Neuropsychiatric symptoms are associated with exacerbated cognitive impairment in covert cerebral small vessel disease.

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 (rs = 0.20, p = 0.019) and inversely with A-IADL score (rs = -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.

Synergistic associations of cognitive and motor impairments with functional outcome in covert cerebral small vessel disease.

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.

Associations of cognitive reserve and psychological resilience with cognitive functioning in subjects with cerebral white matter hyperintensities.

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.

Unilateral Stroke: Computer-based Assessment Uncovers Non-Lateralized and Contralesional Visuoattentive Deficits.

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.

A novel CT-based automated analysis method provides comparable results with MRI in measuring brain atrophy and white matter lesions.

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.

Post-Stroke Cognitive Impairment is Frequent After Infra-Tentorial Infarct.

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.

Global Burden of Small Vessel Disease-Related Brain Changes on MRI Predicts Cognitive and Functional Decline.

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.

Dual-Task in Large Perceptual Space Reveals Subclinical Hemispatial Neglect.

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.

Evaluating severity of white matter lesions from computed tomography images with convolutional neural network.

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.

Cognitive reserve moderates long-term cognitive and functional outcome in cerebral small vessel disease.

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.

Diffusion changes predict cognitive and functional outcome: the LADIS study.

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.

European stroke organisation (ESO) guideline on cerebral small vessel disease, part 2, lacunar ischaemic stroke.

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.

[Posterior variant of Alzheimer's disease and other atypical symptom pictures]. / Posteriorinen kortikaalinen atrofia ja muut Alzheimerin taudin epätyypilliset muodot.

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.

Web-based psychoeducational interventions for managing cognitive impairment-a systematic review.

Objective: Web-based rehabilitation, a branch of telerehabilitation, is carried out over the internet, unrestricted by time or place. Even though web-based interventions have been reported as feasible and effective in cases of mood disorders, for example, such evidence on the effectiveness of web-based cognitive rehabilitation remains unclear. This systematic review summarizes current knowledge on web-based psychoeducational programs aiming to manage cognitive deficits in patients with diseases that affect cognition. Methods: Using the Ovid database and the Web of Science, we systematically searched the Cochrane Database of Systematic Reviews, Medline, and PsycINFO to identify eligible studies. The review protocol (CRD42021257315) was pre-registered with the PROSPERO International Prospective Register of Systematic Reviews. The search was performed 10/13/2022. Two reviewers independently screened titles, abstracts, and full-texts, and extracted data for the selected studies. Two independent reviewers assessed the methodological quality. Results: The search retrieved 6,487 articles. Four studies with different patient groups (stroke, traumatic brain injury, brain tumor, and cancer) met the inclusion criteria of this systematic review. The studies examined systematic cognition-focused psychoeducational rehabilitation programs in which the patient worked independently. Three studies found positive effects on subjective cognitive functions, executive functions, and self-reported memory. No effects were found on objective cognitive functions. However, the studies had methodological weaknesses (non-randomized designs, small sample sizes, vaguely described interventions). Overall, adherence and patient satisfaction were good/excellent. Conclusion: Web-based cognitive intervention programs are a new approach to rehabilitation and patient education. The evidence, although scarce, shows that web-based interventions are feasible and support subjective cognitive functioning. However, the literature to date is extremely limited and the quality of the studies is weak. More research with high-quality study designs is needed. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=257315, identifier: CRD42021257315.

Subjective vs informant-reported cognitive complaints have differential clinical significance in covert cerebral small vessel disease.

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.

Neuroimaging standards for research into small vessel disease-advances since 2013.

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.

Educational history is an independent predictor of cognitive deficits and long-term survival in postacute patients with mild to moderate ischemic stroke.

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.

White matter lesion progression in LADIS: frequency, clinical effects, and sample size calculations.

BACKGROUND AND PURPOSE: White matter lesion (WML) progression has been advocated as a surrogate marker in intervention trials on cerebral small vessel disease. We assessed the rate of visually rated WML progression, studied correlations between lesion progression and cognition, and estimated sample sizes for clinical trials with pure WML progression vs combined WML progression-cognitive outcomes. METHODS: Those 394 participants of the Leukoaraiosis and Disability Study (LADIS) study with magnetic resonance imaging scanning at baseline and 3-year follow-up were analyzed. WML progression rating relied on the modified Rotterdam Progression Scale. The Vascular Dementia Assessment Scale global score and a composite score of specific executive function tests assessed longitudinal change in cognition. Sample size calculations were based on the assumption that treatment reduces WML progression by 1 grade on the Rotterdam Progression Scale. RESULTS: WML progression related to deterioration in cognitive functioning. This relationship was less pronounced in subjects with early confluent and confluent lesions. Consequently, studies in which the outcome is cognitive change resulting from treatment effects on lesion progression will need between 1809 subjects per treatment arm when using executive tests and up to 18 853 subjects when using the Vascular Dementia Assessment Scale score. Studies having WML progression as the sole outcome will need only 58 or 70 individuals per treatment arm. CONCLUSIONS: WML progression is an interesting outcome for proof-of-concept studies in cerebral small vessel disease. If cognitive outcome measures are added to protocols, then sample size estimates increase substantially. Our data support the use of an executive test battery rather than the Vascular Dementia Assessment Scale as the primary cognitive outcome measure.

Post-stroke delirium in relation to dementia and long-term mortality.

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.

Status of Clinical Neuropsychology Training in Finland.

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 km2), 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.