Broad therapeutic benefits in patients with probable vascular dementia or Alzheimer's disease with cerebrovascular disease after treatment with galantamine.
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Activities of Daily Living↗
Biomedical subjects
T Erkinjuntti
Publications and source records attributed to T Erkinjuntti.
CT and MRI rating of white matter lesions.
Rating scales play an important role in the evaluation of computed tomography (CT) or magnetic resonance-detected white matter lesions (WML). Unfortunately, this type of visual semiquantitative assessment is not yet an optimal tool because commonly agreed concepts regarding its use are lacking. To generate a discussion platform for further improvement of CT and MRI rating, we will provide some basic definitions, summarize the advantages and disadvantages of scoring schemes and review current efforts towards the improvement of this tool. Future research will have to concentrate on deepening our understanding of the histopathologic substrates of WML and on strategies to document their progression.
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Insomnia in ischemic stroke patients.
This is the first study that focuses on insomnia in stroke patients. A subgroup of 277 patients from a consecutive series of 486 stroke patients aged 55-85 years was subjected to a comprehensive psychiatric evaluation 3-4 months after ischemic stroke. Of 277 patients, 56.7% reported any insomnia complaint and 37.5% fulfilled the DSM-IV criteria of insomnia. In 38.6%, insomnia complaint/insomnia had already been present prior to the stroke and in 18.1%, it was a consequence of the stroke. Independent correlates of any insomnia complaint/insomnia were anxiety (Zung Anxiety Scale) and the use of psychotropic drug. Independent correlates of poststroke-onset insomnia complaint/insomnia were disability after stroke (Barthel Index), dementia, anxiety and use of psychotropic drug. Insomnia should be taken into consideration in treating and rehabilitating stroke patients.
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Cognitive functions and depression as predictors of poor outcome 15 months after stroke.
The prognostic predictors of poor outcome, as defined by death between 3 and 15 months and dependent living at 15 months, were examined in the Helsinki Stroke Aging Memory (SAM) study cohort. Death between 3 and 15 months was registered from the whole study group of 486 consecutive patients aged 55-85 years. Altogether 286 of the 486 patients went through a detailed follow-up examination both 3 and 15 months after stroke, including structured measures of emotion (Beck's Depression Inventory, BDI), cognition (Mini-Mental State Examination, MMSE), dementia assessment according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-III), and handicap (Rankin scale, RS). The only independent correlate of death between 3 and 15 months was dependent living at 3 months (OR 2.6, 95% CI 1.2-5.8), which also had the most powerful association with dependent living at 15 months (OR 5.8, 95% CI 2.6-13.1). Also, both worsening in cognition (change in MMSE, OR for each point of worsening 1.2, 95% CI 1.1-1.3) and worsening of depression (change in BDI, OR for each point of worsening 1.1, 95% CI 1.02-1.12), between 3 and 15 months follow-up, had an independent effect on dependent living 15 months after ischemic stroke. This challenges the care and rehabilitation of these items even at the stable period after stroke.
Activities of Daily Living↗
Rivastigmine in patients with Alzheimer's disease and concurrent hypertension.
Rivastigmine has demonstrated significant benefits in patients with mild to moderate Alzheimer's disease (AD). We aimed to confirm whether rivastigmine was effective in patients with or without concurrent vascular risk factors (VRF), as previously suggested. We chose to stratify the 725 patients involved in an international dose-ranging study according to the presence of arterial hypertension (a marker of VRF) at baseline. Efficacy in each subgroup was assessed using the ADAS-cog, a measure of cognitive performance, the Progressive Deterioration Scale (PDS) and the Clinician's Interview-Based Impression of Change (CIBIC) with caregiver input. Patients receiving rivastigmine 6-12 mg/day showed better outcomes on the ADAS-cog than those receiving placebo, in both the hypertensive and non-hypertensive subgroups. Hypertensive patients receiving rivastigmine 6-12 mg/day also showed improvement over those receiving 1-4 mg/day (p = 0.023). Rivastigmine 6-12 mg/day also provided better outcomes than placebo on the PDS in the hypertensive (p = 0.031) and non-hypertensive (p = 0.035) subgroups. All patients receiving rivastigmine 6-12 mg/day had superior CIBIC-plus scores than those receiving placebo. There was a trend for lower incidences of nausea and vomiting in rivastigmine-treated patients with hypertension than in those without hypertension. No cardiac adverse events or drug-drug interactions were reported. Our data support the hypothesis that rivastigmine provides benefits to patients with or without hypertension, and contribute to the evidence that particular benefits may be observed in those with vascular risk factors.
