PROJECT SUMMARY NIH RFA AG-24-041 requests applications to determine the neural mechanisms that underlie the association between gait and cognition in aging and Alzheimer's disease (AD) and Alzheimer's disease-related dementias (ADRD). Mobility declines precede mild cognitive impairment (MCI) in most older adults. Understanding the neural control of gait in these individuals will inform the use of gait changes as an early biomarker for AD/ADRD and lead to new, early interventions. Our well-composed, cross disciplinary team has the requisite expertise in aging, cognitive decline, sensorimotor neuroscience, and spatial navigation to address this topic. We propose a novel and transformational perspective that the relationship between mobility disability and MCI lies in vestibular and hippocampal contributions to gait and cognition. Vestibular function declines with aging and is even more impacted in individuals with MCI and Alzheimer's disease (AD). These declines are linked to falls in both typical aging and AD, a major health concern with often devastating consequences in aging. It is well known that vestibular inputs project to the brainstem, cerebellum, and vestibular cortex. What is less understood are vestibular projections to the hippocampus, primary motor cortex, and premotor areas. This is a critical knowledge gap, as the hippocampus and other temporal lobe structures play a key role in spatial navigation, a behavior which also declines in MCI and AD. The hippocampus shows rapid and early atrophy in AD. Here, we test the novel hypothesis that vestibular declines impact walking in those with subjective cognitive decline coupled with a family history of AD (placing them at high risk for AD). We propose that spatial navigation performance during walking is more impaired in this population due to simultaneous cognitive and motor demands on declining vestibular inputs. Aim 1 is to determine whether brain structure and network segregation (how independently a network functions) of vestibular-motor and vestibular-hippocampal brain regions are reduced in individuals with subjective cognitive decline. We will assess whether these brain metrics are linked to declines in mobility and spatial navigation. Under Aim 2, we use cutting edge, mobile EEG approaches to identify spectral power differences between those with subjective cognitive decline and typical aging during actual walking and spatial navigation. In Aim 3, we will determine whether vestibular network segregation can be restored with bilateral vestibular cortical transcranial direct current stimulation. We will further determine whether blood biomarkers for phosphorylated tau and amyloid beta mediate brain-behavior associations in Aim 4. The results will lead to a greater understanding of the neural control of gait and cognitive-motor interactions in subjective cognitive decline, providing insights for new, early biomarkers and interventions for impending declines.