Clinical trial NCT06257823: Vascular Cognitive Decline and Dementia
Official title: Exploring Vascular Contributions to Cognitive Decline and Dementia
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Ischemic Stroke
Transient Ischemic Attack
Keywords: Dementia
Cognitive impairment
MRI
Extracellular vesicles
Stroke
Lead sponsor: Aarhus University Hospital
Sponsor class: OTHER
Collaborators: name: University of Aarhus
First posted: 2024-02-14
Enrollment: 140
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Post-stroke cognitive decline
timeFrame: 12 months
measure: Post-stroke cognitive impairment
timeFrame: 12 months
Secondary outcomes:
measure: Post-stroke cognitive decline
timeFrame: 12 months
measure: Post-stroke cognitive impairment
timeFrame: 12 months
measure: Post-stroke depression
timeFrame: 12 months
measure: Physical activity
timeFrame: 12 months
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
Study officials:
affiliation: Aarhus University Hospital
name: Janne Kaergaard Mortensen, PhD
role: PRINCIPAL_INVESTIGATOR
References: