images would be beneficial., Methods: We developed an automated method to evaluate medial temporal lobe atrophy (MTA), global cortical atrophy (GCA), and the severity of white matter lesions (WMLs) from a CT scan and compared the results to those obtained from MRI in a cohort of 214 subjects gathered from Kuopio and Helsinki University Hospital registers from 2005 - 2016., Results: The correlation coefficients of computational measures between CT and MRI were 0.9 (MTA), 0.82 (GCA), and 0.86 (Fazekas). CT-based measures were identical to MRI-based measures in 60% (MTA), 62% (GCA) and 60% (Fazekas) of cases when the measures were rounded to the nearest full grade variable. However, the difference in measures was 1 or less in 97-98% of cases. Similar results were obtained for cortical atrophy ratings, especially in the frontal and temporal lobes, when assessing the brain lobes separately. Bland-Altman plots and weighted kappa values demonstrated high agreement regarding measures based on CT and MRI., Conclusions: MTA, GCA, and Fazekas grades can also be assessed reliably from a CT scan with our method. Even though the measures obtained with the different imaging modalities were not identical in a relatively extensive cohort, the differences were minor. This expands the possibility of using this automated analysis method when MRI is inaccessible or contraindicated., (© 2021. The Author(s).)

Objective: Patients with unilateral stroke commonly show hemispatial neglect or milder contralesional visuoattentive deficits, but spatially non-lateralized visuoattentive deficits have also been reported. The aim of the present study was to compare spatially lateralized (i.e., contralesional) and non-lateralized (i.e., general) visuoattentive deficits in left and right hemisphere stroke patients., Method: Participants included 40 patients with chronic unilateral stroke in either the left hemisphere (LH group, n = 20) or the right hemisphere (RH group, n = 20) and 20 healthy controls. To assess the contralesional deficits, we used a traditional paper-and-pencil cancellation task (the Bells Test) and a Lateralized Targets Computer Task. To assess the non-lateralized deficits, we developed a novel large-screen (173 × 277 cm) computer method, the Ball Rain task, with moving visual stimuli and fast-paced requirements for selective attention., Results: There were no contralesional visuoattentive deficits according to the cancellation task. However, in the Lateralized Targets Computer Task, RH patients missed significantly more left-sided than right-sided targets in bilateral trials. This omission distribution differed significantly from those of the controls and LH patients. In the assessment of non-lateralized attention, RH and LH patients missed significantly more Ball Rain targets than controls in both the left and right hemifields., Conclusions: Computer-based assessment sensitively reveals various aspects of visuoattentive deficits in unilateral stroke. Patients with either right or left hemisphere stroke demonstrate non-lateralized visual inattention. In right hemisphere stroke, these symptoms can be accompanied by subtle contralesional visuoattentive deficits that have remained unnoticed in cancellation task.

Background and Purpose: Cerebral small vessel disease is characterized by progressive white matter hyperintensities (WMH) and cognitive decline. However, variability exists in how individuals maintain cognitive capabilities despite significant neuropathology. The relationships between individual cognitive reserve, psychological resilience and cognitive functioning were examined in subjects with varying degrees of WMH., Methods: In the Helsinki Small Vessel Disease Study, 152 subjects (aged 65-75 years) underwent a comprehensive neuropsychological assessment, evaluation of subjective cognitive complaints and brain magnetic resonance imaging with volumetric WMH evaluation. Cognitive reserve was determined by education (years) and the modified Cognitive Reserve Scale (mCRS). Psychological resilience was evaluated with the Resilience Scale 14., Results: The mCRS total score correlated significantly with years of education (r = 0.23, p < 0.01), but it was not related to age, sex or WMH volume. Together, mCRS score and education were associated with performance in a wide range of cognitive domains including processing speed, executive functions, working memory, verbal memory, visuospatial perception and verbal reasoning. Independently of education, the mCRS score had incremental predictive value on delayed verbal recall and subjective cognitive complaints. Psychological resilience was not significantly related to age, education, sex, WMH severity or cognitive test scores, but it was associated with subjective cognitive complaints., Conclusions: Cognitive reserve has strong and consistent associations with cognitive functioning in subjects with WMH. Education is widely associated with objective cognitive functioning, whereas lifetime engagement in cognitively stimulating leisure activities (mCRS) has independent predictive value on memory performance and subjective cognitive complaints. Psychological resilience is strongly associated with subjective, but not objective, cognitive functioning., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

