Assessment of visually guided reaching in prodromal Alzheimer’s disease: a cross-sectional study protocol

INTRODUCTION: Recent evidence has implicated the precuneus of the medial parietal lobe as one of the first brain areas to show pathological changes in Alzheimer’s disease (AD). Damage to the precuneus through focal brain injury is associated with impaired visually guided reaching, particularly for objects in peripheral vision. This raises the hypothesis that peripheral misreaching may be detectable in patients with prodromal AD. The aim of this study is to assess the frequency and severity of peripheral misreaching in patients with mild cognitive impairment (MCI) and AD. METHODS AND ANALYSIS: Patients presenting with amnestic MCI, mild-to-moderate AD and healthy older-adult controls will be tested (target N=24 per group). Peripheral misreaching will be assessed using two set-ups: a tablet-based task of lateral reaching and motion-tracked radial reaching (in depth). There are two versions of each task, one where participants can look directly at targets (free reaching), another wheren they must maintain central fixation (peripheral reaching). All tasks will be conducted first on their dominant, and then their non-dominant side. For each combination of task and side, a Peripheral Misreaching Index (PMI) will be calculated as the increase in absolute reaching error between free and peripheral reaching. Each patient will be classified as showing peripheral misreaching if their PMI is significantly abnormal, by comparison to control performance, on either side of space. We will then test whether the frequency of peripheral misreaching exceeds the chance level in each patient group and compare the overall severity of misreaching between groups. ETHICS AND DISSEMINATION: Ethical approval was provided by the National Health Service (NHS) East of England, Cambridge Central Research Ethics Committee (REC 19/EE/0170). The results of this study will be published in a peer-reviewed journal and presented at academic conferences.