This application for an administrative supplement is written in response to NOT-AG-17-008: Alzheimer's Disease and its related Dementias (AD/ADRD), which is targeted for NIH grants that are not focused on Alzheimer's disease (AD). Our funded parent grant (AA010723), "Alcohol: A Modifiable Risk Factor for Ataxia and Decline in MCI," is investigating gait and balance instability together with levels of alcohol consumption as potential contributors to decline in postural stability as occurs in Mild Cognitive Impairment (MCI), often heralding AD. The supplement proposes to expand our directed search for neural substrates and performance factors that contribute to stability declines using advanced multi-modal imaging and analysis combined with innovative gait and stability metrics in men and women with MCI and age- and sex-matched controls with varying levels of alcohol consumption, from none to meeting criteria for Alcohol Use Disorder (AUD). We propose to use a specialized MRI analysis protocol (Quantitative Susceptibility Mapping, QSM) to measure non-heme iron, which accumulates in the brain with age, MCI, AD/ADRD, and AUD. Relevant to this project, iron concentration is greatest in structures serving motor functions, notably, basal ganglia (globus pallidus, caudate nucleus, and putamen), substantia nigra, and dentate nuclei of the cerebellum. Age, alcohol, and disease related accumulation of iron in these brain regions have the potential 1) to disrupt motor performance involving gait and balance and 2) to attenuate functional connections intersecting with these regions. Accordingly, we propose expansion of the parent grant to address the following aims: a) To test regional iron deposition as substrates of selective postural and gait instability metrics in men and women with and without MCI with varying levels of alcohol consumption, from none to AUD. b) To determine whether local iron deposition disrupts or attenuates functional connectivity between subcortical and cerebellar motor substrates and their cortical targets in MCI and how levels of alcohol consumption contribute to the iron-related disruption and potentially accelerate progression from MCI to AD/ADRD. Slowness of gait has been recognized as an early feature of Alzheimer's Disease and its related Dementias. Although postural instability and gait disturbances may be subtle in MCI, quantitative analysis may reveal component factors of declining gait that are precursors to the emergence of AD/ADRD. Gait comprises multiple factors that can be identified and dissociated with our recently devised analysis of videos taken while people walk. Relevantly, this motor and neuroimaging protocol, which is well-tolerated by our older participants, will be readily translated to a future proposal to track postural instability in our current cohort of MCI as some progress to AD/ADRD. Ultimately, we anticipate that identified gait/brain relations may have the sensitivity and specificity to serve as prodro...