Beyond Missing Data: Questionnaire Response Uncertainty as an Early Digital Sign of Dementia-Related Vulnerability

Abstract

Explicit "Do not know" responses are treated as missing data, although their accumulation may encode uncertainty. We analysed 502,234 UK Biobank participants to test associations between response uncertainty and incident dementia-related diagnoses. Compared with participants giving 0--1 such responses, those giving more than seven had higher risks of the dementia-related disease composite (hazard ratio 1.62, 95% confidence interval 1.50--1.74), Alzheimer's disease (1.63, 1.48--1.79), and vascular dementia (1.63, 1.42--1.86) after multivariable adjustment. Associations were approximately linear, persisted after a two-year lag, and were directionally reproduced in Scotland and Wales. Polygenic risk scores minimally attenuated these associations. Domain, molecular, and chronic-disease analyses placed response uncertainty within a broader multisystem vulnerability phenotype. Here, we show that explicit response uncertainty provides a scalable behavioural marker of subsequent dementia-related risk.