Kinematic handwriting impairments in olfactory dysfunction-related post-acute covid syndrome: short and long-term neurophysiological considerations

Abstract

Background: Post-Acute COVID-19 Syndrome (PACS) frequently includes persistent olfactory dysfunction (OD) and may share neurocognitive features with Alzheimer's disease (AD). While fine motor impairments in handwriting are established in AD, they have not been systematically investigated in PACS. Methods: In this prospective-retrospective study, handwriting kinematics from 30 patients with OD-related PACS were compared with those of 30 healthy participants (HP) matched for age, sex, and education. Tasks were performed on a digital tablet which automatically extracted kinematic parameters including average pressure (AVP), maximum pressure (MXP), average speed (AVS), and average jerk (AVJ) across linguistic, cognitive non-linguistic, and non-cognitive non-linguistic tasks. A separate cohort comprising 16 patients with AD or mild cognitive impairment (MCI) and 16 matched controls was also evaluated. Results: Patients with OD-PACS showed significantly lower AVP, MXP, AVS, and AVJ values than HP (all p < 0.01), with deficits evident across all task categories. No significant correlations were found between olfactory test scores and kinematic parameters. In contrast, AD/MCI patients exhibited higher AVP and MXP in specific tasks. Conclusions: This first kinematic handwriting analysis in OD-PACS reveals fine motor slowing, reduced pressure, and decreased movement variability. These alterations, independent of olfactory performance, may affect the reliability of handwriting-based AD screening in this population. Longitudinal studies are warranted to clarify causality and potential reversibility.