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.

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.

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

Ischaemic stroke patients will have been admitted to the Acute Neurology Units of the Austin Hospital (Heidelberg), Royal Melbourne Hospital (Parkville), and Box Hill Hospital (Box Hill).