Observational Study on Determinants of Dementia After Stroke

Study Overview
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Brief Summary
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The primary aim of the DEDEMAS (Determinants of Dementia After Stroke) study is to identify predictors of post stroke dementia (PSD). A particular focus will be on biological markers (neuroimaging, biochemical markers derived from blood) and on interactions between vascular and neurodegenerative mechanisms. For this purpose patients with an acute stroke and without prior dementia will be followed for 10 years. Note: Starting from 01.01.2014 this study is expanded to a multi-centric design funded by the German Center for Neurodegenerative Diseases (The DZNE - Mechanisms of Dementia After Stroke (DEMDAS) Study). This includes the following study sites: DZNE/München - Institute for Stroke and Dementia Research, Klinikum der Universität München (Coordinator); DZNE/Berlin - Neuroscience Research Center - Campus Mitte Charité; DZNE/Bonn - Klinik und Poliklinik für Neurologie, Universitätsklinikum Bonn; DZNE/Göttingen - University Medical Center Göttingen; DZNE/Magdeburg - Universitätsklinikum Magdeburg.

Detailed Description
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Risk of dementia is high after stroke but the mechanisms of post stroke dementia (PSD) are insufficiently understood. Specifically, there are few data on how vascular and neurodegenerative mechanisms interact in determining cognitive decline after stroke. The primary aim of the DEDEMAS/DEMDAS (Determinants of Dementia After Stroke) study is to identify predictors of PSD. A particular focus will be on biological markers (neuroimaging, biochemical markers derived from blood) and on interactions between vascular and neurodegenerative mechanisms. Patients with an acute stroke and without prior dementia will be followed for 5 years with assessments at baseline (< 72 h after onset of stroke), and at 3, 6, 12, 24, 36, 48, and 60 months. In addition, DEDEMAS patients will have an annual telephone follow-up from year 6 to 10. Baseline assessments will include variables previously demonstrated to be associated with PSD as well as novel variables. Brain MRI (structural MRI and resting state fMRI) in combination with detailed neuropsychological testing and blood draws will be done at 6, 12, 36, and 60 months. Patients developing cognitive impairment (with or without dementia) and a subgroup of matched individuals without cognitive decline will be examined by brain FDG-PET and Amyloid-PET scanning. Lumbar puncture will be done on patients who develop cognitive impairment and thus have a clinical indication for the procedure. Efforts will be made to classify demented patients into diagnostic categories (Vascular Dementia, Mixed Dementia, Alzheimer's disease, other categories). Predictive factors for PSD will be identified using multiple Cox-proportional hazards models. Apart from providing insights into the mechanisms of PSD this study holds the potential to identify novel diagnostic markers and novel targets for preventive therapies.

Official Title
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Determinants of Dementia After Stroke

Conditions
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Ischemic Stroke, Hemorrhagic Stroke

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Language: German Acute stroke that occurred within the last 5 days as defined by: acute focal neurological deficit in combination with one of the following: An acute ischemic infarct as documented by either a DWI positive lesion on MR imaging or a new lesion on a delayed CT scan An intracerebral hemorrhage as documented on CT or MRI An informant of the patient is available Written informed consent by patient prior to study participation Willingness to participate in follow-up Exclusion Criteria: IQCODE > 64 or diagnosis of dementia Patients transferred from an outside stroke unit (to avoid possible selection bias) Patients presenting a stroke going back more than 120 hours Patients presenting one of the following diseases: cerebral venous thrombosis, traumatic cerebral haemorrhage, intracerebral haemorrhage because of a known or image-guided assumed vascular malformation, pure meningeal or intraventricular haemorrhage Patients presenting a malignant disease with life expectancy < 3years Contraindication for MRI Participation in an intervention/AMG-study at baseline

Ages Eligible for Study
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Minimum Age: 18 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Acute Stroke<br>Patients over 18 years and without pre-stroke dementia, displaying an ischemic or hemorrhagic stroke, onset within the last 72 hours, language German | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| dementia occurrence | this evaluation will be based on a neurological and general clinical examination, and on the evaluation of activities of daily life using the instrumental activities daily life scale after an interview with the patient and his/her family | 5 years in DEMDAS | 
| dementia occurrence | this evaluation will be based on a neurological and general clinical examination, and on the evaluation of activities of daily life using the instrumental activities daily life scale after an interview with the patient and his/her family | 10 years in DEDEMAS | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| dementia occurrence | this evaluation will be based on a neurological and general clinical examination, and on the evaluation of activities of daily life using the instrumental activities daily life scale after an interview with the patient and his/her family | 6 months | 
| dementia occurrence | this evaluation will be based on a neurological and general clinical examination, and on the evaluation of activities of daily life using the instrumental activities daily life scale after an interview with the patient and his/her family | 12 months | 
| dementia occurrence | this evaluation will be based on a neurological and general clinical examination, and on the evaluation of activities of daily life using the instrumental activities daily life scale after an interview with the patient and his/her family | 36 months | 
| cognitive impairment | Impairment of some tests of cognitive battery without significant impairment in activities of daily living | 6 months | 
| cognitive impairment | Impairment of some tests of cognitive battery without significant impairment in activities of daily living | 12 months | 
| cognitive impairment | Impairment of some tests of cognitive battery without significant impairment in activities of daily living | 36 months | 
| cognitive impairment | Impairment of some tests of cognitive battery without significant impairment in activities of daily living | 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stroke, Dementia, Dementia, Vascular, Alzheimer's Disease, Intracranial Hemorrhage, Brain Ischemia