Methylene Blue Enhances Memory Retrieval and Increases Brain Functional MRI Activity

By Will Boggs MD

NEW YORK - Orally administered methylene blue enhances memory retrieval and increases brain functional MRI activity during sustained attention and short-term memory tasks, researchers report.

"The findings suggest that methylene blue can modulate brain networks related to sustained attention and short-term memory after a single oral low dose," Dr. Timothy Q. Duong from The University of Texas Health Science Center at San Antonio told Reuters Health by email.

Methylene blue has been shown to produce focal effects in brain regions where mitochondrial respiration can accept more electrons because of increased energy demands, and its memory-enhancing effects have been demonstrated in long-term memory tasks in animals and humans.

Dr. Duong's team used multimodal functional MRI (fMRI) to investigate the effects of a single low dose of oral methylene blue and its neural correlates in a randomized, double-blinded, placebo-controlled trial involving 26 healthy volunteers.

During a task that measured reaction time to a visual stimulus, methylene blue led to increased functional MRI activity in the bilateral insular cortices, the researchers report in Radiology, online June 28.

Different networks were influenced by methylene blue during the three phases - encoding, maintenance, and retrieval - of a delayed match-to-sample task.

"The fMRI results also showed an increased response during short-term memory tasks involving the brain's prefrontal cortex, the parietal lobe, primarily associated with the processing of sensory information, and the occipital cortex - the visual processing center of the brain," Dr. Duong explained.

During the memory retrieval task, there was a 7% increase in the correct number of behavioral responses after administration of methylene blue, compared with no change after administration of placebo (p=0.01).

There were no significant differences between the methylene blue and placebo treatments in cerebral blood flow or cerebrovascular reactivity.

A week after drug administration, there were no differences between the treatment groups in affect scores or in the number of recalled words from a crossword puzzle completed immediately after drug administration.

Dr. Duong suggested that methylene blue might be used "to improve memory function and attention in patients with memory disorders such as MCI (mild cognitive impairment) and AD (Alzheimer disease). We are currently conducting such trial with chronic methylene blue administration. Results are expected next year."

Dr. Donovan Tucker from Augusta University's Department of Neuroscience & Regenerative Medicine in Augusta, Georgia, told Reuters Health by email, "I find it intriguing that boosting mitochondrial function imparts a cognitive improvement so rapidly and in such a complex system as working memory in humans. These results demonstrate a link between mitochondrial function and cognition."

"If validated, methylene blue could be helpful to many people suffering from executive deficits in neurodegenerative disorders with mitochondrial dysfunction such as Alzheimer's disease or vascular dementia," he said. "Furthermore, the low side effect profile of low dose methylene blue makes it a promising treatment for mood disorders like major depressive disorder and bipolar disorder where compliance is a significant concern."

"This report highlights the novel effects of drugs long used in the clinic," Dr. Tucker added. "There may be other drugs targeting the mitochondria that are already in use which could confer cognitive benefits to patients in need. Further lines of research should explore drugs that can make it from bench to bedside in such a rapid fashion."

SOURCE: https://bit.ly/29acEt5

Radiology 2016.

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