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Preserved stimulus deviance detection in Alzheimer's disease.
Aging attenuates automatic auditory discrimination to duration change, whereas frequency change detection is relatively unimpaired in aging and in Alzheimer's disease (AD). Here we studied with a whole-head magnetometer whether cortical auditory discrimination to duration change as shown by magnetic mismatch negativity (MMNm) response is impaired in AD. Twenty AD patients with mild to moderate cognitive impairment and 18 age-matched healthy subjects were monaurally presented a sequence of frequent standard tones embedded with occasional deviants with shorter duration. MMNm was significantly delayed in the left hemisphere ipsilaterally to the ear stimulated in the patient group, whereas the MMNm amplitudes over both hemispheres were quite similar in both groups. This suggests that although MMNm is delayed in the left hemisphere, the automatic discrimination to duration change in the auditory cortex is not attenuated in the early stages of AD.
Acoustic Stimulation↗
Magnetic resonance imaging correlates of depression after ischemic stroke.
BACKGROUND: Depression affects up to 40% of patients with ischemic stroke. The relationship between site and size of brain infarcts and poststroke depression is still not well characterized. Further possible contribution and interaction of white matter lesions and brain atrophy has not been studied previously. We conducted a magnetic resonance image-based study of the radiologic correlates of depression in a large, well-defined series of patients with ischemic stroke. METHODS: Modified DSM-III-R and DSM-IV criteria were used to diagnose depressive disorders during a comprehensive psychiatric evaluation in 275 of 486 consecutive patients aged 55 to 85 years 3 to 4 months after ischemic stroke. A standardized magnetic resonance imaging protocol detailed side, site, type, and extent of brain infarcts and extent of white matter lesions and brain atrophy. RESULTS: Depressive disorders were diagnosed in 109 patients (40%). Patients with depression had a higher number and larger volume of infarcts affecting the prefrontosubcortical circuits, especially the caudate, pallidum, and genu of internal capsule, with left-sided predominance. Extent of white matter lesions and atrophy did not differ in patients with and without depression. Independent correlates of poststroke depression in a logistic regression model were mean frequency of infarcts in the genu of internal capsule on the left side (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.0-10.1), mean frequency of infarcts in the pallidum of any side (OR, 1.6; 95% CI, 1.1-2.3), and mean volume of infarcts in the right occipital lobe (OR, 0.98; 95% CI, 0.96-0.99). CONCLUSION: Lesions affecting the prefrontosubcortical circuits, especially on the left side, are correlates of depression after ischemic stroke.
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Depression is an independent predictor of poor long-term functional outcome post-stroke.
The influence of depression on the long-term outcome of stroke patients was examined among 390 of 486 consecutive patients aged 55-85 years. They completed, at 3 months after ischaemic stroke, a detailed medical, neurological, and radiological stroke evaluation, structured measures of emotion (Beck's Depression Inventory, BDI), handicap (Rankin scale, RS), and assessment of activities of daily living (Barthel Index, BI). Further RS and BI was evaluated at 15-month follow-up from these 390 patients and BDI in 276 patients. A group of 256 patients completed, in addition to the 15-month follow-up, a comprehensive psychiatric evaluation, including the Present State Examination 3 months after stroke. The DSM-III-R criteria were used for diagnosis of the depressive disorders. BDI identified depression (cut-off point > or = 10 for depression) in 171 (43.9%) of 390 and in 123 (44.6%) of 276 patients at 3- and 15-month follow-up. DSM-III-R major depression was diagnosed in 66 (25.8%), and minor depression in 32 (12.5%), of 256 patients 3 months after stroke. Patients with BDI > or = 10, or major, but not minor, depression more often had poor functional outcome (RS > II and BI < 17) at 15 months. Poor functional outcome at 3 months also correlated with depression at 15 months. In logistic regression analysis, depression at 3 months (Beck > or = 10) correlated with poor functional outcome at 15 months (RS > II) (OR 2.5, 95% CI 1.6-3.8). More careful examination and treatment of depression in stroke patients is emphasized.
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Suicidal ideas in stroke patients 3 and 15 months after stroke.