'Covert' cerebral small vessel disease (ccSVD) is common on neuroimaging in persons without overt neurological manifestations, and increases the risk of future stroke, cognitive impairment, dependency, and death. These European Stroke Organisation (ESO) guidelines provide evidence-based recommendations to assist with clinical decisions about management of ccSVD, specifically white matter hyperintensities and lacunes, to prevent adverse clinical outcomes. The guidelines were developed according to ESO standard operating procedures and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. We prioritised the clinical outcomes of stroke, cognitive decline or dementia, dependency, death, mobility and mood disorders, and interventions of blood pressure lowering, antiplatelet drugs, lipid lowering, lifestyle modifications, glucose lowering and conventional treatments for dementia. We systematically reviewed the literature, assessed the evidence, formulated evidence-based recommendations where feasible, and expert consensus statements. We found little direct evidence, mostly of low quality. We recommend patients with ccSVD and hypertension to have their blood pressure well controlled; lower blood pressure targets may reduce ccSVD progression. We do not recommend antiplatelet drugs such as aspirin in ccSVD. We found little evidence on lipid lowering in ccSVD. Smoking cessation is a health priority. We recommend regular exercise which may benefit cognition, and a healthy diet, good sleep habits, avoiding obesity and stress for general health reasons. In ccSVD, we found no evidence for glucose control in the absence of diabetes or for conventional Alzheimer dementia treatments. Randomised controlled trials with clinical endpoints are a priority for ccSVD., (© European Stroke Organisation 2021.)

Background: Dementia is among the most frequent causes of institutionalization. To serve the purpose of preventive strategies, there are no follow-up studies that have evaluated the actual impact of post-stroke dementia on institutionalization. We therefore compared the institutionalization rate and length of stay in an institutional care facility of patients with post-stroke dementia with stroke patients without dementia., Methods: We included 410 consecutive patients aged 55 to 85 years with ischemic stroke who were admitted to Helsinki University Hospital (The SAM cohort). Hospitalization and nursing home admissions were reviewed from national registries. Dementia was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders 3rd edition (DSM-III) criteria using extensive clinical assessments performed 3 months post-stroke. The cohort had a follow-up 21 years later., Results: Compared to patients without dementia, post-stroke dementia was associated with shorter survival time (6.60 vs 10.10 years, p < 0.001), shorter time spent not institutionalized (5.40 vs 9.37 years, p < 0.001), but not with time spent permanently institutionalized (0.73 vs 1.10 years, p = 0.08). Post-stroke dementia was associated with higher rates and earlier permanent institutionalization compared to absence of post-stroke dementia (HR 1.53, 95% CI 1.07-2.18) in a Cox regression model adjusting for age, status of living alone at baseline, modified Rankin Scale at baseline, history of atrial fibrillation, and cardiac failure., Conclusions: Post-stroke dementia is associated with earlier permanent institutionalization. Due to significantly shorter survival, the time spent in nursing homes was not significantly longer in patients with post-stroke dementia compared with patients without post-stroke dementia., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Both clinically observable and subclinical hemispatial neglect are related to functional disability. The aim of the present study was to examine whether increasing task complexity improves sensitivity in assessment and whether it enables the identification of subclinical neglect., Method: We developed and compared two computerized dual-tasks, a simpler and a more complex one, and presented them on a large, 173 × 277 cm screen. Participants in the study included 40 patients with unilateral stroke in either the left hemisphere (LH patient group, n = 20) or the right hemisphere (RH patient group, n = 20) and 20 healthy controls. In addition to the large-screen tasks, all participants underwent a comprehensive neuropsychological assessment. The Bells Test was used as a traditional paper-and-pencil cancellation test to assess neglect., Results: RH patients made significantly more left hemifield omission errors than controls in both large-screen tasks. LH patients' omissions did not differ significantly from those of the controls in either large-screen task. No significant group differences were observed in the Bells Test. All groups' reaction times were significantly slower in the more complex large-screen task compared to the simpler one. The more complex large-screen task also produced significantly slower reactions to stimuli in the left than in the right hemifield in all groups., Conclusions: The present results suggest that dual-tasks presented on a large screen sensitively reveal subclinical neglect in stroke. New, sensitive, and ecologically valid methods are needed to evaluate subclinical neglect.

Purpose: Severity of white matter lesion (WML) is typically evaluated on magnetic resonance images (MRI), yet the more accessible, faster, and less expensive method is computed tomography (CT). Our objective was to study whether WML can be automatically segmented from CT images using a convolutional neural network (CNN). The second aim was to compare CT segmentation with MRI segmentation., Methods: The brain images from the Helsinki University Hospital clinical image archive were systematically screened to make CT-MRI image pairs. Selection criteria for the study were that both CT and MRI images were acquired within 6 weeks. In total, 147 image pairs were included. We used CNN to segment WML from CT images. Training and testing of CNN for CT was performed using 10-fold cross-validation, and the segmentation results were compared with the corresponding segmentations from MRI., Results: A Pearson correlation of 0.94 was obtained between the automatic WML volumes of MRI and CT segmentations. The average Dice similarity index validating the overlap between CT and FLAIR segmentations was 0.68 for the Fazekas 3 group., Conclusion: CNN-based segmentation of CT images may provide a means to evaluate the severity of WML and establish a link between CT WML patterns and the current standard MRI-based visual rating scale.

