Cognitive impairment occurs frequently after stroke and has a high impact on patients’ quality of life. Different cognitive trajectories with impairment in specific cognitive domains may occur after stroke. However, evidence on risk factors for different poststroke cognitive trajectories remains limited. In my group, we seek to gain more insights into predictors of different poststroke cognitive trajectories.

We have a special focus on:

• Clinical studies on post-stroke dementia and cognitive trajectories
• Clinical studies on mechanisms of myocardial injury after stroke and its association with poststroke cognitive impairment

At the DZNE study site Berlin I am coordinating the DZNE - Mechanisms of Dementia After Stroke (DEMDAS) Study and the Association of High Troponin levels and Cognitive Impairment: Results from the Berlin Aging Study II (BASE-II). Furthermore, I am coordinating the PRAISE and DELCODE study (DZNE – Longitudinal Cognitive Impairment and Dementia Study) as well as a study focusing on the development of novel compounds for prevention of chemotherapy induced neurotoxicity. More information on these studies and the substudies coordinated in Berlin can be found below.

For more information on the Endres group please visit our Homepage.

At the DZNE study side Berlin I coordinate the following projects:

Project 1:

The DZNE - Mechanisms of Dementia After Stroke (DEMDAS) Study

This study is coordinated by Prof. Martin Dichgans and Berlin was one of the active recruiting sites of this multicenter cohort study. I have contributed as Co-PI and together with colleagues from Berlin we coordinate several substudies. The scientific questions of these substudies include: Role of pathogeneic autoantibodies in dementia after stroke; role of high-sensitivity cardiac troponin for prediction of post-stroke dementia, cognitive decline and progression of cerebral small vessel disease (also see Project 2).

In first subprojects, we were able to analyze the association between high-sensitivity cardiac troponin, anti-NMDA receptor antibodies and cognitive outcome twelve months after stroke. We were able to show that high-sensitivity cardiac troponin is specifically associated with poorer executive function and attention (i. e. cognitive domains that are typically affected by vascular cognitive impairment). On the other hand, anti-NMDA receptor antibodies were specifically associated with poorer memory function. In future subprojects we will analyze whether high-sensitivity cardiac troponin and anti-NMDA receptor antibodies are also associated with long-term cognitive trajectories after stroke.

Publications:

Serum anti-NMDA receptor antibodies are linked to memory impairment 12 months after stroke.
Arlt FA, Sperber PS, von Rennenberg R, Gebert P, Teegen B, Georgakis MK, Fang R, Dewenter A, Görtler M, Petzold GC, Wunderlich S, Zerr I, Dichgans M, Prüss H, Endres M; DEMDAS Investigators.
Mol Psychiatry. 2024 Oct 30. doi: 10.1038/s41380-024-02744-w. Online ahead of print.
PMID: 39478168

KCNA2 IgG autoimmunity in neuropsychiatric diseases.
Arlt FA, Miske R, Machule ML, Broegger Christensen P, Mindorf S, Teegen B, Borowski K, Buthut M, Rößling R, Sánchez-Sendín E, van Hoof S, Cordero-Gómez C, Bünger I, Radbruch H, Kraft A, Ayzenberg I, Klausewitz J, Hansen N, Timäus C, Körtvelyessy P, Postert T, Baur-Seack K, Rost C, Brunkhorst R, Doppler K, Haigis N, Hamann G, Kunze A, Stützer A, Maschke M, Melzer N, Rosenow F, Siebenbrodt K, Stenør C, Dichgans M, Georgakis MK, Fang R, Petzold GC, Görtler M, Zerr I, Wunderlich S, Mihaljevic I, Turko P, Schmidt Ettrup M, Buchholz E, Foverskov Rasmussen H, Nasouti M, Talucci I, Maric HM, Heinemann SH, Endres M; DEMDAS study group; Komorowski L, Prüss H.
Brain Behav Immun. 2024 Mar;117:399-411. doi: 10.1016/j.bbi.2024.01.220. Epub 2024 Feb 2.
PMID: 38309639

High-Sensitivity Cardiac Troponin T and Cognitive Function Over 12 Months After Stroke-Results of the DEMDAS Study.
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 *.
J Am Heart Assoc. 2024 Mar 19;13(6):e033439. doi: 10.1161/JAHA.123.033439. Epub 2024 Mar 8.
PMID: 38456438

Project 2:

Association of High Troponin levels and Cognitive Impairment: Results from the Berlin Aging Study II (BASE-II).

Here, we test the hypothesis whether higher levels of cardiac troponin T levels are independently associated with cognitive impairment and are a risk factor for future dementia (Nolte and Endres, 2014). The Berlin Aging Study II (BASE-II) is a community-dwelling study of the greater metropolitan area of Berlin comprising 1,700 well-characterized residents aged older than 60 years.

Publications:

High-Sensitivity Cardiac Troponin T and Cognitive Decline in Older Adults: Results of the Berlin Aging Study II.
von Rennenberg R, Liman T, Nolte CH, Nave AH, Scheitz JF, Düzel S, Regitz-Zagrosek V, Gerstorf D, Steinhagen-Thiessen E, Demuth I, Endres M.
Gerontology. 2023;69(2):140-148. doi: 10.1159/000523845. Epub 2022 May 5.
PMID: 35512662

Project 3: The Prediction of Acute Coronary Syndrome in acute ischemic stroke (PRAISE) study - a multicenter, prospective observational study.

