From the Guidelines
Methylene blue is not recommended for cognitive function as there is no evidence to support its use in this context, and other pharmaceuticals such as cholinesterase inhibitors and memantine have shown moderate-quality evidence for small improvements in cognition 1. The current evidence does not support the use of methylene blue for cognitive function, and instead, other medications have been studied for their potential cognitive benefits.
- Cholinesterase inhibitors, such as donepezil, rivastigmine, and galantamine, have been shown to have moderate-quality evidence for small improvements in cognition, although they are often complicated by adverse events 1.
- Memantine, an N-methyl d-aspartate receptor antagonist, has also been studied for its potential cognitive benefits, although more work is needed to define its safety and efficacy in patients with dementia after stroke 1. It is essential to prioritize the use of evidence-based treatments for cognitive function, and methylene blue is not currently supported by the literature as a treatment for this condition.
- Patients with cognitive impairment should consult with their healthcare provider to discuss the potential benefits and risks of available treatments, such as cholinesterase inhibitors and memantine, and to determine the best course of treatment for their individual needs 1.
From the Research
Methylene Blue and Cognitive Function
- Methylene blue has been shown to have a positive effect on cognitive function in several studies 2, 3, 4, 5.
- A study published in 2011 found that methylene blue reduces Aβ levels and rescues early cognitive deficit by increasing proteasome activity in a mouse model of Alzheimer's disease 2.
- Another study published in 2014 found that methylene blue attenuates learning and memory deficits caused by carotid occlusion in rats 3.
- Methylene blue has also been shown to have antidepressant, anxiolytic, and neuroprotective properties, which may be beneficial for the treatment of neuropsychiatric disorders 4.
- A review published in 2024 discussed the potential of methylene blue in the treatment of traumatic brain injury, brain ischemia, and Alzheimer's disease, highlighting its antiapoptotic, anti-inflammatory, and autophagy-activating effects 5.
Mechanism of Action
- The mechanisms underlying the effects of methylene blue on cognitive function are thought to be mediated by its ability to increase proteasome activity, reduce Aβ levels, and improve mitochondrial function 2, 3, 5.
- Methylene blue has also been shown to have a dose-dependent effect on the generation of reactive oxygen species, which may contribute to its neuroprotective effects 4.
Comparison with Other Treatments
- A network meta-analysis published in 2021 compared the effects of cholinesterase inhibitors, including donepezil, galantamine, and rivastigmine, on cognition and adverse events in people with vascular cognitive impairment 6.
- The results showed that donepezil 10 mg and galantamine 16 to 24 mg had a slight beneficial effect on cognition, although the size of the change was unlikely to be clinically important 6.
- Methylene blue may have a more favorable profile compared to these treatments, given its potential for neuroprotection and lack of significant adverse effects 4, 5.