Background and objectives: Impaired spatial navigation is considered an early sign in many neurodegenerative diseases. We aimed to determine if spatial navigation was associated with future dementia in patients with subjective cognitive decline (SCD) or mild cognitive impairment (MCI), and to explore associations between spatial navigation and biomarkers of Alzheimer’s disease (AD) and neurodegeneration.

Methods: The study included memory clinic patients without dementia in the longitudinal BioFINDER cohort. The Floor Maze Test (FMT) was used to assess spatial navigation at baseline. Conversion to dementia were evaluated at 2- and 4-year follow-ups. At baseline, amyloid-β 42/40 ratio, phosphorylated-tau (p-tau) and neurofilament light (NfL) were analysed in CSF. Cortical thickness and volume of regions relevant for navigation, and white matter lesion volume were quantified from MRI. The predictive role of the FMT for conversion to all-cause dementia was analysed using logistic regression analyses in two models; 1) controlled for age, sex and education, and 2) adding baseline cognitive status and MMSE. Associations between FMT and biomarkers were adjusted for age, sex, and cognitive status (SCD or MCI).

Results: 156 patients with SCD and 176 patients with MCI were included. FMT total time was associated with progression to all-cause dementia in model 2 at 2-year (OR 1.10, 95% CI 1.04, 1.16) and at 4-year follow-up (OR 1.10, 95% CI 1.04, 1.16), i.e., a 10 % increase in odds of developing dementia per every 10 sec increase in FMT. In the adjusted analyses, P-tau and NfL was associated with FMT total time, as well as hippocampal volume, parahippocampal and inferior parietal cortical thickness. Amyloid-β 42/40 ratio was not associated with FMT total time.

Discussion: Impaired spatial navigation was associated with conversion to dementia within 2 and 4 years, and with key CSF and MRI biomarkers for AD and neurodegeneration in patients with SCD and MCI. This supports its use in early cognitive assessments, but the predictive accuracy should be validated in other cohorts.

Classification of evidence: This is a Class 1 prospective cohort study demonstrating association of baseline markers of spatial recognition with development of dementia in patients with SCD or MCI at baseline.

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