The overall objective of the study was to identify predictors of myocardial infarction in stroke patients. Patients with acute ischemic stroke and troponin elevation were enrolled in a prospective multicenter setting. In addition to our work in the BASE-II and DEMDAS studies, a goal of the PRAISE study is to better understand the relationship between elevated troponin levels and neurocognitive impairment in stroke patients. Study centers are spread across Germany and include neurological as well as cardiological centers. This study was the first to be conducted in a cooperation between the German Center for Cardiovascular Research (DZHK) and the German Center for Neurodegenerative Diseases (DZNE). The study was coordinated at the Center for Stroke Research Berlin (CSB) of the Charité - Universitätsmedizin Berlin.

The PRAISE study showed that elevations of high-sensitivity cardiac troponin above 5 times the upper reference limit are specifically associated with a type 1 myocardial infarction in acute ischemic stroke patients. Currently, we are planning a randomized controlled trial to assess whether an early invasive strategy including coronary angiography improves prognosis in acute ischemic stroke patients with a high likelihood of type 1 myocardial infarction.

Publications:

PRediction of acute coronary syndrome in acute ischemic StrokE (PRAISE) - protocol of a prospective, multicenter trial with central reading and predefined endpoints.
Nolte CH, von Rennenberg R, Litmeier S, Scheitz JF, Leistner DM, Blankenberg S, Dichgans M, Katus H, Petzold GC, Pieske B, Regitz-Zagrosek V, Wegscheider K, Zeiher AM, Landmesser U, Endres M.
BMC Neurol. 2020 Aug 27;20(1):318. doi: 10.1186/s12883-020-01903-0.
PMID: 32854663

Type 1 Myocardial Infarction in Patients With Acute Ischemic Stroke.
Nolte CH, von Rennenberg R, Litmeier S, Leistner DM, Szabo K, Baumann S, Mengel A, Michalski D, Siepmann T, Blankenberg S, Petzold GC, Dichgans M, Katus H, Pieske B, Regitz-Zagrosek V, Braemswig TB, Rangus I, Pepic A, Vettorazzi E, Zeiher AM, Scheitz JF, Wegscheider K, Landmesser U, Endres M.
JAMA Neurol. 2024 Jul 1;81(7):703-711. doi: 10.1001/jamaneurol.2024.1552.
PMID: 38829625

Project 4: DZNE Innovation to Application – Development of novel compounds for prevention of chemotherapy induced neurotoxicity

Neurological side effects are a frequent complication of tumor therapy. In addition to damage to the peripheral nervous system with symptoms such as numbness, paresthesia, pain or paralysis, many patients also suffer from memory impairment. Neurological side effects of tumor therapy frequently force a change in the treatment plan and often lead to a long-lasting reduction in quality of life. To date, treatment options have been limited to symptomatic treatment for pain, for example, but currently no effective preventive treatment options exist for neurological sequelae of tumor therapy. Based on our own preclinical work, in particular the current studies on chemotherapy-induced neurotoxicity (CICARO study, NCT02753036), immune checkpoint inhibitor-associated neurological side effects (TITAN2 study, DRKS00012668) or CAR-T cell therapy-associated side effects (COHERENCY study, DRKS00031604), we are developing preclinical models and novel treatment strategies for the prevention of tumor therapy-induced neurotoxicity.

Publications:

Chemotherapy-induced cognitive impairment and its long-term development in patients with breast cancer: results from the observational CICARO study.
Kerkmann A, Schinke C, Dordevic A, Kern J, Bangemann N, Finck J, Blohmer JU, Ruprecht K, Göpfert JC, Otto C, Materne B, Endres M, Boehmerle W, Huehnchen P.
Oncologist. 2024 Oct 15:oyae268. doi: 10.1093/oncolo/oyae268. Online ahead of print.
PMID: 39403794

Neurofilament proteins as a potential biomarker in chemotherapy-induced polyneuropathy.
Huehnchen P, Schinke C, Bangemann N, Dordevic AD, Kern J, Maierhof SK, Hew L, Nolte L, Körtvelyessy P, Göpfert JC, Ruprecht K, Somps CJ, Blohmer JU, Sehouli J, Endres M, Boehmerle W.
JCI Insight. 2022 Mar 22;7(6):e154395. doi: 10.1172/jci.insight.154395.
PMID: 35133982

Project 5: The DZNE – Longitudinal Cognitive Impairment and Dementia Study (DELCODE)

This project builds on the findings of the BASE-II and DEMDAS studies, namely that levels of high-sensitivity cardiac troponin are associated with domain-specific cognitive decline both in the general population and in stroke patients (see also projects 1 and 2). The primary aim of our research project is to assess the contribution of cardiac damage and dysfunction (measured by high-sensitivity cardiac troponin levels) to cognitive trajectories in subjective cognitive decline. To this end, we plan to perform cross-sectional and longitudinal analyses of the association between troponin and cognitive domain scores from the DELCODE study. In order to assess whether the link between cardiac biomarkers and cognitive is more pronounced in a certain stage of Alzheimer’s disease or whether this association is reproducible across different study populations, we plan to perform our analyses both in the total DELCODE study population as well as the individual DELCODE subpopulations (i. e. patients with subjective cognitive decline, patients with mild cognitive impairment, patients with Alzheimer’s disease and controls). In order to further elucidate the mechanisms underlying the link between cardiac disease and cognitive outcome, we plan to analyze the link between troponin and white matter hyperintensities volume on MRI. We hypothesize that troponin levels are linked to higher severity of cerebral small vessel disease as indicated by higher white matter hyperintensity volume.