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. Therefore, 50 patients with acute IS in the supratentorial brain region will be recruited to the study 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 are 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 are 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 will be done analogously to subproject 4. Blood sampling is performed from each participant at each visit, and these samples will be used for measurements that are essentially the same as in subproject 4. Also, a small amount of blood will be 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 will measure 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, see subproject 4; controls will also be handled as in B4. 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 will be 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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