Cerebral glucose uptake and cognitive functions: A phenome-wide Mendelian randomization study.

Area of Science:

• Neuroscience
• Genetics
• Medical Imaging

Background:

• Increasing cerebral glucose uptake is a potential therapeutic strategy for Alzheimer's disease (AD).
• Observational studies suggest a link, but establishing causality is challenging.
• Limitations in observational data hinder clear causal inference for AD interventions.

Purpose of the Study:

• To investigate the causal relationship between cerebral glucose uptake and cognitive function in Alzheimer's disease (AD).
• To evaluate cerebral glucose uptake as a potential therapeutic strategy for AD.
• To systematically examine the causal impact of brain glucose metabolism on cognition.

Main Methods:

• Utilized [18F] fluoro-2-deoxy-2-D-glucose positron emission tomography (FDG-PET) to measure cerebral glucose uptake.
• Employed phenome-wide Mendelian randomization to assess causal links between glucose uptake in 113 brain regions and 96 cognitive scores.
• Analyzed data from the Alzheimer's Disease Neuroimaging Initiative (ADNI).

Main Results:

• Genetically predicted increases in cerebral glucose uptake showed a trend towards improved cognitive assessment scores across brain regions.
• Causal relationships were robust across sensitivity analyses, pleiotropy assessments, and multiple testing corrections.
• Confirmed causal links between glucose uptake and cognitive scores like the Alzheimer's Disease Assessment Scale and Clinical Dementia Rating.

Conclusions:

• Provided genetic evidence for a causal relationship between cerebral glucose uptake and cognitive function.
• Suggests FDG-PET imaging in specific brain regions may act as a surrogate marker for cognitive function.
• Supports the potential of therapies targeting cerebral glucose uptake to preserve cognitive function in AD patients.