Hely Kalska

Longitudinal Cognitive Decline in Subcortical Ischemic Vascular Disease - The LADIS Study

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.

Cognitive profile of subcortical ischaemic vascular disease

Objectives: Subcortical ischaemic vascular disease (SIVD) is a subtype of vascular cognitive impairment characterised by extensive white matter lesions and multiple lacunar infarcts. Radiologically defined diagnostic criteria for SIVD have been introduced, but only a few studies have presented empirical data on its clinical and cognitive features. The aim of this study is to describe in detail the neuropsychological characteristics of patients with SIVD from a large well defined stroke cohort. Methods: A sample of 323 consecutive patients with ischaemic stroke, aged 55–85 years, was investigated using neuropsychological examination and magnetic resonance imaging (MRI). Patients fulfilling the MRI criteria of SIVD (n = 85) were compared to the other stroke patients (n = 238) and to normal control subjects (n = 38). Results: Cognitive performance of the SIVD group was inferior to that of the normal control group throughout all domains. As compared to the other stroke patients, the SIVD group performed significantly worse in tests measuring executive functions and delayed memory recall. Adjusting for depression had no effect on these results. Instead, after controlling for medial temporal lobe atrophy, the differences disappeared for delayed memory but remained significant for executive functions. Conclusion: Executive deficits are the most prominent cognitive characteristic associated with SIVD. Patients with SIVD also exhibit subtle deficits in delayed memory, which is explained in part by medial temporal lobe atrophy. Cognitive and mood changes seem to be parallel but independent processes related to SIVD. The results support the concept of SIVD as a separate clinical entity.

White matter hyperintensities as a predictor of neuropsychological deficits post-stroke

Objectives: Cerebral white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) are a recognised risk factor for post-stroke dementia. Their specific relations to cognitive impairment are still not well known. The purpose of this study was to explore how the severity and location of WMHs predict neuropsychological test performance in the context of other brain lesions in elderly stroke patients. Methods: In the Helsinki Stroke Aging Memory Study, 323 patients, aged from 55 to 85 years, completed a detailed neuropsychological test battery and MRI 3 months after an ischaemic stroke. The demographic and MRI predictors of cognition were studied with sequential linear regression analyses. Results: After age, education and total infarct volume were controlled for, the overall degree of WMHs predicted poor performance in tests of mental speed, executive functions, memory, and visuospatial functions, but not in those of short term memory storage or verbal conceptualisation. However, the contribution of separate white matter regions was relatively low. Only the lesions along the bodies of lateral ventricles were independently associated with speed and executive measures. Additionally, general cortical atrophy clearly predicted a wide range of cognitive deficits while infarct volume had less relevance. Further analyses revealed that executive functions act as a strong mediator between the relationship of WMHs to memory and visuospatial functions. Conclusions: The degree of WMHs is independently related to post-stroke cognitive decline. The most affected cognitive domains seem to be executive functions and speed of mental processing, which may lead to secondary deficits of memory and visuospatial functions.

MRI-Defined Subcortical Ischemic Vascular Disease: Baseline Clinical and Neuropsychological Findings

Background: Subcortical ischemic vascular disease (SIVD) is a common, but often overlooked cause of vascular cognitive impairment. Diagnostic research criteria for SIVD are based on magnetic resonance imaging (MRI) findings including substantial white matter lesions (WML) and multiple lacunar infarcts. Empirical studies validating these imaging criteria are still few. The purpose of the study was to describe the clinical and cognitive characteristics of the MRI-defined SIVD in a mixed sample of functionally independent elderly subjects with WML. Methods: The subjects of the Leukoaraiosis and Disability (LADIS) study, aged 65–84 years, underwent comprehensive clinical and neuropsychological examinations, and brain MRI at the baseline assessment. The subjects meeting the SIVD imaging criteria (n = 89) were compared to the other subjects of the sample (n = 524). Results: SIVD was associated with lower education, hypertension and, independently, with obesity. The subjects with SIVD had more often motor impairment, a history of falls, and subtle impairment in activities of daily living, but they did not differ for depressive symptoms. SIVD subjects performed significantly inferiorly in tests of global cognitive function, psychomotor speed, attention and executive functions, verbal fluency, and working memory. Conclusion: In this population of nondisabled older adults with WML, SIVD was related to specific clinical and functional characteristics. Neuropsychological features included psychomotor slowing as well as deficits in attention and executive functions.

