Cerebral small vessel disease is a common cause of cognitive impairment. Remote ischemic pre-conditioning (RIC) is a technique to induce brief periods of limb ischemia-reperfusion that is hypothesized to increase tolerance of the brain to hypoperfusion and increase cerebral blood flow. Patients with cognitive impairment, preserved basic activities of daily living, and brain computed tomography (CT) or magnetic resonance imaging (MRI) evidence of confluent white matter hyperintensities or multiple brain infarcts will be randomized to either RIC performed once a day on one arm, or twice per day on one arm, for 30 days, to test tolerability and effects on MRI markers of blood flow.

Cerebral small vessel disease (cSVD) accounts for 20-25% of all strokes and is the most common cause of vascular cognitive impairment (VCI) as well as a major contributor to mixed dementia, potentially interacting with Alzheimer's disease. Remote ischemic pre-conditioning (RIC) is a technique to induce brief periods of limb ischemia-reperfusion that is hypothesized to increase tolerance of the brain to hypoperfusion. This is a prospective, open-label randomized controlled clinical trial with blinded endpoint assessment (PROBE). Participants that complete a 14-day run-in period will be randomized to 30 days of either: a) RIC performed once per day on one arm, or b) RIC performed twice per day on one arm. Each RIC session will consist of 4 cycles of unilateral upper arm ischemia for 5 minutes followed by reperfusion for another 5 minutes, administered by modified blood pressure monitor (under an Investigational Trail Authorization from Health Canada). The primary outcome is tolerability, defined as the proportion in each trial arm that complete 80% or more of the assigned RIC sessions. Secondary outcomes will include pain scores, cognition, and MRI markers of cerebral blood flow and white matter integrity.

Inclusion Criteria:

• Evidence of cerebral small vessel disease on CT or MRI, defined as either beginning confluent white matter hypodensities/hyperintensities (ARWMC scale) or two or more supratentorial infarcts
• Montreal Cognitive Assessment <25
• Concern on the part of the patient, caregiver, or clinician that there has been a decline from previous level of cognitive functioning
• Independent with basic activities of daily living (response (a) to questions 2, 4, 5, 6, 7, 8, 9, and 14 on the Bristol Activities of Daily Living scale).

Exclusion Criteria:

• Cortical infarcts larger than 10 mm axial diameter
• Neuroimaging evidence of mass lesion, intracerebral hemorrhage, vascular malformation, or evidence of non-vascular disease such as hydrocephalus.
• Residence in long-term care facility.
• Other significant neurological or psychiatric disease (e.g. multiple sclerosis).
• Does not have a study partner who can provide corroborative information.
• English or French is not sufficiently proficient for clinical assessment and neuropsychological testing
• Montreal Cognitive Assessment score <13
• Unable to undergo MRI due to medical contraindications or inability to tolerate the procedure.
• Co-morbid medical illness that in the judgment of the study investigator makes it unlikely that the participant will be able to complete three months of study follow-up.
• On therapeutic anticoagulation with doses used for treatment of deep venous thrombosis, pulmonary embolism, or for stroke prevention in atrial fibrillation.
• Significant bleeding diathesis.
• Any symptomatic or previously known arm soft-tissue disease, vascular injury, or peripheral vascular disease
• Hypertension with systolic blood pressure >=180 mmHg despite medical treatment at the time of enrolment.
• Planned revascularization (any angioplasty or vascular surgery) within the next 3 months.
• Planned surgical procedure within the next 3 months.
• Currently receiving an investigational drug or device by other studies
• Blood pressure cuff cannot be sized properly (arm circumference is <23 cm or >42 cm)

The completely de-identified study dataset will be posted to the University of Calgary section of the PRISM dataverse at the time of publication of the main study results in a peer-reviewed journal.

The study dataset will be made publicly available at the time of publication of the main study results in a peer-reviewed journal.

Open to the public.

Outcomes will be assessed masked to treatment assignment. Participants will be aware of treatment assignment.