Austrian Polyintervention Study to Prevent Cognitive Decline After Ischemic Stroke

Study Overview
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Brief Summary
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Aim of this randomized controlled study is to test if intensive polyintervention therapy including life style modifications targeting at reduction of modifiable risk factors of stroke can reduce the risk of post-stroke cognitive decline compared to a group of patients receiving standard care.

Detailed Description
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Stroke is the second most frequent cause of death and cognitive deficits including dementia occur frequently following a stroke. The frequency of cognitive disturbances has been reported up to 30% and thus occurs three times more frequent than recurrent stroke (10%). Major attempts have been made to prevent the occurrence of new strokes by means of effective strategies including preventive drugs. In contrast, hardly any studies have been performed addressing the prevention of deteriorating cognitive function following a stroke. In spite of this high prevalence therapeutic possibilities are extremely limited. It must be expected that cognitive deficits become even a more frequent disability following stroke. This is caused by the increased aging of the population leading to further increase of incidence, furthermore that more people survive their acute stroke due to increased possibilities of acute treatment, and that frequent risk factors (e.g. hypertension, diabetes) are increasingly controlled, thus leading to less severe strokes with less severe and permanent motor deficits, but an increase of potentially disabling cognitive disturbances. The aim of this randomized controlled study is to test an intensive multiple intervention therapy for the first time in stroke and to add life style modifications targeting modifiable risk factors for cognitive deterioration. It is hypothesized that the risk of post-stroke cognitive decline can be significantly reduced compared to a control group with standard care when using polyintervention. These interventions will focus on nutrition, exercise, cognitive and social activity and monitoring and management of metabolic and vascular risk factors. Regular contacts with the subjects shall increase motivation and adherence to the study protocol.

Official Title
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ASPIS-Austrian Polyintervention Study to Prevent Cognitive Decline After Ischemic Stroke

Conditions
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Ischemic Stroke, Cognitive Decline, Dementia

Intervention / Treatment
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* Behavioral: Motivation and lifestyle intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptomatic ischemic stroke with clinical syndrome of stroke and a corresponding ischemic lesion. MRI or CT results compatible with clinical diagnosis of acute ischemic stroke NIH Stroke Scale Score on admission 1 to 14, both inclusive Modified Rankin Scale before stroke 0 to 2, inclusive Randomization within 3 months after stroke onset (goal: 80% within 3 weeks) Sufficient communication possible Informed consent given by the patient and/or the patient's legally acceptable representative Exclusion Criteria: Substantial cognitive decline (Mini Mental State Examination (MMSE) score > 24) or pre-existing dementia or Parkinson disease Persistent disturbed level of consciousness Persistent aphasia Pre-existing significant psychiatric diseases (i.e. Schizophrenia, Major Depression, Bipolar Disorders, all according to DSMIV); Patients with minor Depression (DSM IV) can be included Severe sensory impairment making neuropsychological testing impossible Severe comorbidity (e.g. unstable or severe cardiovascular or pulmonal disease, neoplasm, severe liver or renal insufficiency and symptomatic stenosis of the ipsilateral carotid artery, cancer…) Unreliability for follow up Unwillingness or inability to participate or to sign the informed consent

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Motivation and lifestyle intervention<br>Intensive control and motivation for better compliance with medication, regular blood pressure measurements, diet changes and physical activity. | Behavioral: Motivation and lifestyle intervention<br>* Intensive control and motivation for better compliance with medication, regular blood pressure measurements, diet changes and physical activity.<br>|
| No Intervention: Control<br>Standard stroke care | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of persons having cognitively declined at 24 months | Cognitive decline is defined as a significant decline in the composite scores of at least 2 of 5 neuropsychologically tested domains (speed of mental processing, executive functions, working memory, memory, spatial constructive functions). The alpha level for the decision is 0.05. | 24 months after randomization | 
| Cognitive decline measured on the Cognitive Subscale of the Alzheimer's disease assessment scale (ADAS-cog) at 24 months | Difference between the measures at baseline and at 24 months on the Cognitive Subscale of the Alzheimer's disease assessment scale (ADAS-cog). | 24 months after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of persons having cognitively declined 12 months after randomization | Cognitive decline is defined as a significant decline in the composite scores of at least 2 of 5 neuropsychologically tested domains (speed of mental processing, executive functions, working memory, memory, spatial constructive functions). The alpha level for the decision is 0.05. | 12 months after randomization | 
| Cognitive decline on the Cognitive Subscale of the Alzheimer's disease assessment scale (ADAS-cog) at 12 months | Difference between the measures at baseline and at 12 months on the Cognitive Subscale of the Alzheimer's disease assessment scale (ADAS-cog). | 12 months after randomization | 
| Cognitive impairment on the Mini-Mental-State-Examination (MMSE) scale at 12 months |  | 12 months after randomization | 
| Cognitive impairment on the Mini-Mental-State-Examination (MMSE) scale at 24 months |  | 24 months after randomization | 
| Change in cognitive abilities measured by composite scores for each of 5 cognitive domains | For each of the five cognitive domains (executive functions, working memory, general memory, speed of cognitive processing, visual spatial ability) standardized composite scores are calculated from the differences between baseline and 12 months in individual neuropsychological test results. | 12 months after randomization | 
| Composite outcome for vascular events | vascular events include recurrent stroke, ACS, bypass surgery, PTA and vascular death | 24 months after randomization | 
| Neurological status on the National Institute of Health Stroke Scale (NIHSS) score |  | 12 months after randomization | 
| Functional status on the modified Rankin Scale |  | 12 months after randomization | 
| Activities of daily living on Barthel Index |  | 12 months after randomization | 
| Quality of life on the EQ-5D |  | 12 months after randomization | 
| Depression on the Center for Epidemiologic Studies Depression Scale (CESD) |  | 12 months after randomization | 
| All cause mortality |  | 24 months after randomization | 
| Change in cognitive abilities measured by composite scores for each of 5 cognitive domains | For each of the five cognitive domains (executive functions, working memory, general memory, speed of cognitive processing, visual spatial ability) standardized composite scores are calculated from the differences between baseline and 24 months in individual neuropsychological test results. | 24 months after randomization | 
| Neurological status on the National Institute of Health Stroke Scale (NIHSS)score |  | 24 months after randomization | 
| Functional status on the modified Rankin Scale |  | 24 months after randomization | 
| Activities of daily living on Barthel Index |  | 24 months after randomization | 
| Quality of life on the EQ-5D |  | 24 months after randomization | 
| Depression on the Center for Epidemiologic Studies Depression Scale (CESD) |  | 24 months after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prevention, cognitive decline, post-stroke dementia, life-style intervention, vascular risk factors, polyintervention, multifactorial treatment