Digitised hand movement and plasma NfL are complementary biomarkers of the dementia continuum

BACKGROUND Emerging research suggests hand motor biomarkers help identify dementia, but it is unclear which test is best, or whether combining with a blood-based biomarker may further improve classification. We evaluated combinations of hand motor measures and plasma neurofilament light (NfL) to distinguish dementia, Mild Cognitive Impairment (MCI) and Subjective Cognitive Impairment (SCI) from cognitively-healthy controls (HC). METHODS Three-hundred and seventeen participants (71 dementia, 105 MCI, 59 SCI, 82 HC) completed key-tapping, finger-to-thumb-tapping, grip strength, and NfL analysis in a cognitive clinic. Age-, sex-, and education-adjusted Receiver-Operating-Characteristic curves measured classification accuracy. RESULTS Lower-frequency and higher-variability of key-tapping associated with weaker grip strength and higher NfL levels. Models combining key-tapping and NfL best classified dementia (97%), MCI (97%) and SCI (81%) from HC, outperforming individual measures. CONCLUSION Integration of a brief hand motor test and NfL could aid with distinguishing cognitive diagnosis groups. Findings support multimodal approaches for early dementia detection.