Introduction: To understand the potential influence of diversity on the measurement of functional impairment in dementia, we aimed to investigate possible bias caused by age, gender, education, and cultural differences., Methods: A total of 3571 individuals (67.1 ± 9.5 years old, 44.7% female) from The Netherlands, Spain, France, United States, United Kingdom, Greece, Serbia, and Finland were included. Functional impairment was measured using the Amsterdam Instrumental Activities of Daily Living (IADL) Questionnaire. Item bias was assessed using differential item functioning (DIF) analysis., Results: There were some differences in activity endorsement. A few items showed statistically significant DIF. However, there was no evidence of meaningful item bias: Effect sizes were low (Δ R 2 range 0-0.03). Impact on total scores was minimal., Discussion: The results imply a limited bias for age, gender, education, and culture in the measurement of functional impairment. This study provides an important step in recognizing the potential influence of diversity on primary outcomes in dementia research., Competing Interests: The Amsterdam IADL Questionnaire was developed by S.A.M.S. and P.S., who were involved in the conception of the present study. The other authors report no conflict of interests., (© 2020 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.)

Background and Purpose- Cerebral small vessel disease is characterized by a wide range of focal and global brain changes. We used a magnetic resonance imaging segmentation tool to quantify multiple types of small vessel disease-related brain changes and examined their individual and combined predictive value on cognitive and functional abilities. Methods- Magnetic resonance imaging scans of 560 older individuals from LADIS (Leukoaraiosis and Disability Study) were analyzed using automated atlas- and convolutional neural network-based segmentation methods yielding volumetric measures of white matter hyperintensities, lacunes, enlarged perivascular spaces, chronic cortical infarcts, and global and regional brain atrophy. The subjects were followed up with annual neuropsychological examinations for 3 years and evaluation of instrumental activities of daily living for 7 years. Results- The strongest predictors of cognitive performance and functional outcome over time were the total volumes of white matter hyperintensities, gray matter, and hippocampi ( P <0.001 for global cognitive function, processing speed, executive functions, and memory and P <0.001 for poor functional outcome). Volumes of lacunes, enlarged perivascular spaces, and cortical infarcts were significantly associated with part of the outcome measures, but their contribution was weaker. In a multivariable linear mixed model, volumes of white matter hyperintensities, lacunes, gray matter, and hippocampi remained as independent predictors of cognitive impairment. A combined measure of these markers based on Z scores strongly predicted cognitive and functional outcomes ( P <0.001) even above the contribution of the individual brain changes. Conclusions- Global burden of small vessel disease-related brain changes as quantified by an image segmentation tool is a powerful predictor of long-term cognitive decline and functional disability. A combined measure of white matter hyperintensities, lacunar, gray matter, and hippocampal volumes could be used as an imaging marker associated with vascular cognitive impairment.

Objective: To address the variability in prevalence estimates and inconsistencies in potential risk factors for poststroke cognitive impairment (PSCI) using a standardized approach and individual participant data (IPD) from international cohorts in the Stroke and Cognition Consortium (STROKOG) consortium., Methods: We harmonized data from 13 studies based in 8 countries. Neuropsychological test scores 2 to 6 months after stroke or TIA and appropriate normative data were used to calculate standardized cognitive domain scores. Domain-specific impairment was based on percentile cutoffs from normative groups, and associations between domain scores and risk factors were examined with 1-stage IPD meta-analysis., Results: In a combined sample of 3,146 participants admitted to hospital for stroke (97%) or TIA (3%), 44% were impaired in global cognition and 30% to 35% were impaired in individual domains 2 to 6 months after the index event. Diabetes mellitus and a history of stroke were strongly associated with poorer cognitive function after covariate adjustments; hypertension, smoking, and atrial fibrillation had weaker domain-specific associations. While there were no significant differences in domain impairment among ethnoracial groups, some interethnic differences were found in the effects of risk factors on cognition., Conclusions: This study confirms the high prevalence of PSCI in diverse populations, highlights common risk factors, in particular diabetes mellitus, and points to ethnoracial differences that warrant attention in the development of prevention strategies., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Unobserved diversity, such as undetected genetic structure or the presence of cryptic species, is of concern for the conservation and management of global biodiversity in the face of threatening anthropogenic processes. For instance, unobserved diversity can lead to overestimation of maximum sustainable yields and therefore to overharvesting of the more vulnerable stock components within unrecognized mixed-stock fisheries. We used DNA from archival (otolith) samples to reconstruct the temporal (1976-2011) genetic makeup of two mixed-stock flounder fisheries in the Åland Sea (AS) and the Gulf of Finland (GoF). Both fisheries have hitherto been managed as a single stock of European flounders ( Platichthys flesus ), but were recently revealed to target two closely related species: the pelagic-spawning P. flesus and the newly described, demersal-spawning P. solemdali . While the AS and GoF fisheries were assumed to consist exclusively of P. solemdali , P. flesus dominated the GoF flounder assemblage (87% of total) in 1983, had disappeared (0%) by 1993, and remained in low proportions (10%-11%) thereafter. In the AS, P. solemdali dominated throughout the sampling period (>70%), and P. flesus remained in very low proportions after 1983. The disappearance of P. flesus from the GoF coincides in time with a dramatic (~60%) decline in commercial landings and worsening environmental conditions in P. flesus' northernmost spawning ground, the Eastern Gotland Basin, in the preceding 4-6 years. These results are compatible with the hypothesis that P. flesus in the GoF is a sink population relying on larval subsidies from southern spawning grounds and the cause of their disappearance is a cessation of larval supply. Our results highlight the importance of uncovering unobserved genetic diversity and studying spatiotemporal changes in the relative contribution of different stock components, as well as the underlying environmental causes, to manage marine resources in the age of rapid anthropogenic change.

