SP5 - SASKit

Clinical study of senescence-related and other biomarkers in ischemic stroke patients compared to age- and sex-matched controls

We study the relationship between biomarkers of senescence and the clinical course of mental and physical health after ischemic stroke (IS). This study is based on the evidence indicating that senescence-related mechanisms such as hyperactivation of CDK5 in the central nervous system are associated with neuronal apoptosis and death following IS. Other cell-cycle regulators and components of the senescence associated secretory phenotype (SASP), specifically PAI-1, are implicated as well. To stratify for key protein biomarkers predictive for outcome after IS, we have surveyed studies on biomarkers that predict long-term outcome (≥ 3 months) and that are measured over the first days following the event (Fuellen et al. 2022). We classified the protein biomarkers as immune inflammatory, coagulation-related, and adhesion-related biomarkers, and identified four key biomarkers (TNF alpha, IL6, fibrinogen, and PAI-1) which will be analyzed in the present study. Therefore, 50 patients with acute IS in the supratentorial brain region were recruited to the study with a follow-up over up to 4 years, and data will be compared to that of 50 age- and sex-matched control subjects.
Inclusion criteria for the patients were adult age, diagnosis of acute IS in the supratentorial brain region with onset within the last 5-10 days, with a definite brain infarction volume of >10 mL, and the ability to provide informed consent. Exclusion criteria were the same as in subproject 4. Given that neither PDAC nor stroke cases are particularly gender-biased, and there are many more cases of stroke than PDAC, we expect to recruit both groups of patients in such a way that the age/gender distribution is very similar. Baseline data were done analogously to subproject 4. Data analysis for the two clinical subprojects (4 und 5) together is foreseen in Summer/Fall 2023, as specified in the published study protocol (Henze et al, 2020). Blood sampling is performed from each participant at each visit, and these samples are used for measurements that are essentially the same as in subproject 4. Also, a small amount of blood is drawn and frozen for future on-demand analyses. The general and stroke-specific clinical assessments of study participants include exploration of disease history, clinical investigation and scoring of physical/neurological impairment by a study physician. Scores that the physician measures are the following: mRS, ECOG, CSHA-CFS and NIHSS. Scores that the study nurse will obtain are MOCA, EQ-5D-5L, HADS-D, and WHODAS 2.0.
In patients the clinical assessments and blood sampling are performed at baseline and after 3, 12, 24 36 and 48 months, with essentially the same measurements as in PDAC patients. The tests include the course of neurological and cognitive impairment. Since an important predictor of aging-related quality of life is cognitive functioning, the patients and controls who are identified with cognitive decline during the follow-up visits are further studied applying a more extended neuropsychological assessment to discriminate Alzheimer dementia from vascular dementia. In the same way as subproject 4, we assist the computational groups with biomarker assessment and interpretation.

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