MRI correlates of executive dysfunction in patients with ischaemic stroke

Executive dysfunction (ED) may lead to problem behaviour and impaired activities of daily living in many neuropsychiatric disorders, but the neuroanatomical correlates of ED are still not well known. Different aspects of executive functions were studied by widely used neuropsychological tests in 214 elderly patients 3 months after ischaemic stroke, and a sum score of eight different measures was counted in each patient. The number and site of brain infarcts as well as severity and location of white matter lesions (WMLs) and brain atrophy on magnetic resonance imaging were recorded and compared between patients with and without ED. ED was present in 73 (34.1%) of the 214 patients. The mean frequency of brain infarcts in the brain and in the left hemisphere was higher in the patients with ED. Lesions affecting the frontal‐subcortical circuits (e.g. pallidum, corona radiata or centrum semiovale) were more frequent in patients with ED than in those without. Also, patients with pontine brain infarcts frequently had ED, but this may have been due to more extensive ischaemic changes in these patients in general. Mean number of brain infarcts affecting the pons and posterior centrum semiovale on the left side, moderate to severe medial temporal atrophy, the Fazekas white matter score, the Mini‐Mental State Examination score and low education were independent correlates of ED. Brain infarcts and WML affecting the frontal‐subcortical circuits or the pons may increase risk for ED in stroke patients.

Corpus callosum atrophy is associated with mental slowing and executive deficits in subjects with age-related white matter hyperintensities: the LADIS Study

Background: Previous research has indicated that corpus callosum atrophy is associated with global cognitive decline in neurodegenerative diseases, but few studies have investigated specific cognitive functions. Objective: To investigate the role of regional corpus callosum atrophy in mental speed, attention and executive functions in subjects with age-related white matter hyperintensities (WMH). Methods: In the Leukoaraiosis and Disability Study, 567 subjects with age-related WMH were examined with a detailed neuropsychological assessment and quantitative magnetic resonance imaging. The relationships of the total corpus callosum area and its subregions with cognitive performance were analysed using multiple linear regression, controlling for volume of WMH and other confounding factors. Results: Atrophy of the total corpus callosum area was associated with poor performance in tests assessing speed of mental processing—namely, trail making A and Stroop test parts I and II. Anterior, but not posterior, corpus callosum atrophy was associated with deficits of attention and executive functions as reflected by the symbol digit modalities and digit cancellation tests, as well as by the subtraction scores in the trail making and Stroop tests. Furthermore, semantic verbal fluency was related to the total corpus callosum area and the isthmus subregion. Conclusions: Corpus callosum atrophy seems to contribute to cognitive decline independently of age, education, coexisting WMH and stroke. Anterior corpus callosum atrophy is related to the frontal-lobe-mediated executive functions and attention, whereas overall corpus callosum atrophy is associated with the slowing of processing speed.

Depression-executive dysfunction syndrome in stroke patients.

OBJECTIVE It has been suggested that executive dysfunction could be the core defect in patients with geriatric or vascular depression, and that this depression-dysexecutive syndrome (DES) might be related to frontal-subcortical circuit dysfunction. The authors tested this hypothesis in 158 poststroke patients, of whom 21 had both depression and executive dysfunction. METHODS In this cross-sectional cohort study, a neurological, psychiatric, and neuropsychological examination was carried out 3 months after ischemic stroke, and brain infarcts, white-matter changes, and brain atrophy were recorded by MRI. RESULTS The 21 patients with DES had significantly more brain infarcts affecting their frontal-subcortical circuit structures than the 137 patients without DES, or the 41 patients with depression but without executive dysfunction. Patients with DES also had more severe depressive symptoms and worse psychosocial functioning, and they coped less well in complex activities of daily living. CONCLUSIONS DES is a valid concept and may define a subgroup of poststroke patients with frontal-subcortical pathology and with distinct prognosis and treatment options.

