ABSTRACT The long-term objective of this research is to develop an effective approach that can reduce falls for people with Alzheimer’s disease (AD) and related disorders. This project’s overall goal is to systematically examine if people with AD can acquire fall prevention skills from a novel paradigm - perturbation training. The specific aims of this proposed project are (1) to test if people with AD can adapt to perturbations on a treadmill and learn fall resistant motor skills; (2) to inspect if people with AD can retain motor skills learned in Aim 1 for at least 6 months; and (3) to determine if people with AD can generalize fall resistant skills gained on the treadmill to overground perturbations and daily living conditions. We will use a two-arm randomized, controlled longitudinal design to achieve these goals. A group of 30 older adults with mild AD will be randomized into two groups: A (training) and B (placebo). Group A will undergo a perturbation training-based motor learning session including 20 slips (S1-S20) and 20 trips (T1-T20) on a special treadmill. These perturbation trials will be mixed with regular walking trials in random order. Group B will walk on the treadmill with no perturbations for the same time as group A. Then, both groups will be exposed to a sudden overground slip (initial overground slip) and trip (initial overground trip). Participants will return for a retention session 6 months later to undergo another treadmill slip and trip (treadmill reslip and retrip) followed by an overground slip and trip (overground reslip and retrip). The perturbation outcome (fall or non-fall) and dynamic stability will be determined for slip and trip trials. Self-reported real-life falls over 6 months after the learning session will be collected for both groups. The primary outcome is the binary perturbation outcome following either the slip or trip. Dynamic stability during slips and trips and the all-cause falls in daily living will be our secondary variables. The primary outcome and dynamic stability will be compared between S1 and S20 and between T1 and T20 within group A to test if people with AD can adapt to large-scale slips and trips (Aim 1). To determine whether people with AD can retain the skills learned in Aim 1 for at least 6 months (Aim 2), the primary outcome and dynamic stability on treadmill reslip and retrip during the retention session will be compared between groups. The primary outcome and dynamic stability will also be compared between groups on the overground slips and trips during the acquisition and retention sessions to test if people with AD can immediately transfer the skills learned in Aim 1 to overground and if this transfer can maintain for 6 months (Aim 3). In addition, the prospective falls will be compared between groups to verify if people with AD can transfer the acquired fall resistant skills on the treadmill to everyday living conditions (Aim 3). Perturbation is a promising modality to prevent fa...