After correcting for multiple comparisons, genetically proxied PDE5 inhibition, per one SD lower in diastolic blood pressure, was associated with higher odds of Alzheimer’s disease (OR 1.09, 95% CI 1.07–1.11) and Lewy body dementia (OR 1.32, 95% CI 1.23–1.41), but a trend towards lower odds of vascular dementia across all instruments. Here, PDE5A is linked to early-onset autosomal dominant Alzheimer disease.