Cognitive function during early abstinence from opioid dependence: a comparison to age, gender, and verbal intelligence matched controls

BackgroundIndividuals with opioid dependence have cognitive deficits during abuse period in attention, working memory, episodic memory, and executive function. After protracted abstinence consistent cognitive deficit has been found only in executive function. However, few studies have explored cognitive function during first weeks of abstinence. The purpose of this study was to study cognitive function of individuals with opioid dependence during early abstinence. It was hypothesized that cognitive deficits are pronounced immediately after peak withdrawal symptoms have passed and then partially recover.MethodsFifteen patients with opioid dependence and fifteen controls matched for, age, gender, and verbal intelligence were tested with a cognitive test battery When patients performed worse than controls correlations between cognitive performance and days of withdrawal, duration of opioid abuse, duration of any substance abuse, or opioid withdrawal symptom inventory score (Short Opiate Withdrawal Scale) were analyzed.ResultsEarly abstinent opioid dependent patients performed statistically significantly worse than controls in tests measuring complex working memory, executive function, and fluid intelligence. Their complex working memory and fluid intelligence performances correlated statistically significantly with days of withdrawal.ConclusionThe results indicate a rather general neurocognitive deficit in higher order cognition. It is suggested that cognitive deficit during early abstinence from opioid dependence is related to withdrawal induced neural dysregulation in the prefrontal cortex and is partly transient.

Short cognitive behavioral therapy and cognitive training for adults with ADHD – a randomized controlled pilot study

In clinical practice, a growing need exists for effective non-pharmacological treatments of adult attention-deficit/hyperactivity disorder (ADHD). Here, we present the results of a pilot study of 10 adults with ADHD participating in short-term individual cognitive- behavioral therapy (CBT), 9 adults participating in cognitive training (CT), and 10 controls. Self-report questionnaires, independent evaluations, and computerized neurocognitive testing were collected before and after the treatments to evaluate change. There were distinctive pre-hypotheses regarding the treatments, and therefore the statistical comparisons were conducted in pairs: CBT vs control, CT vs control, and CBT vs CT. In a combined ADHD symptom score based on self-reports, 6 participants in CBT, 2 in CT and 2 controls improved. Using independent evaluations, improvement was found in 7 of the CBT participants, 2 of CT participants and 3 controls. There was no treatment-related improvement in cognitive performance. Thus, in the CBT group, some encouraging improvement was seen, although not as clearly as in previous research with longer interventions. In the CT group, there was improvement in the trained tasks but no generalization of the improvement to the tasks of the neurocognitive testing, the self- report questionnaires, or the independent evaluations. These preliminary results warrant further studies with more participants and with more elaborate cognitive testing.

The relationship between psychotic-like symptoms and neurocognitive performance in a general adolescent psychiatric sample

INTRODUCTION The current criteria for detecting a Clinical High-Risk (CHR) state for psychosis do not address cognitive impairment. A first step for identifying cognitive markers of psychosis risk would be to determine which aspects of neurocognitive performance are related with more severe psychotic-like symptoms. This study assessed cognitive impairment associated with prodromal symptoms in adolescents receiving public psychiatric treatment. METHODS 189 adolescents were recruited from consecutive new patients aged 15-18 attending mainly outpatient adolescent psychiatric units in Helsinki. They had been screened for prodromal symptoms using the Prodromal Questionnaire, and all screen-positives as well as a random sample of screen-negatives were interviewed using the Structured Interview for Prodromal Symptoms (SIPS) and underwent testing using a large, standardized neurocognitive test battery. The sample included 62 adolescents who met the CHR criteria (CHR) and 112 who did not (non-CHR). A healthy control sample (n=72) was also included to provide age- and gender-matched norms. RESULTS The CHR group performed worse on visuospatial tasks than the non-CHR group. Among CHR adolescents, negative symptoms were associated with slower processing speed and poorer performance on verbal tasks. Among non-CHR adolescents, positive symptoms were associated with poorer performance on visuospatial tasks, and negative symptoms with poorer performance on verbal tasks. CONCLUSION Clinical high-risk status is associated with impaired visuospatial task performance. However, both positive, psychotic-like symptoms and negative symptoms are associated with lower levels of neurocognitive functioning among adolescents in psychiatric treatment regardless of whether CHR criteria are met. Thus, even mild positive and negative symptoms may have clinical relevance in adolescents in psychiatric care. Adolescents with both psychotic-like symptoms and neurocognitive deficits constitute a group requiring special attention.