The Effects of Living at Altitude on the Prevalence of Dementia

A lower incidence of dementia has been observed in populations residing at high altitudes compared to those at low altitudes. A possible cause is the inverse relationship between altitude and the partial pressure of inspired oxygen. This paper investigates the long term impact that living at altitude has on mitochondrial function. We use simulation methods to model the dynamics of a population of mtDNA and the proliferation of deletion mutants. Clonal expansion of these deletion mutants over many years impairs mitochondrial function resulting in cell death, notably in post-mitotic cells such as neurons. Neuron loss leads to cognitive impairment, progressing to dementia over time. Our results show that there is a moderate reduction in neuron loss rates and associated cognitive decline with respect to dementia in the elderly. These results are consistent with published data on the regional prevalence of dementia when plotted against altitude.