Urinary formic acid is associated with cerebral amyloid deposition and glucose metabolism in memory clinic patients

Background: Urinary formic acid (FA) has been reported to be a biomarker for Alzheimer's disease (AD). However, the association between FA and pathological changes in memory clinic patients is currently unclear.

Objective: This study aims to investigate associations between FA and pathological changes across different cognitive statuses in memory clinic patients.

Methods: A cohort of patients with mild cognitive impairment (MCI-Aβ- n = 37, MCI-Aβ+ n = 33), AD dementia (n = 39), and cognitively normal subjects (CN-Aβ- n = 98, CN-Aβ+ n = 50) were included. Comprehensive neuropsychological assessment, urinary FA, AD-related plasma biomarkers, MRI scans, [¹⁸F]-flurbetapir and [¹⁸F]-FDG PET scan data were collected from all participants.

Results: Urinary FA levels were higher in patients with MCI and AD than in CN subjects and higher in Aβ+ (CN- Aβ+, MCI-Aβ+, AD dementia) subjects than in Aβ-subjects (CN- Aβ-, MCI-Aβ-). Urinary FA was positively associated with cerebral Aβ deposition and negatively associated with glucose metabolism, both at the global level and in multiple regions of interest cortical regions in participants with different cognitive statuses. Additionally, urinary FA levels were positively correlated with the severity of white matter hyperintensities and hippocampal atrophy. Urinary FA combined with age, Mini-Mental State Examination, plasma p-tau181, and neurofilament light chain could be used to predict Aβ deposition in the brain.

Conclusions: Urinary FA is associated with brain pathological changes in memory clinic patients, including cerebral Aβ deposition, glucose metabolism, white matter hyperintensities, and hippocampal atrophy. It could be used as a biomarker for the early diagnosis of AD and predicting Aβ deposition.