Clinical trial NCT01334749: Observational Study on Determinants of Dementia After Stroke
Official title: Determinants of Dementia After Stroke
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Ischemic Stroke
Hemorrhagic Stroke
Keywords: Stroke
Dementia
Dementia, Vascular
Alzheimer's Disease
Intracranial Hemorrhage
Brain Ischemia
Lead sponsor: Ludwig-Maximilians - University of Munich
Sponsor class: OTHER
First posted: 2011-04-13
Enrollment: 736
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients admitted to a specialized stroke service because of an acute stroke.

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: dementia occurrence
timeFrame: 5 years in DEMDAS
measure: dementia occurrence
timeFrame: 10 years in DEDEMAS
Secondary outcomes:
measure: dementia occurrence
timeFrame: 6 months
measure: dementia occurrence
timeFrame: 12 months
measure: dementia occurrence
timeFrame: 36 months
measure: cognitive impairment
timeFrame: 6 months
measure: cognitive impairment
timeFrame: 12 months
measure: cognitive impairment
timeFrame: 36 months
measure: cognitive impairment
timeFrame: 60 months
Other outcomes:
Locations:
city: Munich
country: Germany
facility: DZNE/Munich-Interdisciplinary Stroke Center Munich, Klinikum der Universität München, Campus Großhadern
state: Bavaria
city: Berlin
country: Germany
facility: DZNE/Berlin - Neuroscience Research Center - Campus Mitte Charité
city: Bonn
country: Germany
facility: DZNE/Bonn - Klinik und Poliklinik für Neurologie, Universitätsklinikum Bonn
city: Göttingen
country: Germany
facility: DZNE/Göttingen - University Medical Center Göttingen
city: Magdeburg
country: Germany
facility: DZNE/Magdeburg - Universitätsklinikum Magdeburg
Study officials:
affiliation: Institute for Stroke and Dementia Research, Klinikum der Universität München
name: Martin Dichgans, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wollenweber FA, Zietemann V, Rominger A, Opherk C, Bayer-Karpinska A, Gschwendtner A, Coloma Andrews L, Burger K, Duering M, Dichgans M. The Determinants of Dementia After Stroke (DEDEMAS) Study: protocol and pilot data. Int J Stroke. 2014 Apr;9(3):387-92. doi: 10.1111/ijs.12092. Epub 2013 Jul 9.
citation: Wollenweber FA, Darr S, Muller C, Duering M, Buerger K, Zietemann V, Malik R, Brendel M, Ertl-Wagner B, Bartenstein P, Rominger A, Dichgans M. Prevalence of Amyloid Positron Emission Tomographic Positivity in Poststroke Mild Cognitive Impairment. Stroke. 2016 Oct;47(10):2645-8. doi: 10.1161/STROKEAHA.116.013778. Epub 2016 Aug 18.
citation: Zietemann V, Kopczak A, Muller C, Wollenweber FA, Dichgans M. Validation of the Telephone Interview of Cognitive Status and Telephone Montreal Cognitive Assessment Against Detailed Cognitive Testing and Clinical Diagnosis of Mild Cognitive Impairment After Stroke. Stroke. 2017 Nov;48(11):2952-2957. doi: 10.1161/STROKEAHA.117.017519. Epub 2017 Oct 17.
citation: von Rennenberg R, Nolte CH, Liman TG, Hellwig S, Riegler C, Scheitz JF, Georgakis MK, Fang R, Bode FJ, Petzold GC, Hermann P, Zerr I, Goertler M, Bernkopf K, Wunderlich S, Dichgans M, Endres M; DEMDAS investigators *. High-Sensitivity Cardiac Troponin T and Cognitive Function Over 12 Months After Stroke-Results of the DEMDAS Study. J Am Heart Assoc. 2024 Mar 19;13(6):e033439. doi: 10.1161/JAHA.123.033439. Epub 2024 Mar 8.
citation: Georgakis MK, Fang R, During M, Wollenweber FA, Bode FJ, Stosser S, Kindlein C, Hermann P, Liman TG, Nolte CH, Kerti L, Ikenberg B, Bernkopf K, Poppert H, Glanz W, Perosa V, Janowitz D, Wagner M, Neumann K, Speck O, Dobisch L, Duzel E, Gesierich B, Dewenter A, Spottke A, Waegemann K, Gortler M, Wunderlich S, Endres M, Zerr I, Petzold G, Dichgans M; DEMDAS Investigators. Cerebral small vessel disease burden and cognitive and functional outcomes after stroke: A multicenter prospective cohort study. Alzheimers Dement. 2023 Apr;19(4):1152-1163. doi: 10.1002/alz.12744. Epub 2022 Jul 25.
citation: Duering M, Adam R, Wollenweber FA, Bayer-Karpinska A, Baykara E, Cubillos-Pinilla LY, Gesierich B, Araque Caballero MA, Stoecklein S, Ewers M, Pasternak O, Dichgans M. Within-lesion heterogeneity of subcortical DWI lesion evolution, and stroke outcome: A voxel-based analysis. J Cereb Blood Flow Metab. 2020 Jul;40(7):1482-1491. doi: 10.1177/0271678X19865916. Epub 2019 Jul 25.