Motor slowing is common in aging and is associated with higher risk of developing future mild cognitive impairment or Alzheimer’s disease up to 12 years later. We hypothesize that two important factors, mitochondria dysfunction and brain iron deposition, act jointly to cause disruptions in the brain and contribute to Alzheimer’s disease. However, current data that connect these two factors with brain health in humans is scarce. We aim to investigate whether mitochondrial dysfunction and brain iron deposition predict future dementia, especially Alzheimer’s disease, with and without motor impairment, in the whole cohort of UK Biobank. We also aim to determine the genetics that are related to mitochondrial dysfunction and brain iron deposition, which may provide new insight into promising drug targets for future treatments. Specifically, we will use the whole genome sequencing data to obtain blood measures related to mitochondria, including mitochondrial DNA copy number (i.e. the number of mitochondrial DNA genomes per cell), heteroplasmy load (i.e. the presence of more than one mitochondrial DNA type), and other mitochondria-related features. We will use brain magnetic resonance imaging data to estimate brain iron deposition. The estimated project duration is 3 years. An advanced understanding of these mechanisms could lead to identifying useful biomarkers and new opportunities to intervene to prevent cognitive decline or delay the onset of dementia.
