Background
Alzheimer’s disease (AD) is associated with metabolic abnormalities linked to critical aspects of neurodegeneration. AD involves parts of the brain that control thought, language, and memory. AD is a progressive disease that begins with mild memory loss and possibly leads to the loss of the ability to carry on a discussion and respond to the environment. Combined metabolic activators (CMA) were recently administered to the AD rat model, and it was observed that CMA improved the AD-associated histological parameters in the animals. CMA promotes mitochondrial fatty acid uptake from the cytosol, promotes fatty acid oxidation in the mitochondria, and alleviates oxidative stress.
Methods
- A randomized, double-blinded, placebo-controlled phase-II clinical trial was designed, and the effect of CMA administration on the global metabolism of AD patients was studied.
- One-dose CMA included 12.35 g L-serine (61.75%), 1 g nicotinamide riboside (5%), 2.55 g N-acetyl-L-cysteine (12.75%), and 3.73 g L-carnitine tartrate (18.65%).
- AD patients received one dose of CMA or a placebo daily during the first 28 days and twice daily between day 28 and day 84.
- The primary endpoint was the difference in cognitive function and daily living activity scores between the placebo and the treatment arms.
- The secondary aim was to assess the safety and tolerability of CMA.
- Comprehensive plasma metabolome and proteome analyses were also conducted to assess the efficacy of the CMA in AD patients.
Results
- A substantial decrease was indicated in the AD assessment Scale-cognitive subscale (ADAS-Cog) score on day 84 vs. day 0 in the CMA group.
- Moreover, there was a substantial decline in ADAS-Cog scores (improvement of cognitive functions) in the CMA compared to the placebo group in patients with higher ADAS-Cog scores.
- Improved cognitive functions in AD Patients were supported by the relevant alterations in the hippocampal volumes and cortical thickness based on imaging analysis.
- The plasma levels of proteins and metabolites associated with NAD+ (nicotinamide adenine dinucleotide) and glutathione metabolism were particularly improved after CMA treatment.
Conclusion
The result of this study suggests that the treatment of AD patients with CMA can lead to enhanced cognitive functions and improved clinical parameters associated with phenomics, metabolomics, proteomics, and imaging analysis.