Digital detection of handwriting impairments in patients with atypical Alzheimer’s disease and frontotemporal dementia

PROJECT SUMMARY/ABSTRACT Patients with neurodegenerative disease and dementia frequently report difficulties writing in their daily lives as an early symptom, and clinical observations suggest that this may be a valuable tool to support differential diagnosis. Nevertheless, the reported challenges often go overlooked by clinicians who do not have the domain expertise to recognize their relevance or identify their etiology. Empirically, written language production is vastly understudied in these populations, particularly when compared to auditory language and speech production, which also limits the clinical utility at present. We propose that using digital tools to collect and characterize handwriting samples could increase access for timely and accurate dementia diagnoses, particularly for those patients who do not have access to the costly neuroimaging and multidisciplinary expertise that are currently required. Accurate diagnoses are paramount for tailoring prognosis and access to increasingly available disease modifying drugs. Before digital handwriting analysis can inform timely and accurate dementia diagnoses or prognosis, it is crucial to characterize the handwriting patterns specific to each of the atypical Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) variants. Prior dementia research has focused on linguistic knowledge by examining spelling errors or on singular aspects of fine motor skill in specific groups (e.g., micrographia in Parkinson’s disease). Exploiting informative elements of handwriting samples requires more comprehensive analysis of the writing process and the written product and direct comparison of handwriting across dementia phenotypes. Writing process variables (e.g., stroke speed) are those extracted during the physical act of writing and must be collected using a digitizing tablet or similar tool. Written product variables (e.g., letter size and spacing) can be extracted from any written sample. This proposal seeks support for the technology, personnel, and statistical support to 1) retrospectively analyze longitudinal changes in written product variables, derived from descriptions of the Western Aphasia Battery picnic scene from a cohort of 90 patients with primary progressive apraxia of speech or agrammatic primary progressive aphasia (PPAOS/agPPA) and 40 healthy controls, with at least two annual visits and 2) characterize the written product and writing process in the same task performed on a digitizing tablet in a prospective cohort of 80 patients with atypical AD and FTLD phenotypes (20 each: posterior cortical atrophy, logopenic primary progressive aphasia, PPAOS/agPPA, and semantic dementia) and 60 healthy controls. Achieving these aims would be a foundational step toward developing a digital marker of neurological impairment across AD and FTLD phenotypes, paving the way for earlier, accurate diagnoses in a highly cost-effective and accessible way.