Approved Research
Understanding two novel factors related to motor impairment in the development of dementia - UK Biobank
Lay summary
Current scope: To examine (1) whether circulating mitochondrial DNA copy number (mtDNA-CN), heteroplasmy load, and other mitochondria-related features as well as brain iron deposition predict future dementia, (2) which baseline factors and (3) genetic variants are associated with circulating mtDNA-CN, heteroplasmy load and other mitochondria-related features and brain iron deposition, (4) whether mitochondria- and iron-related genetic variants predict future dementia, and (5) shared causal pathways underlying the relationship between circulating mtDNA-CN, heteroplasmy load and other mitochondria-related features and with brain iron deposition.
New scope: To examine (1) whether circulating mitochondrial DNA copy number (mtDNA-CN), heteroplasmy load, and other mitochondria-related features as well as brain iron deposition predict future dementia, cognition, and brain structure? If it does, would the relationship differ by the presence of early biological damage (e.g. somatic mutation burden, frailty); (2) whether mtDNA-CN predicts inflammation, physical function (e.g., grip strength, gait speed), telomere length, and anemia, (3) what biomarkers (e.g. proteomics, metabolomics), lifestyle and environmental factors (e.g., diet, physical activity by self-report or accelerometry, sleep, psychosocial factors, traumatic events), disease risk factors (e.g., cardiovascular disease risk factors) and (3) genetic variants are associated with circulating mtDNA-CN, heteroplasmy load and other mitochondria-related features and brain iron deposition; (4) whether mitochondria- and iron-related genetic variants predict future dementia, and (5) What are the shared causal pathways underlying the relationship of circulating mtDNA-CN, heteroplasmy load and other mitochondria-related features and brain iron deposition with dementia.
Aims: We aim to investigate the role of circulating mtDNA-CN, heteroplasmy load and other mitochondria-related features and brain iron deposition in predicting incident dementia, including Alzheimer's disease and other subtypes, with and without motor impairment, in the 500,000 participants from the UK Biobank prospective cohort.