Coach Pilot Study: Assessing Cognitive Function and Related Small Vessel Disease Markers After Intracerebral Hemorrhage

Dementia is a major contributor of dependence and disability in the ageing population and is mainly caused by neurodegenerative and cerebrovascular disease. Vascular cognitive impairment (VCI) occurs in at least 10% of patients who recover from an intracerebral hemorrhage (ICH) and has a major impact on post ICH recovery. In the acute phase of ICH, cognitive impairment may be caused directly by the hemorrhage damaging the brain parenchyma. In the chronic phase, however, further cognitive decline is also prevalent.

Cognitive decline after ICH might be caused by the underlying etiology of the ICH. The most frequent underlying small vessel diseases (SVD) that cause ICH are cerebral amyloid angiopathy (CAA) and hypertensive arteriopathy (HA). CAA and HA have their own radiological signatures of SVD markers which allow for in vivo tracking of disease progression using MRI. Although the initial clinical presentation these two types of SVD differs - CAA classically presents with a lobar ICH, whereas HA causes deep ICH - both groups of patients are at risk of developing dementia. However, it has recently been shown that patients with lobar ICH develop new onset dementia twice as often as patients with deep ICH. Whether underlying CAA pathology causes this increase, remains unclear. In addition, whether ICH accelerates the process of vascular damage and if cognitive decline can be predicted by certain disease markers is uncertain. Understanding the underlying mechanisms for cognitive decline after ICH helps to improve knowledge of prognosis and clinical management of patients who are recovering from ICH. The overall aim is to study cognitive decline in patients who recover from ICH and the relation with SVD markers. The results will be used to design a larger cohort study.

The study population are patients with ICH that have no family history of hereditary forms of ICH such as hereditary CAA (HCHWA-D) and no cognitive impairment before the ICH. Patients will be aged ≥ 55y, since the radiological Boston criteria for CAA-related ICH only include patients ≥ 55y. At baseline, the premorbid functional status will be assessed with the modified Rankin Scale (mRS) and Barthell index. A 3Tesla MRI will be performed to assess the most likely underlying cause of the ICH (patients with either CAA or HA-related ICH will be included). Stroke severity will be assessed with the National Institutes of Health Stroke Scale (NIHSS) and a neurologic exam will be performed. Participants will undergo an extensive interview on life-style, vascular risk factors and medication, and will undergo a blood withdrawal. Neuropsychological testing will be performed and questionnaires will be used for screening for depression, anxiety and psychopathology. In addition, participants will be asked to undergo a lumbar puncture to collect cerebrospinal fluid (CSF). After three months, neurological examination, and neuropsychological testing will be repeated. After six and 12 months, the neurological examination, the 3 Tesla MRI and neuropsychological testing will be repeated. Additionally, participants will be asked for a lumbar puncture at these two time points. The main parameters are cognitive decline (according to the neuropsychological assessment) at 12 months. Secondary outcomes are burden of SVD markers on MRI and CSF markers at baseline, at six months and 12 months.