Phosphodiesterase 5 (PDE5) is an enzyme that affects cell signaling. Inhibiting PDE5 can relax muscles and increase blood flow to specific areas of the body, which is why PDE5 inhibitors such as tadalafil (Cialis™), sildenafil (Viagra™), and vardenafil (Levitra™) are primarily used to treat erectile dysfunction in men. In observational studies, sildenafil is associated with reduced risk for cardiovascular disease and dementia. Small clinical trials suggest PDE5 inhibitors may modestly improve blood flow to the brain, but there is no clear evidence that they improve cognitive function. People who use nitrate drugs should not take PDE5 inhibitors due to safety concerns.
Small clinical trials have examined acute effects of PDE5 inhibitors on cognitive function and/or cerebral blood flow. An observational study examined the relationship between sildenafil use and dementia risk. Our search identified:
An analysis of insurance claims in the United States found that individuals who had used sildenafil, based on their prescription history, had a lower incidence rate of Alzheimer’s disease, relative to individuals with the same chronic conditions that were not prescribed sildenafil [1]. Because sildenafil is primarily prescribed for erectile dysfunction, the majority of individuals in this analysis were men. Women prescribed sildenafil for pulmonary hypertension, high blood pressure in lung blood vessels, also showed a modestly lower risk for Alzheimer’s disease. Cardiovascular dysfunction can reduce blood flow to the brain, and is a risk factor for dementia. Since the conditions for which sildenafil is prescribed are associated with cardiovascular dysfunction, and the sildenafil use has also been associated with reducing adverse cardiovascular events in this population [2], the impact on dementia risk may be due to its effects on the cardiovascular system.
The brain requires increased blood flow to meet its energy demands while engaging in cognitively stimulating activity. By boosting the capacity for activity-dependent blood flow to the brain, PDE5 inhibitors could potentially improve performance on cognitively demanding tasks [3]. Thus far, minor benefits have only been seen in individuals with low baseline performance, and PDE5 inhibitors do not appear to act as cognitive enhancers in cognitively healthy adults.
While improvements to cognitive function relative to baseline were seen with PDE5 inhibitor use in men in two trials that lacked a control group, no changes in cognitive functions were observed in three small randomized controlled trials examining acute effects of PDE5 inhibitors in healthy adults [4; 5; 6; 7; 8].
The ability of brain blood flow to increase in response to heightened cognitive activity is impaired in dementia patients. Small studies have found that PDE5 inhibitors can modestly increase cerebral blood flow at rest in patients with cognitive impairment, but did not adequately address whether treatment can restore the brain activity-dependent blood flow and cognitive function [9; 10; 11; 12].
PDE5 inhibitors are well-tolerated in most people and side effects are generally mild, including headache, flushing, back pain, diarrhea, and gastric symptoms [13; 14; 15]. Rare side effects include vision changes or sudden vision loss, particularly in people with heart disease or diabetes. PDE5 inhibitors can also cause prolonged or painful erections, which can cause permanent damage unless treated.
PDE5 inhibitors can interact with some medications and should not be used if you are taking a nitrate drug for chest pain or heart problems, as this can lead to a sudden and serious decrease in blood pressure. Other potentially dangerous interactions are discussed at Drugs.com.
NOTE: This is not a comprehensive safety evaluation or complete list of potentially harmful drug interactions. It is important to discuss safety issues with your physician before taking any new supplement or medication.
In the US, tadalafil (Cialis™), sildenafil (Viagra™), vardenafil (Levitra™), and avanafil (Stendra™) are on the market to treat erectile dysfunction, while sildenafil (Revatio™) and tadalafil (Adcirca™) are indicated for the treatment of pulmonary hypertension. None of these drugs are approved for treating cognitive decline or dementia. PDE5 inhibitors should not be used if you take nitrate medications, due to the risk of severe and possibly fatal drop in blood pressure.
The Patient Education Center by Harvard Health Publications provides an online comparison of different PDE5 inhibitors here.
Check for drug-drug and drug-supplement interactions on Drugs.com.