Vascular Cognitive Decline and Dementia (ENIGMA)

Exploring Vascular Contributions to Cognitive Decline and Dementia

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.

Study Overview

• Status: Recruiting
• Conditions: Ischemic Stroke; Transient Ischemic Attack
• Intervention / Treatment: Other: No intervention

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 Type: Observational
• Enrollment (Estimated): 140

Contacts and Locations

• Study Contact: Name: Janne Kaergaard Mortensen, PhD; Phone Number: +4521156903; Email: janne.k.mortensen@clin.au.dk
• Study Contact Backup: Name: Sigrid Vestergaard, MD; Phone Number: +4521456903; Email: sigrso@rm.dk

Study Locations

• Denmark
  • Aarhus, Denmark, 8000
    • Recruiting
    • Aarhus University Hospital
    • Contact: Janne Kaergaard Mortensen, PhD; Phone Number: +4521156903; Email: janne.k.mortensen@clin.au.dk
    • Contact: Sigrid Vestergaard, MD; Phone Number: +4521456903; Email: sigrso@rm.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients aged ≥ 60 years admitted with AIS or TIA to the comprehensive stroke center at Aarhus University Hospital within 24 hours of symptom onset.

Description

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 Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-stroke cognitive decline	Change in RBANS index score from three to 12 months follow-up	12 months
Post-stroke cognitive impairment	Total RBANS index score	12 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Aarhus University Hospital
• Collaborators: University of Aarhus
• Investigators: Principal Investigator: Janne Kaergaard Mortensen, PhD, Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: February 6, 2024
• First Submitted That Met QC Criteria: February 6, 2024
• First Posted (Actual): February 14, 2024

Study Record Updates

• Last Update Posted (Actual): February 14, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: MRI; Stroke; Dementia; Cognitive impairment; Extracellular vesicles
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Brain Ischemia; Cognition Disorders; Stroke; Ischemic Stroke; Ischemia; Ischemic Attack, Transient; Dementia; Cognitive Dysfunction
• Other Study ID Numbers: 1-10-72-253-20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All investigators will have access to the entire dataset. Trial metadata, including, but not limited to codebooks, data dictionaries and analysis code will be shared on a repository under a permissive license. Upon completing a collaboration agreement, individual patient trial data may be shared upon reasonable request. Patient data will not be made publicly available.
• IPD Sharing Time Frame: Not decided
• IPD Sharing Access Criteria: Upon completing a collaboration agreement, individual patient trial data may be shared upon reasonable request. Patient data will not be made publicly available.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No