Uncovering the causal link between cerebral glucose metabolism and cognitive function in Alzheimer's disease

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Abstract
Cerebral glucose metabolism is distinctly disrupted in Alzheimer's disease (AD), though its role in downstream cognitive decline remains unclear. Ueda et al. leverage Mendelian Randomization by integrating genetics, imaging and cognitive data to demonstrate that cerebral glucose metabolism is causally linked to cognitive performance. This approach lays the groundwork for novel therapeutic strategies by suggesting that metabolism-focused interventions may mitigate cognitive impairment in AD. Future studies should further integrate single-cell and multi-omics strategies to elucidate cellular and molecular pathways related to causal effects and explore the influence of co-pathologies and epigenetics on metabolic and cognitive performance.
Funding Information
  • National Institute on Aging (RF1AG077627)
  • BrightFocus Foundation (A2023012F)
  • National Institute of Neurological Disorders and Stroke (RM1NS132996)

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