To characterize disease-specific handwriting abnormalities across neurological disorders involving motor and cognitive impairment and to evaluate handwriting as a scalable, non-invasive biomarker for diagnosis, disease stratification, and treatment monitoring.

Handwriting is a complex motor-cognitive task integrating fine motor control, visuospatial organization, and linguistic processing. Neurological disorders often disrupt these functions, producing abnormalities such as dysgraphia, agraphia, and micrographia. Handwriting changes are well established in Parkinson’s disease (PD) and Alzheimer’s disease (AD), but the consistency, task dependence, and disease-specific relevance of handwriting features across other neurological conditions remain incompletely defined.

A PRISMA-guided systematic review of PubMed and Scopus identified studies evaluating handwriting in neurological disorders with motor and cognitive components. Inclusion criteria required original patient-acquired handwriting data or review articles. Non-English studies, non-peer-reviewed publications, case reports or series, and analyses based on pre-existing datasets were excluded. 

Of 806 studies screened, 181 met inclusion criteria. Earlier work primarily used paper-and-pencil tasks; more recent studies increasingly employed digitizing tablets and instrumented pens. Free writing and repetitive character tasks were most common. PD demonstrated consistent micrographia, reduced velocity, increased jerk, and pressure variability, with task-dependent responsiveness to levodopa and deep brain stimulation. AD was characterized by central agraphia, spelling errors, and visuospatial disorganization. Motor-dominant conditions such as multiple sclerosis (MS) and Huntington’s disease (HD) showed timing instability and velocity variability, with HD metrics distinguishing premanifest carriers. Primary progressive aphasia (PPA) demonstrated language-driven dysgraphia, while progressive supranuclear palsy (PSP) showed mixed timing and size-scaling abnormalities. Amyotrophic lateral sclerosis (ALS), normal pressure hydrocephalus (NPH), spinocerebellar ataxia (SCA), and multiple system atrophy (MSA) showed handwriting disturbances, though features remain inconsistently characterized.

Handwriting analysis captures disease-specific motor and cognitive signatures and represents a promising, low-cost biomarker for early detection and longitudinal monitoring across neurological disorders.