Divergent selection may initiate ecological speciation extremely rapidly. How often and at what pace ecological speciation proceeds to yield strong reproductive isolation is more uncertain. Here, we document a case of extraordinarily rapid speciation associated with ecological selection in the postglacial Baltic Sea. European flounders ( Platichthys flesus ) in the Baltic exhibit two contrasting reproductive behaviors: pelagic and demersal spawning. Demersal spawning enables flounders to thrive in the low salinity of the Northern Baltic, where eggs cannot achieve neutral buoyancy. We show that demersal and pelagic flounders are a species pair arising from a recent event of speciation. Despite having a parapatric distribution with extensive overlap, the two species are reciprocally monophyletic and show strongly bimodal genotypic clustering and no evidence of contemporary migration, suggesting strong reproductive isolation. Divergence across the genome is weak but shows strong signatures of selection, a pattern suggestive of a recent ecological speciation event. We propose that spawning behavior in Baltic flounders is the trait under ecologically based selection causing reproductive isolation, directly implicating a process of ecological speciation. We evaluated different possible evolutionary scenarios under the approximate Bayesian computation framework and estimate that the speciation process started in allopatry ∼2,400 generations ago, following the colonization of the Baltic by the demersal lineage. This is faster than most known cases of ecological speciation and represents the most rapid event of speciation ever reported for any marine vertebrate., Competing Interests: The authors declare no conflict of interest.

Metacommunity ecology recognizes the interplay between local and regional patterns in contributing to spatial variation in community structure. In aquatic systems, the relative importance of such patterns depends mainly on the potential connectivity of the specific system. Thus, connectivity is expected to increase in relation to the degree of water movement, and to depend on the specific traits of the study organism. We examined the role of environmental and spatial factors in structuring benthic communities from a highly connected shallow beach network using a metacommunity approach. Both factors contributed to a varying degree to the structure of the local communities suggesting that environmental filters and dispersal-related mechanisms played key roles in determining abundance patterns. We categorized benthic taxa according to their dispersal mode (passive vs. active) and habitat specialization (generalist vs. specialist) to understand the relative importance of environment and dispersal related processes for shallow beach metacommunities. Passive dispersers were predicted by a combination of environmental and spatial factors, whereas active dispersers were not spatially structured and responded only to local environmental factors. Generalists were predicted primarily by spatial factors, while specialists were only predicted by local environmental factors. The results suggest that the role of the spatial component in metacommunity organization is greater in open coastal waters, such as shallow beaches, compared to less-connected environmentally controlled aquatic systems. Our results also reveal a strong environmental role in structuring the benthic metacommunity of shallow beaches. Specifically, we highlight the sensitivity of shallow beach macrofauna to environmental factors related to eutrophication proxies., Competing Interests: The authors have declared that no competing interests exist.

