Cognition And Neocortical Volume After Stroke

Completed

• Conditions: Alzheimer's Disease; Ischaemic Stroke; Vascular Dementia

• Registration Number: NCT02205424
• Lead Sponsor: The Florey Institute of Neuroscience and Mental Health

Brief Summary

Stroke and dementia are two of the most common and disabling conditions worldwide, responsible for an enormous and growing burden of disease. There is increasing awareness that the two conditions are linked, with cognitive impairment and dementia common after stroke, vascular dementia accounting for about one-fifth of all dementia cases and recent evidence on the contribution of vascular risk factors to Alzheimer's disease. Yet little is known about whether brain volume loss - a hallmark of dementia - occurs after stroke, and whether such atrophy is related to cognitive decline. The aim of this research is to establish whether stroke patients have reductions in brain volume in the first three years post-stroke compared to control subjects, and whether regional and global brain volume change is associated with post-stroke dementia in order to elucidate potential causal mechanisms (including genetic markers, amyloid deposition and vascular risk factors). The hypotheses are that stroke patients will exhibit greater brain volume loss than comparable cohorts of stroke-free controls, and further, that stroke patients who develop dementia will exhibit greater global and regional brain volume loss than those who do not dement. An understanding of whether stroke is neurodegenerative, and in which patients, may be used to help guide the early delivery of disease-modifying therapies.

Detailed Description

Our primary outcome measure was total brain volume (TBV) change between the 3-month and 3-year time-points compared between stroke patients and controls.

Secondary outcome 1 was TBV change between 3-months and 3-years comparing CN and CI stroke participants. TBV at 3-months will be adjusted for CCI scores, and years of education; the latter as it is correlated with cognitive performance and post-stroke dementia risk, but not for stroke lesion volume as no conclusive evidence for an effect has been demonstrated previously.

Secondary outcome 2 was hippocampal volume (HV) change between 3-months and 3-years in stroke patients and controls with adjustments identical to primary outcome.

Secondary outcome 3 was the comparison of HV change between 3-months and 3-years comparing CN and CI stroke participants with adjustments identical to secondary outcome 1.

See published protocol and uploaded statistical analysis plan for detailed description.

Study Timeline

• Study Start: 2011-05-01
• Study First Submitted: 2014-03-20
• Study First Submitted QC: 2014-07-30
• Study First Posted: 2014-07-31
• Primary Completion: 2020-12-31
• Study Completion: 2021-06-30
• Status Verified: 2022-06
• Last Update Submitted: 2022-06-09
• Last Update Posted: 2022-06-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 175

Inclusion Criteria

1. Clinical stroke
2. Aged greater than 18 years;
3. Able to have cognitive testing and MRI scan; and
4. Able to give informed consent

Exclusion Criteria

1. Significant medical comorbidities precluding participation in cognitive testing, or making survival for three years unlikely;
2. Normal exclusion criteria for MRI; e.g., implanted metal, severe claustrophobia;
3. Pre-existing dementia
4. Pregnancy, as a precaution to prevent exposing them to multiple MRI scans in a 12-month period
5. People in existing dependent or unequal relationships with any member of the research team, to protect against coercion

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Difference in total brain volume between 3 month and 3 year time-points	Between 3 months and 3 years post-stroke	We will examine changes in brain volume between the 3 month and 3 year time-points in ischemic stroke patients and healthy age-matched control participants

Secondary Outcome Measures

Name	Time	Method
Comparison of hippocampal volume change between 3 month and 3 year time-points in those who were cognitively normal versus cognitively impaired at 3 months post-stroke.	Between 3 months and 3 years post-stroke	Secondary outcome 3 was the comparison of HV change between 3-months and 3-years comparing CN and CI stroke participants with adjustments identical to secondary outcome 1.
Comparison of total brain volume (TBV) change between 3 month and 3 year time-points in those who were cognitively normal (CN) versus cognitively impaired (CI) determined at the 3 months post-stroke time point.	Between 3 months and 3 years post-stroke	Secondary outcome 1 was TBV change between 3-months and 3-years comparing CN and CI stroke participants.
Difference in hippocampal volume between 3 month and 3 year time-points in stroke and control participants.	Between 3 months and 3 years post-stroke	Secondary outcome 2 was hippocampal volume (HV) change between 3-months and 3-years in stroke patients and controls with adjustments identical to primary outcome.

Trial Locations

Locations (3)

Austin Health; 🇦🇺 Heidelberg, Victoria, Australia

Melbourne Health; 🇦🇺 Parkville, Victoria, Australia

Eastern Health; 🇦🇺 Box Hill, Victoria, Australia