Patients with stroke may have an increased risk of suicide. We sought to examine the frequency and clinical correlates of suicidal ideas 3 and 15 months after stroke. The study group comprised 286 of 486 consecutive patients aged 55-85 years who at 3 and 15 months after ischemic stroke completed a detailed medical, neurological and radiological stroke evaluation, structured measures of cognition (Mini Mental State Examination), emotion (Beck Depression Inventory, BDI), disability (Rankin scale), and assessment of dependent living. Suicidal ideas were present in 9.8% (n = 28) at 3 months' follow-up and in 14.0% (n = 40) at 15 months' follow-up. The patients with suicidal ideas were more depressed measured by BDI both at 3 (17.0 vs. 7.9, p < 0.001) and 15 months (20.5 vs. 8.5, p < 0.001) after stroke compared to the patients without suicidal ideas. Patients with suicidal ideas had more often a history of a stroke already before the index stroke (35 vs. 18.3%, p = 0.0154), right-sided stroke (60.0 vs. 41.9%, p = 0.0323), they were more disabled according to the Rankin scale (2.4 vs. 1.9; p = 0.0035) and more dependent in living (45.0 vs. 27.2%, p = 0.023) 15 months after stroke. An independent correlate of suicidal ideas 15 months after stroke was history of prior stroke (OR 2.4; 95% CI 1.14-4.97) in logistic regression analysis. The frequency of suicidal ideas increased with the time elapsed from stroke. Recurrent strokes, depressive symptoms, more disabling stroke and right-sided stroke correlated to suicidal ideas at 15 months after stroke. Early identification of these risk factors may lead to effective therapeutic intervention.
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A new rating scale for age-related white matter changes applicable to MRI and CT.
BACKGROUND AND PURPOSE: MRI is more sensitive than CT for detection of age-related white matter changes (ARWMC). Most rating scales estimate the degree and distribution of ARWMC either on CT or on MRI, and they differ in many aspects. This makes it difficult to compare CT and MRI studies. To be able to study the evolution and possible effect of drug treatment on ARWMC in large patient samples, it is necessary to have a rating scale constructed for both MRI and CT. We have developed and evaluated a new scale and studied ARWMC in a large number of patients examined with both MRI and CT. METHODS: Seventy-seven patients with ARWMC on either CT or MRI were recruited and a complementary examination (MRI or CT) performed. The patients came from 4 centers in Europe, and the scans were rated by 4 raters on 1 occasion with the new ARWMC rating scale. The interrater reliability was evaluated by using kappa statistics. The degree and distribution of ARWMC in CT and MRI scans were compared in different brain areas. RESULTS: Interrater reliability was good for MRI (kappa=0.67) and moderate for CT (kappa=0.48). MRI was superior in detection of small ARWMC, whereas larger lesions were detected equally well with both CT and MRI. In the parieto-occipital and infratentorial areas, MRI detected significantly more ARWMC than did CT. In the frontal area and basal ganglia, no differences between modalities were found. When a fluid-attenuated inversion recovery sequence was used, MRI detected significantly more lesions than CT in frontal and parieto-occipital areas. No differences were found in basal ganglia and infratentorial areas. CONCLUSIONS: We present a new ARWMC scale applicable to both CT and MRI that has almost equal sensitivity, except for certain regions. The interrater reliability was slightly better for MRI, as was the detectability of small lesions.
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Clinical deficits of Alzheimer's disease with cerebrovascular disease and probable VaD.
Vascular dementia (VaD) describes dementia arising from cerebrovascular disease (CVD) and ischaemic brain injury, and relates to a number of different vascular mechanisms and clinical manifestations. The characterisation of brain lesions by neuroimaging analysis, and the study of their relation to clinical deficits such as cognitive and functional decline, are critical to the concept and treatment of VaD, and form an important part of widely used diagnostic criteria for this dementia type. For instance, the extent to which pathological brain lesions cause, compound or coexist with cognitive impairment is a major determinant of other clinical deficits, their nature and the rate of disease progression. Through numerous neuroimaging and epidemiological studies, VaD is now seen to encompass a heterogeneous group of clinical syndromes such as multiple-infarct (cortical) dementia, small-vessel (subcortical) dementia and, less commonly, dementia associated with strategic infarcts. Due to a large number of similarities in clinical symptoms, pathophysiological mechanisms, associated risk factors and neurochemical deficits between VaD and Alzheimer's disease, patients with coexistent Alzheimer's disease and CVD ('mixed' dementia) represent another important, but previously underestimated subgroup. This article reviews the clinical symptoms and neuroimaging findings most commonly observed in patients with VaD. Increased familiarity with the clinical picture of VaD should offer more hope of defining realistic treatment aims for future pharmacotherapy.
Alzheimer Disease↗
[Depression after cerebrovascular disorders].