Background: Cerebral small vessel disease (SVD) is characterised by progressive white matter hyperintensities (WMH), cognitive decline and loss of functional independence. The correspondence between neuroimaging findings and the severity of clinical symptoms has been modest, however, and thus the outcome may be affected by various host factors. We investigated the predictive value of educational and occupational attainments as proxy measures of cognitive reserve on long-term cognitive and functional outcome in patients with different degrees of WMH., Methods: In the Leukoaraiosis and Disability (LADIS) study, 615 older individuals with WMH were evaluated with brain MRI and detailed clinical and neuropsychological assessments at 3-year follow-up. A prolonged follow-up of functional and cognitive status was administered with a structured telephone interview after up to 7 years., Results: Higher levels of educational and occupational attainment were strongly related to baseline cognitive scores and predicted a slower rate of decline at 3-year follow-up in measures of processing speed, executive functions and memory independently of WMH volume and other confounders. The deleterious effect of WMH on processing speed and memory was moderated by education and occupation. Education mitigated the relation of WMH volume on 7-year cognitive status. Moreover, higher education and occupational attainments were related to favourable outcome at 7-year follow-up as defined by sustained functional independence and lower mortality., Conclusions: The results support the presumption that cognitive reserve plays a significant role as a buffer against the clinical manifestations of SVD and may in part explain high individual variability in outcome., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Introduction: The Stroke and Cognition consortium (STROKOG) aims to facilitate a better understanding of the determinants of vascular contributions to cognitive disorders and help improve the diagnosis and treatment of vascular cognitive disorders (VCD)., Methods: Longitudinal studies with ≥75 participants who had suffered or were at risk of stroke or TIA and which evaluated cognitive function were invited to join STROKOG. The consortium will facilitate projects investigating rates and patterns of cognitive decline, risk factors for VCD, and biomarkers of vascular dementia., Results: Currently, STROKOG includes 25 (21 published) studies, with 12,092 participants from five continents. The duration of follow-up ranges from 3 months to 21 years., Discussion: Although data harmonization will be a key challenge, STROKOG is in a unique position to reuse and combine international cohort data and fully explore patient level characteristics and outcomes. STROKOG could potentially transform our understanding of VCD and have a worldwide impact on promoting better vascular cognitive outcomes.

White matter lesions (WML) are the main brain imaging surrogate of cerebral small-vessel disease. A new MRI tissue segmentation method, based on a discriminative clustering approach without explicit model-based added prior, detects partial WML volumes, likely representing very early-stage changes in normal-appearing brain tissue. This study investigated how the different stages of WML, from a "pre-visible" stage to fully developed lesions, predict future cognitive decline. MRI scans of 78 subjects, aged 65-84 years, from the Leukoaraiosis and Disability (LADIS) study were analyzed using a self-supervised multispectral segmentation algorithm to identify tissue types and partial WML volumes. Each lesion voxel was classified as having a small (33%), intermediate (66%), or high (100%) proportion of lesion tissue. The subjects were evaluated with detailed clinical and neuropsychological assessments at baseline and at three annual follow-up visits. We found that voxels with small partial WML predicted lower executive function compound scores at baseline, and steeper decline of executive scores in follow-up, independently of the demographics and the conventionally estimated hyperintensity volume on fluid-attenuated inversion recovery images. The intermediate and fully developed lesions were related to impairments in multiple cognitive domains including executive functions, processing speed, memory, and global cognitive function. In conclusion, early-stage partial WML, still too faint to be clearly detectable on conventional MRI, already predict executive dysfunction and progressive cognitive decline regardless of the conventionally evaluated WML load. These findings advance early recognition of small vessel disease and incipient vascular cognitive impairment.

Objective: To examine social variations in parental rationales for delaying or forgoing human papillomavirus vaccination in their U.S. adolescent children., Methods: Using data from the 2011 National Immunization Survey-Teen, we estimated a series of binary logistic regression models to predict the odds of reporting (1) any vaccine delay (n = 25,229) and (2) specific rationales among parents who reported that they were "not likely at all" to vaccinate their teen (n = 9,964)., Results: The odds of not receiving a recommendation to vaccinate were higher in parents of boys (OR = 2.57; CI = 2.20-3.01). The odds of reporting a lack of knowledge were higher in parents who identified as Hispanic (OR = 1.39; CI = 1.11-1.72), Black (OR = 1.49; CI = 1.19-1.85), and other races (OR = 1.43; CI = 1.13-1.80) than parents who identified as non-Hispanic White. Socioeconomic disparities in parental rationales for delaying human papillomavirus vaccination in their teen children were sporadic and inconsistent., Conclusion: Our results suggest that interventions should focus on increasing information about the benefits of the human papillomavirus vaccine among parents of minority youth. Our findings also suggest that interventions targeting health care providers may be a useful strategy for improving vaccine uptake among adolescent males.

Three aspects of poststroke cognitive impairment and dementia are discussed in this review: prevalence; diagnosis; and treatment. The aim is to increase awareness of poststroke cognitive impairment in order to further stimulate strategies to recognize the condition and to prevent its progression. Approximately two-thirds of all middle-aged and elderly stroke patients develop cognitive impairment, and one in three develops dementia. The standard reference for diagnosis is a detailed neuropsychological examination. Short screening tests have been used for both clinical and research purposes, but their sensitivity is limited and there is no consensus as to which test is the most appropriate. The treatment of poststroke cognitive impairment and dementia is based on effective treatment of vascular risk factors, including lifestyle modification when needed., Competing Interests: The authors report no conflicts of interest in this work., (© 2014 Melkas et al.)

