Vascular Cognitive Decline and Dementia

Recruiting

• Conditions: Ischemic Stroke; Transient Ischemic Attack

• Registration Number: NCT06257823
• Lead Sponsor: Aarhus University Hospital

Brief Summary

The ENIGMA study is a single-centre prospective clinical observational study with the aim to investigate vascular contributions to cognitive decline and dementia. By studying MRI-defined capillary dysfunction and EV profiles, the ENIGMA study links novel imaging and basic research techniques to a clinical cohort of stroke patients. With this study we hope to enhance the understanding of the mechanisms behind post-stroke cognitive decline and dementia.

Detailed Description

Post-stroke cognitive impairment (PSCI) is common. However, the underlying pathophysiology remains largely unknown. Understanding how microvascular changes relate to PSCI and finding markers that can predict PSCI, could be a first step towards better screening and management.

Cerebral capillary dysfunction is characterized by limited oxygen extraction from the brain capillaries due to age- and risk factor-related capillary flow heterogeneity. Capillary dysfunction is a pathophysiological feature of cerebral small vessel disease (cSVD) and may play an important role in the vascular mechanisms underlying PSCI. Extracellular vesicles (EVs) carry molecules between cells. EV profiles may change during acute stroke, in the chronic stroke phase, and according to the level of cSVD, and EV profiles may therefore act as disease biomarkers.

The ENIGMA study aims to investigate capillary dysfunction and EV profiles as predictors of cognitive function one year after acute ischemic stroke (AIS) and transient ischemic attack (TIA). Consecutive patients with AIS and TIA are included and followed for one year with follow-up visits at three and 12 months. An MRI is performed at 24 hours and 12 months after admission. EV profiles will be characterised from blood samples drawn at 24 hours and three months after admission. Cognitive function is assessed three and 12 months after AIS and TIA using the Repeatable Battery for the Assessment of Neuropsychological Status and the Montreal Cognitive Assessment (MoCA).

The study has two main objectives: 1) to study associations between capillary dysfunction and PSCI and 2) to assess associations between EV profiles and PSCI.

Study Timeline

• Study Start: 2021-04-01
• Status Verified: 2024-02
• Study First Submitted: 2024-02-06
• Study First Submitted QC: 2024-02-06
• Last Update Submitted: 2024-02-06
• Study First Posted: 2024-02-14
• Last Update Posted: 2024-02-14
• Primary Completion: 2025-06-01
• Study Completion: 2025-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 140

Inclusion Criteria

• AIS or TIA with a clinically relevant diffusion restriction identified on MRI DWI-sequence on admission
• Admittance within 24 hours from symptom onset
• Age ≥ 60

Exclusion Criteria

• Dependency in activities of daily living (mRS score > 2)
• Known dementia, neurodegenerative disease, or other significant brain disease
• Concomitant life-threatening disease
• Contraindications to undergo MRI
• Allergy or intolerance to MRI contrast agents
• eGFR < 30
• Unable to give written informed consent
• Deemed unfit for follow-up

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Post-stroke cognitive impairment	12 months	Total RBANS index score
Post-stroke cognitive decline	12 months	Change in RBANS index score from three to 12 months follow-up

Secondary Outcome Measures

Name	Time	Method
Physical activity	12 months	Measured on the Physical Activity Scale for the Elderley
Post-stroke cognitive decline	12 months	Change in MoCA score from three to 12 months follow-up
Post-stroke depression	12 months	Measured on the major depression inventory
Post-stroke cognitive impairment	12 months	MoCA score at 12 months follow-up

Trial Locations

Locations (1)

Aarhus University Hospital; 🇩🇰 Aarhus, Denmark