Computerized cognitive training enhances cognitive function in Alzheimer's disease by downregulating...

Area of Science:

• Neuroscience
• Microbiology
• Gastroenterology

Background:

• The microbiota-gut-brain (MGB) axis is increasingly recognized for its role in Alzheimer's disease (AD) pathogenesis.
• However, effective interventional strategies targeting the MGB axis for AD remain limited.

Purpose of the Study:

• To investigate the efficacy of computerized cognitive training (CCT) in individuals with mild cognitive impairment (MCI) or mild AD.
• To explore the impact of CCT on cognitive function, functional connectivity, and the MGB axis, including gut microbiota and plasma trimethylamine N-oxide (TMAO) levels.

Main Methods:

• A 24-week, single-blind, randomized controlled trial involving 84 participants with MCI or mild AD.
• Participants received either CCT or treatment as usual (TAU).
• Outcomes included cognitive assessment (ADAS-cog), functional connectivity (fNIRS), plasma TMAO, and gut microbiota analysis.

Main Results:

• CCT significantly improved cognitive function (ADAS-cog scores) compared to TAU.
• CCT led to changes in prefrontal functional connectivity and reduced plasma TMAO levels.
• CCT mitigated the expansion of Ruminococcus torques (R. torques), a gut bacterium correlated with cognitive and biomarker changes.

Conclusions:

• A 24-week CCT program enhances cognitive function in MCI and mild AD.
• The findings suggest CCT may act via the MGB axis, specifically by downregulating the R. torques-TMAO pathway.
• This pathway presents a potential therapeutic target for multi-domain interventions in AD.