Objective: A study was undertaken to determine whether diffusion-weighted imaging (DWI) abnormalities in normal-appearing brain tissue (NABT) and in white matter hyperintensities (WMH) predict longitudinal cognitive decline and disability in older individuals independently of the concomitant magnetic resonance imaging (MRI) findings., Methods: A total of 340 LADIS (Leukoaraiosis and Disability Study) participants, aged 65 to 84 years, underwent brain MRI including DWI at baseline. Neuropsychological and functional assessments were carried out at study entry and repeated annually over a 3-year observational period. Linear mixed models and Cox regression survival analysis adjusted for demographics, WMH volume, lacunes, and brain atrophy were used to evaluate the independent effect of the DWI measures on change in cognitive performance and functional abilities., Results: The mean global apparent diffusion coefficient (ADC) and the relative peak height and peak position of the ADC histogram in NABT predicted faster rate of decline in a composite score for speed and motor control. Higher mean ADC and lower peak height were also related to deterioration in executive functions and memory (specifically working memory), with peak height also being related to more rapid transition to disability and higher rate of mortality. Mean ADC in WMH had less pronounced effects on cognitive and functional outcomes., Interpretation: DWI microstructural changes in NABT predict faster decline in psychomotor speed, executive functions, and working memory regardless of conventional MRI findings. Moreover, these changes are related to functional disability and higher mortality., (Copyright © 2013 American Neurological Association.)

Neuropathologically confirmed Alzheimer's disease may begin with symptoms other than memory problems, for instance visual perceptual disorders, difficulties in linguistic functions and expression in spoken language or executive functioning, occasionally even with behavioral symptoms. Among the forms of Alzheimer's disease appearing with atypical symptoms, the best know is the so-called posterior variant. The diagnosis is based on neuropsychological examination and findings in imaging. Additional diagnostic help is provided by the determination of markers for Alzheimer's disease in cerebrospinal fluid, as changes in markers correspond to the findings in traditional Alzheimer's disease.

Background and Purpose: Poststroke cognitive decline and white matter lesions (WML) are related to poor poststroke survival. Whether cognitive reserve as reflected by educational history associates with cognitive decline, recurrent strokes, and poststroke mortality independent of WML is not known., Methods: A total of 486 consecutive acute mild/moderate ischemic stroke patients subjected to comprehensive neuropsychological assessment (n=409) and magnetic resonance imaging (n=395) 3 months poststroke were included in the study and followed-up for up to 12 years. Odds ratios (OR) for logistic and hazard ratios for Cox regression analyses are reported (OR and hazard ratio≤1 indicates a beneficial effect)., Results: Long educational history (per tertile) was associated with lower frequency of executive dysfunction in models adjusted for age, sex, marital status, and stroke severity (OR, 0.75; P<0.05) but not when adding WML as a covariate. In contrast, educational history was independently associated with less memory impairment (OR, 0.67; P<0.01), aphasia (OR, 0.69; P<0.05), visuospatial and constructive deficits (OR, 0.70; P<0.05), Mini-Mental State Examination score<25 (OR, 0.53; P<0.0001), and dementia (OR, 0.66; P<0.01). In Cox regression analysis, educational history was not associated with recurrent strokes, but it associated independently with favorable poststroke survival (hazard ratio, 0.86; P<0.05)., Conclusions: Long educational history associates with less poststroke cognitive deficits, dementia, and favorable long-term survival independent of age, gender, marital status, stroke severity, and WML in patients with mild/moderate ischemic stroke. This supports the hypothesis that educational history as a proxy indicator of cognitive reserve protects against deficits induced by acute stroke.

Background: Several risk factors are associated to hip fractures. It seems that different hip fracture types have different etiologies. In this study, we evaluated the lifestyle-related risk factors for cervical and trochanteric hip fractures in older women over a 13-year follow-up period., Methods: The study design was a prospective, population-based study consisting of 1681 women (mean age 72 years). Seventy-three percent (n = 1222) participated in the baseline measurements, including medical history, leisure-time physical activity, smoking, and nutrition, along with body anthropometrics and functional mobility. Cox regression was used to identify the independent predictors of cervical and trochanteric hip fractures., Results: During the follow-up, 49 cervical and 31 trochanteric fractures were recorded. The women with hip fractures were older, taller, and thinner than the women with no fractures (p < 0.05). Low functional mobility was an independent predictor of both cervical and trochanteric fractures (HR = 3.4, 95% CI 1.8-6.6, and HR = 5.3, 95% CI 2.5-11.4, respectively). Low baseline physical activity was associated with an increased risk of hip fracture, especially in the cervical region (HR = 2.5, 95% CI 1.3-4.9). A decrease in cervical fracture risk (p = 0.002) was observed with physically active individuals compared to their less active peers (categories: very low or low, moderate, and high). Moderate coffee consumption and hypertension decreased the risk of cervical fractures (HR = 0.4, 95% CI 0.2-0.8, for both), while smoking was a predisposing factor for trochanteric fractures (HR = 3.2, 95% CI 1.1-9.3)., Conclusions: Impaired functional mobility, physical inactivity, and low body mass may increase the risk for hip fractures with different effects at the cervical and trochanteric levels.

