Vascular cognitive impairment underlies a vast burden of dementing disease worldwide. Vascular dementia is the second most-prevalent cause of dementia, after Alzheimer disease. Increasingly, it is clear that vascular brain pathology interacts with Alzheimer disease, to worsen Alzheimer pathology and speed cognitive decline. The main cause of VaD in older people is cerebral small vessel disease. This affects the small arteries that carry blood to deep brain regions. Small vessel disease makes artery walls become thick and stiff, which prevents them from responding to the brain's changing needs for blood. The result is chronic damage to deep brain structures, due to insufficient blood supply. There is currently no therapy for small vessel disease -- which is unfortunate, as the disease progresses over 20 or more years of later life, allowing abundant opportunities for intervention.Drugs that inhibit the enzyme PDE5 cause dilation of blood vessels. The best known is sildenafil (sold as Viagra®) used to treat erectile dysfunction. In this study we will ask whether tadalafil (currently marketed as Cialis®) causes dilation of blood vessels in brain tissue, allowing heightened blood supply to the deep brain areas susceptible to small vessel disease and VaD. These drugs are safe and well-tolerated. The drugs' selectivity is good, and molecular mechanisms of action are well-understood. Our study will confirm whether this is a sensible approach for use in human brain blood vessels. This clinical test-of-concept is required, prior to progress into a clinical trial of efficacy.