Early diagnosis of Alzheimer's disease through handwriting analysis and deep learning: A review.

内容摘要

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders worldwide, requiring early identification for timely intervention and to slow disease progression. However, existing diagnostic approaches, while effective at later stages, remain limited in detecting early-stage AD. Handwriting analysis has recently emerged as a non-invasive, cost-effective, and ecologically valid digital behavioral biomarker that reflects neurocognitive impairment. This review examines the role of handwriting as a neurocognitive marker for AD, focusing on integrating deep learning methodologies to enhance early diagnostic accuracy. It also elucidates the neurocognitive mechanisms linking handwriting behavior and AD, addressing current methodological and translational challenges. We performed a PRISMA-informed structured literature search and narrative synthesis of handwriting- and drawing-based studies for detecting AD/mild cognitive impairment (MCI), including offline handwriting images and online pen-stroke kinematics captured by digital devices. Task paradigms, data dimensions, preprocessing pipelines, modeling strategies (traditional machine learning and deep learning), evaluation practices, and translational considerations were summarized, and studies were organized by detection purpose and analytic approach. Our findings show that handwriting-based models generally discriminate AD/MCI from healthy controls with accuracy exceeding 80%, while deep learning models (e.g., convolutional neural network and multimodal Transformer fusion) approach 90% in structured tasks like clock drawing and figure copying. Online kinematic markers (e.g., reduced velocity, prolonged in-air time, increased pausing, and pressure instability) recur across studies, and multimodal integration with speech, gait, or facial signals can further improve sensitivity and ecological validity, although most studies are small and single-center.