Cross-sectional studies have suggested that corpus callosum (CC) atrophy is related to impairment in global cognitive function, mental speed, and executive functions in the elderly. Longitudinal studies confirming these findings have been lacking. We investigated whether CC tissue loss is associated with change in cognitive performance over time in subjects with age-related white matter lesions (WML). Two-hundred-fifty-three subjects, aged 65-84 years, were evaluated by using repeated MRI and neuropsychological evaluation at baseline and after 3 years. The effect of overall and regional CC tissue loss on cognitive decline was analyzed with hierarchical linear regression models. After controlling for age, sex, education, and baseline cognitive performance, the rates of tissue loss in the total CC area, and in rostrum/genu and midbody subregions were significantly associated with decline in a compound measure of cognitive speed and motor control, but not in those of executive functions, memory, or global cognitive function. Total CC area and midbody remained significant predictors of speed also after adjusting for baseline WML volume, WML progression, and global brain atrophy. However, the relationship between anterior CC and speed performance was mediated by WML volume. In conclusion, the overall and regional rate of CC tissue loss parallels longitudinal slowing of psychomotor performance. The adverse effect of CC tissue loss on psychomotor function may be driven by altered interhemispheric information transfer between homologous cortical areas., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Delirium is a frequent post-stroke complication that compromises effective rehabilitation and has been associated with poor outcome. We aimed to investigate whether delirium is associated with increased risk of post-stroke dementia and long-term mortality once confounding is taken into account., Methods: The study comprised 263 consecutive acute ischemic stroke patients aged 55-85 years admitted to the emergency department of a university hospital. The cohort included three-month survivors followed up for 10 years. The diagnosis of post-stroke delirium during the first 7 days after stroke was based on the DSM-IV criteria., Findings: Of all the patients, 50 (19.0%) were diagnosed with delirium. Low education, pre-stroke cognitive decline, and severe stroke indicated by a Modified Rankin score between 3 and 5 were risk factors for post-stroke delirium, which was also associated with diagnosis of dementia at 3 months post-stroke. In the Kaplan-Meier analysis, delirium was associated with poor long-term survival (6.1 versus 9.1 years). In the stepwise Cox regression proportional hazards analysis adjusted for demographic factors and risk factors, advanced age (hazard ratio [HR] 1.08) and stroke severity (HR 1.83), but not post-stroke delirium, were associated with poor survival., Interpretation: In our well-defined cohort of post-stroke patients, acute stage delirium was diagnosed in one in five patients and associated with dementia at 3 months. Advanced age and stroke severity were related to the higher long-term mortality among patients with post-stroke delirium., (Copyright © 2011 John Wiley & Sons, Ltd.)

Objective: To examine the impact of corpus callosum (CC) tissue loss on the development of global cognitive and motor impairment in the elderly., Methods: This study was based on the Leukoaraiosis and Disability (LADIS) study. Assessment of cognitive and motor functions and magnetic resonance imaging (MRI) were done at baseline and at a 3-year follow-up in nondemented elderly subjects., Results: 328 of 639 LADIS subjects had MRIs at baseline and at the 3-year follow-up, which allowed for assessment of CC. Logistic regression revealed differential tissue loss rates in posterior CC in subjects converting to dementia, compared to nonconverters (p < 0.05). Anterior and posterior CC tissue loss was significantly correlated with self-perceived memory impairment in nonconverters (p < 0.05). CC tissue loss was also significantly associated with impaired single leg stance time (p < 0.01)., Conclusion: The present longitudinal study on CC supports the role of callosal tissue loss in the development of global cognitive as well as motor impairment., (Copyright © 2012 S. Karger AG, Basel.)

