Vascular Cognitive Decline and Dementia

Ischemic Stroke Clinical Trial

— ENIGMA  

Official title:

Exploring Vascular Contributions to Cognitive Decline and Dementia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06257823
• Other study ID #: 1-10-72-253-20
• Status: Recruiting
• Start date: April 1, 2021
• Est. completion date: June 1, 2025

Study information

• Verified date: February 2024
• Source: Aarhus University Hospital
• Contact: Janne Kaergaard Mortensen, PhD
• Phone: +4521156903
• Email: janne.k.mortensen[@]clin.au.dk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: June 1, 2025
• Est. primary completion date: June 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Dementia
• Ischemia
• Ischemic Attack, Transient
• Ischemic Stroke
• Transient Ischemic Attack

Intervention

Other:
• No intervention
No intervention

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital	Aarhus

Sponsors (2)

Lead Sponsor	Collaborator
Aarhus University Hospital	University of Aarhus

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Post-stroke cognitive decline	Change in RBANS index score from three to 12 months follow-up	12 months
Primary	Post-stroke cognitive impairment	Total RBANS index score	12 months
Secondary	Post-stroke cognitive decline	Change in MoCA score from three to 12 months follow-up	12 months
Secondary	Post-stroke cognitive impairment	MoCA score at 12 months follow-up	12 months
Secondary	Post-stroke depression	Measured on the major depression inventory	12 months
Secondary	Physical activity	Measured on the Physical Activity Scale for the Elderley	12 months