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Antidepressive Agents↗
MRI correlates of dementia after first clinical ischemic stroke.
BACKGROUND AND PURPOSE: Dementia after first clinical stroke frequently has been found, but the clinical and radiological correlates have not been fully detailed. We examined magnetic resonance imaging (MRI) correlates of dementia in a large well-defined series of patients with first clinical ischemic stroke. METHODS: Detailed medical, neurological and neuropsychological examination was conducted 3 months after ischemic stroke for 273 patients with first clinical stroke from a consecutive series of 486 patients aged 55-85 years. MRI of the head categorised infarcts (type, site, side, number, volume), extent of white matter lesions (WMLs) and degree of atrophy. The DSM-III definition for dementia was used. RESULTS: Dementia was diagnosed in 79 (28.9%) of the patients with first clinical stroke. Volumes, numbers, distinct sites of infarcts, extent of WMLs and degree of atrophy were different for the demented and nondemented subjects. Logistic regression analysis showed that the correlates of dementia included the combination of infarct features (volume of infarcts in left-sided anterior corona radiata; OR 1.86), extent of WMLs (OR 1. 37), medial temporal lobe atrophy (OR 3.4) and host factors (low education; OR 1.11). The additive effect of having more than one correlate was detected (OR 2.53). CONCLUSIONS: Dementia occurring after first clinical stroke is frequent and not solely due to a single stroke, but contain a combination of infarcts features, extent of WMLs, medial temporal lobe atrophy and host factors reflecting more than one underlying pathology.
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Efficacy and safety of nimodipine in subcortical vascular dementia: a subgroup analysis of the Scandinavian Multi-Infarct Dementia Trial.
In Western countries, vascular dementia (VaD) is the most common form of cognitive deterioration after Alzheimer's disease. Therapeutic trials in VaD have so far failed to yield satisfactory results. One explanation of this failure may be the etiological and clinical heterogeneity of the included patients. Patients with subcortical VaD, defined on a clinical and radiological basis, may constitute a more homogeneous group. Thus, we conducted a post-hoc subgroup analysis of the Scandinavian Multi-Infarct Dementia Trial that evaluated the efficacy and safety of oral nimodipine administered for 6 months in 259 patients. The original patients sample was divided on the basis of head CT in those with subcortical VaD (n=92, 45 nimodipine, 47 placebo) and those with multi-infarct dementia (n=167, 83 nimodipine, 84 placebo). While in the total trial population a treatment effect could not be proved, in this subgroup analysis, the subcortical VaD patients treated with nimodipine performed better on the majority of neuropsychological tests and functional scales in comparison with patients on placebo. No trend could be evidenced in the multi-infarct dementia patients. Treatment efficacy was in particular suggested for the Zahlen-Verbindungs-Test, Fuld-Object-Memory Evaluation, Word Fluency, and for the Instrumental Activities of Daily Living scale. The results did not reach statistical significance in this small sample. Our study preliminarily indicates that nimodipine could be effective in patients with small vessel subcortical VaD and supports the rationale for a further controlled and adequately powered trial to test nimodipine in patients with subcortical VaD.
Activities of Daily Living↗
The Scandinavian Multi-Infarct Dementia Trial: a double-blind, placebo-controlled trial on nimodipine in multi-infarct dementia.
Vascular dementia is a major cause of mental and physical disability in Western countries. Treatment of vascular dementia is currently based on the recognition and control of vascular risk factors, while specific drugs have not been approved yet. The aim of the present multinational, double-blind, placebo-controlled study was to evaluate the safety and efficacy of nimodipine administered for as long as 26 weeks in improving cognition or slowing cognitive deterioration in patients defined as having multi-infarct dementia (DSM-III-R criteria). Two hundred and fifty-nine patients were included (128 nimodipine, 131 placebo), and 251 were available for the intention-to-treat analysis. No significant difference between drug-treated and placebo patients was noted on the Gottfries-Brâne-Steen scale score (primary efficacy criterion), the remaining neuropsychological tests (Zahlen-Verbindungs-Test, Fuld-Object-Memory Evaluation, Word Fluency Test, Digit Span, Mini-Mental State Examination), and the functional scales (index of Activity of Daily Living, Instrumental Activity of Daily Living, Rapid Disability Scale, Clinical Dementia Rating), although the majority of changes were in favor of the active drug group. A lower incidence of cerebrovascular and cardiac events was observed in the nimodipine-treated patients in comparison with the placebo group. This study failed to show a significant effect of nimodipine on cognitive, social or global assessments in patients defined as affected by multi-infarct dementia according to the DSM-III-R criteria. A post-hoc analysis (presented in an accompanying paper) suggests that nimodipine may have a favorable effect in the subgroup of patients defined as affected by subcortical (small vessel) vascular dementia.