Background: The aim of this study was to investigate the influence of poststroke depression and executive dysfunction on long-term survival after acute stroke., Methods: A total of 257 consecutive acute ischemic stroke patients were included in the study and followed up to 12 years. Depression was diagnosed 3 months after stroke in 99 patients (38.5%)., Findings: In Kaplan-Meier analysis, there was no difference in survival of patients with and without poststroke depression (8.7 versus 8.3 years). Instead, patients with both depression and executive dysfunction had shorter median survival than patients with neither depression nor executive dysfunction (6.6 versus 10.3 years). Comparison between all patients with executive dysfunction and patients without it, not regarding depressive status, showed that executive dysfunction in itself was strongly associated with poor poststroke survival (6.4 versus 10.6 years). In stepwise Cox regression proportional hazards analysis adjusted with covariates, poststroke depression with executive dysfunction (hazard ratio [HR] 1.63) and advanced age (HR 1.11) remained as independent predictors of poor long-term survival., Interpretation: The authors' well-defined poststroke cohort with long-term follow-up indicates that in poststroke depression, the depression-executive dysfunction syndrome is the predictor of poor long-term survival rather than depression in itself.

We evaluated the contribution of lifestyle-related factors, calcaneal ultrasound, and radial bone mineral density (BMD) to cervical and trochanteric hip fractures in elderly women in a 10-year population-based cohort study. The study population consisted of 1,681 women (age range 70-73 years). Seventy-two percent (n = 1,222) of them participated in the baseline measurements. Calcaneal ultrasound was assessed with a quantitative ultrasound device. BMD measurements were performed at the distal and ultradistal radius by dual-energy X-ray absorptiometry. Forward stepwise logistic regression analysis was used to find the most predictive variables for hip fracture risk. During the follow-up, 53 of the women had hip fractures, including 32 cervical and 21 trochanteric ones. The fractured women were taller and thinner and had lower calcaneal ultrasound values than those without fractures. High body mass index (BMI) was a protective factor against any hip fractures, while low functional mobility was a risk factor of hip fractures. Specifically, high BMI protected against cervical hip fractures, while low physical activity was a significant predictor of these fractures. Similarly, high BMI protected against trochanteric fractures, whereas low functional mobility and high coffee consumption were significant predictors of trochanteric fractures. Cervical and trochanteric hip fractures seem to have different risk factors. Therefore, fracture type should be taken into account in clinical fracture risk assessment and preventative efforts, including patient counseling. However, the study is not conclusive due to the limited number of observed fractures during follow-up, and the results have to be confirmed in future studies.

Background: White matter changes (WMC) are related to cognitive deficits and dementia. Our aim was to determine the extent to which the performance in neuropsychological tests would be able to predict the clinical diagnosis of dementia., Methods: The LADIS (Leukoaraiosis and Disability) is a prospective study that evaluates the impact of WMC on the transition of independent elderly to disability. The subjects were evaluated at baseline and yearly during 3 years with a comprehensive clinical, functional and neuropsychological protocol. At each visit, dementia was classified according to clinical criteria. The performance in the neuropsychological batteries was compared according to the clinical diagnosis of dementia., Results: From the initially enrolled 639 subjects, 480 were evaluated at year 3. Dementia was diagnosed in 90 participants. The demented subjects had worse performance in almost all the baseline cognitive tests. Using receiver operating characteristic curves, we found that the Vascular Dementia Assessment Scale (VADAS) battery had higher sensitivity and specificity rates (area under the curve = 82%) to identify dementia compared with the Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale. Worse performance on baseline MMSE (beta = 0.33; p < 0.001) and VADAS (beta = -0.07; p = 0.02) were predictors of dementia (regression analyses)., Conclusion: Performance on the MMSE and the VADAS battery were important predictors of dementia at a 3-year period., (Copyright (c) 2010 S. Karger AG, Basel.)

Background: Cross-sectional studies have indicated that subcortical ischemic vascular disease (SIVD), as defined according to imaging criteria, is associated with a specific clinical and cognitive profile. Much less is known about the long-term cognitive consequences of SIVD. The aim of the study was to investigate the longitudinal cognitive performance and incident dementia in subjects with and without SIVD in a sample of older adults with white matter lesions., Methods: In the Leukoaraiosis and Disability (LADIS) study, 639 participants were examined with annual clinical and neuropsychological evaluations for 3 years. The subjects meeting the MRI criteria of SIVD at baseline were compared to the other subjects of the sample with linear mixed models., Results: The overall level of cognitive performance over the follow-up period was inferior in multiple cognitive domains in SIVD subjects as compared to the reference group. The subjects with SIVD presented significantly steeper decline of performance in the Stroop test (parts I and II), Trail Making A test, Verbal fluency test, and Mini-Mental State Examination. They also had a threefold risk of developing dementia during follow-up independently of age, sex, education and medial temporal lobe atrophy., Conclusions: SIVD, as a manifestation of cerebral small vessel disease, is related to progressive cognitive impairment and a considerable risk of developing dementia. SIVD seems to specifically contribute to the deterioration of psychomotor speed, executive control, and global cognitive function., (Copyright 2009 S. Karger AG, Basel.)