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How complex interactions of ischemic brain infarcts, white matter lesions, and atrophy relate to poststroke dementia.
BACKGROUND: Cerebrovascular disease is a major factor related to cognitive impairment. However, behavioral correlates of ischemic brain lesions are insufficiently characterized. OBJECTIVE: To examine magnetic resonance imaging correlates of dementia in a large, well-defined series of patients with ischemic stroke. METHODS: Detailed medical, neurological, and neuropsychological examinations were conducted 3 months after ischemic stroke for 337 of 486 consecutive patients aged 55 to 85 years. Infarcts (type, site, side, number, and volume), extent of white matter lesions (WMLs), and degree of atrophy were categorized according to magnetic resonance images of the head. The definition for dementia of the Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III) was used. RESULTS: Dementia was diagnosed in 107 (31.8%) of the patients and stroke-related dementia in 87 (25.8%). Volumes, numbers, distinct sites of infarcts, extent of WMLs, and degree of atrophy were different for the demented and nondemented subjects. Particularly, volumes of infarcts in any (right- or left-sided) superior middle cerebral artery territory (27.3 vs 13.7 cm(3), P =. 002) and left thalamocortical connection (14.8 vs 4.0 cm(3), P =. 002) differentiated the 2 groups. Logistic regression analysis showed that the correlates of any dementia included the combination of infarct features (volume of infarcts in any superior middle cerebral artery: odds ratio [OR], 1.11; frequency of left-sided infarcts: OR, 1.21), extent of WMLs (OR, 1.3), medial temporal lobe atrophy (OR, 2.1), and host factors (education; OR, 0.91). In the patients with stroke-related dementia, the main correlate was volume of infarcts in the left anterior corona radiata (OR, 1.68). CONCLUSION: Correlates of poststroke dementia do not include merely 1 feature but a combination of infarct features, extent of WMLs, medial temporal lobe atrophy, and host features.
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Research criteria for subcortical vascular dementia in clinical trials.
Vascular dementia (VaD) incorporate different vascular mechanisms and changes in the brain, and have different causes and clinical manifestations. Variation in defining the cognitive syndrome, in vascular etiologies, and allowable brain changes in current clinical definitions of VaD have resulted in variable estimates of prevalence, of groups of subjects, and of the types and distribution of putative causal brain lesions. Thus current criteria for VaD select an etiologically and clinically heterogeneous group. This definitional heterogeneity may have been a factor in "negative" clinical trials. An alternative for clinical drug trials is to focus on a more homogeneous group, such as those with subcortical (ischemic) VaD. This designation incorporates two small vessel clinical entities "Binswanger's disease" and "the lacunar state". It comprises small vessel disease as the primary vascular etiology, lacunar infarct(s) and ischaemic white matter lesions as the primary type of brain lesions, and subcortical location as the primary location of lesions. The subcortical clinical syndrome is the primary clinical manifestation, a definition which still requires additional empirical data. We expect that subcortical VaD show a more predictable clinical picture, natural history, outcome, and treatment responses. We propose a modification of the NINDS-AIREN criteria as a new research criteria for subcortical VaD.
Clinical Trials as Topic↗
Hippocampal and temporal lobe atrophy and age-related decline in memory.
OBJECTIVES: To evaluate the relationship of memory decline that accompanies aging with structural changes in the medial temporal lobe, in healthy middle-aged and older subjects. MATERIAL AND METHODS: A sample of 35 neurologically non-diseased subjects, between 55 and 70 years of age, were examined in a 5-year follow-up study. Neuropsychological investigation included tests of learning, verbal memory, and visual memory. MRI was performed with a superconducting MRI system operating at 1.0 T, using coronal slices of T1-weighted images. Medial temporal lobe atrophy was rated separately in the neocortical, entorhinal and hippocampal regions. RESULTS: We did not find any statistically significant relationship between mild hippocampal or temporal atrophy and memory test performance. Nor did the longitudinal decline in memory show a relationship with temporal lobe atrophy. CONCLUSIONS: The main outcome of our study was that age-related memory decline was not related to mild temporal lobe atrophy in healthy subjects without mild cognitive impairment. There could be other factors influencing memory functions besides age-related structural changes in temporal lobes.
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